Nelson, Julie A.E. et al. Female genital tract shedding of HIV-1 is rare in women with suppressed HIV-1 in plasma. AIDS: January 1, 2020 – Volume 34 – Issue 1 – p 39–46, doi: 10.1097/QAD.0000000000002373

There has been conflicting data regarding vaginal shedding of HIV in women and its relation to plasma viral load. This has significant clinical implications for both sexual and perinatal transmission. This paper from the U.S. based Women’s Interagency HIV Study (WIHS) looked specifically at the frequency of genital tract HIV-1 shedding in women on suppressive antiretroviral therapy (ART). They also assessed the women for any association with mucosal inflammation. The researchers measured levels of HIV- RNA in cervicovaginal lavage (CVL) samples from 322 women with undetectable viral loads while on suppressive ART for both short (1 year) and long periods (7 years) of time. HIV-1 was quantified in participants with and without clinical evidence of genital inflammation at the time of CVL collection. The study also measured 22 biomarkers of inflammation in CVL sample to compare with clinical markers. HIV was detected in 47% of 38 CVL samples collected pre-ART in the short-term group (median VL of 668 copies/ml) and this was associated with higher ART plasma viral loads. However, virus was only found in one of 38 samples from these women after being on suppressive ART for at least one year. No HIV-1 RNA was detected in 294 CVL samples from women with suppressed PVL and on ART for a median of 7+ years. Clinical inflammation biomarkers correlated with inflammatory biomarkers in CVL specimens, but of note, evidence of genital inflammation was not associated with measurable HIV-1 shedding in participants on ART. The authors conclude that suppression HIV in plasma with effective ART in women concurrently prevents genital tract shedding of virus even when where there is genital tract inflammation.

Author’s Commentary:

This study supports what was seen clinically in the HIV-prevention studies including HPTN 052 which helped support Undetectable = Untransmissible. In a study from Africa published about 2 years ago approximately 6% of women with undetectable plasma VL and 23.6% with detectable VL had genital shedding. [King et al JID Dec.2017]. These data support the concept that HIV shedding is uncommon in women on ART, likely declines with duration of treatment and is not associated with any significant risk of HIV transmission. Sustained ART adherence is critical for success in HIV prevention. It is also likely that other modalities to reduce mucosal inflammation, including treating genital infections, are important to minimize additional risk of HIV transmission.