Accumulation of Protease Mutations among Patients Failing Second-Line Antiretroviral Therapy and Response to Salvage Therapy in NigeriaReportar como inadecuado




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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.



Autor: Holly E. Rawizza , Beth Chaplin, Seema T. Meloni, Kristin M. Darin, Oluremi Olaitan, Kimberly K. Scarsi, Chika K. Onwuamah, Rosem

Fuente: http://plos.srce.hr/



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