| Summary: | <p>Objective: To determine drug resistance mutation (DRM) patterns in a large cohort of patients failing non-nucleoside-reverse-transcriptase-inhibitor (NNRTI)-based first-line antiretroviral therapy (ART) regimens in programmes without routine viral load (VL) monitoring and to examine inter-subtype differences in DRMs. </p> <p>Design: Sequences from 787 adults/adolescents who failed an NNRTI-based first-line regimen in 13 clinics in Uganda, Kenya, Zimbabwe, Malawi were analysed. Multivariable logistic regression was used to determine the association between specific DRMs and Stanford intermediate/high-level resistance and factors including REGA subtype, first-line ART drugs, CD4 and VL at failure. </p> <p>Results: The median first-line treatment duration was 4 years (IQR 30-43 months); 42% of participants had VL ≥100,000 c/ml and 63% had CD4<100cells/mm3. Viral subtype distribution was A1 (40%; Uganda, Kenya), C (31%; Zimbabwe, Malawi) and D (25%; Uganda, Kenya) and recombinant/unclassified (5%). In general, DRMs were more common in subtype-C than in subtypes-A and/or –D (NRTI mutations K65R and Q151M; NNRTI mutations E138A, V106M, Y181C, K101E, H221Y). The presence of tenofovir resistance was similar between subtypes (p(adjusted)=0.32), but resistance to zidovudine, abacavir, etravirine or rilpivirine was more common in subtype-C than D/A (p(adjusted)<0.02). </p> <p>Conclusions: Non-B subtypes differ in DRMs at first-line failure that impact on residual NRTI and NNRTI susceptibility. In particular, higher rates of etravirine and rilpivirine resistance in subtype-C may limit their potential utility in salvage regimens. </p>
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