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
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
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
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.