title: Accumulation of HIV-1 drug resistance after continued virological failure on first-line ART in adults and children in sub-Saharan Africa.
abstract: Limited availability of viral load (VL) monitoring in HIV treatment programmes in sub-Saharan Africa can delay switching to second-line ART, leading to the accumulation of drug resistance mutations (DRMs). The objective of this study was to evaluate the accumulation of resistance to reverse transcriptase inhibitors after continued virological failure on first-line ART, among adults and children in sub-Saharan Africa.
  
  
  
  HIV-1-positive adults and children on an NNRTI-based first-line ART were included. Retrospective VL and, if VL ≥1000 copies/mL, pol genotypic testing was performed. Among participants with continued virological failure (≥2 VL ≥1000 copies/mL), drug resistance was evaluated.
  
  
  
  At first virological failure, DRM(s) were detected in 87% of participants: K103N (38.7%), G190A (21.8%), Y181C (20.2%), V106M (8.4%), K101E (8.4%), any E138 (7.6%) and V108I (7.6%) associated with NNRTIs, and M184V (69.7%), any thymidine analogue mutation (9.2%), K65R (5.9%) and K70R (5.0%) associated with NRTIs. New DRMs accumulated with an average rate of 1.45 (SD 2.07) DRM per year; 0.62 (SD 1.11) NNRTI DRMs and 0.84 (SD 1.38) NRTI DRMs per year, respectively. The predicted susceptibility declined significantly after continued virological failure for all reverse transcriptase inhibitors (all P < 0.001). Acquired drug resistance patterns were similar in adults and children.
  
  
  
  Patterns of drug resistance after virological failure on first-line ART are similar in adults and children in sub-Saharan Africa. Improved VL monitoring to prevent accumulation of mutations, and new drug classes to construct fully active regimens, are required.
authors.affiliation: Amsterdam Institute for Global Health and Development, Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands Global Child Health Group, Emma Children's Hospital/Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands s.boender@amc.nl.
authors.forename: T Sonia
authors.initials: TS
authors.lastname: Boender
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda.
authors.forename: Cissy M
authors.initials: CM
authors.lastname: Kityo
authors.affiliation: Amsterdam Institute for Global Health and Development, Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands Global Child Health Group, Emma Children's Hospital/Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ragna S
authors.initials: RS
authors.lastname: Boerma
authors.affiliation: Amsterdam Institute for Global Health and Development, Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Raph L
authors.initials: RL
authors.lastname: Hamers
authors.affiliation: Amsterdam Institute for Global Health and Development, Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Pascale
authors.initials: P
authors.lastname: Ondoa
authors.affiliation: Newlands Clinic, Harare, Zimbabwe.
authors.forename: Maureen
authors.initials: M
authors.lastname: Wellington
authors.affiliation: Lusaka Trust Hospital, Lusaka, Zambia.
authors.forename: Margaret
authors.initials: M
authors.lastname: Siwale
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda.
authors.forename: Immaculate
authors.initials: I
authors.lastname: Nankya
authors.affiliation: Joint Clinical Research Centre, Kampala, Uganda.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Kaudha
authors.affiliation: Department of Haematology and Blood Transfusion, College of Medicine of the University of Lagos, Lagos, Nigeria.
authors.forename: Alani Sulaimon
authors.initials: AS
authors.lastname: Akanmu
authors.affiliation: Muelmed Hospital, Pretoria, South Africa.
authors.forename: Mariette E
authors.initials: ME
authors.lastname: Botes
authors.affiliation: Department of Molecular Medicine and Haematology, University of the Witwatersrand, Johannesburg, South Africa.
authors.forename: Kim
authors.initials: K
authors.lastname: Steegen
authors.affiliation: Global Child Health Group, Emma Children's Hospital/Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands Department of Pediatric Intensive Care, Emma Children's Hospital/Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Job C J
authors.initials: JC
authors.lastname: Calis
authors.affiliation: Amsterdam Institute for Global Health and Development, Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Tobias F
authors.initials: TF
authors.lastname: Rinke de Wit
authors.affiliation: Amsterdam Institute for Global Health and Development, Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands Department of Internal Medicine, Division of Infectious Diseases, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Kim C E
authors.initials: KC
authors.lastname: Sigaloff
mesh_terms: D000293:Adolescent; D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects; D002648:Child; D002675:Child, Preschool; D024882:Drug Resistance, Viral / Q000235:genetics; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D008297:Male; D009154:Mutation; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors