Background:  A study in Thailand observed that women prescribed nevirapine (NVP) for prevention of mother-to-child HIV transmission (PMTCT) were less likely to achieve virologic suppression when treated with a non-nucleoside reverse transcriptase inhibitor (NNRTI)-regimen than unexposed women. Many studies have detected NNRTI-resistance mutations frequently 4 to 8 weeks after single-dose NVP used for PMTCT. However, as time elapses, mutations are detected less frequently, suggesting that effects of single-dose NVP exposure on treatment response may decline as time passes after exposure. We are testing whether prior exposure to single-dose NVP >18 months earlier would still increase the likelihood of virologic failure among women treated with an NNRTI regimen. 

Methods:  We are conducting a non-experimental clinical trial in Johannesburg, South Africa, to examine virologic response to treatment with NVP/lamivudine/stavudine among women exposed to single-dose NVP 18 to 36 months earlier compared with unexposed women with prior live births in the same interval. We have results to date on 60 exposed and 30 unexposed women who have had the opportunity to be followed to at least 12 weeks post-treatment. All women meet eligibility criteria for antiretroviral treatment (CD4 count<200 or stage III+, and CD4 <350) and have viral load measurements (Roche v1.5 ultra-sensitive) performed every 4 weeks to 24 weeks, and then every 12 weeks thereafter to 96 weeks post-treatment.

Results:  Pre-treatment among NVP-exposed women (median 26 months post-single-dose NVP), the median viral load was 93,325 copies/mL and CD4 count 138 cells/mL; among the unexposed, 199,526 copies/mL, and CD4 count 167. Age, parity, education, clinical stage, weight, and other clinical and social characteristics were similar. By 24 weeks on treatment, all 38 (100%) NVP-exposed women had a viral <50 copies/mL (1 woman, who switched from NVP to Kaletra because of liver toxicity, is included; 2 women lost to follow-up within 2 weeks are excluded. Of the 20 remaining women, 15 (75%) still reached 24 weeks and had <50 copies/mL when last seen. Among the unexposed, 13 of 17 (76%) women had a viral load <50 copies/mL by 24 weeks (4 women [2 failures] switched from NVP due to liver toxicity [2] or severe rash [2] are included, 1 lost to follow-up is excluded; 9 of 12 [75%] remaining women had <50 copies/mL when last seen). 

Conclusions:  We observed excellent virologic response to NNRTI-based treatment among women exposed to single-dose NVP >18 months supporting NNRTI-based treatment regimens as effective options for this group of women.