ABSTRACT
Reducing new HIV and STI infections among South African (SA) adolescent girls and young women
(AGYW) is global public health priority.1 SA has world's largest HIV epidemic,2,3 and SA AGYW acquire
HIV at twice the rate of and seroconvert on average 5 – 7 years earlier than male peers.3 As new
infections continue to outpace access to and availability of PrEP and ART, primary prevention remains the
most viable strategy to stem new transmissions.1,4,5 SA efforts to prevent HIV transmission in youth focus
mostly on individual-level behavior change,6-8 but AGYW's persistent HIV disparities are explained by
broad social and structural inequities that shape and constrain HIV-risk behaviors.9-14 Comprehensive HIV
prevention packages that are integrated, synergistic, and tailored to the local epidemiology and cultural
context are likely to achieve and sustain maximum reductions in HIV-risk.15-22 Female caregivers (FC) are
an untapped resource in the HIV prevention toolbox23,24 and offer a novel opportunity to strengthen AGYW
prevention efforts. AGYW may also be change agents for their FC who want to be positive role models for
AGYW, and thus, adopt HIV prevention behaviors, including HTC and PrEP. Guided by an ecological
framework, our highly experienced multidisciplinary team will adapt (phase 1/UG3) and evaluate the
effectiveness and cost-effectiveness of (phase 2/UH3) IMARA, a multilevel, innovative, family-based HIV
prevention program that targets individual, social, and structural drivers of risk to decrease HIV and STI
incident infections, reduce risky sexual behavior, and increase HTC and PrEP uptake (where appropriate)
in AGYW and FC. IMARA demonstrated a 45% reduction in incident STI at 12-month follow-up among
black 14-18 year-old girls in the US, and increased HIV testing in FC. Pilot data with 71 AGYW and FC at
the Desmond Tutu HIV Foundation (DTHF; study site) confirm feasibility and acceptability of IMARA for
the South African context. This study will be integrated into the adolescent-friendly services at DTHF in the
Western Cape metropolitan area facilitating sustainability if effective. Using the ADAPT-ITT model, we will
systematically tailor IMARA for the SA context and then conduct a 2-arm RCT with 300 15-19 year-old
AGYW and FC. FC and AGYW will complete baseline, 6-, and 12-month assessments, including testing
for 3 STI. We will offer HTC and PrEP at each assessment and track uptake and linkage to care. AGYW
and FC who test positive for a STI and/or HIV will receive free treatment at DTHF. We will collect data to
determine the costs of IMARA. Analyses will compare AGYW and FC across the intervention and control
programs on sexual risk taking, STI and HIV incidence, PrEP and HTC uptake, and theoretical mediators.
The study answers an urgent need to evaluate the effectiveness and cost-effectiveness of combination
HIV prevention packages for AGYW to achieve an AIDS-free generation.
