HIV pre-exposure prophylaxis implementation in Africa: some early lessons

Since antiretrovirals were first shown to prevent sexual transmission of HIV,1Abdool Karim Q Abdool Karim SS Frohlich JA et al.Effectiveness and safety of tenofovir gel, an antiretroviral microbicide, for the prevention of HIV infection in women.Science. 2010; 329: 1168-1174Crossref PubMed Scopus (1991) Google Scholar numerous randomised trials have reported that oral pre-exposure prophylaxis (PrEP) is efficacious in preventing HIV infection in a range of settings and populations.2Fonner VA Dalglish SL Kennedy CE et al.Effectiveness and safety of oral HIV preexposure prophylaxis for all populations.AIDS. 2016; 30: 1973-1983Crossref PubMed Scopus (462) Google Scholar However, there can be a substantial gap between efficacy in controlled clinical trial settings and effectiveness in real-world implementation, generally referred to as the efficacy-effectiveness gap. For example, three large HIV test-and-treatment implementation trials failed to demonstrate effectiveness in community settings, even though the initial individual treatment trial reported very high efficacy.3Abdool Karim SS HIV-1 epidemic control—insights from test-and-treat trials.N Engl J Med. 2019; 381: 286-288Crossref PubMed Scopus (40) Google Scholar But this gap can sometimes be minimal; effectiveness of voluntary medical male circumcision (MMC) in community settings4Davis S Toledo C Lewis L Maughan-Brown B Ayalew K Kharsany ABM Does voluntary medical male circumcision protect against sexually transmitted infections among men and women in real-world scale-up settings? Findings of a household survey in KwaZulu-Natal, South Africa.BMJ Glob Health. 2019; 4e001389Crossref PubMed Scopus (10) Google Scholar has been similar to clinical trial efficacy. Hence, there is a need to measure real-world effectiveness and not simply expect that clinical trial efficacy will translate directly to impact after implementation. In The Lancet Global Health, Elizabeth Irungu and colleagues5Irungu EM Mugwanya KK Mugo NR et al.Integration of pre-exposure prophylaxis services into public HIV care clinics in Kenya: a pragmatic stepped-wedge randomised trial.Lancet Glob Health. 2021; 9: e1730-e1739Summary Full Text Full Text PDF PubMed Scopus (1) Google Scholar conducted a pragmatic stepped-wedge randomised trial in 25 public clinics to evaluate Kenya's PrEP scale-up programme. Their study of 4898 PrEP initiations showed that integration of PrEP in public health-care settings was feasible, with substantial increases in PrEP initiations. This study provides several lessons for the scale-up of PrEP across Africa. First, the early adopters of PrEP in Kenya were mostly individuals in HIV discordant relationships. Although this is an important group of at-risk individuals, they are not the primary target group to obtain the maximal impact of PrEP on the HIV epidemic in Africa. The highest risk groups in Africa are young women,6Abdool Karim Q Baxter C Birx D Prevention of HIV in adolescent girls and young women: key to an AIDS-free generation.J Acquir Immune Defic Syndr. 2017; 75: S17-S26Crossref PubMed Scopus (54) Google Scholar most of whom are rarely aware of their male partner's HIV status. The study indicates that PrEP scale-up in Kenya has yet to reach high-risk individuals, who often do not perceive themselves to be at risk and do not take proactive steps to know their HIV status or initiate PrEP for HIV prevention. Second, the average age of early PrEP adopters in Kenya was 31 years. HIV incidence trends from five African countries show that young women aged 15–24 years and men aged 20–29 years have the highest HIV incidence rates.7Risher KA Cori A Reniers G et al.Age patterns of HIV incidence in eastern and southern Africa: a collaborative analysis of observational general population cohort studies.Lancet HIV. 2021; 8: e429-e439Summary Full Text Full Text PDF PubMed Scopus (4) Google Scholar Since those aged 30 years and older are at much lower HIV risk, PrEP in this age group will have a substantially lower impact on HIV transmission. Third, it is concerning that retention in care dropped off markedly, with only 34% of PrEP initiators still continuing PrEP at 6 months and 23% at 12 months. Although this drop-off might be due to PrEP initiators changing to new HIV-negative partners or to HIV-positive partners taking up antiretroviral therapy (ART), it is likely that they found maintaining daily oral PrEP too onerous. Other studies have also demonstrated high rates of PrEP discontinuation, suggesting that PrEP initiations might not be a reliable measure of PrEP programme effectiveness.8Stankevitz K Grant H Lloyd J et al.Oral preexposure prophylaxis continuation, measurement and reporting.AIDS. 2020; 34: 1801-1811Crossref PubMed Scopus (9) Google Scholar Encouragingly, those who were retained in care in this study were adherent to PrEP as the drug was detectable in 96% of the randomly collected blood samples. High levels of adherence are needed for PrEP to be effective, especially in women.9Donnell D Baeten JM Bumpus NN et al.HIV protective efficacy and correlates of tenofovir blood concentrations in a clinical trial of PrEP for HIV prevention.J Acquir Immune Defic Syndr. 2014; 66: 340-348Crossref PubMed Scopus (208) Google Scholar Finally, conducting pragmatic trials can be methodologically challenging. In this study, the control group included only 8·83 years of observation compared to 53·67 years in the intervention group. For more than two-thirds of the study duration, all clinics were in the intervention group. As a result, HIV incidence rates in both groups and intergroup comparability were compromised, making the study an assessment of PrEP feasibility rather than effectiveness. A major challenge in scaling up PrEP in Africa is that those at high risk seldom recognise, acknowledge, or perceive their risk. The approach of “if you build it, they will come” to PrEP rollout might not achieve sufficiently high PrEP coverage to make a difference to the HIV pandemic. PrEP scale-up needs a paradigm shift. A new approach of provider-facilitated PrEP is needed, whereby PrEP service providers proactively facilitate PrEP initiation and maintenance for all health-service attendees at high risk of HIV, such as those attending for sexually transmitted diseases and contraception. Scale-up could also involve community outreach for those at highest risk, such as via youth clubs, to increase and maintain PrEP coverage in this group. The goal is to make PrEP the norm rather than the exception for people at high risk. A similar approach was adopted for provider-initiated HIV testing10Hensen B Baggaley R Wong VJ et al.Universal voluntary HIV testing in antenatal care settings: a review of the contribution of provider-initiated testing 17: 59-70Crossref PubMed Scopus (75) Google Scholar when many pregnant women were not benefitting from a scale-up of prevention of mother-to-child transmission programmes because they were not proactively seeking HIV testing. Although ART has increased markedly over the past decade, with about 27 million people accessing treatment by 2020, declines in HIV incidence have been slower than expected, highlighting the need to scale up PrEP faster alongside ART. Sustained high levels of PrEP coverage will be needed in addition to high treatment coverage in order to achieve the UN goal of ending AIDS as a public health threat by 2030. The authors are supported by the DSI-NRF Centre of Excellence in HIV Prevention (UID 96354). Integration of pre-exposure prophylaxis services into public HIV care clinics in Kenya: a pragmatic stepped-wedge randomised trialWe observed high uptake, reasonable continuation with high adherence, frequent PrEP restarts, and low HIV incidence. Integration of PrEP services within public HIV care clinics in Africa is feasible. Full-Text PDF Open Access