{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:53:13Z","timestamp":1791669193504,"version":"4.3.4"},"update-to":[{"DOI":"10.1371\/journal.pmed.1004882","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000}}],"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T00:00:00Z","timestamp":1784592000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000865","name":"Bill and Melinda Gates Foundation","doi-asserted-by":"publisher","award":["INV-063625"],"award-info":[{"award-number":["INV-063625"]}],"id":[{"id":"10.13039\/100000865","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosmedicine.org"],"crossmark-restriction":false},"short-container-title":["PLoS Med"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>South Africa accounts for 20% of global HIV infections. Six-monthly injectable lenacapavir (LEN) for HIV pre-exposure prophylaxis (PrEP) has superior efficacy to oral tenofovir disoproxil fumarate\/emtricitabine (TDF\/FTC), and similar efficacy to 2-monthly injectable cabotegravir (CAB). With LEN\u2019s regulatory approval, South Africa faces critical implementation decisions amid constrained domestic resources and reduced international funding. We evaluated the epidemiological impact, cost-effectiveness, and optimal populations for LEN roll-out in South Africa.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods and findings<\/jats:title>\n                    <jats:p>Using Thembisa v4.8, a deterministic compartmental HIV transmission model, we simulated the impact of LEN scale-up, expanded oral TDF\/FTC, and CAB scale-up, compared to a baseline of current TDF\/FTC provision over 20 years (2026\u20132045) in South Africa. We modelled PrEP among women, including adolescent girls and young women (AGYW), female sex workers (FSW), pregnant and breastfeeding women (PBFW), men who have sex with men (MSM), and heterosexual men. For TDF\/FTC scale-up, we doubled baseline initiation rates. For LEN and CAB, conservative and optimistic scenarios assumed initiation rates similar to or double those under TDF\/FTC scale-up, respectively. Duration of use varied by subpopulation under TDF\/FTC (3\u20136 months), conservative (LEN: 6\u201312 months, CAB: 4\u20138 months), and optimistic (LEN: 12\u201324 months, CAB: 8\u201316 months) scenarios. We modelled strategies to maximise impact of ~500,000 LEN doses allocated for 2026\u20132027, and national roll-out by subpopulations. We compared LEN cost-effectiveness to other HIV interventions, including antiretroviral treatment (ART). Costs are presented from the South African government\u2019s perspective in undiscounted 2025 United States Dollars (USD).<\/jats:p>\n                    <jats:p>Providing LEN to 1.7\u20132.9 million South Africans annually averted 19%\u201331% of infections and saved 3%\u20135% of life years lost to HIV, reaching incidence &lt;0.1% in 2039\u20132043, 10\u201314 years earlier than baseline. TDF\/FTC and conservative LEN scale-up increased HIV programme costs by 3%; however, LEN was more cost-effective, costing $2,301\u2013$3,567\/life year saved (LYS) versus $8,143\/LYS (TDF\/FTC scale-up) and $11,114\u2013$16,118\/LYS (CAB). While promising for HIV prevention, scaling up condoms, ART, HIV testing, and medical male circumcision may be more cost-effective than LEN; notably ART at 95% coverage, saved 4.8-8-fold more life years compared to LEN, costing $577\/LYS. Prioritising AGYW, MSM, and FSW for the initial allocation maximised infections averted, while national roll-out prioritising FSW and MSM were most cost-effective, and even cost-saving under scale-up to FSW. Study limitations include uncertainty in achieving modelled uptake, risk-differentiated uptake of long-acting products, and real-world implementation costs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Delivering LEN to persons with elevated HIV risk in South Africa is more cost-effective than existing oral PrEP and can speed up HIV incidence reduction. Prioritising uptake among groups at highest risk is essential to maximise impact and cost-effectiveness.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pmed.1004882","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T17:43:38Z","timestamp":1784655818000},"page":"e1004882","update-policy":"https:\/\/doi.org\/10.1371\/journal.pmed.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Optimising scale-up of injectable lenacapavir for HIV pre-exposure prophylaxis in South Africa: A modelling study and economic evaluation"],"prefix":"10.1371","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2354-4580","authenticated-orcid":true,"given":"Lise","family":"Jamieson","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2717-011X","authenticated-orcid":true,"given":"Leigh F.","family":"Johnson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7728-728X","authenticated-orcid":true,"given":"Jeffrey W.","family":"Imai-Eaton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4277-7587","authenticated-orcid":true,"given":"Hasina","family":"Subedar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0755-4386","authenticated-orcid":true,"given":"Linda-Gail","family":"Bekker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0439-381X","authenticated-orcid":true,"given":"Gesine","family":"Meyer-Rath","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2026,7,21]]},"reference":[{"key":"pmed.1004882.ref001","doi-asserted-by":"crossref","DOI":"10.1016\/S2352-3018(24)00212-1","article-title":"Global, regional, and national burden of HIV\/AIDS, 1990\u20132021, and forecasts to 2050, for 204 countries and territories: the Global Burden of Disease Study 2021","volume":"11","author":"A Carter","year":"2024","journal-title":"The Lancet HIV"},{"key":"pmed.1004882.ref002","author":"UNAIDS"},{"issue":"13","key":"pmed.1004882.ref003","doi-asserted-by":"crossref","first-page":"1261","DOI":"10.1056\/NEJMoa2411858","article-title":"Twice-yearly lenacapavir for HIV prevention in men and gender-diverse persons","volume":"392","author":"CF Kelley","year":"2025","journal-title":"N Engl J Med"},{"issue":"13","key":"pmed.1004882.ref004","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1056\/NEJMoa2407001","article-title":"Twice-yearly lenacapavir or daily F\/TAF for HIV prevention in cisgender women","volume":"391","author":"L-G Bekker","year":"2024","journal-title":"N Engl J Med"},{"key":"pmed.1004882.ref005","author":"SAHPRA Registers Lenacapavir"},{"key":"pmed.1004882.ref006","article-title":"SA gets R520-million to buy the twice-a-year anti-HIV jab \u2014 but there\u2019s a snag.","volume-title":"Bhekisisa","author":"M Malan","year":"2025"},{"key":"pmed.1004882.ref007","author":"Unitaid, CHAI, Wits RHI"},{"issue":"11","key":"pmed.1004882.ref008","doi-asserted-by":"crossref","first-page":"2906","DOI":"10.1093\/jac\/dkae305","article-title":"Lenacapavir to prevent HIV infection: current prices versus estimated costs of production","volume":"79","author":"A Hill","year":"2024","journal-title":"J Antimicrob Chemother"},{"key":"pmed.1004882.ref009","doi-asserted-by":"crossref","DOI":"10.1093\/ofid\/ofaf695.004","article-title":"174. Generic lenacapavir HIV Pre-exposure prophylaxis could be produced for $25 per person per Year.","volume":"13","author":"C Fairhead","year":"2026","journal-title":"Open Forum Infect Dis"},{"issue":"10515","key":"pmed.1004882.ref010","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1016\/S0140-6736(25)01724-6","article-title":"Who pays and what pays off in sexual and reproductive health? A review of the cost and cost-effectiveness of interventions and implications for future funding and markets","volume":"406","author":"G Meyer-Rath","year":"2025","journal-title":"Lancet"},{"issue":"11","key":"pmed.1004882.ref011","article-title":"Health impact, budget impact, and price threshold for cost-effectiveness of lenacapavir for HIV pre-exposure prophylaxis in eastern and southern Africa: a modelling analysis","volume":"11","author":"L Wu","year":"2024","journal-title":"Lancet HIV"},{"issue":"2","key":"pmed.1004882.ref012","doi-asserted-by":"crossref","DOI":"10.1002\/jia2.26427","article-title":"Cost thresholds for anticipated long-acting HIV pre-exposure prophylaxis products in Eastern and Southern Africa: a mathematical modelling study","volume":"28","author":"D Kaftan","year":"2025","journal-title":"J Int AIDS Soc"},{"key":"pmed.1004882.ref013","author":"L Johnson","year":"2025"},{"issue":"23","key":"pmed.1004882.ref014","doi-asserted-by":"crossref","first-page":"2237","DOI":"10.1056\/NEJMoa1506273","article-title":"On-demand preexposure prophylaxis in men at high risk for HIV-1 infection","volume":"373","author":"J-M Molina","year":"2015","journal-title":"N Engl J Med"},{"issue":"10013","key":"pmed.1004882.ref015","doi-asserted-by":"crossref","first-page":"53","DOI":"10.1016\/S0140-6736(15)00056-2","article-title":"Pre-exposure prophylaxis to prevent the acquisition of HIV-1 infection (PROUD): effectiveness results from the pilot phase of a pragmatic open-label randomised trial","volume":"387","author":"S McCormack","year":"2016","journal-title":"Lancet"},{"issue":"2","key":"pmed.1004882.ref016","article-title":"Daily and non-daily pre-exposure prophylaxis in African women (HPTN 067\/ADAPT Cape Town Trial): a randomised, open-label, phase 2 trial","volume":"5","author":"L-G Bekker","year":"2018","journal-title":"Lancet HIV"},{"issue":"10337","key":"pmed.1004882.ref017","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1016\/S0140-6736(22)00538-4","article-title":"Cabotegravir for the prevention of HIV-1 in women: results from HPTN 084, a phase 3, randomised clinical trial","volume":"399","author":"S Delany-Moretlwe","year":"2022","journal-title":"Lancet"},{"key":"pmed.1004882.ref018","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1056\/NEJMoa2101016","article-title":"Cabotegravir for HIV prevention in cisgender men and transgender women","volume":"385","author":"RJ Landovitz","year":"2021","journal-title":"N Engl J Med"},{"issue":"7","key":"pmed.1004882.ref019","doi-asserted-by":"crossref","DOI":"10.1016\/S2352-3018(20)30106-5","article-title":"Tail-phase safety, tolerability, and pharmacokinetics of long-acting injectable cabotegravir in HIV-uninfected adults: a secondary analysis of the HPTN 077 trial","volume":"7","author":"RJ Landovitz","year":"2020","journal-title":"Lancet HIV"},{"issue":"1","key":"pmed.1004882.ref020","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1186\/s12889-025-23529-y","article-title":"User preferences on long-acting pre-exposure prophylaxis for HIV prevention in Eastern and Southern Africa: a scoping review","volume":"25","author":"B Pfau","year":"2025","journal-title":"BMC Public Health"},{"key":"pmed.1004882.ref021","unstructured":"Delany-Moretlwe S. Initial PrEP product choice: results from the HPTN 084 open-label extension. In: Brisbane. 2023. Available from: ps:\/\/www.hptn.org\/sites\/default\/files\/inline-files\/220725%20IAS%202023%20product%20choice%20revised.pdf"},{"key":"pmed.1004882.ref022","author":"(HE2RO)","year":"2023"},{"issue":"1","key":"pmed.1004882.ref023","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1186\/s12889-017-4023-3","article-title":"Designing an optimal HIV programme for South Africa: does the optimal package change when diminishing returns are considered?","volume":"17","author":"C Chiu","year":"2017","journal-title":"BMC Public Health"},{"key":"pmed.1004882.ref024","doi-asserted-by":"crossref","DOI":"10.1136\/bmjgh-2021-005598","article-title":"The cost effectiveness and optimal configuration of HIV self-test distribution in South Africa: a model analysis","volume":"6","author":"L Jamieson","year":"2021","journal-title":"BMJ Glob Health"},{"key":"pmed.1004882.ref025","author":"South African Reserve Bank","year":"2025"},{"issue":"12","key":"pmed.1004882.ref026","doi-asserted-by":"crossref","DOI":"10.1016\/S2352-3018(22)00251-X","article-title":"Relative cost-effectiveness of long-acting injectable cabotegravir versus oral pre-exposure prophylaxis in South Africa based on the HPTN 083 and HPTN 084 trials: a modelled economic evaluation and threshold analysis","volume":"9","author":"L Jamieson","year":"2022","journal-title":"Lancet HIV"},{"key":"pmed.1004882.ref027"},{"key":"pmed.1004882.ref028","author":"C Tomlinson","year":"2024"},{"issue":"2","key":"pmed.1004882.ref029","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0210497","article-title":"The per-patient costs of HIV services in South Africa: systematic review and application in the South African HIV Investment Case","volume":"14","author":"G Meyer-Rath","year":"2019","journal-title":"PLoS One"},{"issue":"10","key":"pmed.1004882.ref030","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1097\/QAD.0000000000004272","article-title":"The cost of the plunge: the impact and cost of a cessation of PEPFAR-supported services in South Africa","volume":"39","author":"G Meyer-Rath","year":"2025","journal-title":"AIDS"},{"issue":"9939","key":"pmed.1004882.ref031","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S0140-6736(14)61053-9","article-title":"Maximising the effect of combination HIV prevention through prioritisation of the people and places in greatest need: a modelling study","volume":"384","author":"S-J Anderson","year":"2014","journal-title":"Lancet"},{"issue":"1","key":"pmed.1004882.ref032","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1186\/s12913-025-12891-7","article-title":"Opportunity for cost savings with a novel differentiated model of PrEP delivery: a comparative costing analysis of six-month PrEP supported by interim HIV self-testing and standard of care PrEP dispensing in Kenya","volume":"25","author":"DI Mangale","year":"2025","journal-title":"BMC Health Serv Res"},{"key":"pmed.1004882.ref033","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1097\/OLQ.0000000000000412","article-title":"A comparison of two mathematical modeling frameworks for evaluating sexually transmitted infection epidemiology","volume":"43","author":"LF Johnson","year":"2016","journal-title":"Sex Transm Dis"},{"key":"pmed.1004882.ref034","article-title":"Estimated impact of long-acting injectable PrEP in South Africa: a model comparison analysis","author":"SE Stansfield","year":"2025","journal-title":"J Int AIDS Soc"},{"issue":"6","key":"pmed.1004882.ref035","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1097\/QAD.0000000000002486","article-title":"The impact of self-selection based on HIV risk on the cost-effectiveness of preexposure prophylaxis in South Africa","volume":"34","author":"L Jamieson","year":"2020","journal-title":"AIDS"}],"updated-by":[{"DOI":"10.1371\/journal.pmed.1004882","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T00:00:00Z","timestamp":1785283200000}}],"container-title":["PLOS Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004882","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,29]],"date-time":"2026-07-29T17:48:35Z","timestamp":1785347315000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pmed.1004882"}},"subtitle":[],"editor":[{"given":"Simon","family":"Cauchemez","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2026,7,21]]},"references-count":35,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pmed.1004882","relation":{},"ISSN":["1549-1676"],"issn-type":[{"value":"1549-1676","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,21]]}}}