Subject: CDC Summary Date: 4/5/93 (233 lines) From: National AIDS Info Clearinghouse Copyright 1993, Information, Inc., Bethesda, MD AIDS Daily Summary April 5, 1993 The Centers for Disease Control and Prevention (CDC) National AIDS Clearinghouse makes available the following information as a public service only. Providing this information does not constitute endorsement by the CDC, the CDC Clearinghouse, or any other organization. Reproduction of this text is encouraged; however, copies may not be sold. Copyright 1993, Information, Inc., Bethesda, MD "Experts Come to Defence of AZT" Financial Times (04/05/93), P. 2 (Kehoe, Louise) AZT will remain the primary treatment for AIDS, even though preliminary results of a large-scale European study, published on Friday, claim that AZT should not be used early in the course of disease, said American AIDS experts. Medical experts and AIDS activists emphasized that the so-called Concorde study should not cause alarm. A spokesman for the San Francisco AIDS Foundation, which offers counseling and support to HIV-positive individuals, said the study "doesn't really change what we already knew or suspected; that AZT when administered as a single therapy is not very effective." In the United States, the current treatment for AIDS uses AZT in combination with drugs like DDI or DDC, both of which have been approved by the Food and Drug Administration. Such a therapy was developed as HIV became resistant to AZT after six to 18 months in most patients, said AIDS experts. Therefore, AIDS experts were not surprised that the European study, which followed HIV-positive people over a three-year period, demonstrated the limitations of AZT. The experts say it is still extremely important to use AZT early in infection, as studies indicate HIV is active in the lymphoid tissues, the lymph nodes, tonsils, and spleen during the latent period, which can last up to 10 years from the time of infection until symptoms appear. One observer said, "It would be a tragedy if the results of the European AZT study discouraged people from seeking early treatment." "Drug Company Doubts Findings of AZT Study" Journal of Commerce (04/05/93), P. 7A A top official with the British pharmaceutical company that makes AZT questioned the results of a European study published Friday in The Lancet that showed no proof that the drug prolonged the onset of AIDS. Andrew Revell of Burroughs Wellcome, in Latvia for a two-day conference on AIDS, said AZT still has a key role to play in fighting the disease. He said many patients had withdrawn from the study and said he was not sure whether the report was representative. "I would cast doubts on the results of information, but even if the result is right I would still intervene [with medial treatment] early to help the quality of life of those living with HIV-AIDS," said Revell. "Drugs on Trial" Financial Times (04/05/93), P. 11 The European researchers who conducted the "Concorde" study should be commended for executing their trial of the leading AIDS drug AZT through to its unanticipated conclusion, write the editors of the Financial Times. The researchers had bravely resisted strong pressure from colleagues, particularly in the United States, to discontinue the study. These colleagues apparently thought that they already knew AZT would benefit people infected with AZT. The study found that the modest benefits discovered after a year's treatment with AZT--the point at which three smaller U.S. trials were stopped--had disappeared by the end of the three-year study. The drug did not delay the onset of full-blown AIDS. These findings are particularly sad for the several thousands of HIV-infected people who had hoped AZT would inhibit the development of the disease. However, the study is a powerful demonstration of the patient European approach to clinical trials, as opposed to the American inclination to rush to premature conclusions with insufficient evidence. This study will help people with HIV in the long run by exposing the inadequacies of AZT and therefore facilitating the testing of other drugs. In the world of AIDS research, activists' persistence has made it difficult for drug companies or government agencies to conduct large enough clinical trials to give worthwhile results. The Concorde study demonstrates why this must stop, the editors conclude. "Around the Nation: AIDS Group Resignations" Washington Post (04/05/93), P. A7 Two senior executives of the Shanti Project in San Francisco, the nation's largest provider of housing for AIDS patients, resigned after being blamed for neglecting to account for $2.7 million in government funds. Executive director Eric Rofes and deputy director Melinda Paras presented their resignations at the board's request. Shanti makes 144 beds available for AIDS patients, as well as support services for 1,000 people. It has an annual budget of $5.4 million. The San Francisco city AIDS office had been investigating Shanti, and in March revealed that the sloppy accounting records could not show where Shanti had spent $2.7 million in public funds from mid-1991 to early 1993. Shanti must pay the money back to the city or show how the money was spent by May 1. "Sexually Transmitted Diseases Abound in Ohio" United Press International (04/02/93) Cleveland--The number of people infected with HIV and syphilis significantly increased in Ohio last year. The Cleveland Plain Dealer conducted a computer analysis that showed that more than 1,500 people died in Ohio between 1989 and 1991 from AIDS-related conditions, while dozens more died from syphilis and hepatitis. Experts said that all of the nationwide attention focusing on AIDS has overlooked the increase in the number of people with other sexually transmitted diseases (STDs). The computer analysis examined the primary cause of death for more than 300,000 people in Ohio during the three-year period. AIDS-defining illnesses, the leading killers among STDs in Ohio, affect 15 times more men than women. Such illnesses were found to be the chief cause of death of more than 1,500 people in Ohio. Syphilis caused 12 deaths, eight of them women, and 72 people died of hepatitis B virus. Authorities said no deaths resulted from gonorrhea or chlamydia, both STDs which can be quickly treated. "MicroGeneSys Drops Out of NIH Trial for AIDS Vaccine" Nature (03/25/93) Vol. 362, No. 6418, P. 277 (Macilwain, Colin) The AIDS vaccine made by MicroGeneSys of Meriden, Conn., has been withdrawn from the main comparative trials being organized by U.S. public health agencies, a move which will exacerbate the already bitter divisions within the AIDS research community. MicroGeneSys withdrew its gp160 vaccine--the same one that is to be used in a $20 million trial program by the U.S. Army--from comparative trials scheduled by the AIDS Clinical Trials Group (ACTG) of the U.S. National Institutes of Health (NIH). The drug company and its development partner, Wyeth-Ayerst Research, opposed the proposed dosing schedule, the duration of the study, and the criteria being used to assess the vaccine. The company said the withdrawal was "driven primarily by the needs of our development program." The vaccine, also known as VaxSyn, consists of the outer envelope protein of HIV and is designed to strengthen the immune systems of people already infected with HIV. One researcher at NIH said, "This was the only study giving direct comparability between rival vaccines. But put yourself in their shoes: why would they want to help generate data showing that their vaccine offers less immunogenicity than others." However, the president of MicroGeneSys, Franklin Volvovitz, says that the mention that his company fears the results of the proposed trials is "preposterous." He said, "It's bizarre for them to say these things. We disagreed with the primary and secondary end-points set for protocol 214. As the firm with the largest database, our views should be considered." Volvovitz added that MicroGeneSys has been repeatedly excluded from another NIH competitive study that observes the effect of vaccines on patients' response to AZT. "HIV Infection is Active and Progressive in Lymphoid Tissue During the Clinically Latent Stage of Disease" Nature (03/25/93) Vol. 362, No. 6418, P. 355 (Pantaleo, Giuseppe et al.) HIV disease is active and progressive even when there is little evidence of disease activity and by readily measured viral parameters in the peripheral blood, and the patient is experiencing asymptomatic HIV infection, write Giuseppe Pantaleo et al. of the National Institute of Allergy and Infectious Diseases at the National Institutes of Health in Bethesda, Md. Primary infection with HIV is typically followed by a burst of viremia with or without clinical symptoms. This is usually followed by a prolonged period of clinical latency. During the latency period there is little, if any, detectable viremia, the numbers of infected cells in the blood are very low, and it is extremely difficult to demonstrate virus expression in these cells. The researchers evaluated viral burden and levels of virus replication simultaneously in the blood and lymphoid organs of the same individuals at various stages of HIV disease. They found that during clinical latency, HIV accumulates in the lymphoid organs and replicates actively despite a low viral burden and low-to-absent viral replication in peripheral blood mononuclear cells (PBMC). Hence, a state of true microbiological latency does not exist during the course of HIV infection. The peripheral blood does not accurately reflect the actual state of HIV disease, particularly early in the clinical course of HIV infection, conclude the authors. "Massive Covert Infection of Helper T Lymphocytes and Macrophages by HIV During the Incubation Period of AIDS" Nature (03/15/93) Vol. 362, No. 6418, P. 359 (Embretson, Janet et al.) Latently infected lymphocytes and macrophages comprise an intracellular reservoir large enough ultimately to contribute to much of the immune depletion in AIDS, write Janet Embretson et al. of the University of Minnesota in Minneapolis, Minnesota. The researchers used polymerase chain reaction (PCR) in situ double-label methods to determine how many CD4 lymphocytes are latently infected by HIV in patient lymph nodes and whether the pool of infected cells is large enough to account for immune depletion through continual activation of viral gene expression and attrition of cells responding to antigens. The researchers found an extraordinarily large number of latently infected CD4 lymphocytes and macrophages throughout the lymphoid system from early to late stages of infection, and confirmed the extracellular association of HIV with follicular dentritic cells. Follicular dentritic cells may transmit infection to cells as they migrate through lymphoid follicles. The extent of infection in the CD4 lymphocyte population in lymphoid organs where 98 percent of these cells reside is sufficient to account for a substantial portion of the immune depletion in AIDS by a mechanism of slow elimination of small fractions of cells in which productive infection is continually activated concomitantly with the immune response to a particular antigen or pathogen. Because the end result of so many CD4 lymphocytes is determined relatively early in the course of infection emphasizes the difficulties in developing treatment programs that can be initiated in time to affect the outcome favorably, the researchers conclude. "Endocrine Effects of HIV Infection" New England Journal of Medicine (03/25/93) Vol. 328, No. 12, P. 889 (Martinez, Esteban et al.) Aerosolized pentamidine can affect pancreatic function, write Esteban Martinez et al. of the Hospital de la Santa Creu in Barcelona, Spain. Grinspoon and Bilezikian write in the Nov. 5 issue of the New England Journal of Medicine that "there is no evidence that pentamidine administered by aerosol alters pancreatic function." However, there have been at least three cases of pancreatitis, one of hypoglycemia, and two of diabetes mellitus reported after treatment with aerosolized pentamidine. The drug can be absorbed systemically after being inhaled in aerosol form, despite typically low plasma levels. Possible predisposing conditions include previous subclinical pancreatic damage, therapy with other drugs associated with acute pancreatitis (such as trimethoprim-sulfamethoxazole and didanosine), and overdosing of pentamidine administered by aerosol as a result of difficulties with nebulizer use, conclude Martinez et al.