Accumulation of Protease Mutations among Patients Failing Second-Line Antiretroviral Therapy and Response to Salvage Therapy in Nigeria
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Author
Meloni, Seema T.
Darin, Kristin M.
Olaitan, Oluremi
Scarsi, Kimberly K.
Onwuamah, Chika K.
Audu, Rosemary A.
Chebu, Philippe R.
Imade, Godwin E.
Okonkwo, Prosper
Note: Order does not necessarily reflect citation order of authors.
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https://doi.org/10.1371/journal.pone.0073582Metadata
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Rawizza, H. E., B. Chaplin, S. T. Meloni, K. M. Darin, O. Olaitan, K. K. Scarsi, C. K. Onwuamah, et al. 2013. “Accumulation of Protease Mutations among Patients Failing Second-Line Antiretroviral Therapy and Response to Salvage Therapy in Nigeria.” PLoS ONE 8 (9): e73582. doi:10.1371/journal.pone.0073582. http://dx.doi.org/10.1371/journal.pone.0073582.Abstract
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.Other Sources
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3775797/pdf/Terms of Use
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