title: Monitoring and switching of first-line antiretroviral therapy in adult treatment cohorts in sub-Saharan Africa: collaborative analysis.
abstract: BACKGROUND
  HIV-1 viral load testing is recommended to monitor antiretroviral therapy (ART) but is not universally available. The aim of our study was to assess monitoring of first-line ART and switching to second-line ART in sub-Saharan Africa.
  
  
  METHODS
  We did a collaborative analysis of cohort studies from 16 countries in east Africa, southern Africa, and west Africa that participate in the international epidemiological database to evaluate AIDS (IeDEA). We included adults infected with HIV-1 who started combination ART between January, 2004, and January, 2013. We defined switching of ART as a change from a non-nucleoside reverse-transcriptase inhibitor (NNRTI)-based regimen to one including a protease inhibitor, with adjustment of one or more nucleoside reverse-transcriptase inhibitors (NRTIs). Virological and immunological failures were defined according to WHO criteria. We calculated cumulative probabilities of switching and hazard ratios with 95% CIs comparing routine viral load monitoring, targeted viral load monitoring, CD4 monitoring, and clinical monitoring, adjusting for programme and individual characteristics.
  
  
  RESULTS
  Of 297,825 eligible patients, 10,352 (3%) switched to second-line ART during 782 ,412 person-years of follow-up. Compared with CD4 monitoring, hazard ratios for switching were 3·15 (95% CI 2·92-3·40) for routine viral load monitoring, 1·21 (1·13-1·30) for targeted viral load monitoring, and 0·49 (0·43-0·56) for clinical monitoring. Of 6450 patients with confirmed virological failure, 58·0% (95% CI 56·5-59·6) switched by 2 years, and of 15,892 patients with confirmed immunological failure, 19·3% (18·5-20·0) switched by 2 years. Of 10,352 patients who switched, evidence of treatment failure based on one CD4 count or viral load measurement ranged from 86 (32%) of 268 patients with clinical monitoring to 3754 (84%) of 4452 with targeted viral load monitoring. Median CD4 counts at switching were 215 cells per μL (IQR 117-335) with routine viral load monitoring, but were lower with other types of monitoring (range 114-133 cells per μL).
  
  
  CONCLUSIONS
  Overall, few patients switched to second-line ART and switching happened late in the absence of routine viral load monitoring. Switching was more common and happened earlier after initiation of ART with targeted or routine viral load testing.
  
  
  BACKGROUND
  National Institute of Allergy and Infectious Diseases, Swiss National Science Foundation.
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Andreas D
authors.initials: AD
authors.lastname: Haas
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland.
authors.forename: Olivia
authors.initials: O
authors.lastname: Keiser
authors.affiliation: Centre de Recherche INSERM U897, Epidemiologie-Biostatistique, Institut de Santé Publique, Epidémiologie et Développement, Université de Bordeaux, Bordeaux, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Balestre
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Steve
authors.initials: S
authors.lastname: Brown
authors.affiliation: Service de Maladies Infectieuses et Tropicales, Centre Hospitalier Universitaire de Treichville, Abidjan, Côte d'Ivoire.
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bissagnene
authors.affiliation: Newlands Clinic, Harare, Zimbabwe.
authors.forename: Cleophas
authors.initials: C
authors.lastname: Chimbetete
authors.affiliation: Centre de Recherche INSERM U897, Epidemiologie-Biostatistique, Institut de Santé Publique, Epidémiologie et Développement, Université de Bordeaux, Bordeaux, France.
authors.forename: François
authors.initials: F
authors.lastname: Dabis
authors.affiliation: Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa.
authors.forename: Mary-Ann
authors.initials: MA
authors.lastname: Davies
authors.affiliation: Johns Hopkins University, Baltimore, MD, USA; Aurum Institute, Johannesburg, South Africa.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Hoffmann
authors.affiliation: Kenya Medical Research Institute - RCTP FACES Program, Kisumu, Kenya.
authors.forename: Patrick
authors.initials: P
authors.lastname: Oyaro
authors.affiliation: Infectious Diseases Institute, Mulago Hospital Complex, Kampala, Uganda.
authors.forename: Rosalind
authors.initials: R
authors.lastname: Parkes-Ratanshi
authors.affiliation: Rakai Health Sciences Program, Entebbe, Uganda; Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA; Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Reynolds
authors.affiliation: Centre for Infectious Disease Research in Zambia, Lusaka, Zambia.
authors.forename: Izukanji
authors.initials: I
authors.lastname: Sikazwe
authors.affiliation: Indiana University School of Medicine, Indianapolis, IN, USA.
authors.forename: Kara
authors.initials: K
authors.lastname: Wools-Kaloustian
authors.affiliation: Faculté des Sciences de la Santé de l'Université d'Abomey-Calavi, and Centre de Traitement Ambulatoire du Centre National Hospitalier Universitaire Hubert Koutoukou Maga, Cotonou, Benin.
authors.forename: D Marcel
authors.initials: DM
authors.lastname: Zannou
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; Department of Infectious Diseases, Bern University Hospital and University of Bern, Bern, Switzerland.
authors.forename: Gilles
authors.initials: G
authors.lastname: Wandeler
authors.affiliation: Institute of Social and Preventive Medicine, University of Bern, Bern, Switzerland; Centre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa. Electronic address: egger@ispm.unibe.ch.
authors.forename: Matthias
authors.initials: M
authors.lastname: Egger
mesh_terms: D000328:Adult; D017954:Africa South of the Sahara / Q000453:epidemiology; D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000706:statistics & numerical data; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D016903:Drug Monitoring; D057915:Drug Substitution / Q000706:statistics & numerical data*; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology; D017320:HIV Protease Inhibitors / Q000627:therapeutic use*; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D008297:Male; D018894:Reverse Transcriptase Inhibitors / Q000627:therapeutic use*; D017211:Treatment Failure; D019562:Viral Load / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D017320:HIV Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors