Nevirapine Protects Chimpanzee Against HIV-1 Infection

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.