Efficacy of integrase inhibitors in the semen

I’m going to present two studies looking at HIV-1 RNA in the genital tract in the context of integrase inhibitors. The background of this issue relates to the fact that the male genital tract forms a separate reservoir of HIV.

The first study presented looked elvitegravir levels in seminal plasma in HIV-1 infected patients. This was a small study of just 10 patients who had already suppressed plasma viral loads at baseline with a median time on ARVs of 50 months. Patients were switched to elvitegravir/cobicistat/emtricitabine/tenofovir (EVG/COBI/FTC/TDF) single tablet regimen and paired blood plasma and seminal plasma samples were examined. All patients had undetectable blood and semen viral loads (<40 copies/ml) 4 weeks later. Some might argue the 4 week follow-up assessment may have missed a transient viral rebound in the seminal plasma. It could also have been too soon to identify viral rebound in this group, especially considering the extensive prior time on treatment (median 50 months). 

The second study from the same group examined the rates of HIV-1 RNA decay in seminal (SP) and blood plasma (BP) in naive patients commencing dolugravir (on ABC/3TC backbone). 15 patients were recruited to this open-label, single-arm study. Rate of HIV-1 RNA decay was initially higher in the BP compared with SP. Due to the lower baseline seminal HIV-1 RNA, viral suppression was achieved sooner in SP, although both groups were quite rapid. By the end of week 24, all but one patient had achieved an undetectable VL (<40 copies/ml) in the seminal fluid despite the groups median DTG concentrations being just 7.8% of total concentrations in the blood plasma.

What is the significance of this? Clearly these are very small studies, however they demonstrate promising findings in terms of efficacy in the male genital tract with these two new INSTI agents. In the day and age of treatment as prevention, viral suppression in this reservoir may be an important consideration. Further information around HIV transmission in MSM on ART should be gained from the Opposites Attract study which also has a semen analysis sub-study.