Abstract
IntroductionIn resource limited settings, patients entering an antiretroviral therapy (ART) program comprise ART naive and ART pre-treated patients who may show differential virological outcomes.MethodsThis retrospective study, conducted in 2010–2012 in the HIV clinic of Calmette Hospital located in Phnom Penh (Cambodia) assessed virological failure (VF) rates and patterns of drug resistance of naive and pre-treated patients. Naive and ART pre-treated patients were included when a Viral Load (VL) was performed during the first year of ART for naive subjects or at the first consultation for pre-treated individuals. Patients showing Virological failure (VF) (>1,000 copies/ml) underwent HIV DR genotyping testing. Interpretation of drug resistance mutations was done according to 2013 version 23 ANRS algorithms.ResultsOn a total of 209 patients, 164 (78.4%) were naive and 45 (21.5%) were ART pre-treated. Their median initial CD4 counts were 74 cells/mm3 (IQR: 30–194) and 279 cells/mm3 (IQR: 103–455) (p<0.001), respectively. Twenty seven patients (12.9%) exhibited VF (95% CI: 8.6–18.2%), including 10 naive (10/164, 6.0%) and 17 pre-treated (17/45, 37.8%) patients (p<0.001). Among these viremic patients, twenty-two (81.4%) were sequenced in reverse transcriptase and protease coding regions. Overall, 19 (86.3%) harbored ≥1 drug resistance mutations (DRMs) whereas 3 (all belonging to pre-treated patients) harbored wild-types viruses. The most frequent DRMs were M184V (86.3%), K103N (45.5%) and thymidine analog mutations (TAMs) (40.9%). Two (13.3%) pre-treated patients harbored viruses that showed a multi-nucleos(t)ide resistance including Q151M, K65R, E33A/D, E44A/D mutations.ConclusionIn Cambodia, VF rates were low for naive patients but the emergence of DRMs to NNRTI and 3TC occurred relatively quickly in this subgroup. In pre-treated patients, VF rates were much higher and TAMs were relatively common. HIV genotypic assays before ART initiation and for ART pre-treated patients infection should be considered as well.
Highlights
In resource limited settings, patients entering an antiretroviral therapy (ART) program comprise ART naive and ART pre-treated patients who may show differential virological outcomes
Minimizing resistance is important in resource limited settings with limited ART options usually restricted to first-line nonnucleoside reverse transcriptase inhibitor (NNRTI)-based and second-line protease inhibitor (PI)based regimens [6]
Access to Viral Load (VL) and drug resistance testing in case of virological failure [VF]) is crucial to limit misdiagnosis of treatment failure which leads to undetected accumulation of resistance mutations or to avoid unnecessary ART switches to more expensive ART [7]
Summary
Patients entering an antiretroviral therapy (ART) program comprise ART naive and ART pre-treated patients who may show differential virological outcomes. The majority of patients are switched to a second-line ART regimen according to WHO clinical and immunologic criteria, due to lack or paucity of viral load (VL) monitoring [2,3]. These criteria lack both sensitivity and specificity and are associated with unacceptable treatment failure misclassification [4,5]. Access to VL and drug resistance testing in case of virological failure [VF]) is crucial to limit misdiagnosis of treatment failure which leads to undetected accumulation of resistance mutations or to avoid unnecessary ART switches to more expensive ART [7]. Late diagnosis of treatment failure is associated with accumulated drug resistance mutations and high level cross resistance to subsequent regimens [10]
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