The

evidence that ART lowers the risk of transmission mainly relates to vaginal sex. Although ART is highly likely to see more reduce the risk of transmission for anal sex, the residual risk could be higher than that seen in studies for vaginal sex. There are currently few data to inform this. High and consistent adherence to ART is required to maintain viral suppression and minimize transmission risk. Taking ART does not result in immediate complete viral suppression; it usually takes several months to achieve an undetectable VL in blood. The use of ART to reduce transmission risk is a particularly important consideration in serodiscordant heterosexual couples wishing to conceive and it is recommended that the HIV-positive partner be on fully suppressive ART. The potential effect of HIV treatment to reduce the risk of onward sexual transmission should be discussed with all patients as a part of safer sex messages in general. The discussion should include the HIV status of their partner(s) and whether ART is indicated for their own health. This discussion should make clear that there is good evidence from one RCT (HPTN 052) [44] that ART treatment can

markedly reduce (by 96%) the risk of transmission to HIV-negative partners. This is supported by the secondary outcomes of another trial [45] that also found a marked reduction in transmission from partners taking ART (by 92%). It is important to note that only 3% of the couples Epigenetics inhibitor in HPTN 052 were men who have sex with men and the Partners in Prevention study was conducted entirely in heterosexual couples. The evidence base thus relates mainly to the risk of transmission for vaginal sex in heterosexual couples.

It seems likely that a reduction in risk will also be seen for anal sex, but this is the subject of ongoing studies. Before these randomized Thiamet G controlled studies, the evidence base for treatment to reduce transmission was based on a number of cohort studies that found that transmission between heterosexual couples where the HIV-positive partner had an undetectable VL on treatment was very rare or did not occur [46-50]. Viral suppression due to ART is usually as effective in reducing VL in semen [51] and in the rectum [52] as in plasma. This suggests that in the absence of other facilitators of transmission such as sexually transmitted infections, ART would be expected to be as effective in reducing infectiousness in men who have sex with men and other populations as it is in heterosexuals. Indirect evidence comes from a study of men who have sex with men attending HIV treatment services where ART was associated with a 96% reduction in HIV transmission [53]. Condoms should still be recommended to protect from other sexually transmitted infections, and to lower further any residual risk of transmission. Patients should be informed that taking ART does not result in immediate viral suppression.