Antiretroviral treatment sequencing strategies to overcome HIV type 1 drug resistance in adolescents and adults in low-middle-income countries

J Infect Dis. 2013 Jun 15:207 Suppl 2:S63-9. doi: 10.1093/infdis/jit109.

Abstract

Antiretroviral treatment (ART) is expanding to human immunodeficiency virus type 1 (HIV-1)-infected persons in low-middle income countries, thanks to a public health approach. With 3 available drug classes, 2 ART sequencing lines are programmatically foreseen. The emergence and transmission of viral drug resistance represents a challenge to the efficacy of ART. Knowledge of HIV-1 drug resistance selection associated with specific drugs and regimens and the consequent activity of residual drug options are essential in programming ART sequencing options aimed at preserving ART efficacy for as long as possible. This article determines optimal ART sequencing options for overcoming HIV-1 drug resistance in resource-limited settings, using currently available drugs and treatment monitoring opportunities. From the perspective of drug resistance and on the basis of limited virologic monitoring data, optimal sequencing seems to involve use of a tenofovir-containing nonnucleoside reverse-transcriptase inhibitor-based first-line regimen, followed by a zidovudine-containing, protease inhibitor (PI)-based second-line regimen. Other options and their consequences are explored by considering within-class and between-class sequencing opportunities, including boosted PI monotherapies and future options with integrase inhibitors. Nucleoside reverse-transcriptase inhibitor resistance pathways in HIV-1 subtype C suggest an additional reason for accelerating stavudine phase out. Viral load monitoring avoids the accumulation of resistance mutations that significantly reduce the activity of next-line options. Rational use of resources, including broader access to viral load monitoring, will help ensure 3 lines of fully active treatment options, thereby increasing the duration of ART success.

Keywords: HIV-1 drug resistance; antiretroviral therapy; resource-limited settings; sequencing.

Publication types

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

MeSH terms

  • Adolescent
  • Adult
  • Anti-Retroviral Agents / pharmacology
  • Anti-Retroviral Agents / therapeutic use*
  • Developing Countries
  • Drug Resistance, Viral*
  • Drug Therapy, Combination
  • Genotype
  • HIV Infections / drug therapy*
  • HIV Infections / virology
  • HIV Protease Inhibitors / pharmacology
  • HIV Protease Inhibitors / therapeutic use
  • HIV-1 / drug effects*
  • HIV-1 / genetics
  • HIV-1 / physiology
  • Humans
  • Mutation, Missense
  • Poverty
  • RNA, Viral / analysis*
  • RNA, Viral / genetics
  • Reverse Transcriptase Inhibitors / pharmacology
  • Reverse Transcriptase Inhibitors / therapeutic use
  • Viral Load

Substances

  • Anti-Retroviral Agents
  • HIV Protease Inhibitors
  • RNA, Viral
  • Reverse Transcriptase Inhibitors