ABSTRACT Rationale. Since their initiation in 2016, oral pre-exposure prophylaxis (PrEP) HIV-1 prevention programs in South Africa (SA) have prioritized access for adolescent girls and young women (AGYW) due to their high HIV prevalence and incidence rates. Despite this effort, PrEP uptake has been low and persistence has been sub- optimal. Data are now emerging to characterize PrEP re-start as a further step in the PrEP cascade. Reasons described for PrEP restart include fluctuations in perceived HIV risk based on dynamic and shifting partnerships and sexual activity. Parallel to the HIV epidemic is a silent raging epidemic of curable but asymptomatic sexually transmitted infections (STI) which can increase risk of HIV acquisition. Recent data indicate SA AGYW as having the highest STI symptom burden nationally with gender disparity highest in the 15-19-year age-group (incidence of STI among females twice as high as males in Gauteng). We believe that targeting this younger age group to recognize and address their HIV/ STI risk during adolescence when they are developing personal autonomy, has potential to inform health seeking behavioral change needed in later years to reduce their exposure to the HIV/STI syndemics. Approach. We aim to develop a package of Neisseria gonorrhea and Chlamydia trachomatis STI kits paired with training (in-person and remote virtual methods) for at-home testing to determine whether AG can self-administer these tests and if this intervention could influence AG re-starting PrEP following receipt of a positive STI result and in clinic guided HIV self-test. The study will be conducted at the Wits Reproductive Health and HIV Institute, Johannesburg. For Aim 1, we will conduct in-depth interviews (IDI) among ~20 AGYW who have used PrEP, 20 parents of AG who have used PrEP and 20 healthcare providers to qualitatively explore barriers and facilitators to PrEP uptake, experiences with PrEP discontinuation, perspectives on re-start and willingness to self-assess STI risk using STI rapid tests and behavioral assessments. For Aim 2, we will recruit 50 AG (ages 16-17), who recently discontinued PrEP and randomize them in a 1:1 ratio to receive 1) the STI testing package coupled with self-administered behavioral risk assessments or 2) self-administered behavioral risk assessments only. Follow-up will be monthly for 6 months through a combination of remote and in-person visits. All participants will receive comprehensive sexual and reproductive health services and behavioral risk reduction counseling. Primary outcomes will include accrual, program continuation, use of STI kits for self-test, and measurement of PrEP adherence. For Aim 3, we will conduct study exit IDI with ~20 AG participating in Aim 2 to assess experiences with STI self-testing, self- administered behavioral risk assessment and re-starting PrEP. Impact. By achieving these aims, we will optimize methods and generate preliminary data to support an R01 proposal for a full trial of at-home STI testing and PrEP re-start among AG. These data will have potential to inform country policy on PrEP re-start among AG using self-identified STIs as a marker of heightened risk.

NARRATIVE Sub-optimal uptake, execution and persistence of oral pre-exposure prophylaxis (PrEP) use for HIV-1 prevention among South African adolescent girls (AG) and young women has led to the emergence of data characterizing PrEP re-start as a further step in the PrEP cascade due to perceived fluctuations in HIV risk. Sexually transmitted infections (STIs) can be used as a marker of heightened HIV risk and PrEP restart however discrete self-testing options for Neisseria Gonorrhea (NG) and Chlamydia trachomatis (CT) are not yet available despite the increasing popularity of HIV self-testing kits. We propose to develop a package of commercially available NG and CT STI rapid test kits paired with AG in person training and at-home virtual support methods for testing procedures, to assess whether AG can self-administer these tests and whether testing outcomes could influence AG re-starting PrEP.