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Notes from ICAAC
By Charles E. Clifton and
Enid Vázquez
Following are some of the HIV highlights
from the 40th Interscience Conference on Antimicrobial Agents
and Chemotherapy (ICAAC), organized by the American Society
for Microbiology, held this past September in Toronto.
Sustiva
vs. Viramune
Pump up
those T-cells
Treat me right
I'd
rather fight than switch
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Sustiva
vs. Viramune
In head-to-head competition,
the two drugs did just as well at lowering viral load. Unfortunately,
these were early results from a small group of 50 people.
“At the last visitī (anywhere from six to 14 months), 76%
of the Viramune group and 80% of the Sustiva group had a viral
load of less than 50.
Sustiva received well-earned
fame in 1998 when it beat out the then-gold standard HIV combo
of Crixivan, AZT and Epivir. It did well even in people witha
high viral load, more than 100,000. The thrill behind this
well-conducted study is that Sustiva (as well as Viramune)
are in an HIV class of drugs, the non-nucleoside analogs,
that was considered to be less potent than protease inhibitors
like Crixivan. The once-a-day Sustiva has continued to do
well since then.
But Viramune is an older
non-nuke that while popular, just wasn’t studied at a time
of advanced HIV knowledge that newer drugs like Sustiva were
able to benefit from. A big question in HIV therapy has been
whether or not Viramune is as potent as Sustiva.
The two drugs have already
both been shown to be equivalent or even superior to Viracept
protease inhibitor. Viramune worked just as well as Viracept
even in people who started therapy with a viral load above
100,000 (although these results are only as of 24 weeks, which
is preliminary). At this conference, one study showed that
they were also able to keep viral load undetectable in a vast
majority of people switching from a protease inhibitor (not
new information, but always good to confirm with more recent
data).
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Pump up those T-cells
A group of researchers from
the National Centre in HIV Epidemiology and Clinical Research,
Sydney, Australia, reported that “the greatest response to
antiretroviral therapy in patients with long-term suppression
of viral replication appears to occur early after treatment
is started, with smaller increases in CD4 cell counts seen
later in the course of treatment.ī In a study of 63 participants,
the greatest increase in CD4 cell count was observed during
the first three months of treatment. Two-thirds of these patients
reached “normalī CD4 cell counts (greater than 500 cells)
after two to three years of highly active antiretroviral therapy
(HAART).
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Treat me right
Results of the DPC-006 study
at Chelsea and Westminster Hospitals, London, England indicate
that current treatment guidelines recommending a viral load
less than 50 copies at 24 weeks is most realistic in individuals
with baseline HIV levels below 100,000 copies to begin with.
Individuals with an initial viral load above 100,000 copies
were found to require at least 36 weeks before a viral load
of less than 50 copies was achieved. This was a study of mainly
treatment naïve persons. One group of 157 people was
randomly treated with AZT + Epivir (3TC) + Sustiva (efavirenz).
A second group of 96 people was treated with AZT + Epivir
+ Crixivan (indinavir).
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I’d rather fight than switch
Community concerns
about the toxic side effects and complicated regimens of therapy
has encouraged a number of “switch studiesī to deliver alternative
and simplified strategies to treat HIV, with an emphasis on
maintaining undetectable viral loads and avoiding or reversing
adverse side effects.
Preliminary data from switch
studies reveals that for most individuals a switch in therapeutic
regimens does not result in a viral load increase. To date,
the majority of ongoing switch studies involve protease inhibitors
(PIs), since they seem to be responsible for most of the toxicities,
and nucleoside reverse transcriptase inhibitors (NRTIs), due
to the metabolic side effects recently acknowledged.
Results from early studies
indicate that the metabolic irregularities are often reversible
upon switching from a PI to a nonnucleoside RTI (NNRTI) or
to a third NRTI (often Ziagen). In addition, reductions in
triglyceride levels and insulin resistance were also observed.
The effects on cholesterol differed depending on which drugs
were used. Cholesterol levels remain high with Sustiva. The
discontinuation of a PI did not have a significant effect
on the reversal of or improvement in fat redistribution, although
an improvement in lipoathrophy (thinning) was noted in a small
study in which an alternative NRTI was substituted for Zerit
(d4T).
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Examples of switch studies:
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A study of patients on
a successful PI-containing HAART to a more simple triple
NRTI regimen; patient’s viral load was below 50 copies
for 6 months or more prior to switch with no 215 resistance
mutation at baseline; patients in the 48 week study were
switched to Ziagen (abacavir) (300 mg twice a day) + Combivir
(150 mg Epivir + 300 mg Retrovir, twice a day). This study
revealed a slight increased risk of viral load failure
in a simplified therapy (11 of 84 participants), as opposed
to the group continuing with PIs (5 of 79). However, the
viral increase in the switch group was observed in patients
with prior mono or dual therapy prior to HAART.
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Results of a 24 week study
on 207 patients (mean age 41 years, 91% male, 70% white,
20% black, 8% Hispanic and 2% other); Sustiva 600 mg was
substituted for PI, where all nucleosides were maintained;
viral load was successfully maintained at less than 50
copies and a minimum increase in CD4 cells (medium change
+40) was observed up to 24 weeks.
All individuals considering
switching their regimens should carefully discuss all medical
treatments and products with a physician. This can not be
over emphasized. Each individual should have her or his treatment
history carefully assessed for detection of resistance or
intolerance before switching.
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