title: Burden of nonnucleoside reverse transcriptase inhibitor resistance in HIV-1-infected patients: a systematic review and meta-analysis.
abstract: The prevalence of HIV drug resistance varies with geographic location, year, and treatment exposure. This study generated yearly estimates of nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance in treatment-naive (TN) and treatment-experienced (TE) patients in the United States (US), Europe (EU), and Canada. Studies reporting NNRTI resistance identified in electronic databases and 11 conferences were analyzed in three groups: (1) TN patients in one of four geographic regions [US, Canada, EU countries with larger surveillance networks ("EU1"), and EU countries with fewer data ("EU2")]; (2) TE patients from any region; and (3) TN patients failing NNRTI-based treatments in clinical trials. Analysis data included 158 unique studies from 22 countries representing 84 cohorts of TN patients, 21 cohorts of TE patients, and 8 trials reporting resistance at failure. From 1995 to 2000, resistance prevalence in TN patients increased in US and EU1 from 3.1% to 7.5% and 0.8% to 3.6%, respectively. Resistance in both regions stabilized in 2006 onward. Little resistance was identified in EU2 before 2000, and increased from 2006 (5.0%) to 2010 (13.7%). One TN Canadian study was identified and reported resistance of 8.1% in 2006. Half of TN clinical trial patients had resistance after treatment failure at weeks 48-144. Resistance in TE patients increased from 1998 (10.1%) to 2001 (44.0%), then decreased after 2004. Trends in NNRTI resistance among TN patients show an increased burden in the US and some EU countries compared to others. These findings signify a need for alternate first-line treatments in some regions.
authors.affiliation: 1 Pharmerit International , Bethesda, Maryland.
authors.forename: Sonya J
authors.initials: SJ
authors.lastname: Snedecor
authors.forename: Lavanya
authors.initials: L
authors.lastname: Sudharshan
authors.forename: Katherine
authors.initials: K
authors.lastname: Nedrow
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Bhanegaonkar
authors.forename: Kit N
authors.initials: KN
authors.lastname: Simpson
authors.forename: Seema
authors.initials: S
authors.lastname: Haider
authors.forename: Richard
authors.initials: R
authors.lastname: Chambers
authors.forename: Charles
authors.initials: C
authors.lastname: Craig
authors.forename: Jennifer
authors.initials: J
authors.lastname: Stephens
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology / Q000627:therapeutic use; D002170:Canada / Q000453:epidemiology; D024882:Drug Resistance, Viral; D005060:Europe / Q000453:epidemiology; D015658:HIV Infections / Q000188:drug therapy / Q000453:epidemiology / Q000821:virology*; D054303:HIV Reverse Transcriptase / Q000235:genetics*; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D020125:Mutation, Missense; D015995:Prevalence; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D017211:Treatment Failure; D014481:United States / Q000453:epidemiology
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase