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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Accumulation of Protease Mutations among Patients Failing Second-Line Antiretroviral Therapy and Response to Salvage Therapy in Nigeria
PLoS ONE, Volume 8, No. 9, Article e73582, Year 2013
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Description
Background:To date, antiretroviral therapy (ART) guidelines and programs in resource-limited settings (RLS) have focused on 1st- and 2nd-line (2 L) therapy. As programs approach a decade of implementation, policy regarding access to 3rd-line (3 L) ART is needed. We aimed to examine the impact of maintaining patients on failing 2 L ART on the accumulation of protease (PR) mutations.Methods and Findings:From 2004-2011, the Harvard/APIN PEPFAR Program provided ART to >100,000 people in Nigeria. Genotypic resistance testing was performed on a subset of patients experiencing 2 L failure, defined as 2 consecutive viral loads (VL)>1000 copies/mL after ≥6 months on 2 L. Of 6714 patients who received protease inhibitor (PI)-based ART, 673 (10.0%) met virologic failure criteria. Genotypes were performed on 61 samples. Patients on non-suppressive 2 L therapy for <12 months prior to genotyping had a median of 2 (IQR: 0-5) International AIDS Society (IAS) PR mutations compared with 5 (IQR: 0-6) among patients failing for >24 months. Patients developed a median of 0.6 (IQR: 0-1.4) IAS PR mutations per 6 months on failing 2 L therapy. In 38% of failing patients no PR mutations were present. For patients failing >24 months, high- or intermediate-level resistance to lopinavir and atazanavir was present in 63%, with 5% to darunavir.Conclusions:This is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a RLS. This information provides insight into the resistance cost of failing to switch non-suppressive 2 L regimens and highlights the issue of 3 L access. © 2013 Rawizza et al.
Authors & Co-Authors
Rawizza, Holly E.
United States, Boston
Brigham and Women's Hospital
United States, Boston
Harvard T.h. Chan School of Public Health
Chaplin, Beth R.
United States, Boston
Harvard T.h. Chan School of Public Health
Meloni, Seema Thakore
United States, Boston
Harvard T.h. Chan School of Public Health
Darin, Kristin M.
United States, Chicago
Northwestern University Feinberg School of Medicine
Olaitan, Oluremi
Nigeria, Abuja
Apin Public Health Initiatives Ltd./gte
Scarsi, Kimberly K.
United States, Chicago
Northwestern University Feinberg School of Medicine
Onwuamah, C.
Nigeria, Yaba
Nigerian Institute of Medical Research
Audu, Rosemary Ajuma
Nigeria, Yaba
Nigerian Institute of Medical Research
Chebu, Philippe R.
Nigeria, Jos
University of Jos
Imade, Godwin Eremwan
Nigeria, Jos
University of Jos
Okonkwo, Prosper I.
Nigeria, Abuja
Apin Public Health Initiatives Ltd./gte
Kanki, Phyllis Jean
United States, Boston
Harvard T.h. Chan School of Public Health
Statistics
Citations: 38
Authors: 12
Affiliations: 6
Identifiers
Doi:
10.1371/journal.pone.0073582
e-ISSN:
19326203
Research Areas
Health System And Policy
Infectious Diseases
Study Locations
Nigeria