Role of co-trimoxazole prophylaxis in reducing mortality in HIV infected adults being treated for tuberculosis: randomised clinical trial

Abstract

Objective To assess the impact of prophylactic oral cotrimoxazole in reducing mortality in HIV positive Zambian adults being treated for pulmonary tuberculosis. Design Double blind placebo controlled randomised clinical trial. Participants Two groups of antiretroviral treatment naive adults with HIV infection: patients newly diagnosed as having tuberculosis and receiving tuberculosis treatment either for the first time or for retreatment after relapse; previously treated patients not receiving treatment. Intervention Oral co-trimoxazole or matching placebo daily. Primary outcome measures Time to death and occurrence of serious adverse events related to study drug. Results 1003 patients were randomised: 835 (416 cotrimoxazole, 419 placebo) were receiving treatment for tuberculosis, 762 (376 co-trimoxazole, 386 placebo) of them newly diagnosed previously untreated patients and 73 (40 co-trimoxazole, 33 placebo) receiving a retreatment regimen; 168 (84 co-trimoxazole, 84 placebo) were not on treatment but had received treatment in the past. Of 835 participants receiving tuberculosis treatment, follow-up information was available for 757, with a total of 1012.6 person years of follow-up. A total of 310 (147 co-trimoxazole, 163 placebo) participants died, corresponding to death rates of 27.3 and 34.4 per 100 person years. In the Cox regression analysis, the hazard ratio for death (co-trimoxazole:placebo) was 0.79 (95% confidence interval 0.63 to 0.99). The effect of cotrimoxazole waned with time, possibly owing to falling adherence levels; in a per protocol analysis based on patients who spent at least 90% of their time at risk supplied with study drug, the hazard ratio was 0.65 (0.45 to 0.93). Conclusions Prophylaxis with co-trimoxazole reduces mortality in HIV infected adults with pulmonary tuberculosis. Co-trimoxazole was generally safe and well tolerated. Trial registration Current Controlled Trials ISRCTN15281875.

Water Filter Provision and Home-Based Filter Reinforcement Reduce Diarrhea in Kenyan HIV-Infected Adults and Their Household Members

“…15,17 Combination antiretroviral therapy (ART) in HIV-infected adults and children also reduces risk of diarrhea and enteric infection. 13,14,18 However, it is estimated that only 34% of 28.3 million HIV-infected individuals globally currently receive ART. 19 Water filtration devices reduce waterborne pathogens and subsequent diarrheal illness without contributing to antibiotic selective pressure or requiring clinic visits, and they can be used at any CD4 count.…”

Effect of cotrimoxazole on mortality in HIV-infected adults on antiretroviral therapy: a systematic review and meta-analysis

“…11 Randomized trials that included ART-naïve Africans found that cotrimoxazole improved survival while reducing the risk of malaria, pneumonia, sepsis, isosporiasis, T. gondii encephalitis, wasting and Kaposi's sarcoma. [12][13][14] However, a Senegalese trial that used half the recommended adult cotrimoxazole dose reported no mortality benefit in ART-naïve adults. 15 A study in Uganda showed that treating HIV-infected adults with cotrimoxazole and ART reduced mortality in their uninfected children and the number of orphans.…”

Implementation of co-trimoxazole prophylaxis and isoniazid preventive therapy for people living with HIV

“…The value of co-trimoxazole in reducing the morbidity and mortality associated with HIV infection has been well established through clinical trials conducted in industrialized 5,6 and developing countries. [7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26] CTXp is associated with a 25-46% reduction in mortality among individuals infected with HIV in sub-Saharan Africa, even in areas with high bacterial resistance to the antibiotic. These improvements in survival have been accompanied by substantial reductions in severe disease events and in the number of hospital admissions linked to invasive bacterial disease, pneumonia, malaria and diarrhoea.…”