Abstract
BackgroundTo 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 FindingsFrom 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.ConclusionsThis 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.
Highlights
Over 8 million individuals living with HIV in low- and middleincome countries are receiving antiretroviral therapy (ART) [1]
This is the first report assessing the impact of duration of non-suppressive 2 L therapy on the accumulation of PR resistance in a resource-limited settings (RLS)
Second-line ART consisted of a ritonavir-boosted protease inhibitor (PI) plus 2 nucleoside reverse transcriptase inhibitors (NRTI)
Summary
Over 8 million individuals living with HIV in low- and middleincome countries are receiving antiretroviral therapy (ART) [1]. As large-scale ART programs in resource-limited settings (RLS) approach a decade of implementation, the 2010 World Health Organization (WHO) public health guidelines for the first time raised the issue of access to third-line ART and called on national programs to delineate policies [2]. A number of studies suggest that the majority of patients who fail 2 L ART do so with minimal drug resistance, suggesting poor adherence rather than resistance as the cause of failure. Wild-type virus was present at the time of failure in up to 67% of patients with no major protease (PR) mutations identified [11,12]. 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
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