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 indicated not being aware of the ring during daily activities. No serious adverse events were considered product-related, no safety concerns were identified, and the DVR was well tolerated. These findings are encouraging as they lend credence to the safe use of DVR in AGYW. In the REACH trial (MTN-034/IPM 045), the safety and acceptability of monthly DVR and daily oral TDF/FTC were evaluated in AGYW (62) . REACH also evaluated PrEP choices in this population of women and the support they may need while using either of these products. Approximately 300 AGYW aged 16 - 21 were enrolled at five sites in Kenya, South Africa, Uganda and Zimbabwe. Participants were required to utilize DVR for 6 months, then TDF/FTC for the next 6 months, and were then afforded the right to choose between either or neither of the two methods in the final 6 months of the study (choice period). Ninety-eight percent of the 227 participants who took part in the choice period of the study opted to use one of the two methods. Among those who participated in the study, 67% chose the ring, 31% chose oral PrEP and only 2% chose neither of the two methods being offered (62) . Both the ring and oral PrEP were highly acceptable (89% and 64%, respectively) and no safety concerns were raised, especially important for DVR. Surprisingly, adherence to both methods was higher than was reported in prior studies. The findings of REACH are particularly important as it supports the safe use of, adherence to and acceptance of DVR among adolescent girls < 18yrs of age. All information provided here point to overwhelming evidence to support the approval of DVR in young girls < 18yrs by regulatory bodies. A discussion of non-ARV-based microbicides is beyond the scope of this review. A Cochrane systematic review on topical microbicides for preventing sexually transmitted infections reported DVR as the only microbicide to probably prevent the acquisition of HIV infection (Relative Risk- 0.71) (63) . All other non-ARV-based gels (cellulose sulphate [Relative Risk- 1.20], Buffer-Gel [Relative Risk-1.05], Carraguard [Relative Risk-0.89], PRO-2000 [Relative Risk-0.93], SAVVY [Relative Risk-1.38]) and TFV-based gels (Relative Risk-0.83) had little or no effect on the prevention of HIV acquisition. Microbicide use, relative to placebo in the 12 trials that were evaluated, did not result in any difference in the acquisition of other sexually transmitted infections either. No adverse events were reported (63) . MICROBICIDESDURINGPREGNANCYAND BREASTFEEDING There are limited data on the efficacy and safety of microbicides in PBFW. In the FACTS 001 trial evaluating the TFV vaginal gel, incidental pregnancy rates were similar in both study and control groups, 8·5 women-years and 8·4 women-years, respectively (52) . Adverse pregnancy outcomes, including congenital anomalies, were infrequent and similar in both groups. The pivotal DELIVER (MTN-042) and B-PROTECTED (MTN-043) trials conducted in South Africa, Malawi and Uganda evaluated DVR and showed no safety concerns with exposure to dapivirine in the third trimester and during breastfeeding (64,65) . Dapivirine levels in breast milk of lactating women who were no longer breastfeeding have been found to be extremely low (66) . The ring doesn’t disrupt the balance of normal vaginal flora in non-pregnant women, suggesting no effect on the natural history of pregnancy (67) . More robust data is required on the effectiveness of PrEP options in PBFW. LONG-ACTINGFORMULATIONS: The challenges of daily adherence to oral PrEP, particularly among AGYW, has prompted the development of extended- release ARV drugs. A myriad of factors, such as gender-based violence, social stigma and judgement all contribute to poor adherence to therapy (68) . Injectable Formulations: Novel long-acting antiretroviral drugs (LARV) have been evaluated in clinical trials for the prevention of HIV infection, with ground breaking results. Cabotegravir ( an intergrase strand transfer inhibitor; InSTI) and lenacapavir (a capsid inhibitor) are long-acting formulations currently available for PrEP. In 2021, long-acting cabotegravir (CAB-LA) was the first extended-release ARV drug to be approved by the FDA for PrEP and subsequently recommended by WHO in 2022. This was on the basis of results from the HPTN 083 and HPTN 084 trials (27,69,70) . Until then, only 2 products had been recommended for PrEP, TFV-based formulations in 2015 and DVR in 2021. Long-acting cabotegravir, administered through a 2 monthly intramuscular (IM) injection by a health care worker, was effective in mitigating the risk of new HIV infections in adults and adolescents weighing ≥ 35kg (27,70) . The HPTN 084, a Phase III randomised controlled trial conducted in seven ESA countries, enlisted 3224 cisgender women 18 - 45yrs who were engaging in receptive vaginal sex. A 2-monthly IM injection of CAB-LA was compared to daily oral TDF/FTC. Incidental new HIV infections were drastically reduced in the CAB-LA group relative to the TDF/FTC group (0·2 cases vs 1·85 cases per 100 person-years) (27) . Subsequent to these results, Zimbabwe was the first African country to approve the use of CAB-LA for PrEP (71) . The South African Health Products Regulatory Authority registered the drug for PrEP late in 2022 and is expected to be rolled out to the public before the end of 2024 (72,73) . Newer ARV drugs continue to be developed at an alarming pace. Lenacapavir (LEN) is a novel, first-in-class, multi-stage HIV-1 capsid inhibitor, with high potency and a long half-life, allowing administration by subcutaneous injection twice yearly. A phase III, double-blind, randomized, controlled trial involving AGYW was conducted in South Africa and Uganda (PURPOSE 1) (74) . The study compared the efficacy and safety of LEN to TDF/ FTC and F/TAF for prevention of HIV acquisition. Approximately 5338 HIV-uninfected women (16 - 25yrs) who were sexually active with a male partner enrolled in the study. No new HIV infections were reported in the lenacapavir group. The rate of new HIV infections was 2.02; (95% CI, 1.44 to 2.76) and 1.69 per 100 person-years; (95% CI, 0.96 to 2.74) in the F/TAF and TDF/FTC groups, respectively. No statistically significant difference in HIV incidence was observed between F/TAF and TDF/FTC (incidence rate ratio, 1.20; 95% CI, 0.67 to 2.14). The background HIV incidence was 2.41 per 100 person-years (95% CI, 1.82 to 3.19). Nomajor safety concernswere raised, however, adherence to the oral PrEP regimens was low, consistent with previous reports (21) . A parallel trial of the same design (PURPOSE 2) was conducted in South Africa, the United States, Thailand, and a selection of a few South American countries (75) . This study evaluated the safety and efficacy of LEN for PrEP among cisgender men, gender diverse individuals, transgender women, and transgender men. Only two new HIV cases were recorded among 2180 participants receiving LEN twice-yearly, compared to nine new cases among the 1087 participants receiving daily oral TDF/FTC. LEN demonstrated a 96% reduction in HIV African Journal of Obstetrics and Gynaecology | Volume 2 | Issue 3 | 2024 | 11