HIV-1 subtype B/B' and baseline drug resistance mutation are associated with virologic failure: a multicenter cohort study in China

J Acquir Immune Defic Syndr. 2015 Mar 1;68(3):289-97. doi: 10.1097/QAI.0000000000000473.

Abstract

Background: Distribution of HIV-1 subtypes, transmitted drug resistance (TDR)/drug resistance mutation (DRM), and their impact on response to combination antiretroviral therapy remain poorly understood in China.

Methods: We analyzed data from our multicenter cohort study with 444 antiretroviral-naive participants recruited between 2008 and 2010. HIV-1 subtype and tropism were determined by V3 sequencing, and TDR/DRM was determined by Pol sequencing. Virologic and immunologic responses were monitored over 96 weeks of follow-up. The initial combination antiretroviral therapy regimen for all patients was nevirapine + lamivudine + zidovudine or stavudine. Analysis 1 included patients who finished 96 weeks of follow-up (n = 379), and analysis 2 included all 444 patients.

Results: Subtype B/B' was associated with higher prevalence of TDR/DRM to nucleoside reverse transcriptase inhibitors and nonnucleoside reverse transcriptase inhibitors. Median time to HIV-1 suppression was 18 weeks in all 3 subtype groups. In Cox proportional models for viral suppression, neither viral tropism nor HIV-1 subtypes had any impact on viral suppression; however, subtypes CRF01_AE and C/CRF07_BC/CRF08_BC were associated with lower risk of virologic failure compared with subtype B/B', with adjusted hazard ratio of 0.11 (P = 0.032) and 0.06 (P = 0.036), respectively in analysis 1, 0.42 (P = 0.047) and 0.22 (P = 0.008), respectively in analysis 2. This association was attenuated by adding DRM profiles to multivariate regression models. Neither subtype nor HIV-1 tropism affected immunologic response.

Conclusions: HIV-1 subtype tended to be associated with virologic but not immunologic response; this effect could be ascribed to baseline DRM.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / pharmacology
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods
  • CD4 Lymphocyte Count
  • China
  • Cohort Studies
  • Drug Resistance, Viral*
  • Female
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / virology*
  • HIV-1 / classification
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / isolation & purification
  • Humans
  • Male
  • Middle Aged
  • Mutation, Missense*
  • Prospective Studies
  • Sequence Analysis, DNA
  • Treatment Failure
  • Viral Load
  • pol Gene Products, Human Immunodeficiency Virus / genetics

Substances

  • Anti-HIV Agents
  • pol Gene Products, Human Immunodeficiency Virus