title: Unnecessary antiretroviral treatment switches and accumulation of HIV resistance mutations; two arguments for viral load monitoring in Africa.
abstract: OBJECTIVE
  This study aimed to investigate the consequences of using clinicoimmunological criteria to detect antiretroviral treatment (ART) failure and guide regimen switches in HIV-infected adults in sub-Saharan Africa. Frequencies of unnecessary switches, patterns of HIV drug resistance, and risk factors for the accumulation of nucleoside reverse transcriptase inhibitor (NRTI)-associated mutations were evaluated.
  
  
  METHODS
  Cross-sectional analysis of adults switching ART regimens at 13 clinical sites in 6 African countries was performed. Two types of failure identification were compared: diagnosis of clinicoimmunological failure without viral load testing (CIF only) or CIF with local targeted viral load testing (targeted VL). After study enrollment, reference HIV RNA and genotype were determined retrospectively. Logistic regression assessed factors associated with multiple thymidine analogue mutations (TAMs) and NRTI cross-resistance (≥2 TAMs or Q151M or K65R/K70E).
  
  
  RESULTS
  Of 250 patients with CIF switching to second-line ART, targeted VL was performed in 186. Unnecessary switch at reference HIV RNA <1000 copies per milliliter occurred in 46.9% of CIF only patients versus 12.4% of patients with targeted VL (P < 0.001). NRTI cross-resistance was observed in 48.0% of 183 specimens available for genotypic analysis, comprising ≥2 TAMs (37.7%), K65R (7.1%), K70E (3.3%), or Q151M (3.3%). The presence of NRTI cross-resistance was associated with the duration of ART exposure and zidovudine use.
  
  
  CONCLUSIONS
  Clinicoimmunological monitoring without viral load testing resulted in frequent unnecessary regimen switches. Prolonged treatment failure was indicated by extensive NRTI cross-resistance. Access to virological monitoring should be expanded to prevent inappropriate switches, enable early failure detection and preserve second-line treatment options in Africa.
authors.affiliation: PharmAccess Foundation, Amsterdam, The Netherlands. k.sigaloff@pharmaccess.org
authors.forename: Kim C E
authors.initials: KC
authors.lastname: Sigaloff
authors.forename: Raph L
authors.initials: RL
authors.lastname: Hamers
authors.forename: Carole L
authors.initials: CL
authors.lastname: Wallis
authors.forename: Cissy
authors.initials: C
authors.lastname: Kityo
authors.forename: Margaret
authors.initials: M
authors.lastname: Siwale
authors.forename: Prudence
authors.initials: P
authors.lastname: Ive
authors.forename: Mariette E
authors.initials: ME
authors.lastname: Botes
authors.forename: Kishor
authors.initials: K
authors.lastname: Mandaliya
authors.forename: Maureen
authors.initials: M
authors.lastname: Wellington
authors.forename: Akin
authors.initials: A
authors.lastname: Osibogun
authors.forename: Wendy S
authors.initials: WS
authors.lastname: Stevens
authors.forename: Michèle
authors.initials: M
authors.lastname: van Vugt
authors.forename: Tobias F Rinke
authors.initials: TF
authors.lastname: de Wit
mesh_terms: D000328:Adult; D000349:Africa / Q000453:epidemiology; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004334:Drug Administration Schedule; D024882:Drug Resistance, Viral / Q000235:genetics*; D057915:Drug Substitution; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012367:RNA, Viral / Q000097:blood; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D019380:Anti-HIV Agents; D012367:RNA, Viral