Subject: GMHC Treatment Issues Vol. 6 No. 7 Date: Sep 1992 (2753 lines) &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& && T R E A T M E N T I S S U E S && &&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&&& The Gay Men's Health Crisis Newsletter of Experimental AIDS Therapies SPECIAL EDITION -- WOMEN'S TREATMENT ISSUES -- Volume 6, Number 7 Summer/Fall 1992 CONTENTS: [items are separated by "*****" for this display] HIV Disease in Women Barriers to Care Women, Immunity, and Sex Hormones Fertility, Menstruation, and Birth Control Sexually Transmitted Diseases Syphilis Pelvic Inflammatory Disease (PID) HPV & Cervical Cancer Glossary Resources ***** Editor's Note The continuing debate about AIDS in women has focused on how the disease differs in female bodies. Survival of women with AIDS depends upon a clear clinical understanding that AIDS is different in women inasmuch as women are different from men. It is important that this debate not obscure the fact that women get virtually all of the HIV-related infections that men get. The one thing we know in 1992 is that aggressive and attentive treatment of symptoms is the single most important factor for the survival of all people with AIDS, male and female. It is time that women with HIV and AIDS get the quality of and access to care and information they deserve. This publication is an effort toward that end. Treatment Issues will resume regular monthly publications in September. -- Mary Beth Caschetta -- Garance Franke-Ruta ***** HIV DISEASE IN WOMEN by Scott Wilson & Brenda Lein In 1982, the Centers for Disease Control (CDC) defined AIDS by pulling together a list of life-threatening disorders indicating severe immune deficiency from HIV disease. Since then the definition has been revised twice. Unfortunately, this list continues to exclude many HIV-related conditions common in women. This means that doctors may not recognize conditions that indicate HIV disease in women; women go misdiagnosed and untreated; women are denied financial entitlements and services; and research does not tell us much about the total AIDS epidemic. All gynecological manifestations of HIV are understood as "HIV- symptomatic but not AIDS," and will be discussed in the following pages. Other conditions that women often get are also not considered AIDS. Some of these conditions include: endocarditis (inflammation of the lining of the heart); pulmonary tuberculosis (TB); idiopathic thrombocytopenic purpura (low platelets and bruising of unknown origin); kidney failure; bacterial infections such as pneumonia, bronchitis, sinusitis; and sepsis (bacteria in the blood). All of these conditions occur commonly in women with HIV. Additionally, some conditions which do qualify a person for an AIDS diagnosis occur more commonly in women than in men. Unfortunately, very little research on HIV in women has been done. This absence of data results in a lack of reliable information on the characteristics of gender-specific AIDS.[1] The following introductory article attempts to offer a brief picture of AIDS as it occurs in women as well as the treatments available. Much of the data reported are from the Community Program for Clinical Research on AIDS, a federally-funded national network of community clinics and hospitals. The program was established in 1989 to conduct scientific trials with people who have traditionally been excluded from HIV/AIDS research. One CPCRA study, the Observational Data Base, observes and records the symptoms in, and the medications used by, people in the trial. PNEUMOCYSTIS CARINII PNEUMONIA Pneumocystis carinii pneumonia (PCP) is an AIDS-defining infection of the lungs that is caused by an organism called P. carinii. Its symptoms include shortness of breath, dry cough, and fever. PCP seems to occur very frequently in women as a first or second AIDS-defining illness. Diagnosis in women is often delayed and the illness may be severe by the time it is detected. These factors contribute to the high incidence of severe PCP in women and may contribute to a higher death rate. PCP is treated with intravenous Bactrim/Septra (different brands of the same drugs made of trimethoprim sulfamethoxazole). For people who have sulfa allergies (toxic side effects from the drug), dapsone with trimethoprim or clindamycin and primaquine are good alternatives. Intravenous pentamidine should be reserved for people who cannot take either Bactrim/Septra or dapsone. Prevention of PCP is with lower doses of Bactrim/Septra or dapsone. Bactrim/Septra is the most widely recommended PCP prophylaxis and treatment for those without allergies to sulfa drugs. If allergies exist, desensitization to the drug (taking a little bit at a time in increasing doses) is recommended when possible. In the observational data base study, only 52% of women with under 200 T4 cells were receiving PCP prophylaxis (preventive medication), and only 70% with a history of PCP were taking medications to prevent the disease from occurring again.[2] Such low numbers of women actually taking preventive medicine is very distressing, since PCP is an opportunistic infection (OI) that can be prevented in 90% of people who take appropriate prophylactic medicine. All HIV-positive women with under 200 T4 cells should take PCP prophylaxis to prevent disease. Inadequate medical attention or lack of access to quality health care clearly causes this failure in prevention. ESOPHAGEAL CANDIDOSIS Women are very likely to develop esophageal candidiasis as a first AIDS-defining illness. Esophageal candidiasis is caused by the same yeast infection that can also infect both the mouth and the vagina. It may start with an infection in the mouth (oral thrush) and spread to the esophagus (the tube that connects the mouth and stomach), causing pain when swallowing, weight loss, and vomiting. Many professionals speculate that controlling and preventing yeast infections in the vagina may also prevent esophageal candidiasis. Of 24 women with AIDS followed in a Rhode Island study,[3] nine (38%) had esophageal candidiasis that qualified them for a diagnosis of AIDS. An additional 11 developed esophageal candidiasis over the course of the study. Of women in the CPCRA observational data base, 31% developed esophageal candidiasis. Other studies show the disease to be the most frequent OI in cohorts of Haitian and Central African HIV-positive women.[4] Prevention of fungal infections is promising. For more information about prevention of this disease see Treatment Issues, Volume 5, Number 7 and Volume 6, Number 4. BACTERIAL PNEUMONIAS AND INFECTIONS Bacterial pneumonia is common in HIV disease and recurs frequently.[5] Up to 10% of people with AIDS have pneumonia caused by a number of different bacteria.[6] Community-acquired bacterial infections of all sorts often affect both women and injecting drug users (IDUs) with HIV. Additionally, bacterial pneumonia is common in pregnancy and may be more common in HIV- positive pregnant women. Some infections are easily treated with standard oral or intravenous (IV) antibiotics, while some lead to life-threatening complications. Symptoms of bacterial pneumonia include fever, wet cough, and chest pain. Pneumococcal vaccination (along with annual influenza vaccination) has been recommended for people with HIV disease with more than 200 T4 cells, although its effectiveness in HIV disease is unknown.[7] Other possible preventive measures include immunoglobulin therapy and antimicrobial prophylaxis. Bacterial pneumonias appear to occur and go undiagnosed more often in IDUs and women than in other populations.[8] One New York City study found that AIDS deaths among IDUs in a methadone maintenance program due to bacterial pneumonia and sepsis from 1984-1987 increased from 3.6 to 13.6 per 1000 deaths.[9] Additionally, it is interesting to note that during the 1980s in New York City there was a marked increase in deaths of young women due to bacterial pneumonias.[10] While this epidemic went unnoted by public health officials and AIDS experts, it is likely that many of these women died from lung disease (specifically undiagnosed PCP or bacterial pneumonia) complicated by HIV infection. MYCOBACTERIUM AVIUM-INTRACELLULARE COMPLEX Mycobacterium avium-intracellulare complex (MAC) is a serious AIDS-defining infection that tends to occur late in the course of the disease. MAC is a complex of mycobacterial organisms that produces wasting, fever, diarrhea, fatigue, anemia, and diseases of the bone marrow, liver, lung, adrenal glands, and gut. Widespread MAC in the body (disseminated) generally occurs in those already diagnosed with AIDS who have under 50 T4 cells. It may be difficult to sort out the symptoms of MAC from the symptoms of advanced HIV-disease and drug side effects. Wasting, severe anemia, and liver damage in women with HIV appear fairly often, especially in the absence of MAC, making diagnosis more difficult.[11] Disputed evidence has recently emerged indicating that MAC occurs more frequently in women than in men. Treatment and prophylaxis are difficult, but promising drugs like clarithromycin and rifabutin offer hope. More information concerning MAC treatment and prophylaxis is available in Treatment Issues, Volume 6, Number 2. TUBERCULOSIS (TB) Tuberculosis is a common infection in people with HIV worldwide,[12] and has recently resurged as an epidemic in the U. S. National rates of tuberculosis have skyrocketed in the 1990s. The disease is particularly complicated for people with HIV. Active infection includes symptoms such as fever, cough, and chest pain. TB exists in two forms: TB in the lungs (pulmonary) is highly contagious through droplets of fluid that enter the air when an infected person coughs or sneezes, and widespread (disseminated) TB, an AIDS-defining illness, causes disease of the liver, central nervous system, adrenal glands, lymph nodes, skin, reproductive organs, and heart. Disseminated TB is more likely to occur in people with suppressed immune systems. It is not, however, the contagious form of the disease. As new TB outbreaks continue to occur in the U. S., especially in urban areas, women with HIV are at risk for TB. TB is more likely to occur in areas without proper ventilation, such as shelters, hospitals, prisons, and many homes. TB in HIV- positive people usually occurs with a new infection or when an old infection reactivates. Both occur when the immune system is relatively intact (300-500 T4 cells). The PPD (Purified Protein Derivative) skin test screens for TB. The test involves injecting some proteins of the TB bacteria just under the skin of the forearm. After 48 hours, a person who is infected may develop a small, red bump at the site of injection. However, people with immune suppression often do not respond to the test, even though they have been exposed to TB. Lack of response to skin tests because of immune suppression is a condition called anergy. Sometimes the PPD test can be given along with other skin tests to see if the immune system is so suppressed that it cannot respond. For successful TB treatment, people who know they have active TB must take medication for a fairly long period of time, usually a year. TB treatment is cumbersome and sometimes requires multiple medications. In most cases, however, TB can be cured. In HIV-positive people, doctors often recommend taking medicine even longer than a year. Alarmingly, multiple drug- resistant (MDR) TB strains have recently emerged in New York and Florida. Seemingly, resistance is the consequence of inadequate care and follow-up that resulted in under medication of TB. MDR TB strains are difficult to treat with the existing range of medicines. In most cases, MDR TB has led to death in people with AIDS. Drug-resistant TB further complicates treatment in HIV- infected women, and public health officials must respond to address the problem quickly and comprehensively. KAPOSI'S SARCOMA The exact cause of Kaposi's sarcoma (KS) is not known. Rather than being a true cancer, KS is now thought to be a collection of abnormal blood vessels caused by a variety of bodily chemicals interacting in concert with immune suppression. Another theory says that KS is caused by an infectious agent. Typically, KS occurs as hard, not-very-painful, purplish splotches on the skin. It can also occur on internal organs. A recent study of KS in bisexual or homosexual men with AIDS in London identified sexual practices in which there was contact with partner's feces as a risk for KS.[13] The epidemiology of KS in women is filled with conflicting reports, but one thing is clear: women develop KS far less frequently than men. However, about 1%-3% of women develop KS.[14] In early stages, KS can be fairly benign, but in late stage AIDS, it can be an aggressive, life-threatening, even fatal, condition involving the gastrointestinal tract and lungs. A 1990 French study of 12 women with AIDS found that KS occurred only in severely immune-suppressed women.[15] An article in the British medical journal the Lancet reported KS lesions were more common among female sexual partners of bisexual men (3%) than among those of exclusively heterosexual IDUs (O. 7%).[16] It is difficult, however, to say that KS in American women is different than in men, since we do not have enough research data. One San Francisco study did find that most KS occurred in women infected through their own IV drug use.[17] For details about KS treatment see the May 1, 1991 edition of AIDS Treatment News (No. 122). ENDOCARDITIS Endocarditis is a bacterial infection that causes inflammation of the heart valves that if left untreated may lead to heart failure and death. The most common cause of endocarditis is a bacteria called Staphylococcus aureus.[18] Since endocarditis has long been associated with intravenous drug use, it is a serious problem in HIV disease for women who are IDUs. The condition is not considered an AIDS-defining illness. The most common symptom is fever, but other symptoms include heart murmurs, irregular heart beats, chills, headache, back and chest pain, stomach ache, nausea, and vomiting. Treatment is with antibiotics. Doctors can usually detect heart murmurs, which may indicate endocarditis. The disease can lead to many complications in the circulatory system, the central nervous system, the lungs, kidneys, and brain. Prophylaxis is usually indicated only in persons who have had endocarditis in the past and who need to have a surgical or dental procedure during which bacteria may enter the blood. In such an instance, single high-dose amoxicillin is recommended, with clindamycin or a two-dose erythromycin regimen for patients who are allergic to penicillin. BLOOD DISORDERS Women are more likely than men to get disorders such as low red blood cells (anemia). Besides anemia, a variety of HIV- related blood conditions cause serious problems in women, including low numbers of neutrophils (neutropenia), low numbers of white blood cells (leukopenia), low numbers of platelets (thrombocytopenia), and an inability to stop bleeding (coagulation disorders). Women, injection-drug users (IDUs), and persons with hemophilia are at increased risk for these conditions. Anemia is a broad term used to describe a decrease in the number of red blood cells. It can have many causes, including deficiency in iron or vitamin B-12, lupus, rheumatoid arthritis diseases causing inflammation, or chronic infections, such as tuberculosis, MAC,[19] parvovirus B-19, autoimmune reactions (where the body attacks its red blood cells), malnutrition, AZT, and other antiviral drugs. Many women frequently experience anemia because iron is lost during menstrual periods and in pregnancy because the growing fetus drains maternal iron stores. Signs of anemia may include paleness, fatigue, shortness of breath, and palpitations of the heart. One study of HIV-negative women found that anemia was more prevalent in black women than in Asian, Mexican, and white women.[20] It is also common among people with low incomes, probably due to malnutrition. In HIV disease, anemia can be a major complicating factor, predicting adverse drug reactions, infections, and sometimes even death.[21] Thrombocytopenia, another serious blood condition, has been associated with progression to AIDS and occurs in more than 40% of people with AIDS. [22] Idiopathic thrombocytopenic purpura (ITP), an AIDS-related condition characterized by easy bruising and mild bleeding from the nose, gums, and rectum, is common among HIV-positive women, IVDUs, and hemophiliacs.[23] Treatment is with steroids: usually prednisone (1 mg/kg by mouth every day); IV gamma globulin; or removal of the spleen (splenectomy). For the most part, response to therapy in HIV-positive people has been good. Neutropenia is a condition characterized by an abnormally low number of a subset of white blood cells called neutrophils. It can be caused by drugs associated with bone marrow damage such as, AZT, Bactrim (TMP/SMX), 5-flucytosine, acyclovir, ganciclovir, pentamidine, pyrimethamine, sulfadiazine, vinblastine, and vitamin deficiency. Neutropenia can lead to severe, life-threatening bacterial infections, but only in rare instances. WASTING In the Rhode Island study by Carpenter et al, wasting syndrome was found to be the second most common AIDS-defining condition in women.[24] Another look at AIDS-defining infection in 618 people diagnosed between 1980 and 1990 found that women were two-and-a-half times more likely than gay men to be diagnosed with wasting.[25] Wasting was added to the CDC definition in 1987 after an evaluation of diseases found often in IDUs. Wasting is generally described as an involuntary loss of 10% or more of a person's usual body weight and can be caused by a variety of conditions associated with disease and drug therapy. Wasting and weight loss accompany most major infections. Weight loss in the absence of an identified cause may result directly from HIV, which can infect intestinal cells, causing inflammation and diarrhea. An added complication of malnutrition and wasting in women is the demographics of HIV disease in women. HIV-positive women are likely to be minority, poor, and drug users or partners of drug users.[26] Weight gain strategies include appetite stimulants such as megestrol acetate (Megace), a synthetic progesterone that seems to promote weight gain in patients with AIDS who do not have significant diarrhea[27]; marijuana therapy (Marinol); or appropriate treatment for underlying causes. Other strategies include total parenteral nutrition (TPN -- also known as tube feeding), which means nutritional liquids are administered through the vein. CONCLUSION It is important to understand that women's needs, lives, and bodies have been excluded from medical attention and consideration. The healthcare system was made for men with easy access to health care. All medicines available in the pharmacy are based on men's weight, men's metabolism, and men's lab markers that measure important blood, protein, and cell levels. Thus doctors must often hazard a guess or rely on experience as to how specific medicines should be taken by women who are smaller, have more body fat, and different water-retention capacities than men. It is clear that women's access to health care is thwarted by racism, sexism and capitalism, a reality which causes significant problems for women with HIV and AIDS. Footnotes 1. Minkoff ML and De Horitz JA. et al. Care of women infected with HIV. JAMA 266:2253-2258, 1991. 2. Statistical Center: Community Programs for Clinical Research on AIDS. Observational Datat Base Project. Baseline Findings, April 17, 1991. 3. Carpenter CCJ et al. Natural history of AIDS in women in Rhode Island. JAMA 86:771-775, 1989. 4. Pape JW et al. Characteristics of AIDS in Haiti. NEJM 309:945-50, 1983; V Int'l Conf on AIDS, Abstract # TH. A. 0.25, Montreal, June 1989. 5. Cohn DL. Bacterial pneumonia in the HIV-infected patient. Infect Dis Clinics of N Amer 5(3):485-507, 1991. 6. Chaisson RE. Bacterial pneumonia in patients with HIV infection. Seminars in Respiratory Infections 4(2):133-8, 1989. 7. Daley CL. Pyogenic bacterial pneumonia in AIDS. Journal of Thoracic Imaging 6($):36-42, 1991. 8. Jiminez ML et al. Fiberoptic bronchoscopic diagnosis of pulmonary disease in 151 HIV-infected patients with pneumonitis. European J Clin Microb & Infect Dis 10(6):491-6, 1991. 9. Selwyn PA et al. Impact of the AIDS epidemic on morbidity and mortality among IVDU in a New York City methadone maintenance program. J Public Health 79(10):1358-62, 1989. 10. "Women's Unexplained Deaths Cited," New York Newsday, June 14, 1988. 11. Sathe SS et al. Severe anemia is an important negative predictor for survival with disseminated MAI in AIDS. Amer Review of Respir Dis 142:1306-12, 1990. 12. Styblo K. Overview and epidemiologic assessment of the current global tuberculosis situation with an emphasis on control in developing countries. Rev Infect Dis 11(2):S339-346, 1989; and Harries AD. Tuberculosis and HIV infection in developing countries. Lancet 335:387-390, 990. 13. Beral V et al. Risk of KS and sexual practices associated with faecal contact in homosexual or bisexual men with AIDS. Lancet 339:632-635, 1992. 14. Personal Communication, Dr. Paula Schuman, May, 1992. 15. Lassoued K et al. AIDS-associated KS in female patients. AIDS 5:877-880, 1991. 16. Huang YQ et al. HPV-16-related DNA sequences in KS. Lancet 339(8792):515-518, 1992. 17. Dodd DL et al. Oral KS in a woman as a first indication of HIV infection. J Amer Dental Assoc 122(4):61-3, 1991. 18. Himelman RB et al. Severe pulmonary hypertension and cor pulmonale in AIDS. Am J Cardiol 64:1396-1399, 1989. 19. Jacobson, MA, et al. Red cell transfusion therapy for anemia in patients with AIDS and ARC: incidence, associated factors, and outcome. Transfusion-Philadelphia 30(2):133-7,1990 20. Klebanoff MA et al. Anemia and spontaneous preterm birth. Amer J Obstet Gynecol 164:5963, 1991. 21. Steinberg, JP et al. Predictors of outcome in AIDS patients receiving zidovudine. JAIDS 2(3):229-34, 1989. 22. Kaslow RA et al. Infection with the human immunodeficiency virus: clinical manifestations and their relationship to immune deficiency. Ann Intern Med 107:474-80, 1987. 23. Finazzi G et al. Low incidence of bleeding from HIV-related thrombocytopenia in drug addicts and hemophiliacs: implications for therapeutic strategies. European J Haematol 45(2):82-5, 1990. 24. Carpenter CCl et al. Natural History of AIDS in Rhode Island. Amer J Med 86:771-775, 1989. 25. Smith E and Orholm, M Trends and Patterns of Opportunistic diseases in Danish AIDS Patients 1980-1990. Scandinavian Journal of Infectious Diseases 22(6):665-672, 1990. 26. Mitchell JL et al. HIV and women: current controversies and clinical relevance. J Women's Health 1(1):35-39, 1992. 27. von Roenn JH et al. Megestrol acetate for treatment of cachexia associated with HIV infection. Ann Intern Med 109:840- 1, 1988. 28. Klein RS et al. Periodontal disease in heterosexuals with AIDS. J Periodontal 62(8):535-40, 1991. ***** Women, Immunity, & Sex Hormones by Risa Denenberg, FNP For some time, women with HIV illness, health care providers, and activists have been concerned with the effects of HIV infection and treatment on women's hormones and the effects of hormones on HIV infection. Sex hormones are important because they make up the system responsible for regulating reproduction and sexual function. Questions about this matter are often asked by women with HIV and include: "Does HIV lead to menstrual abnormalities such as missed periods, heavier, or irregular bleeding?"; "Are these problems caused by AZT?"; "Will my menstrual cramps and problems worsen because of HIV?"; "Am I going through early menopause?"; "Why have I lost my sex drive?"; and "Can I take birth control pills?" Researchers have scrutinized how pregnancy impacts HIV infection in HIV-positive women, but thus far they have barely begun to address these other important concerns. IMMUNE SYSTEM The immune system's purpose is to keep the body healthy. Its job is to recognize what belongs to the body and is therefore part of it, and what is foreign or "other." It must attack and remove disease-causing substances and organisms without causing damage to itself. The immune system is a complicated network of cells and chemicals, and can be thought of as consisting in two parts: the humoral system (substances called antibodies) and the cell-mediated system (mainly white blood cells). Both systems activate white blood cells, called lymphocytes -- T-cells and B- cells and T-cells (including T4s). T-cells recognize foreign substances (antigens), attach to their surfaces, and release substances (lymphokines) which communicate with B-cells. B-cells then produce unique substances called antibodies. Each type of antibody formed in this complicated interaction is highly specific and able to identify and destroy only one antigen. Immune system dysfunction can come from an under- or overproduction of any one or a combination of these substances. ENDOCRINE SYSTEM The function of the endocrine system is to communicate and regulate the body's many complicated activities. This system works by hormones and other substances that are produced in organs called glands.* Hormones are sent to distant locations in the body called "target organs" to communicate specific instructions that regulate important bodily functions. These include energy production, growth, body temperature, certain behaviors, and reproductive and sexual functions. Menstrual and reproductive functions are only a portion of the entire makeup of the endocrine system. However, this article will be limited to the portion of the endocrine system concerned with reproduction. Menstruation occurs by a communication between the pituitary gland in the brain and the ovaries. The menstrual cycle directs the ovaries to produce a ripe egg approximately once a month during a woman's reproductive years. The process works as follows: 1. The hypothalamus gland stimulates the pituitary gland, the brain center which acts as the master switch for the hormone system. 2. The pituitary gland releases two hormones called follicle stimulating hormone (FSH) and luteinizing hormone (LH). These signal the ovary to produce its own hormones (estrogen and progesterone). 3. Estrogen and progesterone, sometimes referred to as the female hormones, stimulate the release of a ripe egg, the thickening of the lining of the uterus, and changes in the breast. If the egg becomes fertilized it will embed itself in the thick lining, which becomes the placenta. If the egg is not fertilized, the lining will be shed from the body as a menstrual period. 4. Estrogen and progesterone levels lessen, signaling the hypothalamus gland to begin the cycle again. WHERE ENDOCRINE AND IMMUNE FUNCTION MEET Research has shown that the endocrine system is affected by: 1) differences in male and female immune responses; 2) administering hormones and hormone therapy (as in the case of oral contraception); 3) pregnancy; and 4) immune deficiency and gynecological disease. Much of this research has been conducted in test tubes or animals. Also, many of the reports offer theoretical explanations for their observations. In other words, even research fails to describe the real life hormonal/immunological phenomena in women's bodies. Differences in male and female immune responses are well documented. It has been determined that female sex hormones, especially estrogen and progesterone, have a distinct effect on immune function.[1] Women seem to be more resistant to a variety of viral, bacterial, and fungal infections than men. Women also bear the burden of greater susceptibility to autoimmune disorders.[2] These occur when the immune system ends up attacking the body.[3] Examples of autoimmune disorders include lupus, rheumatoid arthritis, idiopathic thrombocytopenic purpura (ITP), and thyroiditis. Females are also more likely to reject transplant organs or grafts than males. Some researchers speculate that a woman's better ability to fend off illness may be the reason why women live longer than men. The exact mechanism for this difference between men and women, however, is not clearly understood. Apparently, both humoral and cellular immune activities are more aggressive in women than men.[4] While sex hormones seem to directly affect the activity of the immune system, HIV-related implications remain unexamined at this time. CLINICAL CONCERNS Hormone problems are often faced by women whose treatment may be complicated by immune suppression. The use of hormone therapy, like estrogen replacement for menopause or oral contraception, has neither been approved nor forbidden for women with AIDS by current standards of care. Too often, in an effort to "do no harm," hormones are withheld from patients. This policy may be reinforced by the mistaken idea that immune- suppressed patients will all progress to AIDS in the very near future. There may also be a belief that women with HIV infection are "asexual," or should not have sex, and therefore do not have the same concerns that others do about menstruation, menopause, and sexuality. These attitudes, unfortunately, only deny women the life-enhancing, considerate health care which is their right. MENSTRUAL PROBLEMS HIV-positive women frequently complain of changes in their menstrual cycles, such as irregular periods, heavier or scantier periods, or an increase in noted premenstrual symptoms such as breast pain, swelling, anxiety, depression, and cramps. It is unknown whether these changes are due to HIV itself or to specific medications, particularly AZT. Some other variables that need to be considered include use of other medications, street drugs like cocaine and crack, and weight loss. Certain noted menstrual irregularities can adversely affect a woman's health during HIV illness. For instance, an increase in the amount of period blood (hypermenorrhea) may predispose a woman to anemia. Anemia may already be a chronic problem, especially in women with HIV. Skipped periods (amenorrhea) requires prompt investigation into possible underlying causes such as pregnancy, ovarian cyst or failure, and early menopause. Amenorrhea should be investigated in all women, regardless of a woman's intention to become pregnant in the future. An endocrine specialist should be consulted if easy diagnosis is not possible. All heterosexually active women should have a pregnancy test. All women who have not completed menopause and who miss two periods should receive a pelvic examination, and tests to determine if the problem lies outside the reproductive track (i.e., a thyroid or pituitary tumor). Blood tests include the thyroid stimulating hormone (TSH) and prolactin levels. If these values are normal and pregnancy can be ruled out, the woman is often given progesterone challenge (Provera 10 mg daily for five days) to induce bleeding. If bleeding occurs, this establishes that she is producing estrogen, but is not ovulating. These women are at risk for developing endometrial or breast cancer due to constant estrogen administration. If menstruation does not start after a progesterone challenge, it means that the woman is not producing estrogen and has either an ovarian failure to produce estrogen, or hypothalamic failure to stimulate production of FSH or LH. This indicates a need to run a serum FSH and LH level test to distinguish between the two causes. Hypothalamic failure will demonstrate low levels of FSH and LH. Such a failure is usually stress-related, perhaps due to weight loss, and often will resolve without treatment. High levels of FSH prove that the ovaries are not producing estrogen. Ovarian failure can be due to premature menopause, autoimmune disease, or a destructive disease of the ovaries. The cause should be diagnosed and treated. MENOPAUSE Menopause, the natural ending of the menstrual cycle, is a normal feature of a woman's life cycle and does not generally require treatment. However, premature menopause seems to be more common in immune-suppressed women. Hormone replacement is indicated for severe symptoms of menopause, such as hot flashes, irritation of the vagina (vaginitis), and irritation of the tube through which urine exits the body (urethritis), vaginal dryness, itch, and discomfort during urination. Replacement hormones may also prevent osteoporosis and damage the cardiac system. The main concern about hormone replacement is that it increases the risk of cancer, due to the use o~ estrogen alone. Hormone replacement regimens now include estrogen and progesterone to reduce the risk of cancer. In women with HIV, symptoms of ovarian failure such as hot flashes may be worse at night. They may be commonly mistaken for night sweats which occur due to TB or MAC. Vaginitis and urethritis may be mistakenly treated as thrush, or may lead to openings and sores on the genitals. These symptoms may interfere with normal sleep, appetite, and sexual activities. PREGNANCY Unlike other hormonal states, pregnancy has been studied with greater emphasis in humans. It has been observed that the high levels of sex hormones (particularly progesterone) which exist during pregnancy induce a state of immunesuppression. This is logically assumed to be required in order that the pregnant woman not reject the fetus, which, after all, is a "foreign object" potentially presenting danger to the immune system. Several authors note that the combination of hormonal, immune, and vascular (relating to blood vessel) changes during pregnancy contribute to an increased incidence of herpes and outbreaks of anal and genital warts (HPV), which occur with frequency in pregnant women. Influenza infections also occur more severely in pregnant women. In general, they tend to be more susceptible to various viral, bacterial, and fungal infections than non-pregnant women.[5] The majority of medical articles published on pregnancy report a decrease in T4 counts during pregnancy, which is most apparent in the last months of pregnancy. However, most researchers feel the decrease in cell immunity is best described as a decrease in the ratio of the number of T4 cells to T8 cells. In other words, there are more T8 than T4 cells during pregnancy, a phenomenon which also occurs in people with HIV.[6] Other factors observed in pregnancy include an increase in steroids in the body. Despite the temporary state of immune suppression, it is generally felt that pregnancy will not adversely affect asymptomatic HIV-positive pregnant women. Of course, these women must receive high-quality prenatal and obstetrical care. Treatment for gynecological problems in HIV-positive women is in desperate need of immediate research. In particular need of attention is the role of human papilloma virus (HPV) which is thought to complicate cervical cancer.[7] Additionally, ample documentation exists showing that a depressed immune system makes women susceptible to severe and hard-to-treat vaginal and pelvic infections.[8] CONTRACEPTIVES The use of oral contraception in HIV-positive women should not be confused with concerns regarding transmission of HIV or STDs. The pill has never offered protection from HIV transmission to women or their sexual partners. Use of the pill cannot replace safer sex and the use of latex barriers (condoms and dams). Women may request the pill because they have more control over reproduction and may feel more confident of protection from pregnancy, when this is an important concern. Further, the pill is associated with regular, reasonably short and light periods, a benefit that many women enjoy. HIV-positive women who may be anemic may also benefit from shorter, lighter periods. However, the negative aspects should be considered as well. In research regarding the pill's effect on the female immune system, a study conducted in 1988 concluded that there are no significant differences in blood levels of immunoglobulins (which are substances related to antibodies) in women who take low-dose oral contraceptive as compared to women who do not.9 However, the ability to produce tetanus antibodies after receiving a tetanus shot, and the ability to respond appropriately to the PPD test which injects TB protein under the skin of the arm to test for active infection, may be impaired in women taking the pill.lo This gives rise to some concern that the pill may have an immune-suppressing effect and may also complicate accurate TB testing in these women. It is unknown whether the pill has adverse interactions with other commonly used HIV/AIDS drugs, like AZT. However, some drug interactions have been documented, and must be considered (e.g. antibiotics, barbiturates, anticonvulsants, valium, oral anti- diabetics, prednisone, anti-hypertensives, and tylenol). The usual precautions against the pill apply to women with HIV as well. For instance, women with liver dysfunction should not use the pill, since hormones are metabolized in the liver. In summary, oral contraceptions have medical and psychological benefits, as well as risks when used in HIV-positive women. Therefore, it makes sense that the decision should derive from a dialogue with a well-informed health care provider. TRANSSEXUALS Finally, clinicians and researchers must address the use of hormones in pre- and post-operative transsexuals. These clients are often at risk for HIV infection, or may already be aware of their HIV-positive status. Additionally, many such patients have already taken hormones from medical and/or non-medical sources. Often the hormones are needed to support the desired secondary sexual characteristics such as absent facial hair, enlarged breasts, and change in voice quality. Clients may have had surgical castration (surgical removal of sexual organs) with vaginal reconstruction, and/or breast augmentation with implants. The estrogen doses that are commonly taken far exceed the estrogen doses found in oral contraceptives and estrogen- replacing drugs. It is a questionable practice to refuse to provide a prescription for hormones or medical advice. Perhaps a constructive approach is to supply hormone replacement and work to reach the minimal dose needed to achieve desired effects. Consideration for the client's overall health and relative contraindication, as well as potential for drug interactions, must become part of the discussion. CONCLUSION In HIV disease, as in all areas of women's health and illness, menstruation must be placed at the top of the research agenda so that women's questions can be adequately addressed. More data and understanding of women's bodies are desperately needed. Neither the immune system nor the endocrine system in humans has been fully understood or described. Attempting to understand and synthesize the subtle interaction between these two networks in women is not easy. A roundtable discussion among immunologists, endocrinologists, obstetrician-gynecologists, neurologists, and women with HIV infection and their advocates would be especially useful. FOOTNOTES * It should be noted that lymph nodes are often mistakenly called glands. Lymph nodes are not glands, but are actually small bean-shaped organs widely distributed throughout the body. 1. Erbach GT and Bahr JM. Enhancement of in vivo humoral immunity by estrogen: permissive effect of a thymic factor. Endocrinol 128(3):1352-8, 1991. 2. Grossman C. Regulation of the immune system by sex steroids. Endocrine Review 5(3):435-455, 1984; and Hazzard WR. Why do women live longer than men? Biologic differences that influence longevity. Postgraduate Medicine 85(5):271-8, 1989. 3. Ahmed SA et al. Sex hormones, immune responses and autoimmune diseases. AJP December 1987 (pp.531-551). 4. Racheve C et al. Sex differences information of anti-T-cell antibodies. Nature 263:415418, 1976. 5. Gurka G and Rocklin RE. Reproductive immunology. JAMA 258(20):2983-7,1987; and Minkoff HL. Immune effects in Current Problems in Obstetrics and Gynecology and Infertility: AIDS in Pregnancy. 12(6):214-217, 1989. 6. Castilla IA et al. Decreased levels of circulating CD4 during normal human pregnancy I Repro Immunol 15:103-111, 1985. 7. Schafer A et al. The increased frequency of cervical dysplasia-neoplasia in women infected with HIV is related to degree of immunosuppression. Am J Obstet Gynecol 164 (2):593-99 1991, and Roche JK and Crum CP. Local immunity and the uterine cervix: implications for cancer 8. Forrest BD. Women, HIV and mucosal immunity. Lancet 337:835-836,1991, Mendling W and Kildovsky U. Immunological findings in patients with chronically recurrent vaginal candidiasis and new therapeutic approaches. Mycoses 32(8):386- 90,1989; and Kalo-Klein A and Witkin S. Regulation of the immune response to candida albicans by monocytes and progesterone. Am J OB Gyn 264 (5):1351-1354,1991. 9. Bisset LR and Griffith JFT. Humoral immunity in oral contraceptive users: Plasma immunoglobin levels and in vitro immunoglobin production. Contraception 38(5):567-9,1988. 10. Allen MH. Primary care of women infected with HIV. Obstet Gynecol Clinics of N Amer 17(3):557-69, 1990. 11. Rhoads JL et al. Oral contraceptives and PID. Am J Obstet Gynecol 144: 630-35,1982. ***** FERTILITY, MENSTRUATION, AND BIRTH CONTROL IN HIV by Patricia Kelly, FNP Fertility, or the ability to have children, is a consequence of both biology and behavior. Preliminary research does not indicate HIV affects either. This article will attempt to summarize the understanding of HIV infection and its interaction with reproductive health. Studies from the Bronx, Brooklyn, and Scotland have found that HIV does not affect women's decisions to abort or to continue a pregnancy. The first report, by Selwyn et al. in 1989, found that 50% of 28 HIV-positive women and 44% of 36 HIV- negative women who learned their serostatus prior to 24 weeks gestation chose to abort their pregnancies.[1] Other factors, such as whether or not the pregnancy was planned, seem to play a greater role than serostatus in determining a woman's decision. Johnstone reported similar findings among women studied in Edinburgh, Scotland who found out they were HIV-positive when they registered for prenatal care. Their reproductive decisions were not significantly different from the HIV-negative registrants despite more aggressive "directive" counseling than is customary in the United States.[2] The former two studies focused on drug-using populations while the studies by Sunderland in Brooklyn included a wider range of populations affected by HIV. In the Brooklyn study, it was noted that a small group of women who progressed to AIDS did not have subsequent pregnancies,[3] although there were no significant differences in the rate of subsequent births during follow-up. The overall fertility rate among HIV-positive women followed in central Brooklyn is similar to that in the community in general. Bias against HIV-positive women in abortion clinics in New York City has been documented as clearly affecting women's reproductive decisions. Legislative initiatives, such as laws that prohibit use of federal dollars to fund Medicaid abortions (Hyde Amendment) laws that prohibit counselling about abortion, and the possible Supreme Court overruling of the decision that made abortion legal in this country (Roe vs. Wade) -- have a substantial impact on fertility rates. MENSTRUAL IRREGULARITIES Irregularities in menstrual bleeding can be caused by a number of factors in HIV-positive women. These have been observed by some health care providers in New York City and include: pregnancy and menopause, HIV itself, anti-HIV drugs like AZT and ddI, drugs for opportunistic infections (OIs), cancer therapies, street drugs like heroin and crack, and methadone maintenance treatment. Since more than one of these factors may be present in an HIV-positive woman who is experiencing menstrual irregularities, identifying and treating underlying causes can be difficult. Written materials on this subject are limited. Additionally, menstruation can be affected by many different factors. Any chronic illness, for example, can affect menstrual function. As weight and body fat decrease, male hormones (androgens) do not convert as rapidly to female hormones (estrogens) and may result in a decrease in menstrual blood. A clearly-recalled history of menstrual irregularities predating HIV infection is often not available. Data on the menstrual experience of HIV-infected women are limited. New data from an unpublished pilot survey of 46 women attending a clinic in Brooklyn found that most women experienced a variety of menstrual disorders during the year in which they were observed. Although no group of uninfected women was surveyed for comparison, it is worth noting that complaints were more frequent among women taking AZT. In fact, 89% of the 46 women in the survey who had menstrual problems were taking AZT. Comparatively, only 34% of women not taking AZT complained of menstrual problems. Additionally, of those women with menstrual irregularities, 66% had T4 counts under 500, compared to 28% of complaints from women with T4 counts above 500. There was a significant overlap between the group taking AZT and the group with more marked immune system suppression. Reported problems ran the gamut of possible disorders from irregular, excessive, or painful bleeding to scanty or infrequent bleeding. A study at Columbia University comparing 17 HIV-positive and 20 HIV-negative women with a history of intravenous drug use yielded some interesting results.[4] Absence or abnormal stoppages of menstrual periods occurred in 24% of HIV-positive women, as compared to only 13% in HIV- negative women. Likewise, bleeding between periods occurred more frequently in the HIV- positive group (18%), than in the HIV-negative group (6%). MANAGING MENSTRUAL PROBLEMS Heavy menstrual bleeding can compound the irregularities in blood that occur in HIV disease or as a side effect of AZT (i.e. anemia and neutropenia). Detecting the cause and treating menstrual irregularities in HIV-positive women is similar to that for HIV-negative women. An initial session between a woman and her health care provider should include the following: a complete menstrual history; history of all street and prescribed drugs taken; a blood sample for a complete blood count, including T4 counts; a pelvic examination with a Pap smear; screening to rule out chlamydia and gonorrhea infections, as well as pelvic masses; and a nutritional evaluation. In women over 35 with abnormal bleeding, sampling of cells from the lining of the uterus (the endometrium) should be obtained to rule out abnormally-growing cells which may cause cancer (neoplasia). If a woman has menstrual bleeding despite an absence of ovulation (anovulatory bleeding), a short course of progesterone, a synthetic female hormone, can be administered. To restimulate long-term, regular periods, the use of oral contraceptives (the pill) is helpful. However, it is important to note the considerations for using the pill, outlined in the previous article. Difficult or painful menstrual periods can initially be treated with a series of exercises for the pelvis, abdomen, and back. Additionally, over-the-counter medication such as ibuprofen (brand name, Advil) can be helpful. More severe pain can be countered with Motrin (prescription strength ibuprofen) or Syntex's expensive Anaprox (naproxen sodium). BIRTH CONTROL METHODS Condoms, used with a water-based lubricant, are the only known method that can protect a woman against pregnancy, STDs, and HIV infection. There is a 2% failure rate with condoms in protecting against unwanted pregnancy, so proper use is important. There is concern that women who use other methods of birth control are less likely to use condoms along with the chosen method. These women may put themselves at higher risk for STD and HIV exposure.[5] Therefore, it is important to supplement all of the following contraceptive methods with condom use by male sexual partners. It has been noted that women who use any of the following birth control methods consistently, as opposed to occasionally, may actually be better protected from HIV and STDs.[6] However, many people still assert that condom use is the best method for preventing HIV transmission. ORAL CONTRACEPTIVES Oral contraceptives (the pill) are tablets containing manufactured hormones similar to the ones made by a women's ovaries. Two types of birth control pills are presently available in the United States: the combination pill, which contains both synthetic progesterone (progestin) and synthetic estrogen, and the mini-pill, or progestin-only pill, which does not contain estrogen. The pill works by preventing the ovary from maturing an egg and releasing it at ovulation. It does not work to prevent the transmission of STDs. It should be stressed that the pill does not prevent HIV-infection, and condoms need to be used to prevent HIV transmission. To date, published research about the interaction of HIV infection and the pill has been limited to one study. Plummer and others studied a population of HIV-negative women who worked as prostitutes in Africa, and found that women using the pill were more likely to become HIV-positive.[7] This conversion was attributed to a condition called cervical ectopy, and was more common in women using oral contraceptives and in younger women (adolescents). In cervical ectopy, a group of cell that are highly susceptible to HIV-infection and that normally line the inside of the cervical canal are pushed to the outside of the cervical canal, where they more easily come in contact with HIV- infected semen. Cervical ectopy can also lead to easier infection of the human papilloma virus (HPV), which cause genital warts and lead to cervical cancer. There are no published data on the safety or harmfulness of oral contraceptives in women with HIV infection. It is difficult to assess the pros and cons of taking the pill for women with HIV because animal and test tube evidence exists for both the immune-suppressing and immune- enhancing effect of estrogen.s For more information see the previous article. However, there is not enough information to rule out the use of this method. Contraceptives with progestin- only (Micronor, Nor-QD) may be a useful alternative. NORPLANT Norplant is a relatively new method of contraception. Six matchstick-size rods containing progestin, the female hormone, are surgically inserted under the skin of the upper or lower arm of a woman. This device has been hailed as revolutionary because, once implanted, it provides contraception for up to five years. Although Norplant has already been used by more than half a million women around the world since it was first introduced in 1968, there are no data available concerning the effects of long-term use of Norplant. It is a reversible method of birth control, in that once the device is removed by a health care provider fertility is said to be restored immediately. The side effects may be considerable in light of the menstrual problems commonly affecting HIV-positive women. They include changes in menstrual bleeding, such as more frequent bleeding episodes, spotting between periods, and absence of menstruation. More data are needed in general about this method in both HIV-positive and negative women. Correct condom use by male sex partners is a must for avoiding HIV transmission while using Norplant. INTRAUTERINE DEVICES (IUDS) The intrauterine device, or IUD, is a small plastic device that is inserted into the uterus by a health care provider. It prevents pregnancy as long as it remains in place. The length of time an IUD should be left in the uterus is debatable, possibly as long as five years. Use of an IUD is severely limited. For instance, women with STDs, abnormal uterine bleeding, anemia, pelvic infection, multiple sex partners, and a desire to have children in the future may be advised not to use an IUD. [9] No human studies with HIV-positive women using IUDs exist. However, most health care providers do not consider an IUD a good choice for HIV-positive women because of an increased risk of infection during insertion. Also, insertion may increase the chance of developing pelvic inflammatory disease (PID). HIV- positive women who have IUDs already in place, and who have not had problems with it, should work with their provider to decide whether or not to remove the device. Considerations involved in this decision include sexual activity, risk of PID, history of sexually transmitted diseases, and willingness to use a condom. It is important to note that IUDs do not prevent the transmission of HIV and must be supplemented with condom use by male sex partners. DIAPHRAGMS AND CERVICAL CAPS A diaphragm is a shallow cup of thin latex rubber with a rim of flexible metal that is also covered by rubber. Once sperm- killing cream or jelly is placed inside the dome, the diaphragm is inserted into the vagina over the cervix before intercourse and left in place for 8 hours afterward. A diaphragm should not be left in place for longer than 24 hours. It works in two ways when used correctly: 1) It fits into the top of the vagina, up around the cervix, covering the cervix so that it forms a mechanical barrier to block the sperm. 2) It holds the spermicidal cream or jelly up against the cervix, so that any sperm that do manage to get by are killed before they can reach the cervical opening. A cervical cap works in a similar way but is smaller and fits over the cervix. It stays in place by suction and can remain for several days. Diaphragms and cervical caps used with nonoxynol-9 cream or jelly are excellent contraceptive choices for HIV-positive women. However, since they both cover only the cervix, they must be used with condoms. With these methods, the use of a condom is essential for preventing disease transmission via the vulva or vaginal walls. CONTRACEPTIVE SPONGES One of the newer forms of birth control is the contraceptive sponge. It is marketed under the name Today Contraceptive Sponge and is a round, white sponge with a cup like imprint in the center that is soaked with spermicide. The sponge is moistened and inserted into the top of the vagina before intercourse. It works to prevent pregnancy by blocking the sperm's passage into the cervix and uterus. It also releases spermicide to kill and absorb sperm. The sponge is not as effective as the diaphragm or cervical cap. Safety concerns when using the sponge include toxic shock syndrome (TSS). While the sponge has been called the equivalent of the condom, since it is disposable, one-size fits- all, and can be purchased over the counter, its ability to prevent HIV transmission is unknown. Therefore, condoms should be used by male sexual partners to prevent transmission when using this device. CONTRACEPTIVE FOAM Nonoxynol-9 foam (such as Delfen) can be inserted directly into the vagina. This product has been endorsed by many feminists as a "better than nothing" method that can be used by women whose male partners refuse to use condoms. The idea is that the sperm-killing nonoxynol-9 may be able to kill HIV and prevent transmission. However, two studies have shown an increased number of red cells in the blood and inflammation in women using the sperm-killing products.[10] Additionally, some people are allergic to nonoxynol-9, and irritations can erupt on the skin. These conditions may enhance transmission of viral diseases, STDs, and HIV. More information and research are needed concerning the use of contraceptive foams before a dependable recommendation can be made. STERILIZATION For women who are clear about their desire not to have further pregnancies, sterilization is a viable option. It is important that this option be neither encouraged nor denied based on anything other than a woman's own personal choosing. The decision should not be based on serostatus. Condom use is needed after sterilization to prevent HIV, STDs, and viral transmission. CONCLUSION In addition to the pattern of medical, racial, economic, and gender-based discrimination that burdens HIV-positive women, there is a scarcity of data on gender-specific manifestations and conditions in HIV disease. There is a great need for caring and accurate clinical rigor. As evidence of the unique and serious gynecological manifestations accumulates, clinicians and researchers must turn their attention to these problems. In the meantime, the best reproductive health care services must be provided while researchers work to create clearer guidelines. FOOTNOTES 1. Selwyn PA et al. Knowledge of HIV antibody status and decisions to continue or terminate pregnancy among intravenous drug users. JAMA 261:3567-71, 1989. 2. Personal Communication, Johnstone, F, January, 1992. 3. Sunderland A. Influence of HIV infection on reproductive decisions. OB/GYN Clinics of NA 17:585-94, 1990. 4. VIIth Int'l Conf on AIDS, Abstract # M. C. 3113, Florence, June 1991. 5. VII Int'l Conf on AIDS, Abstract# Tu.D. 109, Florence, June 1990. 6. Stein Z A. HIV Prevention: The need for methods women can use. Amer J Pub Health. 460-462. 7. Plummer FA et al. Cofactors in male-female transmission of human immunodeficiency virus type 1. J Infect Dis 163:233-239, 1991. 8. Grossman C. Possible underlying mechanisms of sexual dimorphism in the immune response, fact and hypothesis. J Steroid Biochem 34:241-51. 9. Lynda Madaras and Jane Peterson Womancare (New York City: Avon, 1984) pp.124-35. 10. VI Int'l Conf on AIDS, Abstract # S. C. 36, San Francisco, June 1990; and Bird. The use of spermicide containing nonoxynol-9 in the prevention of HIV infection AIDS 5:791-6, 1991. ***** SEXUALLY TRANSMITTED DISEASES by Sharon Lerner The alarming increase of STDs in women in the U. S. comprises a significant and complicated epidemic. The presence of STDs may make HIV transmission easier and may cause HIV disease to progress more quickly. Additionally, STDs may be more difficult to treat in HIV-positive women. Some experts consider STDs a cofactor, or a condition which must be present in order for women to become infected. Of particular concern are STDs that cause open sores (ulcers) on the vulva, since they may allow a concentrated amount of virus to come in contact with immune cells.[1] This article will review STDs (yeast infection is technically not an STD, but is addressed here as a disease of the lower genital tract), including treatment in HIV-positive women. HERPES Herpes Simplex virus (HSV) can cause sores on the mouth and in or around the genital area, including the inside and outside of the vagina, the rectum, and anus. It may also cause flu-like symptoms shortly before an outbreak, vaginal discharge, painful urination, and general genital irritation. Repeat outbreaks of HSV are thought to develop due to a wide range of factors, including physical or emotional trauma, hormonal changes due to pregnancy and menstruation, ultraviolet light, sexual stimulation, and HIV progression. Outbreaks are increasingly persistent as immune suppression progresses.[4] In people with normal immune systems, herpes outbreaks on the lips triggered by ultraviolet light can be prevented by sunscreen. Without proper treatment, herpes can sometimes spread to other sites. When an outbreak is present in a delivering woman, surgical removal (Caesarian section) of the infant is recommended to avoid transmission. While there is no way to rid the body of HSV once infection occurs, treatment with acyclovir (Zovirax) can speed up the healing process if it is used within six days of an episode. The drug may also help prevent recurrences, limit the time during which herpes can be passed to another person (viral shedding) through sexual contact, and, in some cases, decrease pain. Acyclovir has been taken safely for more than two years as an effective suppressive treatment. Made by Burroughs Wellcome, the drug is very expensive. For an increasing number of women and men with AIDS in whom acyclovir-resistant strains of HSV have been discovered, a possible alternate therapy is foscarnet. Wearing loose clothing and cotton underwear, taking warm sitz baths, and keeping sores dry with a hair-dryer or towel drying are recommended to alleviate discomfort. Experimental therapies include BW256U87 (BW256 for short), a drug made by Burroughs Wellcome, that is turned into acyclovir once inside the body. Taken in pill form, this drug can achieve the same blood levels of acyclovir that normally require IV treatment. Cheap, safe, natural treatments for herpes include dysine (4000 mg for treatment/500 mg for prophylaxis); Vitamin C -- pills or a paste applied to lesions; Mono-laurin; iodine applied to lesions; zinc, aloe, and vitamin E. [5] CHLAMYDIA Little information is available that examines the relationship between HIV and Chlamydia trachomatis infection. Chlamydia was discovered only 15 years ago, though it is currently thought to be the most common STD in the United States. Chlamydia infection is caused by a group of bacteria which have an incubation period of five to ten days. The initial infection is typically asymptomatic. When present, signs and symptoms include yellow vaginal or cervical discharge, painful urination, bleeding or pain with sex, irregular menstrual periods, and spotting between periods. Rectal chlamydial infections can cause rectal pain and discharge. Left untreated, chlamydia can lead to tubo-ovarian abscesses, infertility, cystitis, inflammation following sexual intercourse, and pelvic inflammatory disease. Based on anecdotal evidence, chlamydial infections are more severe in HIV-positive women.[6] Because chlamydial infection is often asymptomatic and cultures for Chlamydia trachomatis are not easily available to all clinicians, many women go undiagnosed. Diagnosis is often made by ruling out other infections. Women whose sexual partners are infected with Chlamydia have a greater chance of developing chlamydia, as do women who have gonococcal cervicitis, other STDs, and symptoms of urinary tract infections but negative urine cultures. Diagnosis and treatment of partners are also extremely important, since reinfection rates are high. Chlamydia is treated with 500 mg tetracycline taken four times per day for at least a week, or 100 mg doxycycline (Vibramycin), taken by mouth twice each day for at least one week. For women who are pregnant and others who are allergic to tetracycline, 500 mg erythromycin (E-Mycin, Robimycin) taken four times daily for seven days by mouth or a slightly lower dose for a longer period is recommended. Recent studies with azithromycin show that a single dose treatment of 1 gram of the drug equals the safety and efficacy equivalent of a one-week regimen of doxycycline. Azithromycin has excellent tissue penetration, and uptake of the drug is higher in cells where inflammation is present, conveniently targeting the drug to the area most in need of treatment. Azithromycin (1000 mg single dose) has shown microbiological cure rates of 96% -100%.[7] Azithromycin is also useful against mycoplasma, Ureaplasma urealyticum and against gonorrhea at this dose, allowing for broad-spectrum anti-STD treatment before culture results are available. Azithromycin remains in the body for as long as four days,s and the most common side effects are gastrointestinal. It should be taken on an empty stomach (one hour before or two hours after eating). Azithromycin, while approved for use in the U. S., may be difficult to obtain, and still can be purchased through the underground. In New York City, contact the PWA Health Group at (212) 255-0520. GONORRHEA In numerous studies, no association has been found between a history of gonorrhea and HIV infection.[9] Gonorrhea, an extremely common bacterial infection, is transmitted almost exclusively through sexual contact and is thought to increase with lowered immunity in women.[10] The infection must be diagnosed properly and treated when suspected. Women are thought to have a 30% chance of contracting gonorrhea after one sexual contact with an infected partner. The percentage increases to almost 100 percent for women who are on birth control pills.[11] Very little data are available about the course of gonorrheal infection in HIV-positive women. If untreated, the infection can spread beyond the cervix through and into the uterus and tubes, causing infertility and chronic pelvic pain.[12] Like chlamydia, gonorrhea is often asymptomatic, and up to 80% of infected women do not experience symptoms. When present, initial symptoms will appear from three to eleven days after infection and include an increase in vaginal discharge, uncomfortable and more frequent urination, conjunctivitis, menstrual irregularities, swelling of the vulva, and spotting after sexual intercourse. Gonorrhea can be diagnosed by taking a culture from the cervix, anus, mouth or oropharynx; cultures are not very reliable and can test falsely negative if women douche or take antibiotics, or if the infection is further in than the cervix or anus.[13] Because of its prevalence and because it can lead to serious complications, the presence of gonorrhea should be considered in all women with other STDs. Treatment is with Rocephin (250 mg intramuscular injection) and doxycycline (100 mg twice daily) for seven days. TRICHOMONAS VAGINALIS This infection is caused by a protozoan called Trichomonas vaginalis and remains asymptomatic in about 50% of infected women.[14] Symptoms, when present, include itching, irritation, presence of a thin yellow-green odorous discharge, and painful intercourse. Topical clindamycin has been studied for use during pregnancy and appears to be effective in women with HIV. Small, moving organisms may be visible on a wet mount lab test. Recommended treatment is with 250 mg of Metronidazole (Flagyl) three times a day for seven days. Flagyl must be taken with food to avoid nausea, and should never be taken with alcohol. Drinking alcohol while on Flagyl leads to a reaction involving dizziness, nausea, sweating, and bloodshot eyes. VAGINAL CANDIDIASIS (YEAST INFECTION, THRUSH, OR VAGINITIS) Vaginal candidiasis is usually caused by Candida albicans. It is said to be the most common initial clinical manifestation of HIV infection in women and occurs in women with relatively high T4 cell counts.[15] In one study of 29 women at Walter Reed Army Hospital, chronic vaginal candidiasis preceded the development of oral thrush and was the earliest indication of immune suppression in 25% of the women.[16] This fungal infection can occur before any significant lowering in T4 cell counts and before candida infections develop in other parts of the body, such as the mouth, esophagus, and gastrointestinal tract.[17] Though favorable response to treatment has been noted, recurrence rates are high.[18] The possibility of HIV infection should be considered in all women experiencing recurrent, persistent vaginal candidiasis. Symptoms of vaginal candidiasis include thick, odorless, white or yellow discharge. Additional symptoms include vaginal and vulvar itching or burning, pain during urination, and raised white and gray patches on the vaginal skin. While vaginal thrush is common in all women, HIV-positive women experience more frequently recurring hard-to-treat infections. Yeast infections can be diagnosed by looking at a smear under a microscope. Some clinics do not check for yeast under a microscope and may prescribe medications based on symptoms. It is important to advocate other tests, since many yeasts are asymptomatic and can be obscured by the symptoms of HIV infection. Many women have had experience with yeast infections and self-medicate with over-the-counter treatments (Gynelotrimin, Monostat-7, Yeast-guard). If self-treatments do not succeed, a physician should be consulted and an additional infection investigated. If the infection is in fact yeast, and local treatment has not worked or has failed to prevent recurrences, a stronger local antifungal or systemic therapy (fluconazole and ketoconazole) can be tried. If these fail to relieve symptoms, an additional diagnosis should again be considered. Yeast infections developing in women on prophylactic fluconazole are either drug-resistant or unusual organisms (such as Torulopsis glabrata or Candida krusei) that fluconazole does not affect. Resistant yeast is treated with topical or intravenous (IV) amphotericin B, sometimes in combination with Flucytosine. Many drugs used to treat HIV-related diseases will change the vaginal environment and encourage yeast to flourish. Treatment with a variety of antifungals includes the following: * Cream or suppositories include miconazole nitrate (Monostat), terconazole (Terazol-7), clotrimazole (Mycelex), butoconazole (Femstat), nystatin (Mycostatin), or tioconazole (Vagistat). * Boric acid powder, which is not recommended for pregnant women, is also sometimes used. Boric acid is inexpensive and found in any drug store. Poured into a number two gelatin capsule at 600 mg twice daily (available at many health food stores) and inserted into the vagina at bedtime every day for two weeks, it may help re-acidify the vagina and kill yeast. * Acidophilus bacteria (bacteria attracted to acid) such as lactobacillus, an ingredient found in such brands of plain yogurt as Alta Dena, Maya & Continental, may help keep yeast infections in check. A recent six-month long study found that eating eight ounces of lactobacillus-containing yogurt a day produced a threefold reduction in vaginal candida infections in women with chronic, recurrent vaginal candidiasis.[19] It is possible that lactobacillus acidophilus capsules (available at some health food stores) inserted into the vagina may also reduce the frequency of this infection. The refrigerated kind is preferred. * Antifungal pills such as fluconazole, and ketoconazole. Systemic antifungals may cause side effects in some women, such as a rash and inflammation of the liver, and are more likely to be used in women with more pronounced immunesuppression in whom it can also prevent oral and esophageal thrush. These drugs are very expensive. * Garlic capsules may also offer relief. TRANSMISSION OF STDs Sexual transmission of organisms that cause the above diseases (except thrush) occurs during direct contact between infectious lesions (warts, ulcers, blisters) and body fluids (semen, vaginal secretions, saliva, and blood). Condom use by male partners and latex dams* by female sex partners can decrease the likelihood of getting STDs. This is true only if barriers are used every time and correctly (no slippage, breaks, or leaks). Chlamydia can also be transmitted during sex between two women if organisms are present in the mouth or on hands, or if the genitals are touched together. The most efficient means of transmitting an infection to a woman, however, is when male ejaculate (cum) is allowed to enter and stay in the female body. There is no evidence that condoms or latex dams reduce the likelihood of contracting genital warts, HPV, or developing recurrences of cervical cancer. However, barrier contraceptives do reduce the risk of cervical cancer from occurring at all. Condoms do not necessarily protect against transmission of herpes infection, because the site of infection is most commonly the vulva in women and the base of the penis in men, and these sites are left uncovered by condoms. The female condom (Reality brand vaginal pouch) may provide more protection as it covers a larger area. CONCLUSION Until researchers and funders put money and efforts into designing a safe, invisible barrier that is 100% controlled by a woman, condoms are the best way to go. In fact, 70% of condom buyers are women. Negotiating use with a male partner can be difficult, but it is vital. HIV can only be complicated by exposure to disease causing organisms which are transmitted through sexual contact. Women must be especially careful during menstruation and when open genital sores are present. In the meantime, unfortunately, few workshops exploring safer sex are disseminating information that consists of the full range of safety issues for heterosexual, bisexual, or lesbian HIV-positive women. FOOTNOTES 1. Kreiss JK, Coombs R, Plummer F et al. Isolation of HIV from genital ulcers in Nairobi prostitutes. J Infect Dis 160:380-384, 1990. 2. Seigal FP et al. Severe AIDS in male homosexuals manifested by chronic herpes simplex lesions. N Engl J Med 305:1439-1444, 1981. 3. Mosca JD et al. HSV-I can reactivate transcription of latent HIV. Nature 325:67-70, 1987. 4. Moss G. B., Kreiss JK. The relationship between HIV and other STDs. Med Clin N. Amer. 74(6):1647-60, 1990. 5. Personal Communications, Dr. Joan Priestly, May, 1992. 6. Mayer K. Personal Communication February 2, 1992. 7. Lassus, A. Comparative studies of azithromycin in skin and soft tissue infections and sexually transmitted infections by Neisseria and Chlamydia species. J Antimicrob Chemother 25(A):115-121, 1990; and Steingrimsson, O. et al. Azithromycin in the treatment of sexually transmitted disease. J antimicrob chemother 25(A):109-114, 1990 8. Schentag, J. I., et al. Tissue-directed pharmacokinetics. Am J Med. 91(3A):5-11, 1991 9. Moss GB and Kreiss IK. The interrelationship between HIV and other STDs. Med Clin of North Amer. 74 (6):1647-59, 1990. 10. Ibid. 11. Lynda Madaras and Jane Patterson, Womancare (New York: Avon, 1984), P. 563. 12. Ibid. 13. Ibid. 14. Sweet, L. R., Pelvic Inflammatory Disease and Infertility in Women. Sexually Transmitted Diseases in Infectious Disease Clinics of North America 1(1):199-215, 1987 15. Imam N et al. Hierarchical pattern of mucosal candida infections in HIV-seropositive women. Amer J Med 89:142-146, 1990. 16. Rhoades JL et al. Chronic vaginal candidiasis in women with HIV infection. JAMA 257(22):3105-3107,1991. 17. Imam et al. Hierarchical pattern of mucosal infections in HIV-seropositive women. Amer J Med 89:142-146, 1990. 18. Ibid. 19. Hilton, E., et al. Ingestion of Yogurt Containing Lactobacillus Acidophilus as Prophylaxis for Vaginal Candidiasis. Ann Int Med. 116:353-57, 1992 No research has been conducted with dams, three-inch squares of rubber latex, that are laid directly over the vulva during oral sex to create a barrier between a woman's genitals and her partner's mouth. While the author recognizes that the lack of data is problematic in recommending this prevention strategy, she also recognizes this is not the first time a potentially life-saving device for women has not been researched. ***** SYPHILIS TREATMENT IN HIV-INFECTED WOMEN by Janet L. Mitchell, M. D., M. P. H. The incidence of syphilis, a sexually transmitted disease, is increasing at a skyrocketing rate in the United States. In 1985 a flood of syphilis cases began and continues today -- so much so that the current epidemic of syphilis has resulted in the highest rate of infection in the past 40 years. According to the New York City Bureau of Sexually Transmitted Disease Control, syphilis cases in 1987 increased 105% over the previous year. During the first part of 1987, half of syphilis cases occurred in women, producing a 150% increase in female cases over those reported during the first part of the previous year. The rapid rise in syphilis parallels, and is complicated by, the rise in HIV infection. In both HIV and syphilis epidemics, women are hit particularly hard. In fact, the rate per 100,000 adults increased 36% for black men, 43% for black women, 7% for hispanic men, and 24% for hispanic women. Although rates for white women increased 22%, the absolute rates were approximately 10 to 30 times lower than those in black or Hispanic women.[1] Complicating the general situation is the fact that symptoms, tests, and treatment for syphilis may be altered in people who are HIV-positive. PRIMARY SYPHILIS Syphilis develops in several stages. In the first stage (primary syphilis), a woman may get painless, hard, red sores on or around the skin of her genitals, anus, or mouth. Most of these lesions (chancres) are found on the labia, fourchette, or cervix in women and usually occur about two to three weeks after infection. However, the chancres can go unnoticed. SECONDARY SYPHILIS Untreated, the disease proceeds to the second stage within six weeks to three months. This stage can cause hair loss, sore joints, widespread rashes, swollen lymph nodes, and weight loss. The syphilis rash may occur all over the body, but it is usually pale and may not be very noticeable. It tends to occur as spots on the hands and feet bottoms. Because second-stage symptoms are somewhat vague, they often are misdiagnosed. After a period of 3 to 12 weeks, secondary syphilis gets better on its own, leaving the patient free of all symptoms, and leading into a stage of latency, when no symptoms occur. TERTIARY OR LATE-STAGE SYPHILIS The third stage (tertiary syphilis) may not occur until much later, after a latent period when the infection is not active and the person is free of symptoms. This stage only occurs if earlier stages of syphilis go untreated or inadequately treated. The third stage can cause very serious disease of the heart, the eyes, or the nervous system and brain (neurosyphilis). NEUROSYPHILIS Neurosyphilis is an advanced form of syphilis that can cause serious problems in the brain and nervous system. A lumbar puncture (spinal tap) is recommended to confirm diagnosis. Recent reports suggest that patients with HIV infection who acquire syphilis may be more likely to progress to neurosyphilis and may do so more quickly than expected.[2] There are also reports of individuals treated for early syphilis with recommended regimens of benzathine penicillin who seem to get better, but then relapse with syphilis of the brain.[3] Neurosyphilis may result in headache, stiffness of the neck, and confusion. It can also lead to blurred vision, blindness, abnormal eye movements, facial weakness, hearing loss, or loss of balance. There seems to be a consensus that treatment of neurosyphilis is with ten days of intravenous aqueous penicillin at 2 to 4 million units every four hours. Comparative studies may eventually show that ceftriaxone is preferable to penicillin because it is easier to administer and may more effectively penetrate the nervous system.[4] In one case of asymptomatic neurosyphilis, a cure was reported by using ceftriaxone, 1 g/d for two weeks.[5] CONGENITAL SYPHILIS It is important to know that a pregnant woman with syphilis, regardless of the stage of disease, can pass it on to her unborn infant (congenital syphilis). The number of congenital syphilis cases reported in 1988 was the highest since the early 1950s, and in New York City alone that number increased more than 500%.[6] Symptoms in infants who have contracted congenital syphilis (passed from mother to child during some stage of pregnancy or delivery) may develop as follows: distorted bones, misformed teeth, inflamed and clouded eyes, deafness, blindness, and retardation. Pregnant women should be tested for syphilis at least twice during their pregnancy, especially if they are HIV- positive. DETECTING SYPHILIS Historically, syphilis may be the most often misdiagnosed illness, mistaken for everything from hemorrhoids, cancer, and lymphoma, to incarcerated hernia, hepatitis, and multiple sclerosis. Tests to detect syphilis can be done either on blood or on fluid from the spinal cord (cerebrospinal fluid). There are two kinds of tests: one which measures levels of antibodies produced by the immune system to combat syphilis ((RPR) and one that directly measure the presence of the organism which causes syphilis (FTA). That organism is called Treponema pallidum. Although these tests are standard for detecting syphilis, they are far from perfect. Syphilis has been called the "Great Masquerader" because of its vague symptoms, and many physicians have little experience detecting or even suspecting it in patients with symptoms. This is a problem for all persons with syphilis regardless of their serostatus. Because suppression can keep the immune system from responding in order to get rid of the infection, there is some possibility that tests may not be reliable in diagnosing syphilis in HIV-infected persons. TREATMENT HIV-infected persons should be treated with the most effective antibiotic. The best chance for a cure depends upon enough antibiotic entering and staying in the blood. A lot of drug is needed in order for it to enter the central nervous system. While there is consensus about treating neurosyphilis with the aggressive regimen suggested above, there is much debate about treatment for other stages of syphilis. In 1988, the Centers for Disease Control (CDC) published guidelines for treatment of people (by which is meant men) infected with both syphilis and HIV.[7] These guidelines suggest treating HIV-infected patients in the same way as non-HIV- infected patients (namely, with 2.4 million units of benzathine penicillin). Research, however, suggests that higher doses of penicillin must be given to men with HIV in order to reduce the likelihood of a relapse of syphilis to neurosyphilis and, perhaps, to control lesions. While current doses may be adequate for most women (possibly because most women are smaller and may have lower blood levels), pregnancy may be different. TREATMENT OF SYPHILIS IN PREGNANT WOMEN Normal biological changes during pregnancy produce an increased amount of water in women's bodies. This increase is greater in multiple pregnancies (twins, triplets). Therefore, an increase in blood flow to the kidneys results in increased urination and increased elimination of medication taken to control infection. Additionally, the growth of the uterus and fetal compartments (fetus, placenta, and amniotic fluid) creates additional tissue to absorb the drug. Thus, the doses calculated for men may in fact be too low for pregnant women. This concern has led many obstetricians and infectious disease specialists to suggest that HIV-infected pregnant women be treated with a regimen for neurosyphilis, especially if the duration of syphilis is unknown. No empiric data exists to support this approach, and it is based on a public health perspective. Congenital syphilis is rampant in certain areas, especially areas with high rates of HIV. The consequences of inadequate treatment are far greater than the consequences of over-treatment. However, in none of the articles reviewed is over-treatment raised as a concern. Of greater concern to obstetricians and pediatricians is the lack of information on pregnant women who are allergic to penicillin. Prior to HIV the alternate therapies were problematic in pregnancy. Tetracycline, for instance, a common alternative therapy, can cause developmental problems in the teeth and bone of developing fetuses. Erythromycin, another alternative, is associated with treatment failures because it does not cross the placenta very well. The best approach seems to be desensitization to penicillin. In this process, pregnant women with penicillin allergies are given a little drug at a time, in increasing doses. This technique has been used during pregnancy for almost a decade. CONCLUSION The controversy surrounding appropriate treatment for syphilis in HIV-infected persons is yet to be resolved. While changes in the recommended treatment regimen may be indicated in the future, the present CDC recommendations are used in most treatment facilities today. Providers, however, need to be aware that treatment failures have been reported using the recommended doses and that patients treated following those guidelines may need closer follow-up observation. FOOTNOTES 1. CDC. Syphilis and congenital syphilis -- U. S. 1985-1988. MMWR 37:486-489 1988. 2. Johns DR et al. Alteration in the natural history of neurosyphilis by concurrent infection with HIV. N Engl J Med 316:1569-1572, 1987. 3. Barry et al. Neurologic relapse after benzathine penicillin therapy for secondary syphilis in a patient with HIV infection. N Engl J Med 316:1587-89, 1987. 4. Musher DM et al. Effect of HIV infection on the course of syphilis and on the response to treatment. Ann Intern Med 113:872-881,1990. 5. Hook EW et al. Ceftriaxone therapy for asymptomatic syphilis. Case report and Western blot analysis of serum and cerebrospinal fluid IgG response to therapy. Sex Transm Dis 13:185-8, 1986. 6. CDC. Congenital Syphilis -- New York City, 986-1988. MMWR 38:825-889,1989. 7. Centers for Disease Control. Recommendations for diagnosing and treating syphilis in HIV-infected patients. MMWR 37:600- 608,1988. ***** PELVIC INFLAMMATORY DISEASE by Garance Franke-Ruta and Mary Beth Caschetta* * Tracy Morgan supplied some of the research for this article. We thank her for that effort. Pelvic inflammatory disease (PID) is a common, yet complicated, condition which affects the upper genital tract (the fallopian tubes, ovaries, endometrial lining of the uterus, and the ligaments surrounding the upper pelvic organs). PID is a highly variable condition that can span the spectrum from a cervical infection just beginning to move up the reproductive tract, to asymptomatic (latent, showing no signs of infection) tubal infection, to acute inflammation, and abscesses (sacs of pus in the abdomen or fallopian tubes). PID can be caused by a number of organisms and can be sexually or non-sexually acquired. Without prompt, proper diagnosis and treatment, PID can turn into a chronic health problem with constant pain or frequent flare-ups. PID that goes untreated can cause extreme pain, infertility, more frequent periods, and excessively painful periods. In its most severe forms, the disease can lead to bacteria in the blood (sepsis), spread to the liver and kidneys, and cause dangerous internal bleeding or lung failure, possibly ending in death. More than 900 women in the United States die each year from PID. [1] Approximately one million women are treated for acute PID a year.[2] It is unknown how many of these women are HIV-infected. SYMPTOMS The symptoms that occur in women with PID may depend on the kind of organism causing the disease. The severity of symptoms may depend on the strength of the particular strain of bacteria, the organs affected, and the woman's natural immunity to the disease. Symptoms may be mild, moderate, or severe, and may develop gradually or all of a sudden. Women with HIV-impaired immune systems may be more likely to develop chronic PID. Any of the following symptoms may occur with acute PID: stomach pain or tenderness, lower back pain, pain during or after sex, frequent need to urinate, persistent cramps, fever, chills, abnormal pain during bowel movements or urination, fatigue or weakness, cramping or stiffness of stomach muscles, swelling of lymph nodes, nausea, vomiting, headache, or rapid pulse. The pain in PID may range from a mild, bearing-down discomfort to a nagging discomfort of the lower abdomen to severe, sharp pains. The pain may be constant or may come and go. Characteristically, the pain may feel worse just before or during menstruation, and may be exacerbated by motion or walking, resulting in a 'shuffling gait.[3] POSSIBLE CAUSES OF PID Chlamydia and gonorrhea are the most common causes of PID. TB, an overgrowth of normal vaginal bacteria, intestinal bacteria, mycoplasmas (mainly M. hominis, but also M. genitalium, and ureaplasma urealyticum) may also cause PID although rarely.4 Nonsexually transmitted organisms are reported to cause 25% -- 65% of cases of PID,s and include the organisms that cause bacterial vaginosis. Gonorrheal PID tends to occur more acutely, chlamydial PID more mildly. Because chlamydial PID produces symptoms less quickly, it can actually cause more harm from delayed diagnosis and treatment. PID IN HIV-POSITIVE WOMEN In a study of 110 women hospitalized with PID, a higher rate of HIV infection was found, compared to non-HIV-infected women in their community (14% vs. 2%).6 In the HIV-positive women with PID, there was a trend toward more severe disease that was treated with surgery: 27% of HIV-positive vs. 9% of HIV-negative women required surgical removal of uterus, tubes, ovaries (hysterectomy), or fallopian tubes and ovaries (salpingooopherectomy). Abscesses were present in 24% of HIV- positive women, compared to 12% in HIV-negative women. A study at San Francisco General Hospital observed 333 women with acute PID and found that their HIV-infection rate rose from 0% to 7% during 1985-1988.[7] DIAGNOSIS A pelvic exam is an extremely imprecise way to detect PID and is not sufficient to give an accurate diagnosis of PID when lower pelvic pain is present. Yet it is the most common method used by doctors and emergency room personnel. Upon suspecting that pelvic inflammation is present, a doctor gives a pelvic exam by pressing on the outside of the lower abdomen to feel for enlargement of the tubes or abscesses that feel hot and tender. Tenderness of the tubes and pain occurring upon removal of pressure are the two criteria used to diagnose PID. Both chronic and acute PID are frequently mistaken for a number of other conditions, including appendicitis, ovarian cysts and tumors, ectopic pregnancy (where an embryo gets stuck developing in one of the fallopian tubes instead of going into the uterus, leading to swelling and sometimes to rupture of the tube), fibroid tumors of the uterus, and endometriosis (abnormal growth of the uterine lining outside of the uterus). Blood tests may show elevated white blood cell counts (over 10,000 -- a hallmark of PID) and erythrocyte sedimentation rate (ESR) may be taken. ESR tests measure inflammation. HIV- positive women may be less likely to have an elevated white blood cell count. In the study of 110 women, HIV-positive women with PID were significantly less likely to have a white blood cell count over 10,000.[8] A pregnancy test will be done to rule out ectopic pregnancy. A sonogram is a diagnostic test which uses sound waves instead of radiation to create an image of the internal reproductive organs and surrounding tissues. Sonograms can be used to create an image of the upper genital tract, and can provide vital information, such as the size of reproductive organs, placement of other internal organs, and the presence of unusual growths. Growths, such as abscesses, can be a sign of acute PID. The absence of growths does not mean that PID can be ruled out, but does give an indication of disease severity. A pelvic sonogram takes 10-30 minutes to perform and is completely painless, except for the internal pressure caused by the requirement for a full bladder to enhance internal imaging. A sonogram, however, is fairly expensive. A laparoscopy is a surgical procedure by which a small microscope is surgically inserted through a l/2"-to-1" cut in the lower abdominal wall and a sample of pelvic fluid is taken for culturing. A laparoscopy may be performed instead of a sonogram, or if growths are present. A laparoscopy can be done in a walk- in hospital clinic (but usually not the gynecology clinic), hospital, or even a gynecologist's office. The site should be affiliated with a hospital, in case a woman experiences complications and needs to stay overnight. Laparoscopy generally takes 20-30 minutes. A laparoscopy is the most reliable way to diagnose PID. Some professionals recommend that all HIV-positive women complaining of lower stomach pain, lower back pain, pain upon pelvic examination and fever, should receive a laparoscopy. Unfortunately, however, it is an expensive procedure. HOSPITALIZATION Hospitalization is based on the presence of abscesses, pregnancy, fever, nausea and vomiting, adolescent age, use of IUD, failure to respond to outpatient therapy within 48 hours, and (these days) hospital bed availability. If a woman is diagnosed with PID and her pain has not improved substantially within 2-4 days after outpatient treatment, she should be hospitalized. Hospitalization allows the rapid administration of high levels of antibiotics in the body by IV, as well as the use of a more broad-spectrum antibiotic regimen. Hospitalization also allows laparoscopy that is used to diagnose tubo-ovarian abscesses and any other emergency surgery necessary to remove severe inflammation. If IV medication is not needed, outpatient treatment is recommended. TREATMENT The goals of PID treatment are to prevent relapses and preserve fertility. Nevertheless, 20% -- 25% of women will have a recurrence of PID,[9] usually due to a new or repeat infection from untreated or new partners. Once the cellular lining of the fallopian tubes has been disturbed by an infection, it is thought to make it easier for bacteria to take hold in the future. Treatment failures may also occur because of the rising frequency of antibiotic-resistant bacteria.[10] The latest (1989) CDC guidelines for outpatient treatment of PID are as follows: One dose of ceftriaxone (250 mg injected into a muscle) followed by 10-14 days of either doxycycline (100 mg twice a day) or erythromycin (500 mg four times a day). Cefoxitin must be administered with 1 gm probenecid to increase the amount of time it stays in the body. This will also increase the amount of time other drugs -- like AZT -- are in the body, and may lead to side effects unless doses are briefly adjusted. After treatment is completed, repeat cervical cultures are done, or, less commonly, repeat exploration of the upper genital tract with a laparoscopy is performed. A repeat sonogram may be performed to see if abscesses and swelling have resolved. However, there is no standard definition of a cure for the disease. Almost no information has been published about the treatment of PID in HIV-infected women. Giving large doses of broad- spectrum drugs (overmedicating) may be the only way to assure that all disease-causing organisms are eradicated. Nausea and yeast infections are common during PID treatment. Finally, combination use of electric acupuncture and moxibustion (heat therapy) in the treatment of 95 cases of chronic PID was reported to cure 42 women, improve 39, and have no effect in 12. The overall improvement rate of 88.4% was superior to a control group using antibiotics.[11] TREATMENT BY SURGERY Surgery is used in the case of massive inflammation and abscesses. There may be a tendency to be freer with the use of surgery and hysterectomy in an HIV-positive woman, as doctors may feel less hesitant in removing her ability to have children. This may lead to rapid "pelvic sweeps" (total hysterectomy where all upper reproductive organs are removed), rather than antibiotic treatment followed by a conservative use of surgery. Hysterectomy is a major operation requiring a few weeks' hospital stay and months of healing. Treatment first seems to be the more humane way to approach PID, unless the woman indicates otherwise. PREVENTING PID Sexually-transmitted PID is often preventable. Coming in contact with sexually-transmitted organisms that cause PID can usually (but not always) be prevented with constant condom use by male sexual partners. Menstrual blood and sperm both provide a vehicle for PID organisms to "hitchhike" up the reproductive organs. During menstruation, the lining of the uterus is disturbed and there is ample blood to create the ideal growth environment for these blood-loving bacteria. Refraining from sex during menstruation may reduce the risks of getting sexually- transmitted PID. The use of barrier contraceptives such as the condom, the diaphragm, and the cervical cap all keep most bacteria and sperm from traveling into the uterus, and have been shown to be associated with a reduced risk of PID in HIV-negative women. CONCLUSION Ultimately, the occurrence and severity of PID is most related to access to preventive health care and adherence to safer sex measures. Early diagnosis, aggressive and humane treatment, as well as regular monitoring for PID and STDs are desperately needed and, unfortunately, in short supply. FOOTNOTES 1. Moore, M. PID: The Silent Epidemic, Healthsharing, p. 8, 1986. 2. Sweet, L. R., Pelvic inflammatory disease and infertility in women. Sexually Transmitted Diseases in Infectious Dis Cli of No Amer 1(1):199-215, 1987 3. Labadie, L. L., et al. Management of genital infections. Obstric and Gynecologic Emergencies in Emergency Medicine Clinics of North America 5(3):443, 1987 4. Sweet, L. R., op cite. 5. Sweet, L. R., op cite. 6. Hoegsberg, B. et al. Sexually transmitted diseases and human immunodeficiency virus infection among women with pelvic inflammatory disease. Am J Obstet Gynecol 163(4)1:113539, 1990 7. Safrin, S. et al. Seroprevalence and epidemiological correlates of human immunodeficiency virus infection in women with acute PID. Obst Gynecol 75(4):666-70, 1990 8. Hoesgberg, B. et al. op cit. 9. Hoesgberg, B. et al. op cit. 10. Ibid. 11. Wang, XM. On the therapeutic efficacy of electric acupuncture with moxibustion in 95 cases of chronic pelvic inflammatory disease (PID). J Trad Chin Med 9(1):21-4, 1989. ***** HPV and Cervical Cancer by Garance Franke-Ruta The human papillomavirus (HPV), a major cause of cervical cancer, is epidemic in the United States. Cervical cancer is cancer of the cervix -- the head and neck of the uterus. The cervix is round and sticks out from the back of the vagina; in its center is a small slit-like hole, called the os. Approximately 40 million Americans (20% of the adult population) have strains of HPV in their body. The virus can lead to the following: genital warts (condyloma acuminata); vaginal, cervical, and penile lesions (flat warts or subclinical infection); precancerous conditions (dysplasia); superficial cancer (anal or cervical neoplasia); and deeply-embedded (invasive) cervical and anal cancer. There are three main groups of HPV types that affect the genitals: HPV types 6 & 11 most frequently lead to genital warts and lower genital tract infection; HPV 16 & 18 carry the highest risk of invasive cervical cancer; and HPV 31, 33 & 35 carry a lesser, though significant risk of cervical cancer. Sexual partners of HPV-infected people also have the virus in 60%-75% of cases. While sexual transmission of HPV is easy, the risk of cervical cancer is reduced by barrier contraceptives such as condoms and the diaphragm. HPV has also been found in studies of women who have never had sexual intercourse, indicating an unknown method of non-sexual transmission. It can also be transmitted to children during birth. HPV AND CERVICAL CANCER In women infected with cancer causing HPV, the virus kills or changes immune system cells in the cervix, thus leaving a weakened local immune system to respond to the abnormal and potentially cancerous cells. Because HPV causes a state of local immune suppression, it leaves infected women more vulnerable to other STDs, which in turn can cause inflammation, further increasing the risk of cervical cancer. HPV also causes papillations (thus HPV's name), which are small warts of tissue. Immune suppression has long been recognized as a risk factor for cervical cancer, and women with HIV are developing cervical abnormalities at an alarming rate. Additionally, women are developing and dying from cervical cancer at alarmingly young ages. HPV infection has been reported in 31%-95% of HIV-positive women, depending on the study, while groups of HIV-negative women, examined for comparison, were found to have infection rates of 4%-25%. Cervical and anal disease in HIV-positive women is five times more likely than in uninfected women. Finally, women with low T4 counts seem to be more likely to have both HPV and cervical cancer than women who are less immune-suppressed. Cervical cancer in women with HIV also tends to be more resistant to treatment, to recur frequently, and to progress rapidly. HPV-related cancer in women is not limited to the cervix. The anus and lower genital tract may also be affected. OTHER RISK FACTORS FOR CERVICAL CANCER Poor nutrition is a risk factor for cervical cancer, as is smoking.[1] Tobacco products (like nicotine) have been found in high concentrations of cervical secretions, where they may act as carcinogens or suppress local immunity.[2] Former smokers do not have as high a risk as women who are still smoking. While there is no evidence that quitting smoking decreases the risk of cervical cancer in women with HIV, quitting generally reduces the risk of cervical cancer in women, especially in women who have precancerous lesions.[3] Oral contraceptives may make the cervix more vulnerable to HPV,[4] increasing the risk of cancer; however, reports on this matter are conflicting. PAP SMEARS AND HPV TYPING Women are advised to get Pap smears every year for three years after they become sexually active or turn 18, then once every 1-3 years if everything is normal. A Pap smear is a simple test in which a swab of cervical or vaginal cells and secretions is examined under a microscope for such things as abnormal cells, inflammation, and certain STDs. In 1991, the CDC recommended that women with HIV get yearly Pap smears; other physicians recommend that HIV-positive women get a Pap smear every six months for the rest of their lives. Pap smears indicate whether there is abnormal cell growth, and not whether there is HPV (except the ViraPap). In general, Pap smears are about 70%-80% sensitive at detecting abnormal cells, which is one reason they are recommended yearly. There also tends to be a high number of false negatives in women with immune suppression. In order to get the best Pap smear, a woman should refrain from having penetrative sex, douching, or using any products or medications in the vagina for at least two days before the examination.[5] Pap smears can also be performed on samples taken from the anus. However, the lab technician who reads these samples may need some special training. To test for HPV, small amounts of the viral genetic code (DNA) are amplified using the polymerase chain reaction technique (PCR). This is then compared to stock genetic sequences of specific viral types. This technique is exquisitely sensitive, but does not indicate whether there is disease. COLPOSCOPY A colposcope is a type of microscope that magnifies the cervical surface. Colposcopy is used to identify the site, severity, and extent of abnormal cell growth as well as to aid directed biopsy, plan treatment, and allow the use of conservative methods to treat early lesions. The area to be colposcoped is wet with 5% acetic acid, which stains the HPV- affected tissues white. If tissue stains white, small punch biopsies may be performed. Punch biopsies usually cut out about one square centimeter of tissue. Punch biopsies are usually administered without pain killers, or with the anesthetic lidocaine (Xylocaine) wiped over the area a few minutes before the biopsy. Colposcopies are not cheap. Prices range from $200 to $300, plus $50-$60 per biopsy (and often more than one biopsy is necessary per colposcopy). Pap smears cost $25-$50. The problem is that in New York State, Medicaid does not pay for colposcopies when they are used as a screening procedure, meaning a way to find disease rather than to find out how severe the disease is (diagnosis). Blue Cross/Blue Shield, a major New York insurer, will only pay for colposcopies if a woman has had an abnormal Pap smear, which occurs regularly in HIV-positive women. Nonetheless, BC/BS usually requests additional information, which leads to delays and refusals to reimburse, losing many women in the paper shuffle. Additionally, what is considered a normal Pap smear (non-cancerous conditions) in HIV-negative women may be interpreted conservatively in women with HIV as an indication for a colposcopy, leading to delayed reimbursement, or none at all. Likewise, Pap smears, which are indicated twice a year for women with HIV, are only covered once yearly by New York State Medicaid. CONE BIOPSY AND LOOP DIATHERMY If cervical lesions are obvious, cervical conization (also called a cone biopsy) may be performed at the time of colposcopy. This involves cutting a much larger cone-shaped wedge out of the bottom of the cervix around the os. The affected tissue can then be examined while at the same time removing the site of disease and sparing the woman a return visit to the office for treatment. Extensive uncontrolled bleeding (hemorrhage) following this procedure occurs in about 5% of women, and can be stopped by stitching or packing the vagina with absorbent fibers. Cold- knife cone biopsies can narrow the os, making it more difficult for a woman to give birth. They can also weaken the cervix and make it more difficult to carry a child to term. As a portion of the bottom of the cervix has been removed, the fetus becomes at risk for falling out of the uterus (spontaneous abortion) as it and the placenta grow heavier and larger. Laser treatments do not carry the risk of spontaneous abortion that occurs with cold-knife biopsy.[6] More high-tech or well-equipped gynecologist's offices are now offering a technique called loop diathermy which also treats and diagnoses at the same time. Loop diathermy, however, uses a wire loop heated by an electric current to slice out the tissue, kind of like a hot knife through butter. This procedure seals off blood vessels by its electric heat, decreasing bleeding and speeding healing, and allowing the procedure to more easily be performed in clinicians' offices. It is also a much quicker procedure, lasting only 3-4 minutes. TREATMENT Alpha interferon is a protein made by the body produced by cells in response to viral infections. A synthetic version of it has been manufactured as a treatment for HPV. It is injected into genital warts, but rarely used to treat cervical cancer. Cryotherapy (freezing) destroys abnormal lesions or cancer. The procedure uses a metal probe that is usually round and flat. In the middle of the probe is a small protrusion which is cooled to freezing temperatures and inserted into the cervical os. Cryotherapy usually takes 5-10 minutes to perform and can be done in a doctor's office or clinic. It is usually not very painful, and so does not require anesthesia. After the procedure, narrowing the cervical os may cause severe menstrual cramps and a profuse, watery discharge that lasts for 3-4 weeks.[7] The procedure may also result in difficulty conceiving and giving birth. Another common therapy is called electrocautery or electrodessication in which cancerous tissue is burned away by a metal probe heated by an electric current. This procedure usually takes 10-15 minutes, and can be done in an office if the affected area is not extensive. Several medications are also used to treat HPV and cervical cancer. The following is a brief description of each: Podophyllin and podophyllotoxin are toxic plant extracts that are painted on abnormal/cancerous tissue. Retinoic acid, a derivative of Vitamin A, has been used for HPV- related cancers of the non-genital skin with some success. The drug is under investigation for the treatment of cervical and anal cancer, especially in combination with alpha interferon. It is also soon to be studied for preventing cervical or anal cancer in men and women with HIV. Chemotherapy with Mitomycin-C (cisplatin) and 5-FU are used in invasive cervical cancer, in combination with radiation, surgery, or alone.[8] These two drugs have produced mixed reports. 5-FU 5-Fluorouracil (5-FU, Efudex) is a cream applied to the cervix and into the vagina which is absorbed by abnormal cells and kills them. Sometimes this process is hastened by peeling off the abnormal dead cells, a process called chemosurgery. 5-FU covers a larger area than surgical procedures like laser or cone biopsy. However, 5-FU causes vaginal ulcers in up to 10% of women. These ulcers can persist for months after therapy is completed, at which point they are only curable by excising the ulcer and stitching the wound shut. 5-FU works in part by stimulating the immune response to the abnormal cells and causing an inflammatory reaction. A basic rule of thumb with 5-FU is the more uncomfortable (itching, swelling) it makes a person, the more it is causing an appropriate response. It also improves the local immune system which is damaged by HPV, especially Langerhans's cells.[9] This may or may not be something you want in HIV disease as these cells are particularly susceptible to HIV infection and produce HIV in quantity. LASER TREATMENT, SURGERY, AND RADIATION A laser is a high intensity beam of light hot enough to vaporize tissue. It can be used to treat cervical cancer, for which it usually takes 10-15 minutes. It can be done in certain doctors' offices, a shortstay operating room, or the main operating room. It requires either local or general anesthesia and is accompanied by the risk of extensive post-treatment bleeding. Laser therapy, does, however, allow the cervix to remain closest to its pretreatment structure. The chief drawbacks to laser therapy are that large lesions and areas of cancer are difficult to treat. Nonetheless, it is a very precise technique. Surgery is used in cases of invasive cancer. This means that the cancer cannot be removed by superficial destruction of the cervical tissue because it has invaded the underlying cervical tissue, uterus or other organs. Lymph node involvement signals a worse prognosis. Radiation therapy is used along with surgery when there is lymph node involvement, or on its own. A hysterectomy takes 60-90 minutes and must be performed in an operating room under general or regional anesthesia. FOLLOW UP AND PREVENTION After cryosurgery and electrocautery, a woman should avoid penetrative intercourse for 3-4 weeks. Laser vaporization and cone biopsies should be followed by 4-6 weeks of abstaining from penetration. Hysterectomies should be followed by 6-8 weeks of abstaining from penetration. 5-Fluorouracil has been able to decrease the frequency of recurrences of cervical cancer when used on a once-weekly basis in women who are immune-suppressed or women with organ transplants. A U. S. study in women with HIV will compare 5FU to regular monitoring and determine which one prevents recurrences or disease progression more effectively and with less adverse effects. This study will be conducted by the ACTG in 1993. In non-HIV-infected women, physicians recommend repeat Pap smears, and sometimes colposcopies, every 3 months after treatment until the woman has three normal evaluations, and then every 6 months for 1 to 2 years. In HIV-infected women, this followup should continue for life. EMOTIONAL TRAUMA A study of lower-income, minority women with abnormal Pap smears showed they experienced increased worries of cancer, impairments in daily activities, mood, sexual interest, and sleep patterns because of the abnormal smear.[10] Colposcopic biopsies and treatments for cervical cancer have been shown to be very emotionally traumatic experiences.[11] However, one study found that those with an abnormal Pap who did not get the recommended colposcopy were even more strongly affected, possibly because of continued uncertainty about the disease.[12] The effects of the cancer on body image, sexuality, and self-esteem are only compounded and exacerbated by HIV disease and related stigmatization on a woman's sense of self.[13] A good relationship with the health care provider, feeling that the health care provider is competent and caring, and talking to others who are surviving the disease and/or treatments may help. On the other hand, one of the factors in making a treatment decision around cervical/anal cancer is the invasive nature of many therapies. Anecdotally, some HIV-positive women rather be spared the pain of treatment for a disease that keeps coming back, because quality of life decreased without increasing life expectancy.[14] While many of the cervical cancer medical interventions are crucial to survival, women must also maintain the right to say no to invasive medical procedures that offer little hope of cure. CONCLUSION Careful monitoring and access to a competent health care professional can probably prevent most severe cervical and anal cancer, even though HPV-related cancers seem to progress more rapidly and recur more frequently in HIV-positive women. FOOTNOTES 1. Licciardone JC, et al. Uterine cervical cancer risk in cigarette smokers: a meta-analytic study. Am J Prevent Med. 6(5):274-81, 1990. 2. Hellberg D et al. Smoking and cervical intraepithelial neoplasia: nicotine and cotinine in serum and cervical mucus in smokers and nonsmokers. Am J Obstet Gynecol. 158(4):910-3, 1988, and Barton SE, et al. Possible co-factors in the etiology of cervical intraepithelial neoplasia. An immunopathologic study. J Reproduct Med. 34(9):613-6, 1989. 3. Licciardone JC et al. Cigarette smoking and alcohol consumption in the aetiology of uterine cervical cancer. Int J Epidemiol. 18(3):5337, 1989. 4. Chang AR. Hormonal contraceptives, human papillomaviruses and cervical cancer; some observations from a colposcopy clinic. Aust New Zeal J Obstet Gynecol. 29(3,2):329-31, 1989. 5. Baldwin, KA et al. The Papnicolaou smear. J Nurse Midwife. 30:327-32, 1985. 6. Baggish MS, et al. A ten-year experience treating cervical intraepithelial neoplasia with the C02 laser. Am J Obstet Gynecol. 161(1):60-8, 1989. 7. Rubin MM, et al. Assessment and management of cervical intraepithelial neoplasia. Nurse Practioner. 15(9):23-31, 1990. 8. Rotman M, et al. Concomitant continuous infusion chemotherapy and radiation. Cancer. 65(3):823-35, 1990. 9. Morelli AE et al. Assessment of Langerhans's cell density in penile epithelium with human papillomavirus infection: changes observed after topical treatment. I Urol. 147(5):1268- 73, 1992. 10. Lerman C et al. Adverse psychologic consequences of positive cytologic cervical screening. Am J Obstet Gynecol. 165(3):658-62, 1991. 11. McDonald TW, et al. Impact of cervical intraepithelial neoplasia, diagnosis and treatment on self-esteem and body image. Gynecol Oncol. 34:345-49, 1989. 12. Lerman C et al. Op cit. 13. Boag FC et al. Assessment of psychiatric morbidity in patients attending a colposcopy clinic situated in a genitourinary medicine clinic. Genitourinary Med. 67(6):481-4, 1991. 14. Katrina Haslip, Minority Task Force on AIDS, personal communication, 1991. ***** Glossary Anesthetic: A drug or gas that causes a partial or total loss of the sense of pain or touch. Antibiotic: Any natural substance which is used in the treatment of disease to stop or slow the growth of bacteria or other organisms. Penicillin and tetracycline are two of the most commonly used antibiotics. Adrenal gland: A triangular-shaped gland attached to the top of each kidney. It secretes steroid hormones, androgens, estrogens, and progesterones. Asymptomatic: Having an infectious organism within the body but showing no symptoms. Biopsy: The removal of a small amount of tissue or fluid from the body for examination. Carcinogen: Something that causes cancer. Cervix: The lower part of the uterus that extends into the vagina. A woman can usually feel the cervix by putting a finger into her vagina, or can see it by using a speculum for self- examination. Desensitization: The process of taking a little bit of medicine at a time in increasing doses in order to overcome severe allergies or toxic side effects. Drug interaction: The result of taking two or more drugs that cause unexpected or unwanted side effects when used together. Efficacy: The ability of a drug to control or cure an illness. Endometrium: The internal lining of the uterus. Fetus: A developing human from three months to birth. Fourchette: The narrow strip of skin connecting the front and back of the body at the bottom of the opening of the vagina. Gastrointestinal tract: The part of the body that allows for digestion and includes the mouth, the esophagus, the stomach, the small and large intestine and the rectum. Gestation: The period of carrying developing offspring in the uterus after conception. Latent: Describing an organism that is in the body but not yet producing ill side effects. Lesion: A sore, a wound or a small opening in the skin. Manifestations: The outward signs that an illness is present; symptoms or conditions. Menopause: The time in a woman's life -- usually in her forties or fifties -- during which the menstrual pattern changes, until periods stop. Mycoplasma: A kind of organism that make up a bacteria found in humans. Usually it has no cell walls. Opportunistic infection (OI): Infections or cancer that occur when the immune system of a person becomes weaker. Osteoporosis: A condition in which the quantity of bone and skeletal tissue begins to wear away. Prognosis: A prediction of the probable course of disease. Prolactin: A pituitary hormone that stimulates the secretion of milk in women. Prophylaxis: Preventive medication; treatment to prevent the onset or the recurrence of an infection. Reactivation: The process by which an organism that has not caused illness since initial entry into the body begins to create ill effects. Rectum: The end of the large intestine including the anus. Rheumatoid arthritis: A chronic disease with painful swelling of the joints. Sinusitis: Inflammation of the nasal cavity and sinuses. Systemic: Of or affecting the body as a whole. Thyroiditis: Inflammation of the thyroid gland. Topical: The kind of medicine that is applied directly onto an area, like an ointment. Tubo-ovarian: Relating to the tube of the uterus and the ovary. Urethritis: Inflammation of the canal leading from the bladder to allow urination. Vaginitis: Inflammation of the vagina. ***** Resources These resources were reprinted with permission from The Guide to Resources on Women and AIDS. a publication of the Center for Women Policy Studies, 2000 P Street, NW, Suite 508, Washington, DC 20036 (202) 872-1770. AIDS Clinical Trials Information Service PO Box 642 Rockville, MD 20850 (800) TRIALS-A (800) 243-7012 TTY/TTD AIDS Treatment News PO Box 411256 San Francisco, CA 94141 (415) 255-0588 National Minority AIDS Council 300 Eye Street, NE, #400 Washington, DC 20002 (202) 544-1076 National Native American AIDS Prevention Center 1433 East Franklin Avenue, #3A Minneapolis, MN 55404 (800) 283-AIDS The Positive Woman PO Box 34372 Washington, DC 20043 (202) 898-0372 Women's AIDS Network (WAN) and Women and Children Service Program c/o San Francisco AIDS Foundation PO Box 6182 San Francisco, CA 94101 (415) 864-4376, ext. 2007 Women Organized to Respond to Life-Threatening Diseases (WORLD) PO Box 11535 Oakland, CA 94611 (415) 658-6930 Asian AIDS Project 300 4th Street, #401 San Francisco, CA 94107 (415) 227-0946 California Prostitutes Education Project (CAL-PEP) 333 Valencia Street, #101 San Francisco, CA 94103 (415) 558-0450 Project Aware 3180-18th Street, #205 San Francisco, CA 94110 (415) 476-4091 Shanti Project 525 Howard Street San Francisco, CA 94105 (415) 777-2273 University of California, SF AIDS Health Project Women's Services Program PO Box 0884 San Francisco, CA 94143 (415) 476-6430 National Prison Project/ACLU AIDS in Prison Project 1875 Connecticut Avenue, NW, #410 Washington, DC 20009 (202) 234-4830 DC's Women's Council on AIDS Sistercare 725-1 8th Street, SE Washington, DC 20003 (202) 544-8255 Whitman-Walker Clinic AIDS/Medical Services Programs 1407 S Street, NW Washington, DC 2009 (202) 797-3500 Tampa AIDS Network Florida Women's AIDS Resource Movement (WARM) PO Box 8333 Tampa, FL 33674 (813) 237-6455 New Jersey Women and AIDS Network (NJWAN) 5 Elm Row, #112 New Brunswick, NJ 08901 (908) 846-4462 Life Force: Women Fighting AIDS 165 Camden Plaza East, #201 Brooklyn, NY 11201 (718) 797-0937 Lesbian AIDS Project c/o GMHC 129 West 20th Street New York, NY 10011 (212) 337-3505 Cascade AIDS Project Women's Phone Network 408 SW 2nd, #414 Portland, OR 97204 (503) 223-5907 Health Information Network Women and AIDS PO Box 30762 Seattle, WA 98103 (206) 784-5655 Academy for Education Development AIDSCOM 1255 23rd Street, NW Washington, DC 20037 (202) 862-3868 Boston Women's Health Book Collective (BWHBC) Amigas Latinas en Accion Pro-salud (ALAS) 240 A Elm Street Somerville, MA 02144 (617) 625-0271 Center for Development and Population Activities (CEDPA) 1717 Massachusetts Avenue, NW, 202 Washington, DC 20036 (202) 667-1142 United Nations Office in Vienna (UNOV) Division for the Advancement of Women PO Box 500 Vienna, Austria (222) 211-31-42-07 Project Inform 1965 Market Street, #220 San Francisco, CA 94103 (415) 558-8669 Hotline: (800) 822-7422 National Association of People with AIDS 2025 Eye Street, NW, #1101 Washington, DC 20006 (202) 429-2856 National Network of Runaway Youth Services Safe Choices Project 1400 Eye Street, NW, #330 Washington, DC 20005 (202) 682-4114 National Women's Health Network 1325 G Street, NW, Lower Level Washington, DC 20005 (202) 347-1140 Health Information Network Women and AIDS PO Box 30762 Seattle, WA 98103 (206) 784-5655 ACLU National Prison Project AIDS in Prison Project 1875 Connecticut Avenue, NW, #410 Washington, DC 20009 (202) 234-4830 American Association for World Health World AIDS Day 2001 S Street, NW #530 Washington, DC 20009 (202) 265-0286 American Federation of Teachers HIV/AIDS Education Project 555 New Jersey Avenue, NW Washington, DC 20001 (202) 879-4490 American Psychological Association AIDS Office 1200-17th Street, NW Washington, DC 20036 (202) 955-7727 ***** Subscribe to TREATMENT TISSUES Send this coupon to: GMHC Medical Information 129 West 20th Street New York, NY, 10011 I want to help GMHC continue its vital medical information and treatment advocacy work. 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