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Conference Update
by Enid Vázquez
More news from the 7th Conference
on Retroviruses and Opportunistic Infections. This major HIV/AIDS
conference took place in San Francisco, January 29-February
2. Visit www.retroconference.org
for complete information.
Subjects:
When T-cells and
viral load don’t match
Is HAART enough?
Women’s cancer
Women’s deaths
Infants and AZT
Cesarean cost-effective
Viramune in new moms
Once daily, truly
The newest protease
Cholesterol-lowering drugs
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When T-cells and viral
load don’t match
Many people have a “discordant”
response to HAART (highly active antiretroviral therapy).
Either their T-cells go up but their viral load (amount of
HIV in the blood) also goes up, or both numbers go down. A
look at 956 German patients (half of them on therapy for the
first time) found that a third of them had a discordant response.
Researchers reported that an increase in T-cells was more
important for clinical benefit than a decrease in viral load.
People who had a decrease in viral load but no increase in
T-cells had as much disease progression as those who didn’t
have a viral load drop and also didn’t have a T-cell
increase. People who responded well on both measures, not
surprisingly, did the best clinically.
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Is HAART enough?
That was the title of a report
from Philadelphia researchers. They noted that more AIDS deaths
in 1999 were being seen in an urban population despite earlier
access to HIV care and HAART, plus higher T-cells and lower
viral load, when compared to the deaths in their clinic in
1998. The patients also had better adherence and less illicit
drug use. The three most common causes of death for both years
were wasting, complications of hepatitis C infection and mycobacterial
disease. The researchers reported that, “Further research
is needed to develop additional interventions that will impact
the mortality associated with this disease across a broad
range of populations.” They also reported that, “An
increasing number of minority women initially presented undiagnosed
or newly diagnosed with late complications of HIV infection.
This may be due to a variety of factors, including lack of
awareness of HIV, lack of perceived risk of HIV infection
or fear of the stigma of HIV which persists in some communities.”
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Women’s cancer
Certain strains of HPV (human
papilloma virus) are associated with cervical cancer. Baltimore
researchers reported that women benefit from HAART by being
more likely to stop an HPV infection from getting worse, and
even reversing HPV disease. The WIHS doctors (Women’s
Interagency HIV Study) called the finding “a major additional
benefit” of HAART.
A multi-center WIHS analysis
found that while most women with HIV will have an abnormal
finding on a pap smear, the risk of serious abnormalities
is much less.
Positive women with normal
menstrual cycles have the same levels of the hormones progesterone
and estradiol as do HIV negative women. In addition, the hormonal
levels are the same among the positive women regardless of
viral load, immune status or HIV drugs.
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Women’s deaths
The U.S. Centers for Disease
Control (CDC) looked at the causes of death in 176 HIV positive
women between 1993 and 1998. The majority (56%) died of AIDS
or HIV-related causes. For the remaining women, a third died
from drug-related causes, including overdoses (7%), endocarditis
or sepsis (5%) and hepatitis (2%). The CDC urged drug treatment
services and hepatitis vaccinations to help reduce deaths
from these causes.
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Infants and AZT
Infected infants who have
drug resistance to AZT (Retrovir) (received during birth to
prevent transmission from the mom) were twice as likely as
other infected babies to have rapid disease progression, but
the difference was not statistically significant. The information
came from 57 infants in a multi-center Women and Infant Transmission
Study (WITS) in 1994. The report went on to say that infant
use of AZT during the first six months of life was not associated
with disease progression.
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Cesarean cost-effective
An elective cesarean section,
which is major surgery used to prevent HIV transmission, was
found to be cost-effective. This was true whether women received
no prenatal anti-HIV treatment, took AZT or received AZT in
combination with Epivir (3TC). The National Institutes of
Health (NIH) doctors noted that, “Based on the findings
of this study, elective cesarean section is likely to remain
cost-effective over a wide range of clinical and economic
scenarios.Ó While there are health issues surrounding
the use of elective C-sections, cost-effectiveness is helpful
to address because it may help insurance companies to agree
to pay for the surgery. In this report, as in others, elective
C-sections were found to further decrease transmission above
and beyond the use of medicine taken to reduce that risk.
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Viramune
in new moms
There was good news and bad
news on the use of Viramune (nevirapine) to prevent transmission
during childbirth. The good news is that Viramune was better
than short-course AZT at preventing transmission. AZT is currently
the standard of care for preventing infection from the mom
to the infant. Viramune was used only twice (one 200 mg tablet
given to the mom at the onset of labor and then 2 mg per kilogram
of weight given to the infant within 72 hours of birth). The
bad news is that 3 out of 15 moms who received Viramune in
a study went on to develop drug resistance. The risk of losing
future treatment options must therefore be considered.
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Once daily, truly
Preliminary results from
an honest-to-God once-daily HAART combination were provided.
French researchers looked at a combination of Sustiva (efavirenz),
Videx (ddI) and the experimental drug emtricitabine (FTC),
which is in the same drug class as Videx. At 24 weeks, 24
of 28 participants had less than 20 viral load. Of a total
of 40 study participants, 60% experienced what the researchers
called “transient” central nervous system side effects
and 25% had “mild” diarrhea. There were six serious
side effects (Grade 3 or 4) and one discontinuation. The study
was conducted with people who had never before taken HIV therapy.
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The newest protease
Coming soon (well, in several
months) to a pharmacy near you is Aluviran (lopinavir, formerly
ABT-378/r). In a trial with people whose previous protease
inhibitor therapy failed to keep them undetectable, the powerful
new protease inhibitor successfully dropped viral load to
less than 400 copies in 84%. This was 49 of 58 people, at
48 weeks (a good long time, scientifically significant). Looking
at a tougher analysis, intent-to-treat, whereby all participants
are included whether or not they’re still on the drug
or moved out of the country or whatever, 70% were below 400.
The mean T-cell increase was 125 (half the participants had
more than this, half had less). Side effects were nausea,
diarrhea and asthenia (weakness or loss of strength). The
drug is combined with a little bit of Norvir (ritonavir).
Lopinavir is currently available through expanded access,
a program making promising experimental drugs available to
people who desperately need them.
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Cholesterol-lowering drugs
(The following is taken
directly from a newsletter of San Francisco’s Project
Inform).
New information on the “statin”
drugs used to lower cholesterol and their interaction with
protease inhibitors show that they should be used with caution.
Fifty-two volunteers took ritonavir (Norvir) and saquinavir
(Fortovase) at the standard 400 mg dose each taken twice a
day. They also took one of three statins: pravastatin (Pravachol),
simvastatin (Zocor) or atorvastatin (Lipitor). The statin
dose was 40 mg once a day.
The study found that pravastatin
levels decreased 47%, atorvastatin increased 343% and simvastatin
increased 2,676%. These results suggest that pravastatin can
be used safely with protease inhibitors without a dose adjustment.
Other statins like fluvastatin (Lescol), cerivastatin (Baycol)
and lovastatin (Mevacor) behave similarly to pravastatin,
atorvastatin and simvastatin respectively.
The activity of the statins
are not directly related to their drug levels found in blood,
but statin side effects are directly related. Atorvastatin
should be used with great caution. Simvastatin should not
be used with ritonavir and saquinavir and likely applies to
other protease inhibitors as well.
One serious side effect
associated with increased statin levels is a muscle disorder
called “rhabdomyolysis.” People experiencing muscle
aches should report this to their healthcare providers. People
with mild kidney dysfunction (a creatinine clearance above
1.5 mg/dL) are more at risk for developing statin side effects.
Gemfibrozil (Lopid), a drug sometimes combined with the statins
to lower triglyceride levels, can also result in muscle disorders
and kidney failure.
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