Why the proportion of transmission during early-stage HIV infection does not predict the long-term impact of treatment on HIV incidence

Significance Antiretroviral treatment (ART), which prevents both morbidity and HIV transmission for persons infected with HIV, is now thought to be central to strategies for controlling the spread of HIV. One major concern has been that if a large proportion of HIV transmission occurs early in infection, before persons can be diagnosed and treated, the impact of treatment on reducing new infections will be less. We use a mathematical model to quantify how the proportion of early transmission will affect the impact of intervention strategies, and explain underlying epidemiological mechanisms for this. Model simulations suggest that—counter to expectations—the proportion of early transmission at the start of an ART intervention does not predict the long-term intervention impact. Antiretroviral therapy (ART) reduces the infectiousness of HIV-infected persons, but only after testing, linkage to care, and successful viral suppression. Thus, a large proportion of HIV transmission during a period of high infectiousness in the first few months after infection (“early transmission”) is perceived as a threat to the impact of HIV “treatment-as-prevention” strategies. We created a mathematical model of a heterosexual HIV epidemic to investigate how the proportion of early transmission affects the impact of ART on reducing HIV incidence. The model includes stages of HIV infection, flexible sexual mixing, and changes in risk behavior over the epidemic. The model was calibrated to HIV prevalence data from South Africa using a Bayesian framework. Immediately after ART was introduced, more early transmission was associated with a smaller reduction in HIV incidence rate—consistent with the concern that a large amount of early transmission reduces the impact of treatment on incidence. However, the proportion of early transmission was not strongly related to the long-term reduction in incidence. This was because more early transmission resulted in a shorter generation time, in which case lower values for the basic reproductive number (R0) are consistent with observed epidemic growth, and R0 was negatively correlated with long-term intervention impact. The fraction of early transmission depends on biological factors, behavioral patterns, and epidemic stage and alone does not predict long-term intervention impacts. However, early transmission may be an important determinant in the outcome of short-term trials and evaluation of programs.

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