BACKGROUND: Antiretroviral (ARV) regimens used for the prevention of mother-to-child transmission of HIV (PMTCT) have evolved overtime. We evaluated the contribution of different ARV regimens on the reduction of the plasma HIV-RNA viral load (VL) during pregnancy. METHODS: A total of 1,833 VL measurements from ARV-naive pregnant women participating in perinatal prevention trials in Thailand were included. Women received either (1) zidovudine (ZDV) monotherapy, (2) ZDV+lopinavir/ritonavir (LPV/r) or (3) ZDV+lamivudine (3TC)+LPV/r. VL time-course during pregnancy was described as a function of pre-treatment VL and treatment duration using an Emax non-linear mixed effect model. VL reduction and median time to achieve a VL<50 copies/mL were estimated for each regimen. RESULTS: Among 745 women, 279 (37%), 145 (20%) and 321 (43%) received ZDV monotherapy, ZDV+LPV/r, ZDV+3TC+LPV/r, respectively. The predicted VL reduction from baseline to delivery after a median of 10 weeks of treatment were 0.5, 2.7 and 2.9 log10 copies/mL with ZDV monotherapy, ZDV+LPV/r and ZDV+3TC+LPV/r. At delivery, 1%, 57% and 63% of women receiving ZDV monotherapy, ZDV+LPV/r or ZDV+3TC+LPV/r had a VL<50 copies/mL. The addition of 3TC to ZDV+LPV/r reduced the time to achieve a VL<50 copies/mL and the higher the pre-treatment VL, the larger the impact 3TC had on reducing the time to VL<50 copies/mL. CONCLUSIONS: The addition of 3TC to ZDV+LPV/r was associated with a slight further VL reduction but the time to reach a VL<50 copies/mL was shorter. This beneficial effect of 3TC is critical for PMTCT in women who receive ARVs late and with high pre-treatment VL.