title: HIV-1 drug resistance mutations are present in six percent of persons initiating antiretroviral therapy in Lusaka, Zambia.
abstract: OBJECTIVE
  To assess the mutational patterns and factors associated with baseline drug-resistant HIV-1 present at initiation of first-line antiretroviral therapy (ART) at 3 sites in Lusaka, Zambia, in 2007-2008.
  
  
  METHODS
  Population sequencing of the HIV-1 pol gene was performed in the PharmAccess African Studies to Evaluate Resistance Monitoring cohort. Drug resistance-associated mutations (DRMs) were identified using the WHO 2009 Surveillance DRM list. Multiple logistic regression was used to assess factors associated with baseline resistance.
  
  
  RESULTS
  The overall prevalence of baseline resistance was 5.7% [31 of 548 participants; 95% confidence interval (CI): 3.9 to 7.9]; the prevalence of DRMs associated with nucleoside reverse transcriptase inhibitors (NRTIs), nonnucleoside reverse transcriptase inhibitors (NNRTIs) and protease inhibitors was 1.1%, 4.0%, and 1.1%, respectively. Resistance prevalence was 5.2% (27 of 523) in antiretroviral-naive and 16.0% (4 of 25) in antiretroviral-experienced (ie, previous use of ART or antiretroviral prophylaxis for prevention of mother-to-child transmission) participants (P = 0.022). Dual-class resistance to NRTIs and NNRTIs was observed in 0.6% of participants. HIV-1 subtype C was identified in 98.0% (537 of 548) of participants. Prior antiretroviral experience (odds ratio: 4.32, CI: 1.34 to 14.0, P = 0.015) and hemoglobin level (highest tertile versus lowest tertile odds ratio: 2.74, CI: 1.09 to 6.89, P = 0.033) were independently associated with baseline resistance.
  
  
  CONCLUSIONS
  Baseline resistance may compromise the response to standard NNRTI-based first-line ART in 6% of patients in Lusaka, Zambia. Continuous resistance monitoring is warranted to maintain individual and population-level ART effectiveness.
authors.affiliation: PharmAccess Foundation, Amsterdam, The Netherlands. r.hamers@pharmaccess.org
authors.forename: Raph L
authors.initials: RL
authors.lastname: Hamers
authors.forename: Margaret
authors.initials: M
authors.lastname: Siwale
authors.forename: Carole L
authors.initials: CL
authors.lastname: Wallis
authors.forename: Moheb
authors.initials: M
authors.lastname: Labib
authors.forename: Robbert
authors.initials: R
authors.lastname: van Hasselt
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Stevens
authors.forename: Rob
authors.initials: R
authors.lastname: Schuurman
authors.forename: Annemarie M J
authors.initials: AM
authors.lastname: Wensing
authors.forename: Michèle
authors.initials: M
authors.lastname: Van Vugt
authors.forename: Tobias F
authors.initials: TF
authors.lastname: Rinke de Wit
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000494:pharmacology*; D023241:Antiretroviral Therapy, Highly Active; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D015995:Prevalence; D012367:RNA, Viral / Q000235:genetics; D017422:Sequence Analysis, DNA; D015024:Zambia; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral; D054302:pol Gene Products, Human Immunodeficiency Virus