Long-term prophylactic co-trimoxazole beneficial for HIV-positive children in Africa

Image: PD 

1. Among HIV-positive African children being treated with anti-retroviral therapy, continuing rather than stopping prophylactic co-trimoxazole led to less morbidity and mortality. 

Evidence Rating Level: 1 (Excellent) 

Study Rundown: Antiretroviral therapy (ART) directly antagonizes the human immunodeficiency virus and is therefore the cornerstone of treatment for HIV-positive individuals. However, since HIV wreaks its damage by hobbling the body’s ability to defend itself from infection, prophylactic antibiotics can be an important supplemental therapy. Co-trimoxazole (trimethoprim-sulfamethoxazole) is an inexpensive, broad-spectrum antibiotic that has been shown to reduce morbidity and mortality in certain HIV-positive populations. In African populations, co-trimoxazole prevents opportunistic infections, such as Pneumocystis jirovecii, as well as malarial and non-opportunistic bacterial infections. In sub-Saharan Africa, co-trimoxazole is often given to HIV-positive children before and during ART. However, it has been unclear when or if co-trimoxazole should be stopped. This study found significant benefits to continuing co-trimoxazole, even after 2 years of ART and even if the immune system appears healthy. The high rate of serious bacterial and protozoal infections in sub-Saharan Africa makes co-trimoxazole prophylaxis useful and relevant. It may not be as useful in a setting with lower rates of such infections.

Click to read the study in the NEJM (New England Journal of Medicine)

Relevant Reading: Early chemoprophylaxis with trimethoprim-sulphamethoxazole for HIV-1 infected adults in Abidjan, Côte d’Ivoire: a randomized trial

In-Depth [randomized controlled trial]: Almost 800 children aged 3 or older in Uganda and Zimbabwe who had been receiving ART for more than 96 weeks were randomized to either stop or continue daily co-trimoxazole and were followed for more than 120 weeks. This was an open-label trial and those stopping co-trimoxazole were not given placebo pills. The primary end points were hospitalization or death. There was a greater risk of a primary end point occurring among those who stopped co-trimoxazole compared to those who continued (19% vs. 13%; HR 1.64; p=0.007). There was also a greater risk of malaria among those who stopped the antibiotic (20% vs. 10%; HR 2.21; p<0.001). In terms of safety, there was no significant difference in the rate of adverse events between the stopped- and continued-prophylaxis groups (17% vs. 15%; p =0.33). However, there was a higher rate of severe adverse events among the stopped-prophylaxis group (3% vs. 1%; p= 0.04). Overall, the study shows convincingly that among children in sub-Saharan Africa, prolonged co-trimoxazole prophylaxis reduces morbidity and mortality. It also appears to be relatively safe.

By Tomi Jun and Xu Gao

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