Prevalence and correlates of persistent intracellular HIV transcription in individuals on efavirenz versus atazanavir-based regimens: A prospective cohort study.
Title | Prevalence and correlates of persistent intracellular HIV transcription in individuals on efavirenz versus atazanavir-based regimens: A prospective cohort study. |
Publication Type | Journal Article |
Year of Publication | 2018 |
Authors | Pilalas, D., Skoura L., Margariti A., Chatzopoulou F., Chatzidimitriou D., Tsachouridou O., Zebekakis P., Metallidis S., & Papaioannou M. |
Journal | PLoS One |
Volume | 13 |
Issue | 3 |
Pagination | e0194262 |
Date Published | 2018 |
ISSN | 1932-6203 |
Keywords | Adult, Anti-HIV Agents, Atazanavir Sulfate, ATP Binding Cassette Transporter, Sub-Family B, Benzoxazines, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Drug Therapy, Combination, Female, HIV Infections, HIV-1, Humans, Male, Middle Aged, Multidrug Resistance-Associated Proteins, Prospective Studies, Reverse Transcription, RNA, Messenger, RNA, Viral, Viral Load, Virus Latency, Virus Replication |
Abstract | OBJECTIVES: Despite successful virological suppression, HIV transcription frequently persists intracellularly. In this study, we hypothesize that HIV persistent transcription(HIVpt) may affect to a different extent patients on stable efavirenz(EFV) versus atazanavir(ATV)-based regimens. The role of the expression of drug efflux transporters in HIVpt was also investigated.METHODS: We prospectively enrolled 51 virologically suppressed patients on first-line treatment for one year with EFV or ATV combined with emtricitabine and tenofovir and followed them up for one year. Simultaneous ultrasensitive subpopulation staining/hybridization in situ(SUSHI) was performed to identify HIVpt in CD4+ T-cells and in the CD4+CD45RO+ T-cell subpopulation. The differential mRNA expression of P-glycoprotein(P-gp/ABCB1) and multidrug resistance-associated protein-1(MRP1/ABCC1) was also evaluated. Univariate logistic regression models were used to evaluate predictors of HIVpt.RESULTS: In the CD4+ T-cell population, HIVpt affected 13/30 of patients on EFV versus 10/21 on ATV. In the CD4+CD45RO+ T-cell population, HIVpt was present in 14/30 of patients on EFV versus 15/21 on ATV. A trend for association was observed between the risk of HIVpt and ATV treatment in the CD4+CD45RO+ T-cell population (OR 2.86, 95% CI 0.87-9.37, p = 0.083). HIVpt status was not associated with loss of virological suppression or CD4 evolution. We found no evidence of differential expression of the drug efflux transporters P-gp and MRP1.CONCLUSIONS: Further study is required to evaluate whether the HIVpt profile in specific cell populations may differ across different antiretroviral regimens and to elucidate the potential clinical impact. |
DOI | 10.1371/journal.pone.0194262 |
Alternate Journal | PLoS ONE |
PubMed ID | 29534103 |
PubMed Central ID | PMC5849343 |