HIV-1 drug resistance and treatment response

Antiretroviral therapy (ART) has led to a considerable decrease in AIDS mortality. The emergence of the primary and acquired drug resistance mutations (DRM) poses a significant threat to successful antiretroviral therapy (ART) against HIV-infection. Globally there isa substantial increase in both transmitted drug resistance and acquired drug resistance in low- and middle-income countries. Our clinical and translational research on ART includes both cohorts’ studies as well experimental studies evaluating new antiretroviral drugs (ARVs) as well as repurposing and re-using of the approved drugs.Our studiesthus aim to understand the subtype-specific differences in the evolution of drug resistance and treatment response. Using several cohorts from Europe, Asia, and Africa, we try to understand the role of naturally occurring polymorphisms in the drug target sites of cART drugs of class reverse transcriptase inhibitors, protease inhibitors, and integrase inhibitors in treatment response. We use technologies like deep profiling by high throughput sequencing, in vitro and ex vivo phenotypic assays, biochemical and structural biology assay.

Key Publications:

  1. Njenda DT, Aralaguppe SG, Singh K, Rao R, Sönnerborg A, Sarafianos SG, Neogi U(2018). Antiretroviral potency of 4’-Ethnyl-2’-Fluoro-2’-deoxyadenosine, tenofovir alafenamide and second-generation non-nucleoside reverse-transcriptase inhibitors across diverse HIV-1 subtypes. J Antimicrob Chemother, 73(10):2721-2728 [PMID: 30053052].
  2. Häggblom A, Svedhem V, Singh K, Sönnerborg A, Neogi U(2016) Virological failure in patients with HIV-1 subtype C receiving antiretroviral therapy: an analysis of a prospective national cohort in Sweden. Lancet HIV3(4):e166-74 [PMID: 27036992]