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Being Alive

Medical Update-September 23, 1996


Being Alive 1996 Oct 5: 2

* All About Nevirapine Nevirapine (brand name Viramune) is the latest antiviral to be approved by the FDA. This drug is a reverse transcriptase (RT) inhibitor; it works at the same point of the viral life cycle as AZT, 3TC, ddI, ddC and d4T. Nevirapine, however, is chemically structured in a way that differs from AZT and the others; thus, it is classified as a non-nucleoside RT inhibitor. As such, it is the first "non-nuke" to become available.

As more and more medical providers and patients have experience with nevirapine, a standard of use is emerging. First and foremost, this antiviral should always be used in combination with one or preferably two other antivirals. When used as monotherapy, the virus quickly develops resistance to nevirapine. This drug is more effective in penetrating the central nervous system (CNS) than some of the current antivirals. Thus, for those with neuropathy, dementia or other CNS diseases, nevirapine may be a particularly us eful and important addition to their current antiviral regimen.

Right now there is concern about nevirapine's interaction with a protease inhibitor. Reports have indicated that it might lower the levels of protease inhibitor in the blood. As you may know, it is important to take the proper dosage of saquinavir, ritonavir or indinavir; cutting the dosage may encourage viral resistance to the protease inhibitor. Nevirapine might be cutting the level of PI reaching the bloodstream and thus, in effect, encouraging resistance. We don't know if this is, in fact, true. Studies are now underway and we hope to have some answers by early 1997. In the meantime, you should not be combining nevirapine with a protease inhibitor. In the available studies, the main side effect of nevirapine is rash; some 20% of study participants reported this side effect, with about 7% of study participants forced to quit nevirapine because of it. The drug's manufacturer, Boehringer-Ingelheim, is recommending that you begin nevirapine at 200 mg once a day for two weeks and then increase to the standard dosage of 200 mg twice a day. They have prepared a booklet on how to manage nevirapine-related rash. Call 800.274.8651 for a copy.

* Combination Therapy Study The AIDS Clinical Trials Group (ACTG) is forming a study of the much-touted combination of AZT plus 3TC plus indinavir. This particular antiviral combination has been shown in small studies to bring the viral load down to an undetectable level in almost all participants. The ACTG trial is a large scale study that is currently enrolling hiv+ individuals with a viral load of greater than 1000 and no prior use of 3TC or a protease inhibitor.

All study participants will initially receive six months therapy on the full combination. After the six months, those whose viral load has become undetectable will be randomized to one of three regimens: AZT plus 3TC, indinavir alone, or the original combination of AZT plus 3TC plus indinavir.

You might ask: Is such an approach ethical? Is it right to take people off a regimen that has reduced viral load to undetectable? The study designers answer this by pointing out that during the first two weeks on the new regimen, the viral load of all participants will be checked three times a week. After that, viral load will be taken once a month. If an individual's viral load at any point becomes detectable, he/she will be put back on the original three-drug combination. This ACTG study has a two-fold purpose. First, the researchers want to ascertain which of the three regimens is superior in bringing the viral load down to undetectable. Second, they want to determine how long this undetectable level is maintained when therapy is changed.

* More on Hydroxyurea We have reported in the past about the use of the anti-leukemia drug hydroxyurea as an anti-hiv drug. Two years ago, we had the first reports out of France about small studies of the combination of hydroxyurea and ddI in treating hiv disease. Now the Lancet (July 26, 1996) is reporting the one year follow-up of a study of this combination. Twenty-five hiv+ individuals with CD4 counts above 200 were given 200 mg of ddI twice a day and 15 mg of hydroxyurea per kilogram of weight in two equal doses each day. This regimen was well tolerated; the dosage of hydroxyurea is only about a quarter of the level used to treat leukemia.

The mean viral load at the start of the trial was 30,000. Researchers found that this level dropped in all study participants. At six months, 13 of the 24 had undetectable viral levels. Twenty patients were tested at one year out from the start of the study; half of this group still had undetectable virus. In addition, the researchers looked at the lymph nodes of several of the study subjects. Although the number was too small for statistical significance, they were not able to detect virus in the lymph node cells.

This is good news for those who are intolerant of or resistant to other available antivirals. Perhaps hydroxyurea, already FDA-approved for leukemia treatment, should be considered.

* Studies of the KS Herpes Virus This year, researchers identified the virus associated with Kaposi's sarcoma (KS), KSHV or HHV-8. The KS herpes virus is the eighth human herpes virus to be named. It is related to the viruses that cause herpes and shingles, but is not the same. Three recent studies tell us more about KSHV.

One question that is being asked is where the KS herpes virus is localized in the body. A study in the New England Journal of Medicine (May 2, 1996) addressed this issue. KSHV was found in less than 10% of the skin samples studied. However, the virus was found in over 91% of the semen of males with KS and the vaginal secretions of females with KS. KSHV was also detected in 44% of the prostate glands of the males studied. These data imply that KSHV is sexually transmitted. Adding to the evidence that this is so is the fact that almost all women with KS were infected with hiv through sexual contact with bisexual men, rather than through IV drug use. If the KS virus is a human herpes virus, can the use of an antiherpes drug such as acyclovir reduce the risk of developing KS? A retrospective study in the Journal of Infectious Diseases (June 1996) looked at this question. Researchers reviewed data on 935 men enrolled in the Multicenter AIDS Cohort Study (MACS). They found no correlation between acyclovir use and decreased risk for KS. However, they did find that those who were treated for CMV (another herpes virus) with either ganciclovir or foscarnet seemed to have lower incidence of KS.

Finally, another study in the New England Journal of Medicine (July 25, 1996) looked at the prevalence of KSHV. Not surprisingly, 80% of the KS patients tested were found to be positive for KSHV, while only 18% of the people with AIDS, but not KS, tested positive. In contrast, none of the blood donors in the control group tested positive nor did those with Epstein-Barr virus. And none of the hiv+ people with hemophilia, infected with hiv from contaminated blood, were found to carry the KS herpes virus, adding to the evidence that KSHV is sexually transmitted.

* What About Human Growth Hormone? The FDA has approved Serono's human growth hormone (brand name Serostim) for treating of AIDS-related wasting syndrome. Approval was based on a study of 178 people with AIDS who had documented weight loss of greater than 10% of their usual body weight. Half the group received an average of 6 mg of Serostim per day injected under the skin; the other half received a placebo. At week 12, the growth hormone group had an increase of 2 kg (or about 4 lbs) of lean body mass, while the placebo group had no gain. Researchers also noted that treatment with Serostim did not increase viral load. In contrast, studies of Megace showed greater average weight gain (about 4 kg or 8 lbs), but that weight gain was almost all fat.

The problem with human growth hormone is cost. This is the most expensive pharmaceutical ever made. The original cost was over $50,000 per year, but the manufacturers have now put a "cap" of $36,000 per year for one individual. This is still an enormous cost for 4 lbs of weight gain in three months. To date, we have no evidence that this weight gain continues with growth hormone use. Nor do we have any data that show that weight gain in itself results in longer overall survival. To put things in perspective, in terms of hiv care, $36,000 can buy 9000 hiv antibody tests or 16 courses of AZT for pregnant women or 7 annual courses of protease inhibitors or 360 viral load tests. In fact, under current estimates of health care economists, $36,000 represents one-third to one-half the lifetime cost of treating someone with hiv.

So what about human growth hormone? For the individual with wasting syndrome who has gone through other options, it is good that this drug is available. From the wider perspective in this era of reduced funding for hiv treatment, one has to question whether the cost outweighs the benefit.


Information in this article was accurate in October 5, 1996. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.