O-PrEP

Primary Sponsor Details

Secondary Sponsor Details

Zimbabwe 

Inclusion criteria

 Maternal participants

• Maternal participants aged 16 years or older
• PrEP-eligible by local guidelines
• Pregnant with a viable singleton pregnancy of between 14 and 23 completed weeks of gestation (from 14 weeks + 0 days to 23 weeks + 6 days) by ultrasonography at study entry
• HIV-negative based on the study-specific screening algorithm
• Hepatitis B surface antigen (HBsAg)-negative
• Weight >35kg
• Provided informed consent and expressed willingness to participate in study activities with their infants, including daily administration of oral PrEP under direct observation.

Infant participants

• Infant participants enter the study with mother as unborn infants. There are no specific eligibility criteria for infant participation otherwise. If an infant is deemed too ill to undergo study procedures, procedures necessary for clinical management may be prioritised.

Exclusion criteria

• Grade 2 or greater laboratory parameters for alanine transaminase (ALT) or aspartate aminotransferase (AST), haemoglobin (HB), and absolute neutrophil count (ANC).
• Estimated creatinine clearance (CrCl) 90mL/min or below, using the Cockcroft-Gault formula.
• Known history or evidence of current significant disease process, including haematological conditions, renal disease, unexplained bone fractures, environmental enteric dysfunction, or allergies/sensitivities to FTC/TDF.
• Other current significant or uncontrolled disease process (active or chronic) substance use, or social circumstances that, in the judgement of the site investigator, would make participation in the study inappropriate or unsafe.
• Foetuses with known or suspected major foetal anomaly, either from screening ultrasound or via medical record
• Intention to leave the study site’s catchment area before scheduled study exit.
• Current use of prohibited medications listed in the protocol Section 5.8
• Concurrent use of other biomedical HIV prevention interventions (vaginal ring, injectable PrEP, any investigational prevention product).

The  key safety endpoints are 

• maternal renal function, measured via CrCl;
• maternal grade >2 adverse events, including renal events.
• adverse pregnancy outcome composite that includes fetal death (spontaneous abortion and stillbirth), preterm birth, and small for gestational age;
• infant grade >3 adverse events and major congenital anomalies reported between birth and study exit. Gestational age will be determined by best obstetric estimate, based on obstetric ultrasound prior to study entry. We will use the INTERGROWTH-21st standards for weight-for-gestational age at birth.

The area under the dose-concentration curve (AUC) of tenofovir diphosphate (TFV-DP) in peripheral blood mononuclear cells (PBMCs) serves as the primary PK endpoint.

9.0 DESIGN OF THE TRIAL

If controlled