AFJOG

REVIEW African Journal of Obstetrics and Gynaecology | Volume 2 | Issue 3 | 2024 | Pre-Exposure Prophylaxis to prevent HIV infection during Pregnancy and Breast-feeding: A South African Perspective Box 6: Other Services Provided in a PrEP Program HIV testing services/ Including partner Risk reduction counselling ART initiation for those testing positive Pregnancy screening Counselling for mental health TB screening Box 7: Discontinuation of PrEP Any individual who: Tests HIV positive Has persistently low eGFR or sCr (pregnant women) Is non-adherent to PrEP Has safety concerns: The risks of PrEP outweigh the benefits ORALFORMULATIONS : TenofovirDisoproxil Fumerate (300mg), alone or in combination with FTC (200mg), reduces the risk of HIV-1 acquisition by ≥ 50% when used appropriately (6,32,33) . The effectiveness of daily oral PrEP is limited by challenges of adherence. To mitigate this challenge, dosing can be event-driven or “on-demand” in some populations (5,6,21) . On-demand PrEP involves taking the regimen peri-coitally and continuing for 2 days after the sex event. A randomized open-label Phase II trial (ADAPT Cape Town Trial/ HPTN 067) evaluated the feasibility of non-daily dosing of oral PrEP, relative to daily dosing (33) . Daily dosing resulted in higher coverage of sex events, with 75% and 53% adherence to therapy for daily dosing and event-driven dosing, respectively. The results of this study support the recommended daily use of oral PrEP. In just over a decade, a plethora of data has been reported on the safety and efficacy of oral TDF-based PrEP, in diverse population groups. In 2010, the landmark iPrEx trial was the first to report on the safety and efficacy of PrEP in men having sex with men (MSM) and transgender women. Subsequent studies found oral PrEP to be ineffective among African women as a result of poor adherence (34) . In 2012, a phase III randomised controlled trial (PARTNERS- PrEP) conducted in Kenya and Uganda reported results on the safety and efficacy of once-daily TDF or TDF/FTC combination over a period of 36 months (35) . Approximately 4,758 serodiscordant heterosexual couples were enrolled, the HIV-infected partners were not eligible for antiretroviral therapy (ART), as per national guidelines at the time. Sixty- seven percent and 75% efficacy of TDF and TDF/FTC were reported, respectively. The investigators concluded that both Oral TDF and TDF/FTC can protect against HIV-1 infection in heterosexual men and women, including those of African descent (35) . In 2013, a Phase II/III trial evaluated the safety and efficacy of daily oral TDF to prevent HIV infection in people who inject drugs (Bangkok Tenofovir Study/CDC 4370). The study was conducted in Thailand and enrolled 2,400 drug users. Daily oral TDF showed 49% efficacy (33) . Recent studies on daily oral PrEP have also evaluated the safety and effectiveness of the F/TAF combination pill (Descovy). A randomised, double-blind, multi-centre, active-controlled, phase 3, non-inferiority clinical trial evaluating the efficacy and safety of TDF/FTC versus (F/TAF) was conducted in Europe and North America (DISCOVER) (36) . The study commenced in 2016 and enrolled 5400 participants (adult MSM and transgender women who have sex with men). Preliminary results after 96 weeks of follow-up showed F/TAF to have non-inferior efficacy to daily TDF/FTC for HIV prevention. There were similarly low numbers of clinical adverse events reported in both groups. However, TDF/FTC was associated with declining bone density in younger individuals and renal toxicity in older individuals (> 50yrs), and those with pre-existing renal disease. A drawback of the study was the exclusion of adolescents, cisgender women and PBFW, who were key target populations. As a result of these findings, in 2019 the US Food and Drug Administration (FDA) approved F/TAF for PrEP (21) , but limited its approval to men and transgender women who have sex with men. Box 8 summarizes the efficacy of oral PrEP in various pivotal studies conducted over the years. Most of the studies reported a positive outcome, thus supporting regulatory approval of oral PrEP. Box 8: Summary of Oral Pre-Exposure Prophylaxis Studies ORALFORMULATIONSDURINGPREGNANCY ANDBREASTFEEDING There are limited data on the safety and efficacy of oral PrEP during pregnancy and lactation. The safety profile of PrEP for PBFW has largely been extrapolated from data on HIV-infected PBFW, who are on life-long ART (22) . HIV-infected PBFW have been exposed to ART for more than 2 decades without any major concerns (22) . Studies have shown that exposure to TDF or TAF in combination with FTC for treatment of HIV during pregnancy is safe and well tolerated (37) . First-trimester exposure to TDF has not been shown to be associated with increased risk of congenital anomalies (38) . In-utero exposure to TDF has been associated with an increased risk of preterm birth and fetal growth restriction in some, but not all studies (38) . Lamivudine (3TC) has also been shown not to be associated with adverse pregnancy outcomes and is well tolerated during pregnancy (22) . There is emerging evidence on the safety of oral TDF- based PrEP during pregnancy and lactation (39) . There are no contraindications to taking oral TDF-based PrEP during pregnancy and breastfeeding (24,39) . However, there are currently no data on the efficacy and safety of TAF-based PrEP during pregnancy, due to limited pharmacokinetic and safety data (40) . Tenofovir disoproxil fumerate is a pro-drug of tenofovir (TFV). The efficacy of TDF during pregnancy and lactation has been reported to be similar to non-pregnant women, despite lower intracellular levels of the active form of TFV (41,42,43 ) . More data African Journal of Obstetrics and Gynaecology | Volume 2 | Issue 3 | 2024 | 09