UCLA

Understanding the factors of heterosexual HIV-1 serodiscordant couples that lead to risky behaviors for HIV transmission are essential in controlling the HIV epidemic in sub-Saharan Africa. Predictors of HIV transmission within stable discordant couples and trends in family planning over time, as well as predictors of ART initiation provide important information for future studies and prevention and treatment program development. This dissertation evaluates these aspects of HIV-1 serodiscordant couple transmission in an ART naive 10-year observational cohort in Kigali, Rwanda.

The first study evaluated the incident HIV-1 infections and the predictors of HIV-1 transmission in ART na?ve HIV-1 heterosexual serodiscordant couples. Eighty-three partner linked incident HIV-1 infections occurred in the cohort with 37 in women (IR=2.2/100 CY; 95%CI: 1.53.299) and 46 in men (IR=2.49/100 CY; 95%CI: 1.83-3.33). In the adjusted final model of linked HIV infection in females, baseline VL (aHR 2.33; 95%CI: 1.28-4.24), female genital inflammation (cHR 4.77; 95%CI: 1.72-13.21), and having unprotected sex with study partner since last visit (cHR 3.29; 95%CI: 1.27-8.51) were significant predictors. Predictors of linked incident HIV-1 infection in males included baseline VL (aHR 2.14; 95%CI: 1.50-3.07), female genital inflammation (aHR 3.91; 95%CI: 1.71-8.94), any unprotected sex with study partner since previous visit (aHR 3.56; 95%CI: 1.48-8.56), and presence of sperm on a wet prep (aHR 3.35; 95%CI: 0.99-11.36). These findings support the need to include sexual partners in the assessment of risk and target risk reduction strategies.

The second study described pregnancy and analyzed predictors of women ever using hormonal contraception (HC) by HIV status. Overall pregnancy incidence rate was 12.7/100 PY (95%CI: 11.3-14.1) while in M-F+ couples it was 13.2/100 PY (95%CI: 11.3-15.3) and 12.1/100 PY (95%CI: 10.2-14.1) in M+F- couples. 34% of HIV positive women, 26% of HIV- women who did not seroconvert, and 25% of HIV- women who seroconverted had used hormonal contraception at point during the study. In adjusted analyses, being younger (aRR 0.97; 95%CI: 0.95-0.99), ability to read Kinyarwandan easily (aRR 1.28; 95%CI: 1.06-1.55), and no STI in the past year (aRR 0.80; 95%CI: 0.67-0.95) was associated with ever HC use in HIV+ women. Among HIV negative women who did not seroconvert, HC ever use was associated with younger age (aRR 0.98; 95%CI: 0.96-1.0) and not being pregnant at baseline (aRR 0.72; 95%CI: 0.55-0.94). Across HIV groups, injectable methods were the most frequently used type of hormonal contraception at last visit and during most of study follow-up. The overall low uptake of hormonal contraception and high pregnancy rates in both HIV + and HIV- women suggest the need for more effective and widely accessible safer conception methods.

The third study evaluated predictors of time to ART initiation, stratified by gender of seropositive partner. Of the 1837 couples (882 M+F- / 955 M-F+), 30% had an HIV positive partner initiate ART. Of those, 39% had a seropositive male partner (M+F-) and 61% had a seropositive female partner (M-F+). Shorter time to ART initiation in M+F- couples was predicted by baseline viral load (aHR1.54; 95%CI:1.01-2.34), while both baseline viral load (aHR1.43; 95%CI:1.02-2.02) and baseline WHO stage IV (aHR 4.85; 95%CI:1.45-16.26) predicted earlier time to ART initiation in M-F+ couples. As expected, clinical values were the main predictors of time to ART initiation.

In conclusion, partner and partnership characteristics play an important in risk of HIV-1 acquisition and transmission in heterosexual serodiscordant couples. Family planning and fertility desires are particularly complex and important risk factors that may change over time for serodiscordant couples. These findings can help improve the targeted HIV prevention, safer conception and family planning services, and ART treatment programs focusing on sustained viral load suppression among heterosexual serodiscordant couples in Africa.