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

Abstract

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.

Keywords: HIV incidence; HIV prevention intervention; antiretroviral therapy; early infection; mathematical model.

Fig. 1.

Epidemiologic outputs for baseline model calibration and projection without ART. (A) Posterior model calibration to adult male and female HIV prevalence and HIV prevalence among pregnant women attending ANC. (B and C) Posterior distribution in counterfactual simulation with no ART provision: (B) HIV incidence rate among adult men and women; (C) mean percentage of transmission from each stage of infection.

Fig. 2.

(A) Distribution in the percentage of transmission during early infection in 2010. (B) Correlation between the relative infectiousness during early infection (on the log scale) and the proportion of early transmission.

Fig. 3.

Correlation between percentage of early transmission in 2010 (when ART is introduced) and the reduction in HIV incidence rate over time relative to projected incidence in the absence of ART. (A) Scatter plots comparing the percentage of early transmission in 2010 and the percentage reduction in incidence rate in the first, second, 10th, and 30th years (note: vertical axes are not the same). (B) The Pearson correlation coefficient between early transmission at intervention start and the percentage reduction in incidence rate over time.

Fig. 4.

R₀, early transmission, and reduction in incidence. (A) The distribution of R₀ at the start of the epidemic (green) and during the intervention period (blue), after behavior change. (B) The relationship between R₀ at the start of the epidemic and the percentage of early transmission in 2010, at the start of the intervention. (C) The relationship between R₀ during the intervention period and the reduction in HIV incidence rate after 30 y. Red lines indicate the fitted linear relationship between 1/R₀ and early transmission (B) or reduction in incidence rate (C).

Fig. 5.

The relationship between relative infectiousness during early infection and the reduction in HIV incidence rate after 30 y. (A) Results based on sample from posterior distribution of relative infectiousness parameter. (B) Results from calibration of sexual behavior parameters conditional on fixed value of relative infectiousness. In B, horizontal lines represent posterior mean.