title: Resistance to antiretroviral drugs in treated and drug-naive patients in the Democratic Republic of Congo.
abstract: BACKGROUND
  We studied virological outcome and drug resistance in patients on antiretroviral therapy (ART) in health care centers in the Democratic Republic of Congo and looked for the presence of drug resistance in antiretroviral-naive patients attending the same clinics.
  
  
  METHODS
  In 2008, we conducted a cross-sectional survey among patients on ART for ≥ 12 months in 4 major cities [Kinshasa (n = 289), Matadi (n = 198), Lubumbashi (n = 77), and Mbuji-Mayi (n = 103)]. Genotypic drug resistance tests were done with an in-house assay on samples with viral load >1000 copies/mL. ART-naive patients (n = 283) were also consecutively enrolled in the same clinics.
  
  
  RESULTS
  Of the 667 patients on ART, >98% received Lamivudine + Stavudine/azidothymidine + Nevirapine/Efavirenz as first-line regimen and 74.4% were women. Median time on ART was 25 months [interquartile ratio (IQR), 19-32] in Kinshasa, 26 months (IQR, 19-32) in Matadi, 27 months (IQR, 19-44) in Lubumbashi, and 19 months (IQR, 16-24) in Mbuji-Mayi. A total of 97 patients (14.6%) had viral load >1000 copies/mL, and among the 93 successfully sequenced samples, 78 (83.9%) were resistant to at least 1 drug of their ART regimen: 68 harbored resistance mutations to nucleoside reverse transcriptase inhibitor (NRTI) and nonnucleoside reverse transcriptase inhibitor (NNRTI), 2 to NRTI only, 7 to NNRTI only, and 1 to NRTI + NNRTI + protease inhibitor. The majority of patients, 70/78 (89.7%), were resistant to at least 2 of the 3 drugs from their treatment. The use of next-generation NNRTI, etravirine was already compromised for 19.2% (15/78) of the patients and 7 patients had the K65R mutation compromising the use of tenofovir in second-line regimens. The proportion of antiretroviral-resistant patients increased over time from 8.4% to 18.6% for patients on ART for 12-23 months or >35 months (P = 0.013), respectively. Virological failure and rates of drug resistance were significantly higher among men than women, 19.9% versus 8.8%, respectively (P = 0.0001). Among the 253 recently diagnosed patients, 20 (7.9%) harbored resistance mutations.
  
  
  CONCLUSIONS
  The accumulation of drug resistance mutations with time on ART needs further attention, and surveillance should be reinforced in ART programs in sub-Saharan Africa.
authors.affiliation: AIDS National Reference Laboratory, LNRS, General Hospital of Kinshasa, Kinshasa, Democratic Republic of Congo.
authors.forename: Jérémie
authors.initials: J
authors.lastname: Muwonga
authors.forename: Samuel
authors.initials: S
authors.lastname: Edidi
authors.forename: Christelle
authors.initials: C
authors.lastname: Butel
authors.forename: Nicole
authors.initials: N
authors.lastname: Vidal
authors.forename: Marjorie
authors.initials: M
authors.lastname: Monleau
authors.forename: Augustin
authors.initials: A
authors.lastname: Okenge
authors.forename: Jean Lambert
authors.initials: JL
authors.lastname: Mandjo
authors.forename: Henry
authors.initials: H
authors.lastname: Mukumbi
authors.forename: Jean Jacques
authors.initials: JJ
authors.lastname: Muyembe
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Mbayo
authors.forename: Donatien Kayembe
authors.initials: DK
authors.lastname: Nzongola
authors.forename: Eric
authors.initials: E
authors.lastname: Delaporte
authors.forename: François
authors.initials: F
authors.lastname: Boillot
authors.forename: Martine
authors.initials: M
authors.lastname: Peeters
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D003430:Cross-Sectional Studies; D015023:Democratic Republic of the Congo; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents