HIV-1 resistance genotyping by ultra-deep sequencing and 6-month virological response to first-line treatment

J Antimicrob Chemother. 2023 Feb 1;78(2):346-353. doi: 10.1093/jac/dkac391.


Objectives: To evaluate the routine use of the Sentosa ultra-deep sequencing (UDS) system for HIV-1 polymerase resistance genotyping in treatment-naïve individuals and to analyse the virological response (VR) to first-line antiretroviral treatment.

Methods: HIV drug resistance was determined on 237 consecutive samples from treatment-naïve individuals using the Sentosa UDS platform with two mutation detection thresholds (3% and 20%). VR was defined as a plasma HIV-1 virus load <50 copies/mL after 6 months of treatment.

Results: Resistance to at least one antiretroviral drug with a mutation threshold of 3% was identified in 29% and 16% of samples according to ANRS and Stanford algorithms, respectively. The ANRS algorithm also revealed reduced susceptibility to at least one protease inhibitor (PI) in 14.3% of samples, to one reverse transcriptase inhibitor in 12.7%, and to one integrase inhibitor (INSTI) in 5.1%. For a mutation threshold of 20%, resistance was identified in 24% and 13% of samples according to ANRS and Stanford algorithms, respectively. The 6 months VR was 87% and was similar in the 58% of patients given INSTI-based treatment, in the 16% given PI-based treatment and in the 9% given NNRTI-based treatment. Multivariate analysis indicated that the VR was correlated with the baseline HIV virus load and resistance to at least one PI at both 3% and 20% mutation detection thresholds (ANRS algorithm).

Conclusions: The Vela UDS platform is appropriate for determining antiretroviral resistance in patients on a first-line antiretroviral treatment. Further studies are needed on the use of UDS for therapeutic management.

MeSH terms

  • Anti-HIV Agents* / pharmacology
  • Anti-HIV Agents* / therapeutic use
  • Anti-Retroviral Agents / therapeutic use
  • Drug Resistance, Viral / genetics
  • Genotype
  • HIV Infections* / drug therapy
  • HIV Integrase Inhibitors* / therapeutic use
  • HIV Seropositivity* / drug therapy
  • HIV-1* / genetics
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mutation
  • Viral Load


  • Anti-Retroviral Agents
  • HIV Integrase Inhibitors
  • Anti-HIV Agents