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Background  Ad hoc assumptions about the unobserved infection event, which is known only to occur between the latest-negative and earliest-positive test dates, can lead to biased HIV incidence rate estimates. Using a G-imputation approach, we infer the infection dates from covariate data to estimate the HIV incidence rate in a hyper-endemic South African setting.    Methods  A large demographic surveillance system has annually tested a cohort of HIV-uninfected participants living in the KwaZulu-Natal province. Using this data, we estimated a cumulative baseline hazard function and the effects of time-dependent covariates on the interval censored infection dates. For each HIV-positive participant in the cohort, we derived a cumulative distribution function and sampled multiple infection dates conditional on the unique covariate values. We right censored the data at the imputed dates, calculated the annual HIV incidence rate per 100 person-years, and used Rubin’s rules to obtain the 95% confidence intervals.    Results  A total of 20,011 uninfected individuals with a repeat HIV test participated in the incidence cohort between 2005 and 2018. We observed 2,603 infections per 58,769 person-years of follow-up among women and 845 infections per 41,178 person-years of follow-up among men. Conditional on age and circumcision status (men only), the female HIV incidence rate declined by 25%, from 5.0 to 3.7 infections per 100 person-years between 2014 and 2018. During this period, the HIV incidence rate among men declined from 2.1 to 1.1 infections per 100 person-years—a reduction of 49%. We observed similar reductions in male and female HIV incidence conditional on condom-use, marital status, urban residential status, migration history, and the HIV prevalence in the surrounding community.    Conclusion  We have followed participants in one of the world’s largest and longest running HIV cohorts to estimate long-term trends in the population-wide incidence of infection. Using a G-imputation approach, we present further evidence for HIV incidence rate declines in this hyper-endemic South African setting.

HIV incidence declines in a rural South African population: a G-imputation approach for inference