Critical questions for dolutegravir-based antiretroviral therapy in Africa

Dolutegravir will replace medicines used for HIV in Africa as it is safer and less likely to cause resistance. The evidence supporting the use of dolutegravir involved studies that did not include many Africans or women, who are in the largest group in Africa to need the therapy. The studies also excluded people with tuberculosis (TB). Dolutegravir's safety is related to its concentrations in the blood, which are higher in women and in people with a reduced capacity to break down the drug due to a genetic abnormality that is more common in African people. TB treatment enhances the breakdown of the drug. Dolutegravir is effective in second-line treatment when resistance to other medicines is known, but resistance testing is not affordable in Africa.

We propose to find out: what the determinants of safety are when using dolutegravir in Africa; whether standard doses can be used in patients with TB; and if it can be effective as a second-line treatment without testing for resistance.