Kityo, Cissy, Thompson, Jennifer, Nankya, Immaculate, Hoppe, Anne, Ndashimye, Emmanuel, Warambwa, Colin, Mambule, Ivan, van Oosterhout, Joep J, Wools-Kaloustian, Kara, Bertagnolio, Silvia et al (show 4 more authors)
(2017)
HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa.
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, 75 (2).
E45-E54.
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HIV Drug Resistance Mutations in Non-B Subtypes After Prolonged Virological Failure on NNRTI-Based First-Line Regimens in Sub-Saharan Africa.pdf - Published version Download (716kB) | Preview |
Abstract
<h4>Objective</h4>To determine drug resistance mutation (DRM) patterns in a large cohort of patients failing nonnucleoside reverse transcriptase inhibitor (NNRTI)-based first-line antiretroviral therapy regimens in programs without routine viral load (VL) monitoring and to examine intersubtype differences in DRMs.<h4>Design</h4>Sequences from 787 adults/adolescents who failed an NNRTI-based first-line regimen in 13 clinics in Uganda, Kenya, Zimbabwe, and Malawi were analyzed. 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 antiretroviral therapy drugs, CD4, and VL at failure.<h4>Results</h4>The median first-line treatment duration was 4 years (interquartile range 30-43 months); 42% of participants had VL ≥100,000 copies/mL and 63% participants had CD4 <100 cells/mm. Viral subtype distribution was A1 (40%; Uganda and Kenya), C (31%; Zimbabwe and Malawi), and D (25%; Uganda and Kenya), and recombinant/unclassified (5%). In general, DRMs were more common in subtype-C than in subtype-A and/or subtype-D (nucleoside reverse transcriptase inhibitor mutations K65R and Q151M; NNRTI mutations E138A, V106M, Y181C, K101E, and 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 in subtype-D/subtype-A [P (adjusted) < 0.02].<h4>Conclusions</h4>Non-B subtypes differ in DRMs at first-line failure, which impacts on residual nucleoside reverse transcriptase inhibitor and NNRTI susceptibility. In particular, higher rates of etravirine and rilpivirine resistance in subtype-C may limit their potential utility in salvage regimens.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIV, drug resistance, drug resistance mutations, non-B subtype, Africa, first-line failure |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 15 May 2019 08:50 |
| Last Modified: | 16 Mar 2024 13:47 |
| DOI: | 10.1097/QAI.0000000000001285 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3041398 |
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