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 incidence compared to the background HIV incidence of 2.37 per 100 person-years and was 89% more effective than daily oral TDF/FTC. Both LEN and daily oral TDF/FTC were well tolerated, with no significant or new safety concerns identified (75) . The results of these trials are groundbreaking, as a twice- yearly subcutaneous injection has the potential of eliminating adherence concerns and eradicating new HIV infections across the globe. The PURPOSE 3 and 4 trials are currently evaluating the safety and efficacy of LEN among cisgender adult women and people who inject drugs (76) . WHO is working alongside international partners, pharmaceutical companies, and generic manufacturers to create an enabling environment for LEN scale-up. This is crucial in ensuring affordable, sufficient, and equitable access to these novel agents, especially in ESA countries. Guidelines, based on a rigorous assessment of the potential of LEN, evaluating key aspects such as efficacy, safety, cost-effectiveness, values and preferences from stakeholders and communities are in development (75) Subdermal Formulations: Long-acting antiretroviral implants are a promising new technology but are in the early stages of pre-clinical and clinical development. These products offer more consistent and predictable drug release and can be discontinued as the need arises, unlike injectable products. Several partner drugs can be combined in one implant, thus presenting tantalizing options for prevention and treatment of HIV infection. Novel subdermal delivery systems that are refillable, removable, and biodegradable are currently being developed and assessed (77) . Any highly potent ARV drug, with a long half-life is a suitable candidate for subdermal delivery formulations. Ultra-long- acting dolutegravir delivered via a removable implant system has been tested in animals for treatment and prevention of HIV infection (77) . Subdermal implants have also been evaluated for PrEP with relatively positive results (78) . Islatravir demonstrated high potency in pre-clinical studies and in trials in adults with HIV infection (79) . Because of its high potency, islatravir is a candidate drug for PrEP administered using a subdermal implant, with a potential for long-lasting delivery (MK8591 Implant). A placebo- controlled, double-blind, phase 1 clinical trial of islatravir delivered using a radiopaque implant over 12 weeks, in adults at low risk of acquiring HIV offered encouraging results (80) . The device was demonstrated to be safe and well tolerated and has the potential to be an effectivemethod for administering PrEP to individuals at risk of acquiring HIV-1 infection. The widespread use of contraceptive implants in low- income countries proves that these devices can be implemented cheaply and safely in remote areas, for treatment and prevention of HIV infection (81) . LONG-ACTINGFORMULATIONSDURINGPREGNANCY ANDBREASTFEEDING Unsurprisingly, there are limited data on the safety and pharmacokinetics of these novel long-acting formulations in PBFW. In 2018, there were concerns that oral dolutegravir (an InSTI) was associated with an increased risk of neural tube defects, when used in the first trimester. This has largely been resolved, with dolutegravir-based regimens now being recommended as the treatment of choice for HIV infection, due to its superior efficacy and high resistance barrier (82,83,84) . The HPTN 084 trial estimated the rate of incidental pregnancies at 1·3 per 100 person-years with no reported congenital abnormalities (27) . On-going pregnancies continue to be assessed and outcomes monitored in the PURPOPSE-1 trial (75) . Lenacapavir pharmacokinetics in pregnancy and infant exposure are also being evaluated (74) . VACCINES: Antiretroviral-based PrEP has been shown to be highly effective in at risk individuals, however, barriers to its use, such as adherence challenges, fear of stigma and concerns about side- effects, may limit its uptake and retention in care. More robust population based, long-acting agents are a necessity, to eradicate the HIV scourge. Vaccines have the potential of conferring life- long immunity and have been in use for centuries. These agents have saved more lives than any other medical intervention globally (85) . It is, therefore, no surprise that attempts have been undertaken for decades, to develop an effective HIV vaccine that is applicable in real-world situations. HIV 1 vaccines: Creating an effective HIV vaccine has proven to bemost challenging as the virus has a highmutating capability, with millions of variants. As a result, the virus is able to evade the immune system (86) . Live and attenuated HIV vaccines are not safe enough for human clinical trials. The manufacturing of recombinant HIV vaccines containing viral proteins is time consuming and can be costly (86) . Different recombinant HIV vaccines have been evaluated over the past 40yrs, with poor results (87) . The Thai RV144, was a phase III trial that evaluated a prime- boost regimen consisting of a recombinant canarypox vector- based vaccine expressing Gag, Pro, and Env-antigens (ALVAC- HIV) and a recombinant bivalent gp-120 subunit vaccine (AIDSVAX B/E). Out of several trials, the Thailand study was the only one to show a modest estimated efficacy (31·2%) in reducing HIV-1 transmission over 42 months. The results were statistically significant, but not effective enough for regulatory approval (88). The STEP (HVTN 502) and PHAMBILI (HVTN 503) trials evaluated the MRKad5 adenovirus type 5 vaccine expressing Gag, Pol, and Nef-antigens in phase 2b studies. An increased risk of HIV-1 acquisition was reported in all vaccinated participants in HVTN 503 and in a subgroup of male participants in HVTN 502. The efficacy in vaccinated female participants could not be evaluated in HVTN 502 due to low HIV-1 acquisition rates (89,90) . IMBOKODO (HVTN 705/HPX2008) was a double-blind, phase IIb trial assessing the efficacy and safety of a heterologous tetravalent mosaic Ad26 (Ad26.Mos4.HIV) and aluminium phosphate adjuvanted clade C gp-140 vaccine regimen in young women (aged 18–35 years) at risk of HIV-1 in Southern Africa. Between 2017 to 2019, 2636 participants were randomised to either the vaccine or placebo. The vaccine regimen was safe and well tolerated but did not show efficacy in preventing HIV-1 acquisition. IMBOKODO also noted high rates of HIV-1 acquisition among participants (91) . The reported high rates of incidental HIV infection in these studies, underscores the need for continued funding of biomedical interventions, to prevent HIV-1 acquisition. With the currently available evidence, no vaccine candidate has elicited any potent and durable protective efficacy, to support regulatory approval. Immunoglobulins: Immunoglobulins are the body’s natural response to infections. Broadly neutralizing antibodies (bNAbs) can neutralize different genetic variants of HIV. A few individuals do naturally develop these antibodies in small amounts. These antibodies (administered intravenously or intramuscularly) have been evaluated as non-traditional vaccines for the prevention of HIV infection. The Antibody Mediated Prevention (AMP) trials African Journal of Obstetrics and Gynaecology | Volume 2 | Issue 3 | 2024 | 12