On-and-off
trial
The National Institutes of
Health has opened a study to compare a group of HIV-positive
people receiving continuous HAART (highly active antiretroviral
therapy) to a group using HAART on and off (“intermittent
therapy”), with intervals of one week on/one week off. Participants
must have a T-cell count of at least 175, no history of opportunistic
infections, a viral load less than 500 for six months prior
to enrollment, and a viral load less than 50 on screening.
NIH will provide travel to the Clinical Center in Bethesda,
Maryland. For more information, contact Diane Rock, RN, at
1-800-772-5464, ext. 58003. (See “Structured
Treatment Interrupton”)
Stress
and HIV
Stress “enables HIV to spread
more quickly in infected persons and prevents antiretroviral
drugs from restoring immune system function.” So say researchers
at the University of California, Los Angeles. In a press release,
lead author Dr. Steve Cole says that, “Popular science has
widely suspected that stress weakens the immune system. Now
we’ve uncovered two reasons why.” UCLA reported test tube
results from the blood of 13 HIV-positive men. “When a person
is under stress, the nervous system’s ‘fight or flight’ syndrome
kicks in. The body’s nerves release the hormone norepinephrine
into the lymph nodes, where the immune system’s T-cells reside.
The UCLA team recreated this scenario in the laboratory, exposing
T-cells in culture to the same concentrations of norepinephrine
released by the nerves during stress. They discovered that
the hormone increased viral replication 10-fold via two molecular
mechanisms. First, norepinephrine increases T-cells’ vulnerability
to infection fivefold by increasing levels of CCR5 and CXCR4—two
co-receptor molecules that enable HIV to bind to the cell’s
surface and invade the T-cell. Second, the hormone increases
HIV’s rate of viral gene expression in the cells it has already
infected. This allows the AIDS virus to spread five times
more quickly.” The university said this was the first report
of molecular mechanisms linking stress and HIV. The UCLA researchers
also looked at four health indicators of stress: blood pressure,
skin moisture, heart rate and pulse rate at rest. Together,
these four measures gave the level of a person’s autonomic
nervous system (ANS) activity. The researchers measured the
ANS of a small group of 13 HIV-positive men before they went
on HIV therapy for 11 months. “Even anti-HIV drugs prove more
effective in people with low [ANS] activity,” Cole said. The
higher the stress level, the less response to the antiretroviral
drugs. The average drop in viral load was more than 40 times
for men with low ANS activity—yet less than 10 times for men
with high ANS activity. “After several months on antiretroviral
drugs, the viral loads of five of the seven men with low ANS
activity plummeted to undetectable levels in their blood,”
said Cole. This happened to only one of the six men who exhibited
high ANS activity. In addition, the men with low ANS activity
on average showed the most striking cell-count increases.
In comparison, men with high ANS activity displayed little
increase in T-cell counts, or none at all. The study was published
in the October 23 Proceedings of the National Academy of Sciences.
Visit www.ucla.edu.
Hypocrisy
The World Trade Organization
meeting in November in Doha, Qatar raised issues of drug patents.
Many countries wanted poor nations to have the right to override
pharmaceutical company drug patents in order to buy or produce
inexpensive generic versions in health emergencies. This struggle
is supremely important in the worldwide battle against AIDS,
which threatens to destroy populations and economies of many
nations. U.S. Trade Representative Robert Zoellick suggested
an alternative that would give poor countries the right to
override drug company patents until the year 2016 and stop
the U.S. from taking actions against sub-Saharan African countries
for violations of drug patents held by companies in this country.
AIDS activists disapproved of the proposal, preferring the
unrestricted right to override patents to protect health.
The Zoellick proposal was accepted, but many countries do
not have the machinery to make their own medicines. Also,
left open was a country’s ability to exercise parallel importation,
so that it can simply import generic meds from another country.
Activists pointed to the
U.S. government’s demand that the Bayer company cut the price
of the antibiotic Cipro to treat inhalation anthrax infection
in case of outbreaks, and threats to override the company’s
patent in order to acquire large quantities of the medicine
at a steep discount. James Love of Consumer Project on Technology
told the San Francisco Chronicle, “When the United States
did not like the price of a medicine, we were very fast to
say we might override patent rights. When Brazil did the same
thing (for AIDS drugs), they were savaged.” An editorial in
the British medical journal The Lancet also noted the “stark
contrast,” and suggested that the U.S. government work to
allow patent overrides. (Special thanks to the Kaiser Daily
HIV/AIDS Report for its news round-up of early November 2001;
visit www.kff.org.)
To
tell or not to tell
People with HIV have
a hard time telling casual sexual partners that they have
the virus. Researchers talked with 269 people living with
HIV, half of them men. Of people with a main sex partner,
74% disclosed their HIV status. For those who had been with
a casual sex partner, however, only 25% had disclosed their
HIV status. Still, a full 25% did not tell their main sex
partner nearly three years (on average for the entire group)
after their diagnosis. The researchers said their study shows
that “few [people with HIV] disclose their status to a casual
sex partner. Interventions to improve skills building for
HIV disclosure are needed.”
In another study, more than
half of the self-identified gay men and bisexual men with
HIV interviewed who had had sex with women as well as men
in the previous six months also did not “always” disclose
their positive status. A third of them had had unprotected
anal or vaginal sex. Moreover, the people who did not tell
their casual partners about their status were also less likely
to use a condom. Researchers reported that, “Non-adherence
to HIV medications, recreational drug use, tobacco use, and
feeling the effects of drugs or alcohol during sex were significantly
associated with sexual risk behaviors.” The studies were reported
at the 129th annual meeting of the American Public Health
Association in October in Atlanta. Visit www.apha.org.
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Conference
News
Our annual HIV Drug Guide
is a good time to round up some of the combination news from
conferences during the past several months. Also check www.medscape.com
and www.hivandhepatitis.com
for more reports. See www.natap.org
for detailed technical information about clinical trials and
conference updates.
Once
a day
After two years, the majority
of people on a triple, once-a-day combo continued to be undetectable.
Forty participants took Sustiva and once-a-day buffered Videx
along with the experimental nucleoside analog emtricitabine
(FTC). After 96 weeks, 34 (85%) had less than 400 viral load.
Eighty percent had less than 50 (using an ultrasensitive viral
load test). Moreover, of those people who started out with
more than 100,000 viral load, 8/9 (89%) were under 400. Generally,
HIV specialists believe in using a protease inhibitor combination
for people with this high of a viral load. Half of all participants
had a T-cell increase of greater than 272; the other half
had an increase of less than this. Three people dropped out
due to side effects. Serious side effects seen were high levels
of triglycerides and transaminases (an indicator of liver
function—an increase may indicate drug-induced hepatitis).
Results are from 40 participants. (From the 8th European Conference
on Clinical Aspects and Treatment of HIV Infection—ECCATHI—in
Athens, Greece, in October.)
Switching
back and forth
What would happen if you took
a triple combination for three months and then switched to
a different combo for the next three months? In a Barcelona
study, participants who switched back and forth did better
than people who stayed on the same regimen for 48 weeks. They
took Zerit, Hivid and Sustiva for three months, followed by
Retrovir, Epivir and Viracept, and then went back and forth.
Seventy percent of the people who switched were undetectable
(under 400 viral load), compared to 60% of the people who
stayed on the same combo. All three groups gained about 70
T-cells. There were 160 participants total in the study, all
of them taking HIV meds for the first time. The switchers
had less severe side effects. The researchers said they believed
these participants were prepared for the side effects and
were therefore better able to deal with them. (From the 5th
International Workshop on HIV Drug Resistance and Treatment
Strategies, in June, in Scottsdale, Arizona.)
Trizivir
vs. Crixivan
At 48 weeks—a scientifically
significant amount of time—Trizivir, the triple therapy in
one pill, was just as good as a Crixivan triple combination
at lowering viral load (the amount of HIV in the blood). That’s
great, except that practically no one takes the original Crixivan
dosing of every eight hours on a near-empty stomach that was
used here. That dosing has long since given way to Crixivan
taken twice a day with food with a mini-dose of Norvir. Still,
it’s an impressive result for one pill taken twice a day that’s
only made up of one of the three HIV drug classes out on the
market. What about people who started the study with a viral
load above 100,000? Previous results with Trizivir have been
mixed for this group. In this study, the drop in viral load
was also the same. All viral load decreases were good. T-cell
increase was also the same. But Grade 3 or 4 lab abnormalities
(considered serious) were two times greater in the people
taking Crixivan,14% vs. 7%. A total of 342 people entered
the study. (From the 1st International AIDS Society—IAS—Conference
on HIV Pathogenesis and Treatment, in July, in Buenos Aires,
Argentina.)
New
PI
The experimental HIV protease
inhibitor atazanavir, taken once a day, compared well to Viracept
protease inhibitor. They were taken along with Zerit and Epivir.
Results were from 48 weeks in almost 500 people. The study
participants were taking HIV meds for the first time, so you
would expect them to do well at lowering viral load and raising
T-cells. Viral load for both groups dropped about 2.5 logs
(for example, from about 40,000 to 400). T-cells increased
by about 200. However, cholesterol and triglyercides did not
increase as much in the atazanavir group (7% saw a marked
rise vs. 25% for the Viracept group). Side effects included
infection and headache in both groups. (ECCATHI)
Viread—and
resistance—at two years
How does the newest HIV drug
on the market do resistance-wise? It’s an important question
because HIV is a tricky character that mutates (changes) in
order to resist any medication thrown at it. The search for
resistance is still a new field, and one that’s very complicated
with lots of ups and downs. In this study, a group of 189
people had a lot of previous treatment experience, which generally
means they won’t respond as well to new meds that they go
on. Still, the people who took the 300 mg dose of Viread (tenofovir
DF), that eventually became FDA approved dosage, had a half-log
decrease in viral load at 24 weeks. The drop continued out
for two years. That’s not bad for heavily pre-treated people.
Here’s where the resistance pattern comes in. Researchers
reported that the resistance mutations people had when they
started Viread—the primary Epivir mutation, Retrovir-associated
mutations, plus non-nuke and protease inhibitor resistance
mutations—did not stop them from lowering their viral load,
as you would have expected. Moreover, the primary Viread resistance
mutation, called K65R, developed in only 3% of the people
taking the 300 mg dose, and it did not keep them from having
a viral load drop, contrary to what you would have expected.
It’s a good start for the new drug. (IAS)
Switching
from PIs to Ziagen
In a recent study, 87 people
either continued their PI combo or switched over to one containing
Ziagen, which is a nucleoside analog (nuke for short). After
24 weeks, the switch group was doing as well as the PI group
in terms of viral load and T-cells. Although these are preliminary
results, HIV specialist Stephen Becker had this to say in
his report at HIVandHepatitis.com: “Unless they use a novel
design, no further switch studies appear to be necessary.
The accumulated weight of evidence from European and American
studies suggests that a switch to a simplified regimen, replacing
a PI with [Ziagen], [Sustiva], or [Viramune], is successful.
Equally clear is that this switch strategy should not be used
in those patients whose antiretroviral regimen included NRTI
agents before their PI-based HAART [for example, Retrovir
by itself or Retrovir/Hivid]. Tolerability, adherence, and
quality of life can be expected to improve, while dysmorphic
[body] changes are unlikely to show significant change.” (39th
Annual Meeting of the Infectious Diseases Society of America—IDSA,
in October in San Francisco. Visit www.idsociety.org.)
Sparing
the PIs
How about using a four-drug
combo that has no protease inhibitor and is easy to take?
One complaint about the PIs is that there are too many pills
to pop. Standard of care calls for at least a three-drug combination,
no matter what drug classes you choose to use. In a small
study of only 29 people, good viral load drops were seen out
to one year (a significant amount of time). These people had
never used HIV meds before or had less than a week of therapy.
Here they took a four-drug combo that consisted of Combivir
(which is two drugs in one), Sustiva (taken once a day) and
Ziagen (one pill twice a day). Altogether, that’s “only” seven
pills a day total, with pill-popping also only twice daily.
The majority (63%) had less than 50 viral load (undetectable
on an ultrasensitive test). In fact, using an even more ultrasensitive
test (not available to the general public), researchers found
that a full 59% of them (16 people) had a viral load of less
than three. Half of them saw T-cell increases of more than
172, and the combo was well-tolerated. Moreover, looking at
on-treatment analysis—only those people who actually stayed
on the meds instead of dropping out of the study—100% had
less than 400 viral load and 93% had less than 50. Additionally,
people did well even if they started out with a viral load
of 100,000. That’s a group that would make most doctors reach
for a protease inhibitor to prescribe. (IDSA)
Sustiva
vs. Viramune
Although Sustiva has shown
impressive results in almost every study it’s been in, the
question of how it compared to Viramune remained up in the
air. Viramune is Sustiva’s closest competitor, in a sense,
because it’s also been a long time favorite non-nuke. In this
cohort study of 1,078 people taking HIV meds for the first
time, 555 were on combination therapy including Sustiva and
523 took a Viramune combination. The people on Sustiva had
a longer time to treatment failure (589 days) than did the
people on Viramune (307 days). Treatment “failure” was defined
as an HIV viral load of more than 400. Also, 51% of the Sustiva
people were undetectable (under 400) at one year, compared
to 45% of the people on Viramune (a statistically significant
difference in this analysis). (ECCATHI)
Facial
filling
French researchers reported
good results using New-Fill polylactic acid in 50 people with
facial lipoatrophy resulting from HIV therapy (loss of fat
in the face that leads to a severe gaunt look, although most
of the people are actually healthy). The group went from a
median facial thickness of 2.1 mm to 9.5 mm after six months.
The doctors aimed for an 8 mm thickness following a series
shots with New-Fill during outpatient plastic surgery. Getting
there took three sets of shots for four people, four sets
for 29 people and five sets of shots for 17 people. The surgeons
said all patients reported “good satisfaction” with their
new appearance. New-Fill was pioneered in France for plastic
surgery for about the last five years before its use in HIV
lipoatrophy was discovered. A clinic for people with HIV opened
in Tijuana, Mexico in the past year, but surgery in the U.S.
was halted in the past few months. The Direct AIDS Alternative
Information Resources buyers club in New York City (DAAIR)
had started acquiring the product under special import law
through the U.S. Food and Drug Administration, but the FDA
has gone back to setting up road blocks for New-Fill, which
is not approved in the U.S. Still, dozens of U.S. people with
HIV who were able to have the surgery were quite happy with
it. For updates, visit www.daair.org
or call tollfree 1-888-951-5433. [See “The
Buzz.”](ECCATHI)
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