Background: Women with HIV and prior exposure to combination antiretroviral therapy (cART) solely for prevention of Mother to Child Transmission (pMTCT) need to know whether they can later be treated successfully with a commonly used regimen of efavirenz (EFV) and co-formulated emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) Methods: Non-pregnant women with plasma HIV-1 RNA of ≥ 500 copies/mL, previously cART- exposed for pMTCT only, were eligible if they were off ART for ≥ 24 weeks prior to entry, were without evidence of drug resistance on standard genotyping, and were ready to start EFV plus FTC/TDF. The primary endpoint was virologic response (defined as plasma HIV RNA <400 copies/mL) at 24 weeks. Results: 54 women were enrolled between 10/07 and 12/09; 52/54 completed 24 weeks of follow- up. Median baseline CD4+ T-cell count was 265/mm3 and baseline plasma HIV-1 RNA was 4.6 log10 copies/mL. Median prior cART duration was 14 weeks, and median time elapsed from the last pMTCT dose to entry was 22 months. Virologic response at 24 weeks was observed in 42/52 women or 81% (exact 95% CI: 68%–90%). There were no differences in response by country, by number or class of prior pMTCT exposures. While confirmed virologic failure occurred in 8 women, no virologic failures were observed in women reporting perfect early adherence. Conclusions: In this first prospective clinical trial studying combination antiretroviral re- treatment in women with a history of pregnancy-limited cART, the observed virologic response to TDF/FTC and EFV at 24 weeks was 81%. Virologic failures occurred and correlated with self-reported non-adherence.