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In a multicenter, open-label phase 3b trial, 512 African adults with HIV-1, stable on first-line oral therapy, with screening plasma viral load (VL) &lt;50 copies\u2009ml\n                    <jats:sup>\u22121<\/jats:sup>\n                    and without past virologic failure were randomized (1:1) to continue oral therapy or switch to cabotegravir (600\u2009mg) and rilpivirine (900\u2009mg) intramuscular injections every 8\u2009weeks (optional 4-week oral lead-in). VL was monitored every 24\u2009weeks. Here the primary outcome for our analysis up to 96 weeks was VL &lt;50 copies\u2009ml\n                    <jats:sup>\u22121<\/jats:sup>\n                    , using the Food and Drug Administration snapshot algorithm (noninferiority margin 10%) in the intention-to-treat exposed population. At 96\u2009weeks, 247\/255 (97%) in the long-acting group and 250\/257 (97%) in the oral therapy group had VL &lt;50 copies\u2009ml\n                    <jats:sup>\u22121<\/jats:sup>\n                    (difference \u22120.4%; 95% confidence interval \u22123.1% to 2.0%), demonstrating noninferiority. Adverse events of severity grade \u22653 occurred in 41\/255 (16%) in the long-acting group and in 22\/257 (9%) in the oral therapy group, mostly considered unrelated to the study drug; only one treatment-related adverse event in the long-acting group led to a decision to discontinue treatment (injection-site abscess). Cabotegravir and rilpivirine long-acting therapy produced durable virologic suppression, met the prespecified noninferiority endpoint compared with oral therapy and demonstrated an acceptable safety and tolerability profile. Long-acting therapy may be considered for use in African treatment programs. PACTR registration: 202104874490818.\n                  <\/jats:p>","DOI":"10.1038\/s41591-025-04041-7","type":"journal-article","created":{"date-parts":[[2025,11,4]],"date-time":"2025-11-04T10:04:06Z","timestamp":1762250646000},"page":"168-177","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Cabotegravir and rilpivirine for treatment of HIV infection in Africa: week 96 results from the phase 3b randomized, open-label, noninferiority CARES trial"],"prefix":"10.1038","volume":"32","author":[{"given":"Cissy","family":"Kityo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0888-8695","authenticated-orcid":false,"given":"Ivan K.","family":"Mambule","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Musaazi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2707-1533","authenticated-orcid":false,"given":"Simiso","family":"Sokhela","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry","family":"Mugerwa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ibrahim","family":"Yawe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5070-532X","authenticated-orcid":false,"given":"Fiona","family":"Cresswell","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham","family":"Siika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Josphat","family":"Kosgei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1729-5012","authenticated-orcid":false,"given":"Reena","family":"Shah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-7370","authenticated-orcid":false,"given":"Logashvari","family":"Naidoo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimton","family":"Opiyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Otike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karlien","family":"M\u00f6ller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Max","family":"Okwero","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charity","family":"Wambui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Van Eygen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Perry","family":"Mohammed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9650-1965","authenticated-orcid":false,"given":"Fafa","family":"Addo Boateng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7003-9838","authenticated-orcid":false,"given":"Nicholas I.","family":"Paton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"on behalf of the CARES trial team","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veerle","family":"Van Eygen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,4]]},"reference":[{"key":"4041_CR1","unstructured":"Consolidated Guidelines on HIV Prevention, Testing, Treatment, Service Delivery and Monitoring: Recommendations for a Public Health Approach (WHO, 2021)."},{"key":"4041_CR2","doi-asserted-by":"publisher","first-page":"e666","DOI":"10.1016\/S2352-3018(20)30241-1","volume":"7","author":"WDF Venter","year":"2020","unstructured":"Venter, W. 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S.S. reports funding paid to institution and personal fees for speaking at symposia from Janssen and donation of drugs to institution from ViiV, all outside the work reported in this manuscript. F.C. reports funding paid to institution and donation of drugs to institution from Janssen and funding paid to institution from ViiV, Gilead, Wellcome Trust and the National Institute of Health Research UK outside the work reported in this manuscript; and unpaid role as Chair of Steering Committee for an investigator-initiated long-acting implementation trial. K.M. reports personal fees for speaking at symposia from Janssen outside of the work reported in this manuscript. V.E. is an employee of Johnson and Johnson and holds stock options of Johnson and Johnson; and a patent related to rilpivirine. P.M. was an employee of Janssen at the time of trial design; and then an employee of ViiV during the time of trial conduct and manuscript submission; and holds stock from GSK as an employee of ViiV. F.A.B. was an employee of Johnson and Johnson at the time of trial design and conduct. N.I.P. reports grants paid to institution, donation of drugs to institution and personal fees for speaking at symposia from Janssen outside the work reported in this manuscript; and is the Chief Investigator on a trial with funding paid to institution by the European Union for testing anti-tuberculosis drug combinations based on the drug ganfeborole, owned by GSK. I.K.M., J.M., H.M., I.Y., A.S., J.K., R.S., L.N., K.O., C.O., M.O. and C.W. declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}