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Determination of HIV-1 coreceptor tropism using proviral DNA in women before and after viral suppression

BACKGROUND: An HIV-1 tropism test is recommended prior to CCR5 antagonist administration to exclude patients harboring non-R5 virus from treatment with this class of antiretrovirals. HIV-1 tropism determination based on proviral DNA (pvDNA) may be useful in individuals with plasma viral RNA suppress...

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Autores principales: Baumann, Russell E, Rogers, Amy A, Hamdan, Hasnah B, Burger, Harold, Weiser, Barbara, Gao, Wei, Anastos, Kathryn, Young, Mary, Meyer, William A, Pesano, Rick L, Kagan, Ron M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403710/
https://www.ncbi.nlm.nih.gov/pubmed/25897314
http://dx.doi.org/10.1186/s12981-015-0055-x
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author Baumann, Russell E
Rogers, Amy A
Hamdan, Hasnah B
Burger, Harold
Weiser, Barbara
Gao, Wei
Anastos, Kathryn
Young, Mary
Meyer, William A
Pesano, Rick L
Kagan, Ron M
author_facet Baumann, Russell E
Rogers, Amy A
Hamdan, Hasnah B
Burger, Harold
Weiser, Barbara
Gao, Wei
Anastos, Kathryn
Young, Mary
Meyer, William A
Pesano, Rick L
Kagan, Ron M
author_sort Baumann, Russell E
collection PubMed
description BACKGROUND: An HIV-1 tropism test is recommended prior to CCR5 antagonist administration to exclude patients harboring non-R5 virus from treatment with this class of antiretrovirals. HIV-1 tropism determination based on proviral DNA (pvDNA) may be useful in individuals with plasma viral RNA suppression. We developed a genotypic tropism assay for pvDNA and assessed its performance in a retrospective analysis of samples collected longitudinally. RESULTS: We randomly selected paired plasma/PBMC samples from the Women’s Interagency HIV Study with plasma viral load ≥5,000 cp/mL at time 1 (T1), undetectable viral load maintained for ≥1 year and CD4+ >200 cells/μL at time 2 (T2). pvDNA was isolated from cryopreserved PBMCs. Sequences were analyzed in triplicate from 49/50 women, with tropism assigned using the geno2pheno (g2p) algorithm. The median time between T1 and T2 was 4.1 years. CXCR4-using virus was detected in 24% of the RNA samples and 33% of the pvDNA samples at T1, compared to 37% of the pvDNA samples at T2. Concordance between plasma RNA and pvDNA tropism was 88% at T1 and 80% at T2. The g2p scores for RNA (T1) vs DNA (T1, T2) were strongly correlated (Spearman rho: 0.85 (T1); 0.78 (T2)). In women with evidence of tropism switch at T2 (either R5 to non-R5 or non-R5 to R5), there was a correlation between change in tropism and time. Mean pvDNA viral load decreased by 0.4 log10 copies/106 cells between T1 and T2 (p < 0.0001), but this decrease was not significantly associated with tropism status. CONCLUSIONS: We demonstrated that pvDNA tropism in women with HIV-1 suppression is concordant with prior RNA tropism results, even after a median time of >4 years. pvDNA tropism testing may be useful to determine eligibility of patients with viral suppression to switch to a CCR5-antagonist based regimen as well as for research purposes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12981-015-0055-x) contains supplementary material, which is available to authorized users.
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spelling pubmed-44037102015-04-21 Determination of HIV-1 coreceptor tropism using proviral DNA in women before and after viral suppression Baumann, Russell E Rogers, Amy A Hamdan, Hasnah B Burger, Harold Weiser, Barbara Gao, Wei Anastos, Kathryn Young, Mary Meyer, William A Pesano, Rick L Kagan, Ron M AIDS Res Ther Research BACKGROUND: An HIV-1 tropism test is recommended prior to CCR5 antagonist administration to exclude patients harboring non-R5 virus from treatment with this class of antiretrovirals. HIV-1 tropism determination based on proviral DNA (pvDNA) may be useful in individuals with plasma viral RNA suppression. We developed a genotypic tropism assay for pvDNA and assessed its performance in a retrospective analysis of samples collected longitudinally. RESULTS: We randomly selected paired plasma/PBMC samples from the Women’s Interagency HIV Study with plasma viral load ≥5,000 cp/mL at time 1 (T1), undetectable viral load maintained for ≥1 year and CD4+ >200 cells/μL at time 2 (T2). pvDNA was isolated from cryopreserved PBMCs. Sequences were analyzed in triplicate from 49/50 women, with tropism assigned using the geno2pheno (g2p) algorithm. The median time between T1 and T2 was 4.1 years. CXCR4-using virus was detected in 24% of the RNA samples and 33% of the pvDNA samples at T1, compared to 37% of the pvDNA samples at T2. Concordance between plasma RNA and pvDNA tropism was 88% at T1 and 80% at T2. The g2p scores for RNA (T1) vs DNA (T1, T2) were strongly correlated (Spearman rho: 0.85 (T1); 0.78 (T2)). In women with evidence of tropism switch at T2 (either R5 to non-R5 or non-R5 to R5), there was a correlation between change in tropism and time. Mean pvDNA viral load decreased by 0.4 log10 copies/106 cells between T1 and T2 (p < 0.0001), but this decrease was not significantly associated with tropism status. CONCLUSIONS: We demonstrated that pvDNA tropism in women with HIV-1 suppression is concordant with prior RNA tropism results, even after a median time of >4 years. pvDNA tropism testing may be useful to determine eligibility of patients with viral suppression to switch to a CCR5-antagonist based regimen as well as for research purposes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12981-015-0055-x) contains supplementary material, which is available to authorized users. BioMed Central 2015-04-18 /pmc/articles/PMC4403710/ /pubmed/25897314 http://dx.doi.org/10.1186/s12981-015-0055-x Text en © Baumann et al.; licensee BioMed Central. 2015 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Baumann, Russell E
Rogers, Amy A
Hamdan, Hasnah B
Burger, Harold
Weiser, Barbara
Gao, Wei
Anastos, Kathryn
Young, Mary
Meyer, William A
Pesano, Rick L
Kagan, Ron M
Determination of HIV-1 coreceptor tropism using proviral DNA in women before and after viral suppression
title Determination of HIV-1 coreceptor tropism using proviral DNA in women before and after viral suppression
title_full Determination of HIV-1 coreceptor tropism using proviral DNA in women before and after viral suppression
title_fullStr Determination of HIV-1 coreceptor tropism using proviral DNA in women before and after viral suppression
title_full_unstemmed Determination of HIV-1 coreceptor tropism using proviral DNA in women before and after viral suppression
title_short Determination of HIV-1 coreceptor tropism using proviral DNA in women before and after viral suppression
title_sort determination of hiv-1 coreceptor tropism using proviral dna in women before and after viral suppression
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4403710/
https://www.ncbi.nlm.nih.gov/pubmed/25897314
http://dx.doi.org/10.1186/s12981-015-0055-x
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