Genotypic HIV-1 Drug Resistance Among Patients Failing Tenofovir-Based First-Line HAART in South India

AIDS Res Hum Retroviruses. 2016 Dec;32(12):1234-1236. doi: 10.1089/AID.2016.0110. Epub 2016 Jul 14.

Abstract

According to 2013 WHO guidelines, tenofovir (TDF) is the preferred first-line regimen for adults and adolescents. A total of 167 HIV-1-infected patients attaining immunological failure after TDF-based first-line HAART were included in this study, RT region of HIV-1 pol gene was sequenced for them, IAS-USA 2014 list and Stanford HIV drug resistance database were used for mutation interpretation. REGA V3.0 was used for HIV subtyping. The predominant NRTI and NNRTI mutations observed were M184IV (59.9%), K65R (28.1%), and thymidine analogue mutations (TAMs, 29.3%) and K103NS (54.5%), V106AM (39.5%), and Y181CIV (19.8%), respectively. Mutational association shows, K65R was negatively associated with TAMs (OR 0.31, p .008), M184V (OR 0.14, p .57), and K70E (OR 0.29, p .02). Genotypically predicted level of drug resistance based on mutation pattern shows 88% can be opted for azidothymidine (AZT) and still 65% can be opted for TDF. Considering the nature of K65R mutation in increasing susceptibility to AZT and its low prevalence, we conclude that in most patients failing TDF-based first-line therapy, AZT can be considered for second-line therapy followed by TDF itself.

Keywords: K65R; NRTI; TDF; first-line; immunological failure.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-HIV Agents / therapeutic use*
  • Antiretroviral Therapy, Highly Active / methods*
  • Cross-Sectional Studies
  • Databases, Genetic
  • Drug Resistance, Viral*
  • Female
  • Genotype*
  • HIV Infections / drug therapy
  • HIV Infections / virology*
  • HIV Reverse Transcriptase / genetics
  • HIV-1 / classification
  • HIV-1 / drug effects
  • HIV-1 / genetics*
  • HIV-1 / isolation & purification
  • Humans
  • India
  • Male
  • Mutation, Missense
  • Prevalence
  • Sequence Analysis, DNA
  • Tenofovir / therapeutic use*
  • Treatment Failure
  • pol Gene Products, Human Immunodeficiency Virus / genetics

Substances

  • Anti-HIV Agents
  • pol Gene Products, Human Immunodeficiency Virus
  • Tenofovir
  • reverse transcriptase, Human immunodeficiency virus 1
  • HIV Reverse Transcriptase