Background:  Decreased genital HIV-1 shedding in women is associated with lower risk of vertical transmission and should also reduce heterosexual transmission. However, little is known about the time course and magnitude of decay in genital HIV-1 RNA levels as women initiate ART. Our purpose was to evaluate genital HIV-1 shedding among women beginning ART and compare HIV-1 RNA decay rates in plasma, cervical, and vaginal secretions during the first month of therapy.

Methods:  In Mombasa, Kenya, 20 ART-naïve female sex workers completed an intensive study of genital HIV-1 shedding after ART initiation with stavudine, lamivudine, and nevirapine. Standardized interviews and exams were conducted at each visit. Samples were collected on days 0, 2, 7, 14, and 28 for plasma and days 0, 1, 2, 4, 7, 14, and 28 for genital swabs. HIV-1 RNA quantitation was performed on genital samples. RNA levels at different time-points were compared using Wilcoxon signed ranks. Nonlinear random effects statistical models and Perelson’s 2-phase decay model were used to investigate differences in first- and second-phase decay rates in plasma, cervical and vaginal RNA.

Results:  Median adherence was 100% (range, 98.9 to 100%). On day 0, the median plasma viral load was 5.4 log₁₀ copies/mL (IQR, 5.0, 5.9) and CD4 count 120 cells/μL (IQR, 58, 161). All women had genital HIV-1 RNA shedding at baseline, with median 3.7 log₁₀ copies/swab (IQR, 3.0, 4.5) in cervical secretions and 3.8 log₁₀ copies/swab (IQR, 3.1, 4.5) in vaginal secretions. Significant decreases were observed by day 2 in plasma (p <0.001), day 2 in cervical secretions (p = 0.001), and day 4 in vaginal secretions (p <0.001). Initial decay rates in plasma, cervical, and vaginal compartments were 0.6, 0.8, and 1.2 log₁₀ virions per day. Subsequent decay rates were 0.04, 0.05, and 0.06 log₁₀ virions per day, respectively. The initial decay rate for vaginal HIV-1 RNA was significantly faster than for plasma (p = 0.02). At day 28, 19 women had detectable HIV-1 RNA in plasma (range, 2.2 to 4.3 log₁₀), 6 in cervical secretions (range, 1.7 to 3.1 log₁₀) and 4 in vaginal secretions (range, 2.1 to 3.1 log₁₀).

Conclusions:  Genital HIV-1 RNA shedding decreased rapidly after ART initiation, but 7 of 20 women had detectable genital HIV-1 shedding after 1 month of ART. These findings are consistent with a rapid decrease in infectivity. However, persistent genital HIV-1 shedding may indicate an ongoing risk of transmission by some women.