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.
