Drug interactions and the role of pharmacokinetic trials in guiding choices in first-line HIV therapy in low-income and middle-income countries.

PURPOSE OF REVIEW: Low- and middle-income countries (LMICs) face specific challenges in the treatment of people living with HIV. Drug-drug interactions (DDIs) involving antiretrovirals (ARVs) are prevalent in all settings and have considerable potential to cause clinical harm to patients via toxicity or reduced efficacy of treatment. Differing comorbidities, endemic infections and traditional medicines may complicate ARV therapy (ART) in LMICs, which usually takes a public health approach in these settings, with fewer alternative regimens available. This review discusses the issues surrounding pharmacokinetic DDI studies and their application to ART in LMICs, with particular reference to first-line ART regimens.

RECENT FINDINGS: Pharmacokinetic studies with clinical endpoints are the gold standard for informing management of DDIs; however, data relevant to LMICs are sparse and of low quality. There is significant potential for clinically relevant DDIs between ARVs and antimalarials, antimycobacterials and drugs used in the treatment of neglected tropical diseases.

SUMMARY: Many pharmacokinetic studies are difficult to interpret in LMICs due to differences in patient factors including weight, disease state and genetic polymorphisms. DDI studies relevant to LMICs may also be lacking due to the neglected nature of relevant comorbidities. The ARVs currently available as first-line ART in LMICs are among those with highest propensity for DDIs.