HIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan Africa
<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-s...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Journal article |
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Lippincott, Williams & Wilkins
2017
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| _version_ | 1797065537864335360 |
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| author | Kityo, C Thompson, J Nankya, I Hoppe, A Ndashimye, E Warambwa, C Mambule, I van Oosterhout, J Wools-Kaloustian, K Bertagnolio, S Easterbrook, P Mugyenyi, P Walker, A Paton, N For the Europe Africa Research Network for Evaluation of Second-line Therapy (EARNEST)Trial Team |
| author_facet | Kityo, C Thompson, J Nankya, I Hoppe, A Ndashimye, E Warambwa, C Mambule, I van Oosterhout, J Wools-Kaloustian, K Bertagnolio, S Easterbrook, P Mugyenyi, P Walker, A Paton, N For the Europe Africa Research Network for Evaluation of Second-line Therapy (EARNEST)Trial Team |
| author_sort | Kityo, C |
| collection | OXFORD |
| description | <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> |
| first_indexed | 2024-03-06T21:30:02Z |
| format | Journal article |
| id | oxford-uuid:446236b1-c225-43af-bfd7-7fb818a015aa |
| institution | University of Oxford |
| last_indexed | 2024-03-06T21:30:02Z |
| publishDate | 2017 |
| publisher | Lippincott, Williams & Wilkins |
| record_format | dspace |
| spelling | oxford-uuid:446236b1-c225-43af-bfd7-7fb818a015aa2022-03-26T15:01:16ZHIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan AfricaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:446236b1-c225-43af-bfd7-7fb818a015aaSymplectic Elements at OxfordLippincott, Williams & Wilkins2017Kityo, CThompson, JNankya, IHoppe, ANdashimye, EWarambwa, CMambule, Ivan Oosterhout, JWools-Kaloustian, KBertagnolio, SEasterbrook, PMugyenyi, PWalker, APaton, NFor the Europe Africa Research Network for Evaluation of Second-line Therapy (EARNEST)Trial Team<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> |
| spellingShingle | Kityo, C Thompson, J Nankya, I Hoppe, A Ndashimye, E Warambwa, C Mambule, I van Oosterhout, J Wools-Kaloustian, K Bertagnolio, S Easterbrook, P Mugyenyi, P Walker, A Paton, N For the Europe Africa Research Network for Evaluation of Second-line Therapy (EARNEST)Trial Team HIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan Africa |
| title | HIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan Africa |
| title_full | HIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan Africa |
| title_fullStr | HIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan Africa |
| title_full_unstemmed | HIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan Africa |
| title_short | HIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan Africa |
| title_sort | hiv drug resistance mutations in non b subtypes after prolonged virological failure on nnrti based first line regimens in sub saharan africa |
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