title: Virological failure and HIV-1 drug resistance mutations among naive and antiretroviral pre-treated patients entering the ESTHER program of Calmette Hospital in Cambodia.
abstract: BACKGROUND
  In resource limited settings, patients entering an antiretroviral therapy (ART) program comprise ART naive and ART pre-treated patients who may show differential virological outcomes.
  
  
  METHODS
  This retrospective study, conducted in 2010-2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia) assessed virological failure (VF) rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL) was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF) (>1,000 copies/ml) underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms.
  
  
  RESULTS
  On a total of 209 patients, 164 (78.4%) were naive and 45 (21.5%) were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30-194) and 279 cells/mm3 (IQR: 103-455) (p<0.001), respectively. Twenty seven patients (12.9%) exhibited VF (95% CI: 8.6-18.2%), including 10 naive (10/164, 6.0%) and 17 pre-treated (17/45, 37.8%) patients (p<0.001). Among these viremic patients, twenty-two (81.4%) were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3%) harbored ≥1 drug resistance mutations (DRMs) whereas 3 (all belonging to pre-treated patients) harbored wild-types viruses. The most frequent DRMs were M184V (86.3%), K103N (45.5%) and thymidine analog mutations (TAMs) (40.9%). Two (13.3%) pre-treated patients harbored viruses that showed a multi-nucleos(t)ide resistance including Q151M, K65R, E33A/D, E44A/D mutations.
  
  
  CONCLUSIONS
  In Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for ART pre-treated patients infection should be considered as well.
authors.affiliation: Agence Nationale de Recherche sur le VIH et les Hepatites (ANRS), Phnom Penh, Cambodia; ISPED, Centre INSERM U897-Epidemiologie-Biostatistique, Univ. Bordeaux, Bordeaux, France; Epidemiology Unit, Pasteur Institute, Phnom Penh, Cambodia.
authors.forename: Hubert
authors.initials: H
authors.lastname: Barennes
authors.affiliation: Agence Nationale de Recherche sur le VIH et les Hepatites (ANRS), Phnom Penh, Cambodia; Assistance Publique - Hôpitaux de Paris (AP-HP), Département de Médecine Interne et Immunologie Clinique, Centre Hospitalier Universitaire de Bicêtre, Le Kremlin-Bicêtre, France.
authors.forename: Stéphanie
authors.initials: S
authors.lastname: Guillet
authors.affiliation: Hospital Calmette, Phnom Penh, Cambodia.
authors.forename: Setha
authors.initials: S
authors.lastname: Limsreng
authors.affiliation: Hospital Calmette, Phnom Penh, Cambodia; Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau (ESTHER), Phnom Penh, Cambodia.
authors.forename: Sovanvatey
authors.initials: S
authors.lastname: Him
authors.affiliation: HIV/Hepatitis Unit, Pasteur Institute, Phnom Penh, Cambodia; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
authors.forename: Janin
authors.initials: J
authors.lastname: Nouhin
authors.affiliation: Hospital Calmette, Phnom Penh, Cambodia; Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau (ESTHER), Phnom Penh, Cambodia.
authors.forename: Chanroeurn
authors.initials: C
authors.lastname: Hak
authors.affiliation: Hospital Calmette, Phnom Penh, Cambodia.
authors.forename: Chanvatey
authors.initials: C
authors.lastname: Srun
authors.affiliation: Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau (ESTHER), Phnom Penh, Cambodia.
authors.forename: Gerald
authors.initials: G
authors.lastname: Viretto
authors.affiliation: Hospital Calmette, Phnom Penh, Cambodia; Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau (ESTHER), Phnom Penh, Cambodia.
authors.forename: Vara
authors.initials: V
authors.lastname: Ouk
authors.affiliation: Assistance Publique - Hôpitaux de Paris (AP-HP), Département de Médecine Interne et Immunologie Clinique, Centre Hospitalier Universitaire de Bicêtre, Le Kremlin-Bicêtre, France; Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau (ESTHER), Phnom Penh, Cambodia.
authors.forename: Jean Francois
authors.initials: JF
authors.lastname: Delfraissy
authors.affiliation: Assistance Publique - Hôpitaux de Paris (AP-HP), Département de Médecine Interne et Immunologie Clinique, Centre Hospitalier Universitaire de Bicêtre, Le Kremlin-Bicêtre, France; Ensemble pour une Solidarité Thérapeutique Hospitalière En Réseau (ESTHER), Phnom Penh, Cambodia.
authors.forename: Olivier
authors.initials: O
authors.lastname: Ségéral
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D002160:Cambodia; D024882:Drug Resistance, Viral / Q000235:genetics*; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000235:genetics; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012189:Retrospective Studies; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D044966:Anti-Retroviral Agents