Evaluating risk factors and synergistic effects of two common HIV-1 coinfections: schistosomiasis and trichomoniasis

Thesis (Ph.D.)--University of Washington, 2018Introduction: HIV-1 coinfections have long been suspected of catalyzing the HIV-1 epidemic by increasing HIV-1 transmission or acquisition risk. The geographical distribution of coinfections may explain why some regions have been more heavily impacted by HIV-1. The primary objective of this dissertation was to expand our understanding of two common HIV-1 coinfections that have been hypothesized to increase the risk of HIV-1 transmission and acquisition: schistosomiasis and trichomoniasis. The specific aims of this dissertation were 1) Identify correlates of T. vaginalis infection within a population of HIV-1 serodiscordant heterosexual couples, 2) Estimate the association between schistosomiasis and HIV-1 acquisition, 3) Evaluate the impact of schistosome coinfection on HIV-1 set-point genital viral load levels, and 4) Evaluate the association between schistosome coinfection and HIV-1 set-point plasma viral load levels. Methods: To conduct these analyses, we used data from four cohort studies: the Partners in Prevention HSV/HIV Transmission Study, the Couples Observational Study, the Partners PrEP Study, and the Mombasa Cohort. All analyses utilized data from multiple cohorts. For all cohorts, a large amount of individual-level information was collected, including characteristics associated with HIV-1 acquisition risk and the prevalence of coinfections, permitting thorough adjustment for possible confounding factors. Results and Conclusions: Correlates of T. vaginalis infection: In a cross-sectional analysis of 8,155 HIV-1 serodiscordant couples, the strongest predictor of a prevalent T. vaginalis infection was having an infected sexual partner. Thus, concurrent treatment of sexual partners is critical to prevent reinfection. Among women, having a circumcised male partner was associated with reduced T. vaginalis risk while bacterial vaginosis (detected via Nugent Score) was associated with an increased risk, so expanding male circumcision programs and bacterial vaginosis treatment has the potential to reduce the prevalence of trichomoniasis. Schistosomiasis and HIV-1 acquisition risk: In nested case-control analyses including 575 HIV-1 seroconverters and 1,675 controls, S. mansoni infection was not associated with an increased the risk of HIV-1 acquisition. In addition, S. haematobium infection was not associated with a statistically significant increase in HIV-1 acquisition risk, though our result suggested that women with S. haematobium could face a moderate increased risk of HIV-1 acquisition. Schistosomiasis and set point HIV-1 RNA viral loads: Schistosomiasis was not associated with increased plasma HIV-1 viral loads. Our results do not support the hypothesis that schistosome coinfection increases the rate of HIV-1 disease progression. Schistosomiasis and genital HIV-1 RNA viral loads: Schistosomiasis was not associated with increased genital HIV-1 viral loads. Our results do not support the hypothesis that schistosome coinfection increases HIV-1 transmission risk