Sustained HIV Viral Suppression With Dolutegravir, Tenofovir, and Emtricitabine as Initial Therapy Despite High-Level Transmitted Multiclass Resistance

Multiclass high-level transmitted HIV drug resistance is uncommon, and the selection of the optimal initial antiretroviral drug regimen may be challenging. We report a case of extensive transmitted multiclass resistance successfully treated with dolutegravir, tenofovir, and emtricitabine even though the baseline genotype demonstrated full susceptibility to only 1 drug class, integrase strand transfer inhibitors. Our case highlights both the high resistance barrier of dolutegravir and the residual antiviral activity of nucleoside reverse transcriptase inhibitors despite extensive resistance on genotype

The major genetic determinants of HIV-1 control affect HLA class I peptide presentation.

Infectious and inflammatory diseases have repeatedly shown strong genetic associations within the major histocompatibility complex (MHC); however, the basis for these associations remains elusive. To define host genetic effects on the outcome of a chronic viral infection, we performed genome-wide association analysis in a multiethnic cohort of HIV-1 controllers and progressors, and we analyzed the effects of individual amino acids within the classical human leukocyte antigen (HLA) proteins. We identified >300 genome-wide significant single-nucleotide polymorphisms (SNPs) within the MHC and none elsewhere. Specific amino acids in the HLA-B peptide binding groove, as well as an independent HLA-C effect, explain the SNP associations and reconcile both protective and risk HLA alleles. These results implicate the nature of the HLA-viral peptide interaction as the major factor modulating durable control of HIV infection