Need for clear inclusion criteria in reviews of antiretroviral treatments

Abstract

On behalf of the writing group, we appreciate the correspondence from Alexandra Calmy and colleagues regarding our Review. Our main goal was to provide clinicians with an overview of two-drug antiretroviral therapy, by means of relevant data from the literature that would inform clinical practice. On the basis of these criteria, dolutegravir plus emtricitabine did not meet our selection standard. First, this combination for HIV treatment had previously been examined only in a small retrospective study. Furthermore, the SIMPL’HIV trial, an open-label study that randomly assigned 93 participants to dolutegravir plus emtricitabine, showed non-inferiority with a primary endpoint that used a 12% margin for the proportion of participants with HIV RNA less than 100 copies per mL up to 48 weeks. This study is very small and had a primary endpoint that deviates from the US Food and Drug Administration recommendation of a 4% non-inferiority margin for the proportion with HIV RNA greater than 50 copies per mL for switch trials. The clinical relevance of SIMPL’HIV to our comprehensive review was further lowered by the absence of any scenario, to our knowledge, in which the two-pill dolutegravir plus emtricitabine regimen would be preferred over single-pill dolutegravir plus lamivudine. In addition to not being available as a fixed-dose combination, in many low-income and middle-income countries, lamivudine, a generic drug, is substantially cheaper than emtricitabine. We believe that inclusion of SIMPL’HIV would have neither advanced the understanding of clinicians seeking relevant information on two-drug therapy nor benefitted researchers seeking to advance HIV therapeutics.

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Citation

Lancet HIV . 2023 Mar;10(3):e150-e151. doi: 10.1016/S2352-3018(23)00006-1.