Initiation of antiretroviral therapy leads to a rapid decline in cervical and vaginal HIV-1 shedding

Abstract

Genital HIV-1 shedding decreased rapidly after ART initiation, consistent with a rapid decrease in infectivity. However, incomplete viral suppression in half of these women may indicate an ongoing risk of transmission.

ART influences HIV persistence in the female reproductive tract and cervicovaginal secretions

“…Consistent with results obtained in humans, ART treatment of infected BLT mice resulted in a significant decrease in the levels of HIV in both PB and CVS (15,16). However, our finding showing the absence of cell-free HIV in CVS during ART, concurrent with the continued presence of infected cells producing HIV-RNA, could have important implications for HIV prevention and eradication strategies.…”

“…The prevailing hypothesis for the success of HPTN 052 is that ART reduces genital cell-free and/or genital cell-associated HIV to levels that are too low to support HIV transmission (12). This hypothesis is supported by observational studies suggesting a strong correlation between plasma/genital HIV-RNA levels and risk of heterosexual transmission (13,14); it is also supported by the ability of ART to decrease the genital levels of HIV in both men and women (15)(16)(17). There is very limited data in the literature to determine whether transmission occurs from cell-free virus only or if productively infected cells themselves can transmit HIV in the absence of cell-free virions (18).…”

Persistence of Genital Tract T Cell Responses in HIV-Infected Women on Highly Active Antiretroviral Therapy

“…We found that HAART Ϫ women had significantly higher frequencies of HIVspecific CD8 T cell IFN-␥ responses detectable in blood than HAART ϩ women (P, 0.03) (Fig. 3A and B, top), suggesting that HAART significantly reduces the magnitude of CD8 T cell responses in blood to HIV (21,29). In contrast, HAART Ϫ and HAART ϩ women did not differ in the magnitude of their cervical CD8 T cell responses to Gag (P, 0.2) (Fig.…”

The impact of highly active antiretroviral therapy on high-risk behaviour of HIV-infected patients in sub-Saharan Africa

“…The danger of high-risk behavior being manifested by persons with or at highrisk of HIV infection is increased by the fact that HIV infectiousness decreases but does not entirely disappear with therapy. In a study conducted in the United States to evaluate the time course and magnitude of decay in cervical and vaginal HIV-1 shedding as women initiate HAART [30], genital HIV-1 shedding decreased rapidly after HAART initiation, which is consistent with a rapid decrease in infectivity. In a study from Kenya assessing the effect of acquisition and treatment of cervical infection on genital HIV shedding in women on HAART [31], most cervical HIV-1 RNA concentrations were near the threshold for detection, which suggested that HIV infectivity remains low, and thus HAART reduces genital HIV-1 shedding.…”

“…Several studies have, however, reported that although genital shedding of HIV decreases after initiation of HAART, there is often incomplete viral suppression [30,33,34], especially among patients with poor adherence to antiretroviral medication [30] or with concurrent sexually transmitted infections such as herpes simplex virus type 2 infection [34]. The risk of HIV transmission is dependent on an individual's adherence to the HAART regimen, which affects viral suppression, the viral load, and subsequent development of drug resistance in case of poor adherence [35].…”