title: Emergence of HIV drug resistance during first- and second-line antiretroviral therapy in resource-limited settings.
abstract: BACKGROUND
  Antiretroviral therapy (ART) in resource-limited settings has expanded in the last decade, reaching >8 million individuals and reducing AIDS mortality and morbidity. Continued success of ART programs will require understanding the emergence of HIV drug resistance patterns among individuals in whom treatment has failed and managing ART from both an individual and public health perspective. We review data on the emergence of HIV drug resistance among individuals in whom first-line therapy has failed and clinical and resistance outcomes of those receiving second-line therapy in resource-limited settings.
  
  
  RESULTS
  Resistance surveys among patients initiating first-line nonnucleoside reverse-transcriptase inhibitor (NNRTI)-based therapy suggest that 76%-90% of living patients achieve HIV RNA suppression by 12 months after ART initiation. Among patients with detectable HIV RNA at 12 months, HIV drug resistance, primarily due to M184V and NNRTI mutations, has been identified in 60%-72%, although the antiretroviral activity of proposed second-line regimens has been preserved. Complex mutation patterns, including thymidine-analog mutations, K65R, and multinucleoside mutations, are prevalent among cases of treatment failure identified by clinical or immunologic methods. Approximately 22% of patients receiving second-line therapy do not achieve HIV RNA suppression by 6 months, with poor adherence, rather than HIV drug resistance, driving most failures. Major protease inhibitor resistance at the time of second-line failure ranges from 0% to 50%, but studies are limited.
  
  
  CONCLUSIONS
  Resistance of HIV to first-line therapy is predictable at 12 months when evaluated by means of HIV RNA monitoring and, when detected, largely preserves second-line therapy options. Optimizing adherence, performing resistance surveillance, and improving treatment monitoring are critical for long-term prevention of drug resistance.
authors.affiliation: University of North Carolina Project, Lilongwe, Malawi. mina_hosseinipour@med.unc.edu
authors.forename: Mina C
authors.initials: MC
authors.lastname: Hosseinipour
authors.forename: Ravindra K
authors.initials: RK
authors.lastname: Gupta
authors.forename: Gert
authors.initials: G
authors.lastname: Van Zyl
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Eron
authors.forename: Jean B
authors.initials: JB
authors.lastname: Nachega
mesh_terms: D044966:Anti-Retroviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D017320:HIV Protease Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D015497:HIV-1 / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006295:Health Resources / Q000191:economics; D006801:Humans; D009154:Mutation; D020125:Mutation, Missense; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism*; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D044966:Anti-Retroviral Agents; D017320:HIV Protease Inhibitors; D012367:RNA, Viral; D018894:Reverse Transcriptase Inhibitors
keywords: antiretroviral drug resistance; resource-limited settings; second-line therapy