Clin Infect Dis. 2021 Mar 21:ciab252. doi: 10.1093/cid/ciab252. Online ahead of print.
ABSTRACT
BACKGROUND: Daily co-trimoxazole is recommended for African adults living with 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 two sites in Malawi that enrolled HIV-infected adults with undetectable viral load and CD4 count of >250/mm 3 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 modelling, 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=0.20) versus no prophylaxis and 25% (95%CI -10-48%, p=0.14) versus chloroquine. When WHO HIV/AIDS Stage 2 events were added to the primary endpoint, preventive effect increased to 31% (95%CI 3-51%, p=0.032) and 32% (95%CI 4-51%, p=0.026), respectively. Co-trimoxazole and chloroquine prophylaxis effectively prevented clinical malaria episodes (3.8 and 3.0, respectively, versus 28/100 person-years, p<0.001).
CONCLUSIONS: Malawian adults living with HIV who immune reconstituted on ART and continued co-trimoxazole prophylaxis experienced fewer deaths and WHO HIV/AIDS Stage 3-4 events compared to prophylaxis discontinuation, though statistical significance was not achieved. Cotrimoxazole 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.
PMID:33744963 | DOI:10.1093/cid/ciab252
