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HIV drug resistance mutations among patients failing second-line antiretroviral therapy in Rwanda

Jean d’Amour Ndahimana, David J Riedel, Ribakare Muhayimpundu, Sabin Nsanzimana, Gad Niyibizi, Emmanuel Mutaganzwa, Augustin Mulindabigwi, Cyprien Baribwira, Athanase Kiromera, Linda L Jagodzinski, Sheila A Peel, Robert R Redfield

Corresponding author name: David J Riedel
Corresponding author e-mail: driedel@ihv.umaryland.edu

Citation: Antiviral Therapy 2016; 21:253-259
doi: 10.3851/IMP3005

Date accepted: 04 October 2015
Date published online: 12 November 2015

Abstract

Background: Studies of patients failing second-line antiretroviral therapy (ART) in resource-limited settings (RLS) are few. Evidence suggests most patients who appear to be virologically failing do so not due to drug resistance but to poor adherence, which, if properly addressed, could allow continued use of less expensive first- and second-line regimens. Drug resistant mutations (DRMs) were characterized among patients virologically failing second-line ART in Rwanda.

Methods: A total of 128 adult patients receiving second-line ART for at least 6 months were invited to participate; 74 agreed and had HIV-1 viral load (VL) measured. Resistance genotypes were conducted in patients with virological failure (VF; that is, VL ≥1,000 copies/ml).

Results: In total, 35 patients met the criteria for VF. The median time on lopinavir/ritonavir-based second-line ART was 2.7 years. Of 30 successful resistance genotype analyses, 13 (43%) had ≥1 nucleoside reverse transcriptase inhibitor (NRTI) mutation, 18 (60%) had at least 1 non-NRTI mutation and 5 (17%) had at least 1 major protease inhibitor mutation. Eleven (37%) had virus without significant mutations that would be fully sensitive to first-line ART; 12 (40%) had DRM to first-line ART but sensitive to second-line ART. Only 7 patients (23%) demonstrated a DRM profile requiring third-line ART.

Conclusions: Among 30 genotyped samples of patients with VF on second-line ART, more than one-third had no significant DRMs, implicating poor adherence as the primary cause of VF. The majority of patients (77%) would not have required third-line ART. These findings reinforce the need for intensive adherence assessment and counselling for patients who appear to be failing second-line ART in RLS.

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