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Background:  PACTG 1022 is a prospective, open-label, randomized clinical trial designed to compare the efficacy and safety of a nelfinavir (NFV) to a nevirapine (NVP)-based regimen in HIV-infected antiretroviral-naïve pregnant women.

Methods:  We randomized 38 pregnant women at 10 to 30 weeks’ gestation to ZDV/3TC/NFV or ZDV/3TC/NVP. Study treatment was stopped for virologic failure or serious toxicity including ≥grade 3 ALT, symptomatic hepatitis at any grade ALT, or ≥ grade 2B cutaneous toxicity. In an intent-to-treat analysis, toxicity leading to treatment discontinuation was compared between groups for all subjects and for the subset with entry CD4 count ≥250 cells/mL, using a 2-tailed Fisher’s exact test.

Results:  We randomized 21 and 17 women to the NFV and NVP arms, respectively. Demographic and clinical characteristics were similar for both groups. At entry, the median CD4 counts were 324 (NFV) and 359 (NVP), and 3 subjects in the NVP arm had grade 1 ALT, while all subjects in the NFV arm had grade 0 ALT. None of the subjects had hepatitis B or C. The median length of follow-up as of October 1, 2003 was 25 weeks. Treatment limiting hepatotoxicity was seen in 1 NFV and 3 NVP subjects (1 with grade 1 ALT at entry), 1 of whom developed fulminant hepatic failure on NVP at 34 weeks’ gestation and died (grade 0 ALT at entry). Another subject discontinued NVP after developing Stevens-Johnson syndrome. These toxicities occurred at 6 weeks on NFV and at 2 to 26 weeks on NVP. The one toxicity event in the NFV arm occurred in a subject with an entry CD4 <250, while all 4 events in the NVP arm occurred among subjects with an entry CD4 count ≥250. The table below summarizes the observed toxicity leading to treatment discontinuation by arm.

Conclusions:  We observed greater than expected toxicity in the NVP arm during the initial phase of this randomized trial, possibly associated with higher CD4 count at entry. Although the difference in toxicity rates between arms was not statistically significant, the serious nature of the observed toxicities combined with recent changes in NVP prescribing information merit modifying the trial. The safety of continuous NVP for pregnant women with lower CD4 counts deserves additional investigation.

Keywords: pregnancy; nevirapine; hepatotoxicity