Revisiting Co-trimoxazole Prophylaxis for African Adults in the Era of Antiretroviral Therapy: A Randomized Controlled Clinical Trial

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. We...

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Veröffentlicht in:Clinical infectious diseases 2021-09, Vol.73 (6), p.1058-1065
Hauptverfasser: Laurens, Matthew B, Mungwira, Randy G, Nampota, Nginache, Nyirenda, Osward M, Divala, Titus H, Kanjala, Maxwell, Mkandawire, Felix A, Galileya, Lufina Tsirizani, Nyangulu, Wongani, Mwinjiwa, Edson, Downs, Matthew, Tillman, Amy, Taylor, Terrie E, Mallewa, Jane, Plowe, Christopher V, van Oosterhout, Joep J, Laufer, Miriam K
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Sprache:eng
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Zusammenfassung: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. 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. 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 
ISSN:1058-4838
1537-6591
DOI:10.1093/cid/ciab252