Background:  We studied the response to HAART of women exposed to single-dose nevirapine (sdNVP) or short course zidovudine±lamivudine (ZDV±3TC) for prevention of mother-to-child transmission (PMTCT) regimens.

Methods:  From a prospective cohort of the Côte d’Ivoire MTCT-Plus program, all women eligible were HIV-1 infected, had had ≥1 pregnancy, and had initiated HAART with stavudine (d4T)/ZDV, 3TC, and NVP/efavirenz (EFV). Exposed women received short course (ZDV±3TC)+sdNVP during previous pregnancy. Genotypic resistance testing was performed at week-4 post partum. Immunological failure was defined by a fall of >30% from peak CD4 count, virological failure by a plasma HIV RNA>500 copies/mL 12 months after HAART initiation. Multivariate logistic regression investigated factors associated to treatment failure.

Results:  Among 247 HAART-treated women, 109 (44%) were unexposed, 81 received sc(ZDV+3TC)+sdNVP, 5 short course (ZDV+3TC), 50 short course ZDV+sdNVP, and 2 sdNVP only. No ZDV mutation was detected (n = 115); 11 of 73 (14.6%) 3TC-exposed women tested post partum had 3TC resistance mutations. Of 73 short course (ZDV+3TC)+sdNVP exposed women, 3/ (4.1%) had NVP-resistance mutations, and of 42  short course ZDV+sdNVP exposed women, 16 (38.1%) did so. HAART was initiated 19 months in median after exposure. Baseline median CD4 count was 188 cells/mm³ (IQR 126 to 264). Of 219 women, virological failure was identified in 42 (19.2%). In multivariate analysis, factors associated with virological failure were a poor self-reported adherence (adjusted odds ratio [aOR] 12.7, 95% confidence interval [CI] 3.0 to 53.9), 3TC-resistance mutations post partum (aOR 6.9, CI 1.1 to 42.9), and a baseline CD4⁺ count <200/mm³ (aOR 0.3, CI 0.2 to 0.8), controlling for resistance mutations / exposure to NVP, maternal age, WHO clinical stage, and hemoglobinemia. 3TC-exposed women who did not develop resistance mutations post partum were not at increased risk of virological failure (p = 0.11 in adjusted analysis). Exposure to sdNVP was not statistically associated with virological failure (aOR 1.8, CI 0.5 to 6.5 for NVP resistance; aOR 0.4, CI 0.1 to 1.4 for NVP exposure without resistance). Immunological failure was identified in 26 women of 235 (11.1%); the only associated factor was poor adherence (aOR 12.3; CI 3.2 to 47.8). Exposure to 3TC and NVP ± post-partum resistance mutations to these drugs did not predict immunological failure (p = 0.57 and 0.12, respectively in multivariate analysis), like baseline CD4⁺ count, WHO clinical stage, age and hemoglobinemia.

Conclusions:  Short course (ZDV±3TC) and sdNVP may induce viral resistance to NVP or 3TC that can impair the subsequent women’s response to HAART, an adverse phenomenon to be taken into account in PMTCT guidelines.