{"doi":"10.1093/cid/ciab252","title":"Revisiting Co-trimoxazole Prophylaxis for African Adults in the Era of Antiretroviral Therapy: A Randomized Controlled Clinical Trial","abstract":"BACKGROUND: 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. METHODS: We conducted a randomized controlled trial at 2 sites in Malawi that enrolled adults with HIV with undetectable viral load and CD4 count of >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 3-4 events, using Cox proportional hazards modeling, in an intention-to-treat population. RESULTS: 1499 adults were enrolled. The preventive effect of co-trimoxazole on the primary endpoint was 22% (95% CI: -14%-47%; P = .20) versus no prophylaxis and 25% (-10%-48%; P = .14) versus chloroquine. When WHO HIV/AIDS stage 2 events were added to the primary endpoint, preventive effect increased to 31% (3-51%; P = .032) and 32% (4-51%; P = .026), respectively. Co-trimoxazole and chloroquine prophylaxis effectively prevented clinical malaria episodes (3.8 and 3.0, respectively, vs 28/100 person-years; P < .001). CONCLUSIONS: Malawian adults with HIV who immune reconstituted on ART and continued co-trimoxazole prophylaxis experienced fewer deaths and WHO HIV/AIDS stage 3-4 events compared with prophylaxis discontinuation, although statistical significance was not achieved. Co-trimoxazole prevented a composite of death plus WHO HIV/AIDS stage 2-4 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. Clinical Trials Registration. NCT01650558.","journal":"Clinical Infectious Diseases","year":2021,"id":180157,"datarank":0.8514311712763404,"base_score":2.8903717578961645,"endowment":2.8903717578961645,"self_citation_contribution":0.4335557636844247,"citation_network_contribution":0.41787540759191566,"self_endowment_contribution":0.4335557636844247,"citer_contribution":0.41787540759191566,"corpus_percentile":null,"corpus_rank":null,"citation_count":17,"citer_count":11,"citers_with_citation_signal":8,"citers_with_endowment":8,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9625,"is_data_producer":true,"deposit_databanks":{"ClinicalTrials.gov":["NCT01650558"]},"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":424753,"name":"Randy G. 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Mkandawire","orcid":null,"position":6,"is_corresponding":false},{"id":729295,"name":"Lufina Tsirizani Galileya","orcid":null,"position":7,"is_corresponding":false},{"id":728658,"name":"Wongani Nyangulu","orcid":"0000-0001-6192-6534","position":8,"is_corresponding":false},{"id":729296,"name":"Edson Mwinjiwa","orcid":null,"position":9,"is_corresponding":false},{"id":729297,"name":"Matthew Downs","orcid":null,"position":10,"is_corresponding":false},{"id":728659,"name":"Amy Tillman","orcid":"0000-0002-1777-9597","position":11,"is_corresponding":false},{"id":75970,"name":"Terrie E. Taylor","orcid":"0000-0001-7416-3986","position":12,"is_corresponding":false},{"id":324973,"name":"Jane Mallewa","orcid":null,"position":13,"is_corresponding":false},{"id":290875,"name":"Christopher V. Plowe","orcid":"0000-0002-0045-9888","position":14,"is_corresponding":false},{"id":728660,"name":"Joep J. van Oosterhout","orcid":"0000-0002-3441-0804","position":15,"is_corresponding":false},{"id":260137,"name":"Miriam K. Laufer","orcid":"0000-0001-8300-9593","position":16,"is_corresponding":false},{"id":429806,"name":"Matthew B. Laurens","orcid":"0000-0003-3874-581X","position":0,"is_corresponding":true}],"reference_count":28,"raw_metadata":null,"created_at":"2026-07-18T23:47:53.089578Z","pmid":"33744963","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}