Biological impact of recurrent sexually transmitted infections on HIV seroconversion among women in South Africa: Results from frailty models

Abstract

Introduction: Understanding the impact of curable sexually transmitted infections (STIs) on HIV transmissibility is essential for effective HIV prevention programs. Investigating the impact of longitudinally measured recurrent STIs on HIV seroconversion is the interest of the current paper. Methods: In this prospective study, data from a total of 1456 HIV-negative women who enrolled in a HIV biomedical trial were used. It was hypothesized that women who had recurrent STI diagnoses during the study share a common biological heterogeneity which cannot be quantified. To incorporate this "unobserved" correlation in the analysis, times to HIV seroconversion were jointly modelled with repeated STI diagnoses using Cox regression with random effects. Results and discussion: A total of 110 HIV seroconversions were observed (incidence rate of 6.00 per 100 person-years). In a multivariable model, women who were diagnosed at least once were more likely to seroconvert compared to those who had no STI diagnosis [hazard ratio (HR): 1.63, 95% confidence interval (CI): 1.04, 2.57]; women who had recurrent STI diagnoses during the study were 2.5 times more likely to be at increased risk of HIV infection (95% CI: 1.35, 4.01) with an estimated frailty variance of 1.52, with p >0.001, indicating strong evidence that there is a significant correlation (heterogeneity) among women who had recurrent STIs. In addition to this, factors associated with incidence of STIs, namely not being married and having a new sexual partner during the study follow-up, were all significantly associated with increased risk for HIV seroconversion (HR: 2.92, 95% CI: 1.76, 5.01 and HR: 2.25, 95% CI: 1.63, 3.83 respectively). Conclusions: The results indicated that women who were at risk for STIs were also at risk of HIV infection. In fact, they share the similar risk factors. In addition to this, repeated STI diagnoses also increased women's susceptibility for HIV infection significantly. Decreasing STIs by increasing uptake of testing and treatment and reducing partner change plays a significant role in the trajectory of the epidemic.