New antiretroviral inhibitors and HIV-1 drug resistance: more focus on 90% HIV-1 isolates?

Combined HIV antiretroviral therapy (cART) has been effective except if drug resistance emerges. As cART has been rolled out in low-income countries, drug resistance has emerged at higher rates than observed in high income countries due to factors including initial use of these less tolerated cART regimens, intermittent disruptions in drug supply, and insufficient treatment monitoring. These socioeconomic factors impacting drug resistance are compounded by viral mechanistic differences by divergent HIV-1 non-B subtypes compared to HIV-1 subtype B that largely infects the high-income countries (just 10% of 37 million infected). This review compares the inhibition and resistance of diverse HIV-1 subtypes and strains to the various approved drugs as well as novel inhibitors in clinical trials. Initial sequence variations and differences in replicative fitness between HIV-1 subtypes pushes strains through different fitness landscapes to escape from drug selective pressure. The discussions here provide insight to patient care givers and policy makers on how best to use currently approved ART options and reduce the emergence of drug resistance in similar to 33 million individuals infected with HIV-1 subtype A, C, D, G, and recombinants forms. Unfortunately, over 98% of the literature on cART resistance relates to HIV-1 subtype B.

Automated summary

Combined HIV antiretroviral therapy (cART) has been effective in controlling HIV, but drug resistance is a significant concern, particularly in low-income countries. This review explores the factors contributing to higher rates of drug resistance in these countries, including the initial use of less tolerated cART regimens and issues with drug supply and monitoring. The study also compares the inhibition and resistance of different HIV-1 subtypes to approved drugs and provides insights for patient care and policymakers to reduce drug resistance.