title: Tenofovir in second-line ART in Zambia and South Africa: collaborative analysis of cohort studies.
abstract: OBJECTIVE
  Tenofovir (TDF) is increasingly used in second-line antiretroviral treatment (ART) in sub-Saharan Africa. We compared outcomes of second-line ART containing and not containing TDF in cohort studies from Zambia and the Republic of South Africa (RSA).
  
  
  METHODS
  Patients aged 16 years and older starting protease-inhibitor-based second-line ART in Zambia (1 cohort) and RSA (5 cohorts) were included. We compared mortality, immunological failure (all cohorts), and virological failure (RSA only) between patients receiving and not receiving TDF. Competing risk models and Cox models adjusted for age, sex, CD4 count, time on first-line ART, and calendar year were used to analyze mortality and treatment failure, respectively. Hazard ratios (HRs) were combined in fixed-effects meta-analysis.
  
  
  RESULTS
  1687 patients from Zambia and 1556 patients from RSA, including 1350 (80.0%) and 206 (13.2%) patients starting TDF, were followed over 4471 person-years. Patients on TDF were more likely to have started second-line ART in recent years and had slightly higher baseline CD4 counts than patients not on TDF. Overall, 127 patients died, 532 were lost to follow-up, and 240 patients developed immunological failure. In RSA, 94 patients had virologic failure. Combined HRs comparing TDF with other regimens were 0.60 (95% confidence interval [CI]: 0.41 to 0.87) for immunologic failure and 0.63 (0.38-1.05) for mortality. The HR for virologic failure in RSA was 0.28 (0.09-0.90).
  
  
  CONCLUSIONS
  In this observational study, patients on TDF-containing second-line ART were less likely to develop treatment failure than patients on other regimens. TDF seems to be an effective component of second-line ART in southern Africa.
authors: Division of International and Environmental Health, Institute of Social and Preventive Medicine, University of Bern, Finkenhubelweg 11, CH-3012 Bern, Switzerland. gwandeler@ispm.unibe.ch
authors: Gilles
authors: G
authors: Wandeler
authors: Olivia
authors: O
authors: Keiser
authors: Lloyd
authors: L
authors: Mulenga
authors: Christopher J
authors: CJ
authors: Hoffmann
authors: Robin
authors: R
authors: Wood
authors: Thom
authors: T
authors: Chaweza
authors: Alana
authors: A
authors: Brennan
authors: Hans
authors: H
authors: Prozesky
authors: Daniela
authors: D
authors: Garone
authors: Janet
authors: J
authors: Giddy
authors: Cleophas
authors: C
authors: Chimbetete
authors: Andrew
authors: A
authors: Boulle
authors: Matthias
authors: M
authors: Egger
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000328:Adult; D017954:Africa South of the Sahara; D044966:Anti-Retroviral Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D018791:CD4 Lymphocyte Count; D015331:Cohort Studies; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D063065:Organophosphonates / Q000627:therapeutic use*; D013019:South Africa; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D015024:Zambia
chemical_list: D044966:Anti-Retroviral Agents; D063065:Organophosphonates; D000068698:Tenofovir; D000225:Adenine