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

Abstract

BackgroundStudies 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.MethodsHIV-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.ResultsA 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) = 1.55; PAF = 8%), bilateral inguinal adenopathy (BIA; aHR = 2.33; PAF = 8%), genital ulceration (aHR = 2.08; PAF = 7%) and the man’s STI genital inflammation (aHR = 3.33; PAF = 5%), BIA (aHR = 3.35; PAF = 33%) and genital ulceration (aHR = 1.49; PAF = 9%). Infection among men was associated with a man’s BIA (aHR = 4.11; PAF = 22%) and genital ulceration (aHR = 3.44; PAF = 15%) as well as with the woman’s non-STI genital inflammation (aHR = 1.92; PAF = 13%) and BIA (aHR = 2.76; PAF = 14%). In HIV-M+F- couples, the man being uncircumcised. with foreskin smegma. was associated with the woman’s seroconversion (aHR = 3.16) relative to being circumcised. In F+M- couples, uncircumcised men with BIA had an increased hazard of seroconversion (aHR = 13.03 with smegma and 4.95 without) relative to being circumcised. Self-reporting of symptoms was low for ulcerative and non-ulcerative STIs.ConclusionsOur findings confirm the role of STIs and highlight the contribution of non-specific 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.

HIV Incidence and Predictors of HIV Acquisition From an Outside Partner in Serodiscordant Couples in Lusaka, Zambia

“…Our unlinked infection incidence rate is similar to other studies in the region, 3 demonstrating the importance of outside partners as a risk for HIV acquisition in generalized HIV epidemics. Our study also demonstrated that factors associated with unlinked infection are similar to those reported for HIV acquisition more broadly: heavy alcohol use among both men and women, 18 , 43 and genital discharge, ulceration and inflammation 1 , 19 , 23 were important predictors of unlinked seroconversion. Studies of the newly infected partner in this cohort also confirm that genital inflammation is associated with transmission of multiple variants from outside partners.…”

“…From 1995 to 2003, both partners were seen quarterly, had routine physical and genital exams, and received laboratory screening for HIV (rapid antibody test) trichomonas (vaginal wet prep) and syphilis (RPR: positive RPR was batched for later treponema pallidum hemagglutination assay, confirming a low rate of false positive RPR). 23 , 30 In 2003, the study procedures were streamlined and physical exams and STI screenings were performed at baseline, annually, and when participants reported symptoms. Vaginal wet mounts were prepared using self-administered swabs at every visit that did not include a gynecologic examination (validated at the time of use in the study).…”

“…A time-varying composite genital ulcer variable was developed and considered positive if the patient reported ulcers, had ulcers noted on physical exam, had been treated for ulcers, or had a newly positive RPR. 23 …”

“…Genital inflammation measures included in the time-varying composite included physical examination findings including cervical, vaginal or external genital inflammation (redness, swelling, exudate, irritation, or tenderness), or inguinal adenopathy (80% of which was bilateral adenopathy); candida or bacterial vaginosis on vaginal wet mount including KOH prep, sniff test; reported vaginal discharge, odor, or discomfort; and self-report or treatment for gonorrhea/chlamydia (diagnosed syndromically based on endocervical pus in women or urethral discharge in men) or trichomonas (vaginal wet mount) in the past 3 months. 23 , 31 , 32 …”

“… 20 – 22 Studies among African serodiscordant couples have demonstrated that HIV acquisition is associated with younger age, alcohol use, genital inflammation and discharge, and non-ART use by HIV-positive partner. 19 , 22 , 23 However, there is limited research on factors associated with acquiring HIV from an outside partner or an “unlinked infection.” Learning that one is in an HIV-serodiscordant relationship may cause the HIV-negative partner to have sex with outside partners, often of unknown HIV serostatus, who might be perceived to pose lower risk of HIV infection than the primary HIV-positive partner. 1 , 3 , 4 Greater understanding of HIV-negative partners' behaviors with outside or concurrent sex partners, and these behaviors' associations with HIV acquisition, will inform HIV risk-reduction messages for uninfected partners.…”