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The Body Covers: The 4th Conference on Retroviruses and Opportunistic Infections
Nevirapine Protects Chimpanzee Against HIV-1 Infection
Coverage provided by Ramon Torres, M.D.
January 1997
Nevirapine (Viramune) is a potent and highly selective
non-nucleoside inhibitor of
HIV-1 reverse transcriptase, which can rapidly inhibit HIV replication and
reduce
viral load, yet can lead to the rapid emergence of resistant mutants within
weeks
of administration. Due to its long half-life it is also being investigated
for short-term
courses of therapy such as during labor or post exposure prophylaxis.
A study presented by Grob and colleagues from Boeringher Ingelheim,
manufacturers
of Viramune evaluated the prophylactic effect of nevirapine in the
chimpanzee. The
chimpanzee is the only other primate which can be infected with HIV-1, and
similar
to the human undergoes seroconversion within 2 months. HIV-1 infection can
be detected inthe
chimpanzee through cultures of peripheral blood mononuclear cells (PBMCs)
and lymphoid
tissue, PCR for HIV RNA and DNA within PBMCs or PCR or bDNA for plasma
levels of
HIV RNA. In an experiment involving four chimpanzees, a control animal was
challenged
with an intravenous inoculum (40 TCID 50) of HIV-1 IIIB and observed to
seroconvert
and become viremic, with virus isolated from PBMCs via co-culture, HIV
proviral DNA
detected within PBMCs and HIV RNA detected from plasma via bDNA and PCR.
In contrast
three chimpanzees which received nevirapine (800 mg ) at six hours, at 12
and 36
hours or at 12, 24 and 36 hours pre-challenge, and for either 10 or 20 days
post
challenge remained negative for all viral markers with the exception of
nested PCR analysis of
PBMCs for proviral DNA. The PCR for proviral DNA within PBMCs completely
disappeared
and remained negative for the three nevirapine treated chimpanzees during
the final
five months of the study.
None of the treated chimpanzees seroconverted or had HIV
detected in lymphoid tissue biopsies after a follow-up period of 5-6
months. An intermittent
positive plasma bDNA for HIV RNA was noted in each of the three chimps,
but may have been due to contamination. This experiment indicates that
nevirapine can abort
infection in the chimpanzee model of HIV infection, and has potential
implications
for post-exposure prophylaxis in humans.
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