High Incidence Is Not High Exposure: What Proportion of Prevention Trial Participants Are Exposed to HIV?

<div><p>Objective</p><p>Randomized clinical trials of HIV prevention in high-risk populations of women often assume that all participants have similar exposure to HIV. However, a substantial fraction of women enrolled in the trial may have no or low exposure to HIV. Our objective was to estimate the proportion of women exposed to HIV throughout a hypothetical high-risk study population.</p><p>Methods</p><p>A stochastic individual-based model was developed to simulate the sexual behavior and the risk of HIV acquisition for a cohort of sexually active HIV-uninfected women in high HIV prevalence settings. Key behavior and epidemic assumptions in the model were based on published studies on HIV transmission in South Africa. The prevalence of exposure, defined as the proportion of women who have sex with HIV-infected partner, and HIV incidence were evaluated.</p><p>Results</p><p>Our model projects that in communities with HIV incidence rate of 1 per 100 person years, only 5-6% of women are exposed to HIV annually while in communities with an HIV incidence of 5 per 100 person years 20-25% of women are exposed to HIV. Approximately 70% of the new infections are acquired from partners with asymptomatic HIV.</p><p>Conclusions</p><p>Mathematical models suggest that a high proportion of women enrolled in HIV prevention trials may be unexposed to HIV even when incidence rates are high. The relationship between HIV exposure and other risk factors should be carefully analyzed when future clinical trials are planned.</p></div

Characteristics of the simulated female cohort based on the last month of sexual activity.

<p>Characteristics of the simulated female cohort based on the last month of sexual activity.</p

Results from each of the simulations conducted under the assumptions in Table 1 are plotted, illustrating A) prevalence of exposure (PoE) and B) HIV incidence among 2000 originally uninfected women (blue), high-risk group (red) and low-risk group (black) over 1-year period for different values of HIV prevalence among male partners in 10 simulations (dots) per male prevalence level and averaged (thick lines); C) Distribution of female HIV acquisitions over 1-year period by the stage of HIV infection of the transmitting male partner; D) Scatter plot of the infected vs. exposed fractions over 1-year period.

<p>All simulations assume assortative mixing between different risk groups when partnerships are formed, i.e. high risk women have greater chance to partner with high risk men and similarly low-risk women partner more often with low-risk men.</p

Parameters values used in the main analysis.

<p>Parameters values used in the main analysis.</p

sj-pdf-1-ctj-10.1177_17407745231203327 – Supplemental material for Estimating counterfactual placebo HIV incidence in HIV prevention trials without placebo arms based on markers of HIV exposure

Supplemental material, sj-pdf-1-ctj-10.1177_17407745231203327 for Estimating counterfactual placebo HIV incidence in HIV prevention trials without placebo arms based on markers of HIV exposure by Yifan Zhu, Fei Gao, David V Glidden, Deborah Donnell and Holly Janes in Clinical Trials</p

Demographic characteristics and risk behaviors reported at the baseline visit.

†<p>Serosorting Cohort compared to the entire EXPLORE Cohort.</p>‡<p>Seropositioning Cohort compared to the entire EXPLORE Cohort.</p

Comparison between serosorters (score> = 4) and non-serosorters (score< = 1) at baseline visit within the EXPLORE serosorting subcohort (n = 2623).

<p>Comparison between serosorters (score> = 4) and non-serosorters (score< = 1) at baseline visit within the EXPLORE serosorting subcohort (n = 2623).</p

Predictors of HIV seroconversion in the EXPLORE seropositioning subcohort.

<p>Adjusted for race, number male partners, self-reported gonorrhea, depression, alcohol or drug use before sex, amphetamine use.</p

Distribution of seropositioning and serosorting scores.

<p>Distribution of seropositioning and serosorting scores.</p

Predictors of HIV seroconversion in the EXPLORE serosorting subcohort.

<p>Adjusted for race, number male partners, self-reported gonorrhea, depression, alcohol or drug use before sex, amphetamine use.</p