Benefits reported for continued use of cotrimoxazole prophylaxis at high CD4 counts in Malawi

Simon Collins, HIV i-Base

Although cotrimoxazole prophylaxis is discontinued in high-income countries following CD4 recovery on ART to >200 cells/mm3, guidelines in many low-income countries recommend continued use even at much higher CD4 counts.

Researchers who ran a randomised controlled study in Malawi support this continued use, even though the primary endpoint results were not significant.

The study randomised almost 1500 participants with CD4 counts >250 cells/mm3 to either continue or discontinue daily cotrimoxazole, or switch to daily hydroxychloroquine. Mean CD4 count was actually much higher (568 cells/mm3, SD+/– 236).

Neither active arm produced significant benefits based on preventing death or WHO stage 3-4 events (approximate 20% reductions were p=0.20 and p=0.14, respectively). The was linked to the lower event rate than predicted (3.9 vs per 100 patient years of follow-up), reducing the power of the study.

However, when stage 2 secondary endpoints were included, the preventive effect increased to 31% (95%CI: 3 to 51%; p=0.032) and 32% (95%CI: 4 to 51%; p=0.026), for cotrimoxazole and hydroxychloroquine respectively. Both drugs significantly reduced the risk of malaria (p<0.001).

Although co-trimoxazole prophylaxis can cause hematologic toxicity, including neutropenia, which was higher in this arm, it didn’t cause higher rates of bacterial infections.

However the low event rate also means that the number needed to treat (NNT) to prevent and even also becomes much higher, and these data were not presented.

These results were first published online in March 2021.


The benefits in this study are likely relevant in high malaria settings and where rates of bacterial pneumonia much greater.

Although the confidence intervals are still wide, cotrimoxazole is so safe that this makes sense, especially if vaccination is not available.


Laurens MB et al. Revisiting co-trimoxazole prophylaxis for African adults in the era of antiretroviral therapy: a randomized controlled clinical trial. Clinical Infectious Diseases, 73 (6): 1058–1065. doi: 10.1093/cid/ciab252. (15 September 2021).

This report was first published on 7 October 2021.

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