Trimethoprim-Sulfamethoxazole Prophylaxis Reduces Mortality Among African Patients on Antiretroviral Therapy

Trimethoprim-sulfamethoxazole (TMP-SMX) prophylaxis has well-known survival benefits in HIV-infected patients who have not yet received antiretroviral therapy (ART). However, little is known about its benefits among patients on ART, in part because the prophylaxis is usually stopped once a patient's CD4 count exceeds 200 cells/mm³ and the risk for Pneumocystis jirovecii pneumonia is presumed to have passed. In this observational analysis from the DART trial, investigators evaluated the benefits of using TMP-SMX after ART initiation.

The analysis included 3179 HIV-infected patients in Uganda or Zimbabwe who were initiating ART. TMP-SMX was prescribed at the discretion of the treating clinician: 1959 participants (62%) were already receiving TMP-SMX at ART initiation, 896 (28%) commenced while on ART, and 324 (10%) never received it during follow-up (median, 4.9 years).

Overall, TMP-SMX prophylaxis reduced mortality during follow-up by 35% (odds ratio, 0.65; 95% CI, 0.50–0.85). The reduction was greatest in the first 12 weeks of concurrent use with ART (OR, 0.41; 95% CI, 0.27–0.65) and remained statistically significant through 72 weeks (OR, 0.56; 95% CI, 0.37–0.86). The magnitude of effect was not influenced by duration of TMP-SMX prophylaxis or by current CD4-cell count.

TMP-SMX prophylaxis also reduced malaria risk by 26% (OR, 0.74; 95% CI, 0.63–0.88), a benefit that was maintained throughout follow-up. No effect was observed on new WHO stage 4 events, CD4-cell count, or body-mass index.