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HIV diversity and drug resistance from plasma and non-plasma analytes in a large treatment programme in western Kenya

INTRODUCTION: Antiretroviral resistance leads to treatment failure and resistance transmission. Resistance data in western Kenya are limited. Collection of non-plasma analytes may provide additional resistance information. METHODS: We assessed HIV diversity using the REGA tool, transmitted resistanc...

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Autores principales: Kantor, Rami, DeLong, Allison, Balamane, Maya, Schreier, Leeann, Lloyd, Robert M, Injera, Wilfred, Kamle, Lydia, Mambo, Fidelis, Muyonga, Sarah, Katzenstein, David, Hogan, Joseph, Buziba, Nathan, Diero, Lameck
Formato: Online Artículo Texto
Lenguaje:English
Publicado: International AIDS Society 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238965/
https://www.ncbi.nlm.nih.gov/pubmed/25413893
http://dx.doi.org/10.7448/IAS.17.1.19262
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author Kantor, Rami
DeLong, Allison
Balamane, Maya
Schreier, Leeann
Lloyd, Robert M
Injera, Wilfred
Kamle, Lydia
Mambo, Fidelis
Muyonga, Sarah
Katzenstein, David
Hogan, Joseph
Buziba, Nathan
Diero, Lameck
author_facet Kantor, Rami
DeLong, Allison
Balamane, Maya
Schreier, Leeann
Lloyd, Robert M
Injera, Wilfred
Kamle, Lydia
Mambo, Fidelis
Muyonga, Sarah
Katzenstein, David
Hogan, Joseph
Buziba, Nathan
Diero, Lameck
author_sort Kantor, Rami
collection PubMed
description INTRODUCTION: Antiretroviral resistance leads to treatment failure and resistance transmission. Resistance data in western Kenya are limited. Collection of non-plasma analytes may provide additional resistance information. METHODS: We assessed HIV diversity using the REGA tool, transmitted resistance by the WHO mutation list and acquired resistance upon first-line failure by the IAS–USA mutation list, at the Academic Model Providing Access to Healthcare (AMPATH), a major treatment programme in western Kenya. Plasma and four non-plasma analytes, dried blood-spots (DBS), dried plasma-spots (DPS), ViveST(TM)-plasma (STP) and ViveST-blood (STB), were compared to identify diversity and evaluate sequence concordance. RESULTS: Among 122 patients, 62 were treatment-naïve and 60 treatment-experienced; 61% were female, median age 35 years, median CD4 182 cells/µL, median viral-load 4.6 log(10) copies/mL. One hundred and ninety-six sequences were available for 107/122 (88%) patients, 58/62 (94%) treatment-naïve and 49/60 (82%) treated; 100/122 (82%) plasma, 37/78 (47%) attempted DBS, 16/45 (36%) attempted DPS, 14/44 (32%) attempted STP from fresh plasma and 23/34 (68%) from frozen plasma, and 5/42 (12%) attempted STB. Plasma and DBS genotyping success increased at higher VL and shorter shipment-to-genotyping time. Main subtypes were A (62%), D (15%) and C (6%). Transmitted resistance was found in 1.8% of plasma sequences, and 7% combining analytes. Plasma resistance mutations were identified in 91% of treated patients, 76% NRTI, 91% NNRTI; 76% dual-class; 60% with intermediate-high predicted resistance to future treatment options; with novel mutation co-occurrence patterns. Nearly 88% of plasma mutations were identified in DBS, 89% in DPS and 94% in STP. Of 23 discordant mutations, 92% in plasma and 60% in non-plasma analytes were mixtures. Mean whole-sequence discordance from frozen plasma reference was 1.1% for plasma-DBS, 1.2% plasma-DPS, 2.0% plasma-STP and 2.3% plasma-STB. Of 23 plasma-STP discordances, one mutation was identified in plasma and 22 in STP (p<0.05). Discordance was inversely significantly related to VL for DBS. CONCLUSIONS: In a large treatment programme in western Kenya, we report high HIV-1 subtype diversity; low plasma transmitted resistance, increasing when multiple analytes were combined; and high-acquired resistance with unique mutation patterns. Resistance surveillance may be augmented by using non-plasma analytes for lower-cost genotyping in resource-limited settings.
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spelling pubmed-42389652014-11-21 HIV diversity and drug resistance from plasma and non-plasma analytes in a large treatment programme in western Kenya Kantor, Rami DeLong, Allison Balamane, Maya Schreier, Leeann Lloyd, Robert M Injera, Wilfred Kamle, Lydia Mambo, Fidelis Muyonga, Sarah Katzenstein, David Hogan, Joseph Buziba, Nathan Diero, Lameck J Int AIDS Soc Research Article INTRODUCTION: Antiretroviral resistance leads to treatment failure and resistance transmission. Resistance data in western Kenya are limited. Collection of non-plasma analytes may provide additional resistance information. METHODS: We assessed HIV diversity using the REGA tool, transmitted resistance by the WHO mutation list and acquired resistance upon first-line failure by the IAS–USA mutation list, at the Academic Model Providing Access to Healthcare (AMPATH), a major treatment programme in western Kenya. Plasma and four non-plasma analytes, dried blood-spots (DBS), dried plasma-spots (DPS), ViveST(TM)-plasma (STP) and ViveST-blood (STB), were compared to identify diversity and evaluate sequence concordance. RESULTS: Among 122 patients, 62 were treatment-naïve and 60 treatment-experienced; 61% were female, median age 35 years, median CD4 182 cells/µL, median viral-load 4.6 log(10) copies/mL. One hundred and ninety-six sequences were available for 107/122 (88%) patients, 58/62 (94%) treatment-naïve and 49/60 (82%) treated; 100/122 (82%) plasma, 37/78 (47%) attempted DBS, 16/45 (36%) attempted DPS, 14/44 (32%) attempted STP from fresh plasma and 23/34 (68%) from frozen plasma, and 5/42 (12%) attempted STB. Plasma and DBS genotyping success increased at higher VL and shorter shipment-to-genotyping time. Main subtypes were A (62%), D (15%) and C (6%). Transmitted resistance was found in 1.8% of plasma sequences, and 7% combining analytes. Plasma resistance mutations were identified in 91% of treated patients, 76% NRTI, 91% NNRTI; 76% dual-class; 60% with intermediate-high predicted resistance to future treatment options; with novel mutation co-occurrence patterns. Nearly 88% of plasma mutations were identified in DBS, 89% in DPS and 94% in STP. Of 23 discordant mutations, 92% in plasma and 60% in non-plasma analytes were mixtures. Mean whole-sequence discordance from frozen plasma reference was 1.1% for plasma-DBS, 1.2% plasma-DPS, 2.0% plasma-STP and 2.3% plasma-STB. Of 23 plasma-STP discordances, one mutation was identified in plasma and 22 in STP (p<0.05). Discordance was inversely significantly related to VL for DBS. CONCLUSIONS: In a large treatment programme in western Kenya, we report high HIV-1 subtype diversity; low plasma transmitted resistance, increasing when multiple analytes were combined; and high-acquired resistance with unique mutation patterns. Resistance surveillance may be augmented by using non-plasma analytes for lower-cost genotyping in resource-limited settings. International AIDS Society 2014-11-18 /pmc/articles/PMC4238965/ /pubmed/25413893 http://dx.doi.org/10.7448/IAS.17.1.19262 Text en © 2014 Kantor R et al; licensee International AIDS Society http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Kantor, Rami
DeLong, Allison
Balamane, Maya
Schreier, Leeann
Lloyd, Robert M
Injera, Wilfred
Kamle, Lydia
Mambo, Fidelis
Muyonga, Sarah
Katzenstein, David
Hogan, Joseph
Buziba, Nathan
Diero, Lameck
HIV diversity and drug resistance from plasma and non-plasma analytes in a large treatment programme in western Kenya
title HIV diversity and drug resistance from plasma and non-plasma analytes in a large treatment programme in western Kenya
title_full HIV diversity and drug resistance from plasma and non-plasma analytes in a large treatment programme in western Kenya
title_fullStr HIV diversity and drug resistance from plasma and non-plasma analytes in a large treatment programme in western Kenya
title_full_unstemmed HIV diversity and drug resistance from plasma and non-plasma analytes in a large treatment programme in western Kenya
title_short HIV diversity and drug resistance from plasma and non-plasma analytes in a large treatment programme in western Kenya
title_sort hiv diversity and drug resistance from plasma and non-plasma analytes in a large treatment programme in western kenya
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4238965/
https://www.ncbi.nlm.nih.gov/pubmed/25413893
http://dx.doi.org/10.7448/IAS.17.1.19262
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