This study demonstrated that cervical infections may increase detection of HIV-1 RNA in cervical secretions. However, even when HIV-1 RNA was detected, most cervical HIV-1 RNA concentrations remained near the threshold for quantitation (100 copies/swab). Higher levels of HIV-1 RNA shedding are generally seen in ART-naïve women even in the absence of cervical infections. For example, in an earlier study of cervicitis among untreated HIV-1-seropositive women, median cervical HIV-1 RNA was 11,220 copies/swab at diagnosis. This was reduced to a median of 1,738 HIV-1 RNA copies/swab after successful treatment (11
). In contrast, the present study of ART-treated women found that the majority have undetectable cervical HIV-1 RNA even in the presence of cervical infections.
While, acquisition of a cervical infection was associated with a statistically significant increase in cervical HIV-1 RNA, it is interesting to note that the prevalence of detectable cervical HIV-1 RNA at the final visit did not return to the pre-cervicitis baseline. This may simply reflect variation in detection in a study with a modest sample size, or could represent a gradual decline in genital HIV-1 shedding following infection. A similar finding has been observed in men treated for urethritis (14
), with progressive reductions in seminal HIV-1 at 1 and 2 weeks post-treatment. At completion of follow-up, seminal HIV-1 RNA remained higher than in a control group without urethritis.
Our study used genital HIV-1 RNA as a surrogate marker for infectivity. Recent studies among HIV-1-serodiscordant couples have demonstrated that higher genital HIV-1 levels are associated with increased transmission risk (15
). This association was present even after adjustment for plasma HIV-1 RNA concentration, suggesting that genital HIV-1 RNA level is a useful surrogate marker for infectivity.
Recently, there has been interest in the use of ART to reduce HIV-1 transmission. A systematic review found that the overall risk of transmission was reduced by 92% in HIV-1-serodiscordant couples on ART compared to couples in which the index case was untreated (16
). Our results further highlight the potential benefits of ART as a prevention strategy. Nonetheless, it should be noted that even low concentrations of genital HIV-1 RNA could present some risk of transmission.
This study had several strengths. Women were followed prospectively. Therefore, it was possible to compare genital HIV-1 RNA concentrations before, during, and after successful treatment for cervicitis. With prolonged follow-up of this cohort, we accrued 31 cervical infections for analysis. High ART adherence provided an opportunity to determine the effect of cervicitis on HIV-1 shedding under near-optimal conditions. With lower ART adherence, cervicitis could have a greater impact on genital HIV-1 shedding.
There were limitations to this study. Because of the modest sample size, we did not have adequate power to evaluate each cervical infection separately. Cervical HIV-1 RNA was below the limit for quantitation at 71% of visits, limiting the power to detect changes in cervical HIV-1 shedding. This study did not evaluate shedding of cell-associated HIV-1 proviral DNA, which may provide a better measure of the potential for cell-cell transmission. Risk factors for HIV-1 RNA and proviral DNA shedding may differ (17
), and it is not known which of these markers is most closely associated with transmission risk (2
In conclusion, even in the setting of cervicitis, cervical HIV-1 RNA concentrations remain low in the majority of women who are adherent to ART. Nonetheless, increases in cervical HIV-1 RNA occur in a minority of women during cervicitis, and could increase transmission risk. Identification and treatment of cervical infections may help to optimize the secondary HIV-1 prevention benefits of ART.