{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T03:05:22Z","timestamp":1790737522046,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2021,3,21]],"date-time":"2021-03-21T00:00:00Z","timestamp":1616284800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U01AI089342"],"award-info":[{"award-number":["U01AI089342"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["K24AI114996"],"award-info":[{"award-number":["K24AI114996"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,9,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Daily co-trimoxazole is recommended for African adults living with human immunodeficiency virus (HIV) irrespective of antiretroviral treatment, immune status, or disease stage. Benefits of continued prophylaxis and whether co-trimoxazole can be stopped following immune reconstitution are unknown.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a randomized controlled trial at 2 sites in Malawi that enrolled adults with HIV with undetectable viral load and CD4 count of &amp;gt;250\/mm3 and randomized them to continue daily co-trimoxazole, discontinue daily co-trimoxazole and begin weekly chloroquine, or discontinue daily co-trimoxazole. The primary endpoint was the preventive effect of co-trimoxazole prophylaxis against death or World Health Organization (WHO) HIV\/AIDS stage 3\u20134 events, using Cox proportional hazards modeling, in an intention-to-treat population.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>1499 adults were enrolled. The preventive effect of co-trimoxazole on the primary endpoint was 22% (95% CI: \u221214%\u201347%; P\u2005=\u2005.20) versus no prophylaxis and 25% (\u221210%\u201348%; P\u2005=\u2005.14) versus chloroquine. When WHO HIV\/AIDS stage 2 events were added to the primary endpoint, preventive effect increased to 31% (3\u201351%; P\u2005=\u2005.032) and 32% (4\u201351%; P\u2005=\u2005.026), respectively. Co-trimoxazole and chloroquine prophylaxis effectively prevented clinical malaria episodes (3.8 and 3.0, respectively, vs 28\/100 person-years; P\u2005&amp;lt;\u2005.001).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Malawian adults with HIV who immune reconstituted on ART and continued co-trimoxazole prophylaxis experienced fewer deaths and WHO HIV\/AIDS stage 3\u20134 events compared with prophylaxis discontinuation, although statistical significance was not achieved. Co-trimoxazole prevented a composite of death plus WHO HIV\/AIDS stage 2\u20134 events. Given poor healthcare access and lack of routine viral load monitoring, co-trimoxazole prophylaxis should continue in adults on ART after immune reconstitution in sub-Saharan Africa.<\/jats:p><jats:p>Clinical Trials Registration. NCT01650558.<\/jats:p><\/jats:sec>","DOI":"10.1093\/cid\/ciab252","type":"journal-article","created":{"date-parts":[[2021,3,18]],"date-time":"2021-03-18T20:12:26Z","timestamp":1616098346000},"page":"1058-1065","source":"Crossref","is-referenced-by-count":15,"title":["Revisiting Co-trimoxazole Prophylaxis for African Adults in the Era of Antiretroviral Therapy: A Randomized Controlled Clinical Trial"],"prefix":"10.1093","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3874-581X","authenticated-orcid":false,"given":"Matthew B","family":"Laurens","sequence":"first","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randy G","family":"Mungwira","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nginache","family":"Nampota","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osward M","family":"Nyirenda","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Titus H","family":"Divala","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maxwell","family":"Kanjala","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Felix A","family":"Mkandawire","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lufina Tsirizani","family":"Galileya","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wongani","family":"Nyangulu","sequence":"additional","affiliation":[{"name":"Dignitas International, Zomba, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edson","family":"Mwinjiwa","sequence":"additional","affiliation":[{"name":"Dignitas International, Zomba, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew","family":"Downs","sequence":"additional","affiliation":[{"name":"Statistics Collaborative, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy","family":"Tillman","sequence":"additional","affiliation":[{"name":"Statistics Collaborative, Washington, DC, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Terrie E","family":"Taylor","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi"},{"name":"College of Osteopathic Medicine, Michigan State University, East Lansing, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Mallewa","sequence":"additional","affiliation":[{"name":"Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher V","family":"Plowe","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joep J","family":"van Oosterhout","sequence":"additional","affiliation":[{"name":"Dignitas International and University of Malawi College of Medicine, Blantyre, Malawi"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam K","family":"Laufer","sequence":"additional","affiliation":[{"name":"Center for Vaccine Development and Global Health, University of Maryland School of Medicine, Baltimore, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2021,3,21]]},"reference":[{"key":"2021091515522276300_CIT0001","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/S0140-6736(98)07399-1","article-title":"Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1-infected adults in Abidjan, C\u00f4te d\u2019Ivoire: a randomised trial. 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