Risk of heterosexual HIV transmission attributable to sexually transmitted infections and non-specific genital inflammation in Zambian discordant couples, 1994-2012

Background: Studies have demonstrated the role of ulcerative and non-ulcerative sexually transmitted infections (STI) in HIV transmission/acquisition risk; less is understood about the role of non-specific inflammatory genital abnormalities. Methods: HIV-discordant heterosexual Zambian couples were enrolled into longitudinal follow-up (1994-2012). Multivariable models estimated the effect of genital ulcers and inflammation in both partners on time-to-HIV transmission within the couple. Population-attributable fractions (PAFs) were calculated. Results: A total of 207 linked infections in women occurred over 2756 couple-years (7.5/ 100 CY) and 171 in men over 3216 CY (5.3/100 CY). Incident HIV among women was associated with a woman's non-STI genital inflammation (adjusted hazard ratio (aHR) ¼ 1.55; PAF ¼ 8%), bilateral inguinal adenopathy (BIA; aHR ¼ 2.33; PAF ¼ 8%), genital ulceration (aHR ¼ 2.08; PAF ¼ 7%) and the man's STI genital inflammation (aHR ¼ 3.33; PAF ¼ 5%), BIA (aHR ¼ 3.35; PAF ¼ 33%) and genital ulceration (aHR ¼ 1.49; PAF ¼ 9%). Infection among men was associated with a man's BIA (aHR ¼ 4.11; PAF ¼ 22%) and genital ulceration (aHR ¼ 3.44; PAF ¼ 15%) as well as with the woman's non-STI genital inflammation (aHR ¼ 1.92; PAF ¼ 13%) and BIA (aHR ¼ 2.76; PAF ¼ 14%). In HIV-MþF- couples, the man being uncircumcised. with foreskin smegma. was associated with the woman's seroconversion (aHR ¼ 3.16) relative to being circumcised. In FþM- couples, uncircumcised men with BIA had an increased hazard of seroconversion (aHR ¼ 13.03 with smegma and 4.95 without) relative to being circumcised. Self-reporting of symptoms was low for ulcerative and non-ulcerative STIs. Conclusions: Our findings confirm the role of STIs and highlight the contribution of nonspecific genital inflammation to both Male-to-feMale and feMale-to-Male HIV transmission/acquisition risk. Studies are needed to characterize pathogenesis of non-specific inflammation including inguinal adenopathy. A better understanding of genital practices could inform interventions.