ICAAC's Small Advances

Not all the research presented at the San Francisco ICAAC meeting (the Inter-Science Conference on Antimicrobial Agents and Chemotherapy; see coverage in AIDS TREATMENT NEWS #231, and in following issues) was dramatically important, but much of it could help answer the small, day to day questions that both doctors and their patients must consider. The following is a brief summary of some abstracts we found interesting.

* Researchers from the University of Miami and the University of California in Los Angeles proposed conditions that enhance HIV penetration of the central nervous system. In the laboratory, they created a model of the blood-brain barrier with human brain endothelial cells and a sublayer of fetal astrocytes, and found that this "barrier" could be disrupted by migrating monocytes, by tumor necrosis factor inflammation, and by exposure to cocaethylene, which simulated drug abuse. (Earlier research has long implicated tumor necrosis factor with the development of dementia, as well as in wasting and disease progression.) The authors of this work theorize that in people, the blood-brain barrier can also resist HIV unless challenged by one of the above disruptions. [Abstract I71]

* NIH researchers, with others, reported that NAC (N-acetyl- L-cysteine), a mucolytic agent, could inhibit the germination of spores of several species of fungi that can cause pulmonary infections in people who are immunocompromised. One of the fungi used in the cultures was aspergillus, which can definitely be a problem for people with HIV. NAC has already been in wide use in the HIV community since Stanford researchers described its potential to inhibit HIV replication. In this new work, a concentration of 10% NAC was said to work better than more dilute solutions, or than a 10% solution of L-cysteine. These were laboratory experiments, but since NAC is safe and already FDA-approved to treat certain pulmonary disorders, it could conceivably become an adjunctive treatment for aspergillus infections. [abstract E82]

* A number of other new antifungals were presented at the conference, including those code-named L-733560, Sch 56592, UK-109,496, UR-9746, UR-9751, ER-30346, and D0870, as well as some new antimycobacterials, such as U100-480, T9, CRL-1018, CRL-1072, KRM-1648, tryptanthrin and azaindoloquinazoline- diones. New drugs from both classes are very much needed, because some evolving strains of candida, cryptococcus, tuberculosis, and MAC have lost susceptibility to the older medicines. Apparently only a few of the new agents are in human trials.

* Azithromycin, an antimicrobial which is often used in AIDS medicine, is capable of causing ototoxicity, or hearing and balance deficits, according to Toronto researchers. They said that eight of 46 patients on azithromycin reported various otologic complaints, including vertigo, hearing loss, tinnitus and a feeling of plugged ears. When the drug was discontinued, the problems resolved within two to eleven weeks [abstract LM19]. (Amikacin, another antibiotic sometimes used to treat MAC, can be ototoxic as well. Patients should be warned about this danger when they are given these drugs.)

* Johns Hopkins researchers reviewed the follow-up data on patients who had participated in two controlled clinical studies of rifabutin as MAC prophylaxis and found an association with improved survival on the drug. The trials had already established that rifabutin could reduce MAC bacteremia, but its effect on survival has been in question. The authors said that for patients on rifabutin for one year, the relative hazard of dying was 8% lower than for patients not on prophylaxis. After a year and a half, the risk was 14% lower. [abstract I204]

* A number of presentations supported the use of cytokines, chemical messengers that travel between cells, in AIDS therapies. Stanford researchers, for example, reported that interleukin-12 significantly enhanced the effectiveness of atovaquone and clindamycin in mice with toxoplasmosis. They suggested that the combination could be useful in human toxoplasmosis as well [abstract G99]. Other San Francisco area researchers reported that GM-CSF (granulocyte macrophage-colony stimulating factor) may improve the immune response to MAC bacteremia when added to MAC treatments [abstract G109]. French researchers likewise reported that GM-CSF appeared to enhance the effect of the standard treatment for toxoplasmosis, which is a combination of sulfadiazine and pyremethamine. They surmised that the benefit was from bolstered host responses. [abstract I225]

* Physicians from Madrid described some modest benefits for patients with PML (progressive multifocal leukoencephalopathy) who were treated with intravenous cytarabine. In a retrospective study of thirteen biopsy- confirmed infections, three people improved on the drug, and five others did not. The five untreated patients did not improve. The patients who received cytarabine had a median survival of 100 days, compared to 36 days for the untreated. The authors added that the treatment was well-tolerated. [abstract I227]

Except for similar humane attempts to address it, PML is probably the longest-running neglect story in the AIDS epidemic. There are no convincing treatments for it, and no convincing research organized to change that. Cytarabine is the only drug that has ever been seriously considered. Most clinicians simply offer AZT to their patients diagnosed with PML, because AZT crosses the blood-brain barrier and has been reported anecdotally to reverse some cases. (The Spanish authors said their results were not affected by the use of AZT.) Treatment advocate Peter Brosnan in Los Angeles has been like a lone lighthouse in this situation, compiling the meager research data for the last several years and sending it to concerned patients and physicians. We look forward to the conference that offers more than one small study for this infection.

* Researchers in Nigeria and Washington, DC, reported that immune globulin was helpful for preventing a number of infections of the ear, respiratory and urinary tracts in children with HIV. This helped to confirm research from previous years, and in fact, immune globulin is considered by some clinicians to be similarly useful in HIV-infected adults with low CD4 counts. [abstract G45]

* French researchers studied CD8 cell counts, and found that individuals with higher counts, in this case greater than 600 cells/ml, experienced significantly fewer opportunistic illnesses--4% vs. 27.5%--while followed over the course of one year [abstract G49]. And New York researchers reported that HIV-infected infants who had not yet developed CD8- mediated viral inhibition fared much worse than those who did [abstract I8]. These observations support a long-standing contention of Jay Levy of the University of California in San Francisco. Dr. Levy has asserted that CD8 cells can secrete an anti-HIV factor which, at its most effective, explains why some HIV-infected people appear to have the virus under control for many years, perhaps indefinitely. The French researchers suggest the pursuit of strategies to enhance the activity of CD8 cells.

* Researchers at Henry Ford Hospital observed that HIV levels increase significantly during a bout with an opportunistic infection. They monitored ten patients diagnosed with an opportunistic infections, and of the eight who had detectable baseline levels of HIV RNA, all showed a "striking" increase in viral burden. All eight also experienced a significant decline in plasma RNA upon their recovery from the infection. Interestingly, CD4 counts and p24 antigen levels did not change much [abstract I236]. This could be useful information to physicians who make antiretrovirals a low priority or even discontinue HIV drugs when their patients face a new infection.

* ACTG researchers reported that apart from mild anemia, AZT does not adversely affect infants whose mothers took the drug during pregnancy. This observation followed a critical study, ACTG 076, which found that AZT could reduce the transmission of HIV from mother to fetus by almost 70%. AZT-exposed infants were compared to those whose mothers got a placebo, and no important differences were seen in parameters such as weight, CD4 and CD8 counts, head circumference and neurodevelopmental tests. [abstract I2]

* A distressing pattern of undiagnosed infections was reported by physicians at Howard University Hospital. When they reviewed the autopsy findings on 40 HIV-infected women, they found that fully half of them had diseases that were identified only postmortem. Seven had more than one disease. The authors added that even when the infection or neoplasm was diagnosed before death, the extent of organ involvement was often underestimated. Thirty-eight of the women were African-American. [abstract I62]

* Additional disturbing facts about access to treatments emerged from a survey of HIV clinicians by the Centers for Disease Control and Dun and Bradstreet HealthCare Information. The survey was drawn from selected providers in Atlanta, Chicago, Long Island, Oakland, Portland, Tampa and Washington, DC. It found that women were less likely than men to receive AZT, ddI, or d4T; injection drug users were less likely to get d4T (the newest approved HIV drug) than were gay or bisexual men; patients on public assistance were less likely than those with private insurance to receive any antiretroviral treatment at all, and, among all patients on antiretrovirals, those on public assistance were much less likely to receive combination therapy than were privately- insured individuals. [abstract I19]

Comment

Not clear is whether those discrepancies were a function of bias on the part of individual providers, or of disparate patient populations observed between providers. But either scenario, in our opinion, would be unsurprising under the current system--or nonsystem--of access to medicine in the U.S. The delivery of health care has become astonishingly undemocratic: some employed persons are insured and are welcomed to comprehensive care with physicians in private practice (who much prefer the reimbursements of insurance to those of Medicaid), while the underemployed, the unemployed and the indigent are not insured and must settle for patchwork services at urban clinics and hospitals which creak along with too many patients and too few resources. Which venue would be more likely to foster an attentive physician and an informed, motivated patient? Souring the inequity all the more is the influence that sex, race and class hold over who gets stable employment in the first place, especially the kind with health benefits.

Unfortunately, the Republicans in Congress lack the heart-- and the Democrats in the White House the spine--to lead America into the developed world on this issue.