title: Genotypic impact of prolonged detectable HIV type 1 RNA viral load after HAART failure in a CRF01_AE-infected cohort.
abstract: HIV subtype-specific data on mutation type, rate, and accumulation following HAART treatment failure are limited. We studied patterns and accrual of drug resistance mutations in a Cambodian CRF01_AE-infected cohort continuing a virologically failing first-line, nonnucleoside reverse transcriptase inhibitor- (NNRTI-) based, HAART. Between 2005 and 2007, 837 adult HIV-infected patients had regular plasma HIV-1 RNA viral load measurements at Sihanouk Hospital Centre of Hope (SHCH), Cambodia. Drug resistance testing was performed in all patients with HIV-1 RNA >1000 copies/ml after at least 6 months of HAART. Seventy-one patients with a mean age of 34 years, of whom 68% were male, were retrospectively assessed at virological failure. The median duration of antiretroviral therapy was 12.3 (IQR 7.1-18.23) months, the median CD4 cell count was 173 (IQR 118-256) cells/mm(3), and the mean plasma HIV-1 RNA viral load was 3.9 log (SD 0.72) at failure. NNRTI mutations, M184I/V mutation, thymidine analogue mutations, and K65R were observed in 78.9%, 69%, 20%, and 12.7% of patients, respectively. For 33 patients, genotypic testing was carried out on at least two occasions before the switch to second-line HAART after a median duration of 5.8 (IQR 4.3-6.1) months of virological failure: 54.5% of patients accumulated new mutations with a rate of 1.6 mutations per person-year. Accumulation was seen both for nucleoside and nonnucleoside reverse transcriptase inhibitors, and also in patients with low-level viremia. Subtype-specific data on mutation type, rate, and accumulation after HAART failure are urgently needed to optimize treatment strategies in resource-limited settings.
authors.affiliation: Institute of Tropical Medicine, Antwerp, Belgium. mzolfo@itg.be
authors.forename: Maria
authors.initials: M
authors.lastname: Zolfo
authors.forename: Jonathan M
authors.initials: JM
authors.lastname: Schapiro
authors.forename: Vichet
authors.initials: V
authors.lastname: Phan
authors.forename: Olivier
authors.initials: O
authors.lastname: Koole
authors.forename: Sopheak
authors.initials: S
authors.lastname: Thai
authors.forename: Marc
authors.initials: M
authors.lastname: Vekemans
authors.forename: Katrien
authors.initials: K
authors.lastname: Fransen
authors.forename: Lutgarde
authors.initials: L
authors.lastname: Lynen
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000008:administration & dosage*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D002160:Cambodia; D024882:Drug Resistance, Viral; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology*; D015497:HIV-1 / Q000145:classification / Q000235:genetics* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D012367:RNA, Viral / Q000097:blood / Q000235:genetics; D017422:Sequence Analysis, DNA; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral