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High levels of HIV-1 viremia exist in peripheral blood during acute and early infection; however, data on HIV-1 viral loads in female genital secretions during this period are sparse.Prospective cohort of 188 African women with primary HIV-1 infection.HIV-uninfected and infected women were followed quarterly; we tested serial plasma specimens by HIV PCR to estimate infection dates. We used the Loess procedure to estimate the magnitude and timing of viral setpoints in plasma and cervical secretions and generalized estimating equations (GEE) to identify predictors of plasma and cervical viral setpoints.We estimated the mean HIV-1 plasma setpoint to be 4.20 log10 HIV-1 RNA copies/ml [95% confidence interval (CI) 4.04–4.35] at 121 days (95% CI 91–137) from infection; an analogous mean cervical viral setpoint was 1.64 log10 HIV-1 RNA copies/swab (95% CI 1.46–1.82) at 174 days (95% CI 145–194) from infection. Cervical loads were significantly higher (0.7–1.1 log10 copies/swab) during acute infection than subsequently. Subtype D infection, pregnancy, breastfeeding, and older age at the time of infection were associated with higher plasma viral setpoint. Subtype C infection, nonviral sexually transmitted infections, having a partner spending nights away from home, recent unprotected sex, and shorter time since infection were associated with higher cervical HIV-1 loads. Hormonal contraception was not associated with either the HIV-1 plasma setpoint or cervical loads during early infection.Cervical HIV-1 viral loads were highest during acute infection and then declined up to 6 months following infection, when a ‘setpoint’ was attained. The prognostic value of a cervical ‘setpoint’ on future transmission risk remains unclear.