Reduction of concentration of HIV-1 in semen after treatment of urethritis: Implications for prevention of sexual transmission of HIV-1

Background. Transmission of HIV-1 is predominantly by heterosexual contact in sub-Saharan Africa, where sexually transmitted diseases (STDs) are also common. Epidemiological suggest studies that STDs facilitate transmission of HIV-1, but the biological mechanism remains unclear. We investigated the hypothesis that STDs increase the likelihood of transmission of HIV-1 through increased concentration of the virus in semen. Methods. HIV-1 RNA concentrations were measured in seminal and blood plasma from 135 HIV-1-seropositive men in Malawi; 86 had urethritis and 49 controls did not have urethritis. Men with urethritis received antibiotic treatment according to the guidelines of the Malawian STD Advisory Committee. Samples were analysed at baseline and at week 1 and week 2 after antibiotic therapy in urethritis patients, and at baseline and week 2 in the control group. Findings. HIV-1-seropositive men with urethritis had HIV-1 RNA concentrations in seminal plasma eight times higher than those in seropositive men without urethritis (12.4 vs 1.51 x 104 copies/mL, p = 0.035), despite similar CD4 counts and concentrations of blood plasma viral RNA. Gonorrhoea was associated with the greatest concentration of HIV-1 in semen (15.8 x 104 copies/mL). After the urethritis patients received antimicrobial therapy directed against STDs, the concentration of HIV-1 RNA in semen decreased significantly (from 12.4 x 104 copies/mL to 8.9l x 1O4 copies/mL at 1 week [p = 0.03] and 4.12 x 104 copies/mL at 2 weeks [p = 0.0001]). Blood plasma viral RNA concentrations did not change. There was no significant change in seminal plasma HIV-1 RNA concentrations during the 2-week period in the control group (p = 0.421). Interpretation. These results suggest that urethritis increases the infectiousness of men with HIV-1 infection. HIV-1-control programmes, which include detection and treatment of STDs in patients already infected with HIV-1, may help to curb the epidemic. Targeting of gonococcal urethritis may be a particularly effective strategy.