HIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan Africa

for the Europe Africa Research Network for Evaluation of Second-line Therapy (EARNEST)Trial Team

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

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. 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. 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/mm. 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). 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.

Original languageEnglish (US)
JournalJournal of Acquired Immune Deficiency Syndromes
DOIs
StateAccepted/In press - Jan 25 2017

Fingerprint

Rilpivirine
Reverse Transcriptase Inhibitors
Africa South of the Sahara
etravirine
Drug Resistance
Uganda
Kenya
Viral Load
HIV
Malawi
Zimbabwe
Mutation
Tenofovir
Zidovudine
R Factors
Logistic Models
Drug Therapy
Therapeutics

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Infectious Diseases

Cite this

HIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan Africa. / for the Europe Africa Research Network for Evaluation of Second-line Therapy (EARNEST)Trial Team.

In: Journal of Acquired Immune Deficiency Syndromes, 25.01.2017.

Research output: Contribution to journalArticle

@article{e43dc5aa4b5043be92b618a1993616ae,
title = "HIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan Africa",
abstract = "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. 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. 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/mm. 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). 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.",
author = "{for the Europe Africa Research Network for Evaluation of Second-line Therapy (EARNEST)Trial Team} and Cissy Kityo and Jennifer Thompson and Immaculate Nankya and Anne Hoppe and Emmanuel Ndashimye and Colin Warambwa and Ivan Mambule and {van Oosterhout}, {Joep J.} and Kara Wools-Kaloustian and Silvia Bertagnolio and Easterbrook, {Philippa J.} and Peter Mugyenyi and Walker, {Sarah S.} and Nicholas Paton",
year = "2017",
month = "1",
day = "25",
doi = "10.1097/QAI.0000000000001285",
language = "English (US)",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",

}

TY - JOUR

T1 - HIV drug resistance mutations in non-B subtypes after prolonged virological failure on NNRTI-based first-line regimens in sub-Saharan Africa

AU - for the Europe Africa Research Network for Evaluation of Second-line Therapy (EARNEST)Trial Team

AU - Kityo, Cissy

AU - Thompson, Jennifer

AU - Nankya, Immaculate

AU - Hoppe, Anne

AU - Ndashimye, Emmanuel

AU - Warambwa, Colin

AU - Mambule, Ivan

AU - van Oosterhout, Joep J.

AU - Wools-Kaloustian, Kara

AU - Bertagnolio, Silvia

AU - Easterbrook, Philippa J.

AU - Mugyenyi, Peter

AU - Walker, Sarah S.

AU - Paton, Nicholas

PY - 2017/1/25

Y1 - 2017/1/25

N2 - 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. 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. 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/mm. 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). 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.

AB - 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. 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. 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/mm. 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). 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.

UR - http://www.scopus.com/inward/record.url?scp=85010900106&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85010900106&partnerID=8YFLogxK

U2 - 10.1097/QAI.0000000000001285

DO - 10.1097/QAI.0000000000001285

M3 - Article

C2 - 28129253

AN - SCOPUS:85010900106

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

ER -