Gay Men's Health Crisis: Treatment Issues, Volume 7 no. 8 September, 1993
David Gold

A study, reported in The Journal of Infectious Diseases (1993; 168: 314-7), found that two-thirds of 130 HIV-positive patients taking aerosolized pentamidine (AP) could be successfully switched to Bactrim or Septra (TMP/SMX) without allergic reactions or hematological toxicity. TMP/SMX is the most effective preventive treatment for Pneumocystis carinii pneumonia (PCP), a common, life-threatening infection in people with HIV. TMP/SMX is also less expensive and easier to administer than AP. Those who could not be switched developed fever and rash within the first two weeks, which resolved when the drug was discontinued. Significantly, patients with CD4 cell counts under 200 did not tolerate the crossover as well as those with higher CD4 cell counts. Fifty-seven percent of the lower CD4 group developed skin reactions to TMP/SMX compared with 27 percent in the higher CD4 group.

Splenectomy for Thrombocytopenia ^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^^ Splenectomy (surgical removal of the spleen) is a common therapeutic intervention for patients with AIDS or ARC who have thrombocytopenia (low platelet counts). A study reported in AIDS (1993;7: 1063-7) of 22 HIV-positive patients who had their spleens surgically removed secondary to thrombocytopenia showed that the surgical procedure led to reversal of the blood disorder in most patients, including those with MAI, lymphoma, and Kaposi's sarcoma. Previous studies had shown that patients with MAI die soon after splenectomies, yet this did not occur in the study. Two patients developed pneumococcal infections after the splenectomy, but they had not received Pneumovax, the pneumococcal vaccine, prior to the operation. None of the patients had an acceleration of their HIV illness after the splenectomy and all but one of the patients had a complete or partial response in their platelet counts.

Viral Strains, Progression, and AZT

A team of Dutch researchers report in The Journal of Infectious Diseases (1993;168:733-6) a viral substudy from a randomized, double-blinded, placebo-controlled trial of AZT. The researchers found that the presence of certain HIV strains - syncytium-inducing (SI) or non-syncytium-inducing (NSI) variants - affected disease progression and the efficacy of AZT. Syncytia are groups of originally separate cells which clump together to form a single mass. The formation of syncytia in CD4 cells causes cell dysfunction and eventual cell death in laboratory experiments. Researchers do not yet know if syncytia form in vivo.

The researchers found that patients who entered the study with SI variants at baseline progressed rapidly to AIDS and death despite AZT treatment. An equal percentage of placebo and AZT patients with SI variants at baseline progressed to AIDS by two years. In contrast, patients who entered with NSI variants at baseline progressed more slowly and received benefit from AZT. No patient treated with AZT who remained NSI throughout the study progressed to AIDS by two years. Thirty-eight percent of placebo patients who remained NSI throughout the study progressed to AIDS by two years. The researchers noted that SI variants can develop in NSI patients through an unknown mechanism. In fact, AZT treatment did not prevent the emergence of SI variants. The researchers observed, "In this small study, conversion to SI phenotype even tended to occur more rapidly in the AZT-treated group." Six AZT-treated patients converted from NSI to SI during the study period compared with two placebo patients.

Assays to determine SI/NSI variants require sophisticated laboratory equipment found only in specialized research centers. Commercially available tests of SI/NSI variants are unlikely to become available in the foreseeable future. However, several research teams are now investigating this phenomenon. More information on the significance of these viral variants for clinical research and care should be forthcoming.

Treatment Information for Prisoners

AmFAR runs a program which provides AIDS/HIV treatment information, including complimentary copies of Treatment Issues, to prison libraries across the country. Joe Guimento at AmFAR coordinates the program. Call him at 212/682-7440 for more information.

Pregnancy Hormone Studied For KS

Human Chorionic Gonadotropin (HCG), an approved treatment for inducing fertility in women, cryptorchidism (the failure of the testicles to descend), and male hypogonadism (inadequate gonad function), has been proposed as a KS treatment based on an anecdotal report of spontaneous resolution of KS lesions in a pregnant Belgian woman and unpublished animal data from Robert Gallo at the National Cancer Institute. Sharon Lee, a Kansas physician who is affiliated with San Francisco's Project Inform, will perform a study of HCG on six of her male KS patients. The study will examine 5000 units of HCG three times a week for up to six months. In addition to HCG's effect on KS lesions, the study will also examine any possible penile or testicular changes in the men.

DHEA Study Results

DHEA (dehydroepiandrosterone) is a testosterone precursor with unknown physiological significance which may have immunomodulatory effects, according to several laboratory studies. DHEA has been proposed as an alternative approach to treating HIV and is available through buyers' clubs in New York and San Francisco. An open-label, dose-ranging study of the drug in 31 asymptomatic people with 250 to 600 CD4 cells was reported in the Journal of AIDS (1993; 6(5): 459-465). Doses ranged from 750mg/day to 2250mg/day. No side effects were observed. CD4 counts did not improve in study participants. Neither p24 antigen nor B-2 microglobulin levels decreased. The authors state that a randomized clinical trial of this agent is now necessary to evaluate efficacy.

Two Foscarnet Reports

Foscarnet may be the drug of choice for CMV encephalitis, a research team from the National Cancer Institute reports in Antimicrobial Agents and Chemotherapy (1993; 37(5): 1010-14). Foscarnet crosses the blood brain barrier and can be detected at therapeutic levels in cerebrospinal fluid after a single dose. However, the clinical efficacy of foscarnet for CMV or herpes encephalitis is still unresolved. In addition, a small randomized study of 32 AIDS patients with CMV retinitis suggests that higher maintenance doses of foscarnet may be superior to lower doses. The study, published in The Journal of Infectious Diseases (1993; 168: 444-448), found a daily dose of 120mg/kg significantly extended survival time and prolonged the time to retinitis progression compared with lower maintenance doses of the drug (60 or 90mg/kg/day). Median survival was 157 days for the 90mg dose compared with 336 days with the 120mg dose. Kidney toxicities, a well-known side effect of foscarnet, were slightly more common at the 120mg dose; other adverse effects did not occur more frequently.

CRIA Begins Aspirin Study

The Community Research Initiative on AIDS (CRIA), a New York- based community AIDS research group, has announced a clinical trial of aspirin for HIV disease. Dr. Donald Kotler of St. Lukes Hospital, the study's principal investigator, will test aspirin's ability to reduce HIV-related inflammation. Certain inflammatory mechanisms, such as increased levels of inflammatory cytokines, may increase HIV replication. The placebo-controlled trial is open to asymptomatic HIV-positive people with 50-350 CD4 cells. Call 212/924-3934 for more information.

Other New Trials in New York City

Two new trials for CMV retinitis have opened at New York Hospital. One study compares intravitreal ganciclovir implants (small pellets of drug sewn into the eye which release drug directly to the infected area) with standard intravenous ganciclovir therapy. The other study compares three treatment regimens for CMV retinitis: high-dose ganciclovir versus high-dose foscarnet versus the combination of both. Call 212/639-7237 for more information on these studies. New York University has started a trial of recombinant human growth factor (r-HGF) for HIV-related wasting syndrome. Call 212/561- 3906 for more information. Finally, a study at St. Vincent's Hospital (212/790-7625), and Memorial/Sloan Kettering (212/639-7163), will compare liposomal doxorubicin (Doxil) with adriamycin, bleomycin, and vincristine (ABV), a common Kaposi's arcoma treatment regimen, for advanced KS.

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