Assessing risk for HIV infection among adolescent girls in South Africa: an evaluation of the VOICE risk score (HPTN 068)

Abstract

Introduction To maximize impact and minimize costs, antiretroviral pre‐exposure prophylaxis (PrEP) interventions should be offered to those at highest risk for HIV infection. The risk score derived from the VOICE trial is one tool currently being utilized to determine eligibility in adolescent PrEP trials in sub‐Saharan Africa. This study is aimed at evaluating the utility of the risk score in predicting HIV incidence among a cohort of adolescent girls in rural South Africa. Methods We utilized data from HIV Prevention Trials Network (HPTN) 068, a phase III randomized controlled trial conducted in rural Mpumalanga province, South Africa. School‐attending young women aged 13 to 20 years were enrolled into the trial from 2011 to 2012 and followed for up to three years. A risk score based on individual‐level risk factors measured at enrolment was calculated for HPTN 068 participants who completed a one‐year follow‐up visit and were HIV seronegative at enrolment. Possible scores ranged from 0 to 10. A proportional hazards model was then used to determine if risk score at enrolment was predictive of incident HIV infection at follow‐up and an area under the curve analysis was used to examine the predictive ability of the score. Results and Discussion The risk score had limited variability in the HPTN 068 sample. Scores ≥5 identified 85% of incident infections from 94% of the sample, compared to the VOICE sample in which scores ≥5 identified 91% of incident infections from only 64% of participants. The risk score did not predict HIV incidence after one year of follow‐up (hazard ratio = 1.029; 95% confidence interval (CI): 0.704, 1.503, p = .884) and showed poor predictive ability (area under the curve = 0.55; 95% CI: 0.44, 0.65). Certain individual risk factors that comprise the risk score may be context specific or not relevant for adolescent populations. Additional factors should be considered when assessing risk for the purposes of determining PrEP eligibility. Conclusions The VOICE risk score demonstrated low utility to predict HIV incidence in the HPTN 068 sample. Findings highlight the need for an age and developmentally appropriate tool for assessing risk for HIV infection among adolescents. Use of the VOICE risk score for determining PrEP eligibility in younger populations should be carefully considered.

Age-Specific Risk Scores Do Not Improve HIV-1 Prediction Among Women in South Africa

“… 17 , 18 The MTN-003/VOICE risk score was previously developed and externally validated in 3 cohorts of women aged 18–45 participating in clinical trials of HIV-1 prevention products in sub-Saharan Africa. 9 , 19 However, the VOICE risk score performed poorly among adolescent girls and young women in recent research, 20 suggesting that a different set of risk factors may be more predictive of HIV-1 acquisition among younger age groups. Given high HIV-1 incidence in this group of women, 1 risk scores tailored to their unique risk profile are needed.…”

Risk scores for predicting HIV incidence among adult heterosexual populations in sub-Saharan Africa: a systematic review and meta-analysis

“…Most studies found that HIV incidence increased monotonically with the risk scores, except for Giovenco [25] (Table S6). Figure 5 shows the proportion of participants identified as high risk compared to the percentage of incident cases contributed by the high-risk group.…”

“…One additional conference abstract was available after initial screening, adding to a total of 13 risk score literature (9 peer-reviewed articles, 2 posters, 1 editorial letter, 1 abstract) that met the inclusion criteria and were included in this review (Figure 1) [5,6,[20][21][22][23][24][25][26][27][28][29][30]. Critical appraisal according to the PROBAST checklist concluded that one out of twelve models developed and two out of nine validated were of low risk of bias (Figure S1, Table S3 & S4).…”

“…The majority (10 of 13) were RCTs or quasi-experimental studies that restricted recruitment and/or eligibility to specific at-risk population groups: (i) sexually active, contraceptionseeking women who attended the family-planning, STIs or research clinics (7 of 10, all RCTs) [5,6,[20][21][22][23][24], or (ii) school-attending AGYW (3 of 10) [25][26][27]. The remaining three were large-scale cohort studies or community trials that recruited all consenting members within the communities [28][29][30].…”

“…This undermines the appropriateness of our pooled risk ratio estimates. In many validation studies, some selected risk factors were not available or defined differently [25, 26, 39].…”