Antiretroviral therapy (ART) reduces the HIV
transmission probability by >20-fold within heterosexual couples. However, a subset of individuals receiving effective ART continue to have detectable levels of HIV RNA in genital secretions, despite an undetectable blood HIV load and a lack of detectable sexually transmitted infections. This phenomenon is known as isolated HIV RNA shedding (IHS) and has been described in men and women [11]. Levels of virus during IHS are often low and of uncertain clinical
importance. However, high-level shedding (ie, shedding of >5000 RNA copies/mL) has been described in a substantial subset of individuals, and this level was associated with an increased risk of HIV transmission in vitro [12]. Interestingly, the 92%–96% reduction in HIV transmission events that was seen in clinical studies of ART for prevention [2,13] was very similar to the 92% reduction in high-level HIV semen shedding that was seen in men starting ART [14], and the rare transmission events that have occurred in recent studies all took place soon after starting therapy.

IHS became progressively less common with an increasing duration of effective ART, with no IHS seen beyond 3 years of ART.