AEGiS-14IAC: Nevirapine prophylaxis for prevention of sexual/blood HIV transmission in HIV uninfected subjects.

14th International AIDS Conference

Barcelona, Spain - July 7-12, 2002

Nevirapine prophylaxis for prevention of sexual/blood HIV transmission in HIV uninfected subjects.

Int Conf AIDS 2002 Jul 7-12; 14:(abstract no. MoOrD1105)

Jackson JB, Barnett S, Apuzzo L, Raines C, Gallant J, Hendrix C, Piwowar-Manning E, Hamzeh F
Johns Hopkins University, Baltimore, United States

BACKGROUND: A two dose regimen of Nevirapine (NVP) has been shown to be effective in protecting newborns from becoming HIV infected when given perinatally. A low dose NVP regimen may be effective in protecting against sexual or blood transmission of HIV. Therefore, a Phase I/II trial (HIVHOP 101) of giving a 200 mg tablet of NVP once/wk or twice/wk for 12 wks to HIV uninfected subjects at high HIV risk was carried out to evaluate the safety, tolerance, and NVP trough levels achieved with these regimens.

METHODS: In Cohort A (one 200 mg tablet NVP once/ wk) and cohort B (one 200 mg tablet NVP twice/wk), there were 11 and 8 evaluable subjects, respectively, who completed the 12 wk regimen. One subject was HBsAg pos and 3 were anti-HCV pos. A CBC and blood levels for liver enzymes, creatinine, and plasma NVP trough levels were drawn at entry, 1, 2, 4, 6, 9, 12 wks and a follow-up sample at 16 wks which included an HIV Ab test. Subjects were assessed for signs/symptoms of potential toxicity at the same timepoints and follow-up by phone at 20 wks.

RESULTS: No subject in the 2 cohorts experienced clinical symptoms attributed to drug including rash. There were no significant changes attributable to study drug in hematology values or in ALT, AST or GGT levels from baseline to week 12 in either cohort except for an average 2-fold increase in GGT for cohort B with 2 subjects having a 3-fold increase. Mean and (median) NVP trough levels at weeks 1 and 12 were 119 (108) ng/mL and 206 (135) ng/mL respectively for cohort A, and 820 (569) ng/mL and 952(430) ng/mL for cohort B. Risk behavior did not increase during the study. No subject became HIV antibody positive.

CONCLUSIONS: A single dose of NVP taken once or twice/wk for 12 wks was safely tolerated and resulted in NVP levels well above the IC50(10ng/mL) over the 12 wk period in nearly all subjects.

Keywords: AEGIS, Nevirapine, HIV Infections, HIV Seropositivity, Antiretroviral Therapy, Highly Active, Risk-Taking, Drug Therapy, Combination, Clinical Trials, Infant, Newborn, transmission, blood, prevention & control, therapy, drug therapy

020707
MoOrD1105