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

Russell E. Baumann, Amy A. Rogers, Hasnah B. Hamdan, Harold Burger, Barbara Weiser, Wei Gao, Kathryn Anastos, Mary Young, William A. Meyer, Rick L. Pesano, Ron M. Kagan

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number11
JournalAIDS Research and Therapy
Volume12
Issue number1
DOIs
StatePublished - Apr 18 2015

Fingerprint

Tropism
HIV-1
DNA
Viral Load
RNA
Viruses
Viral RNA

Keywords

  • HIV
  • pvDNA
  • Tropism

ASJC Scopus subject areas

  • Virology
  • Molecular Medicine
  • Pharmacology (medical)

Cite this

Baumann, R. E., Rogers, A. A., Hamdan, H. B., Burger, H., Weiser, B., Gao, W., ... Kagan, R. M. (2015). Determination of HIV-1 coreceptor tropism using proviral DNA in women before and after viral suppression. AIDS Research and Therapy, 12(1), [11]. https://doi.org/10.1186/s12981-015-0055-x

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.

In: AIDS Research and Therapy, Vol. 12, No. 1, 11, 18.04.2015.

Research output: Contribution to journalArticle

Baumann, RE, Rogers, AA, Hamdan, HB, Burger, H, Weiser, B, Gao, W, Anastos, K, Young, M, Meyer, WA, Pesano, RL & Kagan, RM 2015, 'Determination of HIV-1 coreceptor tropism using proviral DNA in women before and after viral suppression', AIDS Research and Therapy, vol. 12, no. 1, 11. https://doi.org/10.1186/s12981-015-0055-x
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. In: AIDS Research and Therapy. 2015 ; Vol. 12, No. 1.
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AU - Weiser, Barbara

AU - Gao, Wei

AU - Anastos, Kathryn

AU - Young, Mary

AU - Meyer, William A.

AU - Pesano, Rick L.

AU - Kagan, Ron M.

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N2 - 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.

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