title: Treatment failure and drug resistance in HIV-positive patients on tenofovir-based first-line antiretroviral therapy in western Kenya.
abstract: Tenofovir-based first-line antiretroviral therapy (ART) is recommended globally. To evaluate the impact of its incorporation into the World Health Organization (WHO) guidelines, we examined treatment failure and drug resistance among a cohort of patients on tenofovir-based first-line ART at the Academic Model Providing Access to Healthcare, a large HIV treatment programme in western Kenya.
  
  
  
  We determined viral load (VL), drug resistance and their correlates in patients on ≥six months of tenofovir-based first-line ART. Based on enrolled patients' characteristics, we described these measures in those with (prior ART group) and without (tenofovir-only group) prior non-tenofovir-based first-line ART using Wilcoxon rank sum and Fisher's exact tests.
  
  
  
  Among 333 participants (55% female; median age 41 years; median CD4 336 cells/µL), detectable (>40 copies/mL) VL was found in 18%, and VL>1000 copies/mL (WHO threshold) in 10%. Virologic failure at both thresholds was significantly higher in 217 participants in the tenofovir-only group compared with 116 in the prior ART group using both cut-offs (24% vs. 7% with VL>40 copies/mL; 15% vs. 1% with VL>1000 copies/mL). Failure in the tenofovir-only group was associated with lower CD4 values and advanced WHO stage. In 35 available genotypes from 51 participants in the tenofovir-only group with VL>40 copies/mL (69% subtype A), any resistance was found in 89% and dual-class resistance in 83%. Tenofovir signature mutation K65R occurred in 71% (17/24) of the patients infected with subtype A. Patients with K65R had significantly lower CD4 values, higher WHO stage and more resistance mutations.
  
  
  
  In this Kenyan cohort, tenofovir-based first-line ART resulted in good (90%) virologic suppression including high suppression (99%) after switch from non-tenofovir-based ART. Lower virologic suppression (85%) and high observed resistance levels (89%) in the tenofovir-only group impact future treatment options, support recommendations for widespread VL monitoring in such resource limited settings to identify early treatment failure and suggest consideration of individualized resistance testing to design effective subsequent regimens.
authors.affiliation: Division of Infectious Diseases, Alpert Medical School, Brown University, Providence, RI, USA.
authors.forename: Katherine
authors.initials: K
authors.lastname: Brooks
authors.affiliation: Academic Model Providing Access to Healthcare (AMPATH), Eldoret, Kenya.|Department of Medicine, School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya.
authors.forename: Lameck
authors.initials: L
authors.lastname: Diero
authors.affiliation: Center for Statistical Sciences, Brown University, Providence, RI, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: DeLong
authors.affiliation: Division of Infectious Diseases, Alpert Medical School, Brown University, Providence, RI, USA.
authors.forename: Maya
authors.initials: M
authors.lastname: Balamane
authors.affiliation: Division of Infectious Diseases, Alpert Medical School, Brown University, Providence, RI, USA.
authors.forename: Marissa
authors.initials: M
authors.lastname: Reitsma
authors.affiliation: Academic Model Providing Access to Healthcare (AMPATH), Eldoret, Kenya.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Kemboi
authors.affiliation: Academic Model Providing Access to Healthcare (AMPATH), Eldoret, Kenya.
authors.forename: Millicent
authors.initials: M
authors.lastname: Orido
authors.affiliation: Academic Model Providing Access to Healthcare (AMPATH), Eldoret, Kenya.|Department of Medicine, School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya.
authors.forename: Wilfred
authors.initials: W
authors.lastname: Emonyi
authors.affiliation: Division of Infectious Diseases, Alpert Medical School, Brown University, Providence, RI, USA.
authors.forename: Mia
authors.initials: M
authors.lastname: Coetzer
authors.affiliation: Academic Model Providing Access to Healthcare (AMPATH), Eldoret, Kenya.|Center for Statistical Sciences, Brown University, Providence, RI, USA.|Department of Biostatistics, School of Public Health, Brown University, Providence, RI, USA.
authors.forename: Joseph
authors.initials: J
authors.lastname: Hogan
authors.affiliation: Division of Infectious Diseases, Alpert Medical School, Brown University, Providence, RI, USA; rkantor@brown.edu.
authors.forename: Rami
authors.initials: R
authors.lastname: Kantor
mesh_terms: D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D007630:Kenya / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D000068698:Tenofovir / Q000008:administration & dosage / Q000627:therapeutic use*; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D000068698:Tenofovir
keywords: HIV; Kenya; drug resistance; subtype; tenofovir