Title |
Determination of HIV-1 coreceptor tropism using proviral DNA in women before and after viral suppression
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Published in |
AIDS Research and Therapy, April 2015
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DOI | 10.1186/s12981-015-0055-x |
Pubmed ID | |
Authors |
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 |
Abstract |
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. 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. 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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Unknown | 1 | 100% |
Demographic breakdown
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 20 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 5 | 25% |
Researcher | 3 | 15% |
Student > Ph. D. Student | 3 | 15% |
Student > Doctoral Student | 1 | 5% |
Student > Bachelor | 1 | 5% |
Other | 3 | 15% |
Unknown | 4 | 20% |
Readers by discipline | Count | As % |
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Biochemistry, Genetics and Molecular Biology | 6 | 30% |
Nursing and Health Professions | 4 | 20% |
Agricultural and Biological Sciences | 4 | 20% |
Neuroscience | 1 | 5% |
Medicine and Dentistry | 1 | 5% |
Other | 0 | 0% |
Unknown | 4 | 20% |