title: Third-line antiretroviral therapy in Africa: effectiveness in a Southern African retrospective cohort study.
abstract: BACKGROUND
  An increasing number of patients in Africa are experiencing virologic failure on second-line antiretroviral therapy (ART) and those who develop resistance to protease inhibitors (PI) will require third-line ART, but no data on the outcomes of third-line are available from the region. We assessed the virologic outcomes and survival of patients started on salvage ART in a Southern African private sector disease management programme.
  
  
  METHODS
  Retrospective observational cohort study with linkage to the national death register. Adults (≥18 years) who started salvage ART between July 2007 and December 2011 were included. Salvage ART was defined by inclusion of darunavir or tipranavir in an ART regimen after having failed another PI. For Kaplan-Meier (KM) analysis, patients were followed up until event, or censored at death (only for virologic outcomes), leaving the programme, or April 2014.
  
  
  RESULTS
  152 patients were included. Subtype was known for 113 patients: 111 (98 %) were infected with subtype C. All 152 had a genotype resistance test demonstrating major PI resistance mutations. Salvage drugs included were: darunavir/ritonavir (n = 149), tipranavir/ritonavir (n = 3), raltegravir (n = 58), and etravirine (n = 8). Median follow-up was 2.5 years (IQR = 1.5-3.3). 82.9 % achieved a viral load ≤400 copies/ml and 71.1 % ≤50 copies/ml. By the end of the study 17 (11.2 %) of the patients had died. The KM estimate of cumulative survival was 87.2 % at 2000 days.
  
  
  CONCLUSIONS
  Virologic suppression was comparable to that demonstrated in clinical trials and observational studies of salvage ART drugs conducted in other regions. Few deaths occurred during short term follow-up. Third-line regimens for patients with multidrug resistant subtype C HIV in Africa are virologically and clinically effective.
authors.affiliation: Clinical Infectious Diseases Research Initiative (CIDRI), Institute of Infectious Disease and Molecular Medicine (IDM), Faculty of Health Sciences, University of Cape Town, Anzio Road, Observatory, Cape Town, 7925 South Africa ; Division of Infectious Diseases and HIV Medicine, Department of Medicine, University of Cape Town, Cape Town, South Africa ; Department of Medicine, Imperial College London, London, UK.
authors.forename: Graeme
authors.initials: G
authors.lastname: Meintjes
authors.affiliation: Aid for AIDS Management, Afrocentric Health Pty Ltd, The Boulevard, Block G, Searle Street, Woodstock, 7925 South Africa.
authors.forename: Liezl
authors.initials: L
authors.lastname: Dunn
authors.affiliation: Aid for AIDS Management, Afrocentric Health Pty Ltd, The Boulevard, Block G, Searle Street, Woodstock, 7925 South Africa.
authors.forename: Marla
authors.initials: M
authors.lastname: Coetsee
authors.affiliation: Aid for AIDS Management, Afrocentric Health Pty Ltd, The Boulevard, Block G, Searle Street, Woodstock, 7925 South Africa.
authors.forename: Michael
authors.initials: M
authors.lastname: Hislop
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Groote Schuur Hospital Old Main Building, Observatory, Cape Town, 7925 South Africa.
authors.forename: Rory
authors.initials: R
authors.lastname: Leisegang
authors.affiliation: Aid for AIDS Management, Afrocentric Health Pty Ltd, The Boulevard, Block G, Searle Street, Woodstock, 7925 South Africa.
authors.forename: Leon
authors.initials: L
authors.lastname: Regensberg
authors.affiliation: Division of Clinical Pharmacology, Department of Medicine, University of Cape Town, Groote Schuur Hospital Old Main Building, Observatory, Cape Town, 7925 South Africa.
authors.forename: Gary
authors.initials: G
authors.lastname: Maartens
keywords: Antiretroviral therapy; HIV; Human immunodeficiency virus; Salvage; Third-line; Virologic failure