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HIV-1 second-line failure and drug resistance at high-level and low-level viremia in Western Kenya

Kantor, Ramia; DeLong, Allisonb; Schreier, Leeanna; Reitsma, Marissaa; Kemboi, Emanuelc; Orido, Millicentc; Obonge, Salomec; Boinett, Robertc; Rono, Maryc; Emonyi, Wilfredc; Brooks, Katiea; Coetzer, Miaa; Buziba, Nathanc,d; Hogan, Josephb; Diero, Lameckc,d

doi: 10.1097/QAD.0000000000001964
CLINICAL SCIENCE
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Objective: Characterize failure and resistance above and below guidelines-recommended 1000 copies/ml virologic threshold, upon second-line failure.

Design: Cross-sectional study.

Methods: Kenyan adults on lopinavir/ritonavir-based second-line were enrolled at AMPATH (Academic Model Providing Access to Healthcare). Charts were reviewed for demographic/clinical characteristics and CD4+/viral load were obtained. Participants with detectable viral load had a second visit and pol genotyping was attempted in both visits. Accumulated resistance was defined as mutations in the second, not the first visit. Low-level viremia (LLV) was detectable viral load less than 1000 copies/ml. Failure and resistance associations were evaluated using logistic and Poisson regression, Fisher Exact and t-tests.

Results: Of 394 participants (median age 42, 60% women, median 1.9 years on second-line) 48% had detectable viral load; 21% had viral load more than 1000 copies/ml, associated with younger age, tuberculosis treatment, shorter time on second-line, lower CD4+count/percentage, longer first-line treatment interruption and pregnancy. In 105 sequences from the first visit (35 with LLV), 79% had resistance (57% dual-class, 7% triple-class; 46% with intermediate-to-high-level resistance to ≥1 future drug option). LLV was associated with more overall and NRTI-associated mutations and with predicted resistance to more next-regimen drugs. In 48 second-visit sequences (after median 55 days; IQR 28–33), 40% accumulated resistance and LLV was associated with more mutation accumulation.

Conclusion: High resistance upon second-line failure exists at levels above and below guideline-recommended virologic-failure threshold, impacting future treatment options. Optimization of care should include increased viral load monitoring, resistance testing and third-line ART access, and consideration of lowering the virologic failure threshold, though this demands further investigation.

aDivision of Infectious Diseases, Alpert Medical School

bCenter for Statistical Sciences, Brown University, Providence, Rhode Island, USA

cAcademic Model Providing Access to Healthcare (AMPATH)

dDepartment of Medicine, School of Medicine, College of Health Sciences, Moi University, Eldoret, Kenya.

Correspondence to Rami Kantor, MD, Professor of Medicine, Division of Infectious Diseases, Brown University Alpert Medical School, The Miriam Hospital, RISE 154, 164 Summit Avenue, Providence, RI 02906, USA. Tel: +1 401 7934997; fax: +1 401 7934709; e-mail: rkantor@brown.edu

Received 5 December, 2017

Accepted 13 March, 2018

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Copyright © 2018 Wolters Kluwer Health, Inc.