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Treatment outcomes of patients on second-line antiretroviral therapy in resource-limited settings: a systematic review and meta-analysis

Ajose, Olawalea; Mookerjee, Siddharthb; Mills, Edward J.c; Boulle, Andrewd; Ford, Nathand,e

doi: 10.1097/QAD.0b013e328351f5b2
Clinical Science

Background: A growing proportion of patients on antiretroviral therapy in resource-limited settings have switched to second-line regimens. We carried out a systematic review in order to summarize reported rates and reasons for virological failure among people on second-line therapy in resource-limited settings.

Methods: Two reviewers independently searched four databases and three conference websites. Full text articles were screened and data extracted using a standardized data extraction form.

Results: We retrieved 5812 citations, of which 19 studies reporting second-line failure rates in 2035 patients across low-income and middle-income countries were eligible for inclusion. The cumulative pooled proportion of adult patients failing virologically was 21.8, 23.1, 26.7 and 38.0% at 6, 12, 24 and 36 months, respectively. Most studies did not report adequate information to allow discrimination between drug resistance and poor adherence as reasons for virological failure, but for those that did poor adherence appeared to be the main driver of virological failure. Mortality on second-line was low across all time points.

Conclusion: Rates of virological failure on second-line therapy are high in resource-limited settings and associated with duration of exposure to previous drug regimens and poor adherence. The main concern appears to be poor adherence, rather than drug resistance, from the limited number of studies accessing both factors. Access to treatment options beyond second-line remains limited and, therefore, a cause for a concern for those patients in whom drug resistance is the identified cause of virological failure.

aClinton Health Access Initiative, Dar es Salaam, Tanzania

bNational Centre for Infection Prevention and Management, Imperial College, London, UK

cFaculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada

dCentre for Infectious Disease Epidemiology and Research, University of Cape Town, Cape Town, South Africa

eMédecins Sans Frontières, Geneva, Switzerland.

Correspondence to Dr Nathan Ford, Médecins Sans Frontières, rue de Lausanne, 1211 Geneva, Switzerland. E-mail:

Received 28 November, 2011

Revised 13 January, 2012

Accepted 30 January, 2012

© 2012 Lippincott Williams & Wilkins, Inc.