BACKGROUND: Whether pregnancy has an impact on the evolution of CD4 cell counts in women treated with highly potent antiretrovirals before conception remains largely unknown. METHODS: Among patients enrolled in the ANRS CO8 (APROCO/COPILOTE) cohort, we selected all women aged between 18 and 50 years at initiation of combination antiretroviral therapy (cART). Slopes of CD4 cell counts during follow-up were estimated using mixed longitudinal models with time-dependent indicators for pregnancy and delivery. RESULTS: Of the 260 selected HIV-infected women, a pregnancy occurred in 39 women in a median follow-up time of 66 months. Women who became pregnant had higher CD4 cell count at baseline but this difference progressively lessened during follow-up because they had a slower increase than women who did not become pregnant. The estimated slope of CD4 cell count decreased significantly from +2.3 cells/muL/month before pregnancy and in women who did not become pregnant to -0.04 cells/microL/month after delivery (P=0.0003). CONCLUSION: A significant increase in CD4 cell count may be preferable before pregnancy in women treated with cART, in order to overcome the evolution observed after pregnancy.