title: Virological failure after 1 year of first-line ART is not associated with HIV minority drug resistance in rural Cameroon .
abstract: OBJECTIVE
  The aim of this study was to describe clinical and virological outcomes in therapy-naive HIV-1-positive patients treated in a routine ART programme in rural Cameroon.
  
  
  METHODS
  In a prospective cohort, 300 consecutive patients starting first-line ART were enrolled and followed for 12 months. Among 238 patients with available viral load data at Month 12, logistic regression was used to analyse risk factors for virological failure (≥1000 HIV RNA copies/mL) including clinical, immunological and virological parameters, as well as data on drug adherence. Population sequencing was performed to detect the presence of drug-resistance mutations in patients with virological failure at Month 12; minority drug-resistance mutations at baseline were analysed using next-generation sequencing in these patients and matched controls.
  
  
  RESULTS
  At Month 12, 38/238 (16%) patients experienced virological failure (≥1000 HIV RNA copies/mL). Patients with virological failure were younger, had lower CD4 cell counts and were more often WHO stage 3 or 4 at baseline. Sixty-three percent of patients with virological failure developed at least one drug-resistance mutation. The M184V (n = 18) and K103N (n = 10) mutations were most common. At baseline, 6/30 patients (20%) experiencing virological failure and 6/35 (17%) matched controls had evidence of minority drug-resistance mutations using next-generation sequencing (P = 0.77). Lower CD4 count at baseline (OR per 100 cells/mm(3) lower 1.41, 95% CI 1.02-1.96, P = 0.04) and poorer adherence (OR per 1% lower 1.05, 95% CI 1.02-1.08, P < 0.001) were associated with a higher risk of virological failure. Unavailability of ART at the treatment centre was the single most common cause for incomplete adherence.
  
  
  CONCLUSIONS
  Virological failure after 1 year of ART was not associated with minority drug resistance at baseline but with incomplete adherence. Strategies to assure adherence and uninterrupted drug supplies are pivotal factors for therapy success.
authors.affiliation: Infectious Diseases Unit, Department of Medicine 1, University Medical Center Hamburg-Eppendorf, Hamburg, Germany Department of Medicine 4, Kaiser Franz Josef Hospital, Vienna, Austria alex_zoufaly@yahoo.com.
authors.forename: A
authors.initials: A
authors.lastname: Zoufaly
authors.affiliation: Infectious Diseases Unit, Department of Medicine 1, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Jochum
authors.affiliation: Clinical Research Unit, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: R
authors.initials: R
authors.lastname: Hammerl
authors.affiliation: Clinical Research Unit, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Nassimi
authors.affiliation: Bamenda Regional Hospital, Bamenda, Cameroon.
authors.forename: Y
authors.initials: Y
authors.lastname: Raymond
authors.affiliation: Clinical Research Unit, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany.
authors.forename: G D
authors.initials: GD
authors.lastname: Burchard
authors.affiliation: Infectious Diseases Unit, Department of Medicine 1, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: S
authors.initials: S
authors.lastname: Schmiedel
authors.affiliation: Institute of Virology, University of Bonn, Bonn, Germany.
authors.forename: J F
authors.initials: JF
authors.lastname: Drexler
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: N K
authors.initials: NK
authors.lastname: Campbell
authors.affiliation: Bamenda Regional Hospital, Bamenda, Cameroon.
authors.forename: N
authors.initials: N
authors.lastname: Taka
authors.affiliation: Bamenda Regional Hospital, Bamenda, Cameroon.
authors.forename: C
authors.initials: C
authors.lastname: Awasom
authors.affiliation: Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland.
authors.forename: K J
authors.initials: KJ
authors.lastname: Metzner
authors.affiliation: Infectious Diseases Unit, Department of Medicine 1, University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors.forename: J
authors.initials: J
authors.lastname: van Lunzen
authors.affiliation: Clinical Research Unit, Bernhard Nocht Institute for Tropical Medicine, Hamburg, Germany Clinic of Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Düsseldorf, Germany.
authors.forename: T
authors.initials: T
authors.lastname: Feldt
mesh_terms: D000328:Adult; D000368:Aged; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D002163:Cameroon; D015331:Cohort Studies; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy*; D015497:HIV-1 / Q000302:isolation & purification*; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D020125:Mutation, Missense; D011446:Prospective Studies; D012424:Rural Population; D017422:Sequence Analysis, DNA; D017211:Treatment Failure; D019562:Viral Load; D055815:Young Adult
chemical_list: D044966:Anti-Retroviral Agents
keywords: Africa; HIV drug resistance; adherence