To assess the acceptance rate, adherence, acceptability, and continuation of oral pre-exposure prophylaxis (PrEP) among young southern African women.

A Phase IV randomized multi-site prospective study to assess PrEP acceptance and adherence among HIV-uninfected young women. All women who accept open-label daily oral PrEP will be randomized 1:1 to receive enhanced adherence counselling based on feedback from observed drug levels or standard adherence support. A subset of up to ~25 women per site (maximum 75), will participate in qualitative assessments of facilitators and barriers for PrEP acceptance, adherence and continuation.

Inclusion Criteria:

Young women who meet all of the following criteria are eligible for inclusion in this study:

• Female at birth
• Age 16-25 years
• Per participant report, sexually active, defined as having vaginal or anal intercourse at least once in the month prior to screening
• Literate in one or more of the study languages
• Willing and able to provide informed consent or assent (if parental consent is required per local regulations)
• If parental consent is required per local regulations, parent/legal guardian willing and able to consent to all study procedures including HIV testing
• Able and willing to provide adequate locator information, as defined in site Standard Operating Procedures (SOPs)
• Have a score of 5 or greater on the Vaginal and Oral Intervention to Control the Epidemic (VOICE) risk score tool
• Interest in PrEP (ascertained by selected questions from the HIV Prevention Readiness Measure (HPRM) and Prep Belief Measure (PBM) defined in the Study Specific Procedures [SSP] Manual)
• Regular access to a mobile phone with SMS capacity
• Agrees not to participate in other research studies involving drugs or medical devices for the next 12 months
• Hepatitis B virus (HBV) seronegative and accepts HBV vaccination.

Exclusion Criteria:

Young women who meet any of the following criteria will be excluded from this study:

• Planning to relocate in the next 12 months
• Has a job or other obligations that would require long absences from the area (> 4 weeks at a time) for 12 months
• Any health condition that may interfere with participation, including any debilitating or life-threatening conditions
• Currently pregnant or planning to become pregnant in the next 12 months
• Any reactive or positive HIV test at Screening or Enrollment, even if subsequent testing indicates that the person is HIV-uninfected
• Renal dysfunction (Creatinine Clearance < 60 ml/min, Schwartz Equation)
• Any reported PrEP use within the last 12 months
• Concomitant participation in a clinical trial using investigational agents, including placebo-controlled clinical trials using such agents
• Prior participation in the active arm, or current participation in any arm, of an HIV vaccine trial
• Signs or symptoms of acute HIV infection (as described in the SSP Manual)
• Current active and serious infections which could interfere with study participation, including active tuberculosis infection, osteomyelitis, and all infections requiring parenteral antibiotic therapy (other than STIs requiring intramuscular injections of antibiotics); active clinically significant medical problems including poorly-controlled cardiac disease (e.g., symptoms of ischemia, congestive heart failure), or previously diagnosed malignancy expected to require further treatment.
• Current use of ARV drugs for post-exposure prophylaxis (PEP) or completion of a PEP regimen within 4 weeks prior to Screening
• History of pathological bone fracture not related to trauma
• Known allergy/sensitivity to the study drug or its components
• Receiving ongoing therapy with any of the following: investigational ARV agents, interferon or interleukin therapy, agents with substantial nephrotoxic potential, other agents that may inhibit or compete for elimination via active renal tubular secretion (e.g., probenecid), and/or other investigational agents
• Any other condition that, based on the opinion of the site Investigator of Record (IoR) or designee, would preclude provision of informed consent, make participation in the project unsafe, complicate interpretation of outcome data, or otherwise interfere with achieving the project objectives.

Data will be pooled by PID for central analysis by the Fred Hutch in Seattle, Washington

From the start of the treatment until the resolution of all Adverse Events after completion of discontinuity of the study treatment (Up till 1 year after the start of the study treatment)

For the purposes of this study, only serious adverse events (SAEs) and adverse events Grade 3 and above [with the exception of Creatinine Clearance, which will be measured using the Schwartz Equation and documented at Grade 2 or higher].

There was very little community awareness about PrEP at the time of this study, which may have impacted adherence and persistence. We did not have the power to detect a modest effect of retrospective drug level feedback on subsequent PrEP adherence. There was not a placebo control to ethical concerns about withholding an effective intervention, so the contribution of PrEP to the low HIV incidence cannot be determined.