Lessons on PrEP from the SEARCH study in east Africa
Authors: Connie Celum, Jared M Baeten
Journal: The Lancet HIV (2020)

In 2010–11, evidence from clinical trials showed that pre-exposure prophylaxis (PrEP) was effective and safe for HIV prevention.1Baeten JM Donnell D Ndase P et al.Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.N Engl J Med. 2012; 367: 399-410Crossref PubMed Scopus (2252) Google Scholar, 2Grant RM Lama JR Anderson PL et al.Preexposure chemoprophylaxis for HIV prevention in men who have sex with men.N Engl J Med. 2010; 363: 2587-2599Crossref PubMed Scopus (3647) Google Scholar In high-income countries, where the epidemic is mainly concentrated among men who have sex with men, PrEP uptake initially grew slowly, then expanded in the second half of the decade as PrEP became more normalised through prevention guidelines, public health promotion, community conversations, and mass advertising. In countries and cities where PrEP has been delivered at scale in tandem with HIV testing, antiretroviral treatment, and other prevention strategies, new HIV infections in the past several years have declined substantially for the first time in at least a decade.3Grulich AE Guy R Amin J et al.Population-level effectiveness of rapid, targeted, high-coverage roll-out of HIV pre-exposure prophylaxis in men who have sex with men: the EPIC-NSW prospective cohort study.Lancet HIV. 2018; 5: e629-e637Summary Full Text Full Text PDF PubMed Scopus (208) Google Scholar, 4Buchbinder SP Havlir DV Getting to Zero San Francisco: a collective impact approach.J Acquir Immune Defic Syndr. 2019; 82: S176-S182Crossref PubMed Scopus (24) Google Scholar In The Lancet HIV, Catherine Koss and colleagues5Koss CA Charlebois ED Ayieko J et al.Uptake, engagement, and adherence to pre-exposure prophylaxis offered after population HIV testing in rural Kenya and Uganda: 72-week interim analysis of observational data from the SEARCH trial.Lancet HIV. 2020; (published online Feb 19.)https://doi.org/10.1016/S2352-3018(19)30433-3Summary Full Text Full Text PDF PubMed Scopus (51) Google Scholar describe the delivery of PrEP at scale in the Sustainable East Africa Research in Community Health (SEARCH) study, a community-randomised trial of universal HIV testing and treatment as prevention in rural Kenya and Uganda. PrEP was introduced in the final year of SEARCH (which took place in 2013–17), ahead of national PrEP policies or public health promotion work in the host countries. Using a community-based HIV testing and treatment strategy based on multi-disease testing campaigns, PrEP counselling was provided to individuals who were identified as being at high risk. These individuals were either in HIV serodifferent relationships, identified using a risk score derived from machine learning of HIV acquisition risk in the first 2 years of SEARCH, or self-identified as being at risk. 27% of individuals who were identified as being at risk initiated PrEP within 90 days of HIV testing. Perhaps not surprisingly, PrEP uptake was higher among individuals in serodifferent relationships and who felt themselves to be at risk (both 45%) than among individuals identified through the risk score (17%). A flexible PrEP delivery model provided options for same-day PrEP start and community-based follow-up, and the majority (82%) started PrEP on the same day (including men, for whom out-of-clinic PrEP services might have improved access). 78% of individuals who initiated PrEP had at least one follow-up visit, and more than half remained engaged in the PrEP programme at 72 weeks. Tenofovir concentrations in hair samples showed that among those reporting current risk and any PrEP adherence, 57% had concentrations consistent with taking four or more doses per week, which has been associated with 100% HIV protection.6Anderson PL Glidden DV Liu A et al.Emtricitabine-tenofovir concentrations and pre-exposure prophylaxis efficacy in men who have sex with men.Sci Transl Med. 2012; 4151ra25Crossref Scopus (680) Google Scholar Men aged 25 years and younger and individuals in serodifferent partnerships had the highest adherence, whereas young women had lower adherence, which has also been observed in other African settings.7Bekker LG Roux S Sebastien E et al.Daily and non-daily pre-exposure prophylaxis in African women (HPTN 067/ADAPT Cape Town Trial): a randomised, open-label, phase 2 trial.Lancet HIV. 2018; 5: e68-e78Summary Full Text Full Text PDF PubMed Scopus (79) Google Scholar The SEARCH study highlights the dynamic nature of risk, with one-fifth of participants changing their self-assessment of risk between week 4 and week 24. PrEP stopping and restarting was common: half of those who stopped PrEP had restarted by week 72. For HIV serodifferent couples, stopping PrEP is to be expected when used as a time-limited bridge to viral suppression in the HIV-positive partner.8Baeten J Heffron R Kidoguchi L et al.Integrated delivery of antiretroviral treatment and pre-exposure prophylaxis to HIV-1-serodiscordant couples: a prospective implementation study in Kenya and Uganda.PLoS Med. 2016; 13e1002099Crossref PubMed Scopus (135) Google Scholar PrEP use in general is expected to be dynamic and to follow fluctuations in HIV risk. Of the large population-based studies of HIV treatment as prevention,9Ortblad KF Baeten JM Cherutich P Wamicwe JN Wasserheit JN The arc of HIV epidemics in sub-Saharan Africa: new challenges with concentrating epidemics in the era of 90-90-90.Curr Opin HIV AIDS. 2019; 14: 354-365Crossref PubMed Scopus (22) Google Scholar the SEARCH study was unique in offering PrEP, and the study team should be applauded for that foresight. The results of these population-based studies were mixed, with only two of four trials showing a statistically significant effect on community-level HIV incidence, and with HIV incidence in all studies remaining above that required for epidemic control despite high levels of HIV treatment coverage and viral suppression. These findings emphasise that epidemics can only begin to be contained through combining HIV testing with both strategies to sustain HIV treatment and primary prevention interventions such as PrEP.4Buchbinder SP Havlir DV Getting to Zero San Francisco: a collective impact approach.J Acquir Immune Defic Syndr. 2019; 82: S176-S182Crossref PubMed Scopus (24) Google Scholar The interim results from the SEARCH study show the feasibility of population-level delivery of PrEP in Africa. Sadly, nearly a decade after PrEP was definitively shown to be effective for HIV prevention, largely on the basis of data from clinical trial volunteers in Africa,1Baeten JM Donnell D Ndase P et al.Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.N Engl J Med. 2012; 367: 399-410Crossref PubMed Scopus (2252) Google Scholar PrEP delivery at scale in Africa lags behind its delivery in high-income countries. Uptake of and adherence to PrEP in SEARCH do not differ substantially from that seen in the first years of PrEP roll-out in the USA—showing that African populations can access and use PrEP just as well as populations in high-income countries.10Pyra MN Haberer JE Hasen N Reed J Mugo NR Baeten JM Global implementation of PrEP for HIV prevention: setting expectations for impact.J Int AIDS Soc. 2019; 22e25370Crossref PubMed Scopus (34) Google Scholar Key challenges in PrEP delivery are getting PrEP to the individuals who most need it and developing marketing and messaging about PrEP in a positive wellness and empowerment frame. Risk algorithms, such as that used in the SEARCH study, might be insensitive given the dynamic nature of risk, might be stigmatising, and might exclude individuals who could benefit from PrEP. Thus, making PrEP broadly available and normalised might result in the best uptake and respond to the dynamic needs of users. To have a population-level effect, PrEP needs to be delivered at scale and in combination with universal access to HIV testing and treatment. The SEARCH study shows that such universal access is possible. These results should motivate additional innovations in ways to increase PrEP uptake and adherence overall, and particularly among young adults and mobile populations. CC has received fees from Merck and Gilead outside of this work. JMB has received fees from Merck, Gilead, and Janssen outside of this work. Uptake, engagement, and adherence to pre-exposure prophylaxis offered after population HIV testing in rural Kenya and Uganda: 72-week interim analysis of observational data from the SEARCH studyDuring population-level HIV testing, inclusive risk assessment (combining serodifferent partnership, an empirical risk score, and self-identification of HIV risk) was feasible and identified individuals who could benefit from PrEP. The biggest gap in the PrEP cascade was PrEP uptake, particularly for young and mobile individuals. Participants who initiated PrEP and had perceived HIV risk during follow-up reported taking PrEP, but one-third had drug concentrations consistent with poor adherence, highlighting the need for novel approaches and long-acting formulations as PrEP roll-out expands. Full-Text PDF Open Access