Abstract
ObjectivesDespite 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.MethodsWe 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.ResultsIn 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.ConclusionsFurther 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.
Highlights
Combination antiretroviral therapy(cART), albeit not curative, has improved substantially the morbidity and mortality of HIV disease through prolonged and sustained suppression of viral replication.[1]
We found no evidence of differential expression of the drug efflux transporters P-gp and MRP1
The importance of persistent HIV transcription(HIVpt) in patients on suppressive ART is unclear, but several studies suggest that biomarkers of HIVpt may be promising to assess residual viral replication.[7]
Summary
Combination antiretroviral therapy(cART), albeit not curative, has improved substantially the morbidity and mortality of HIV disease through prolonged and sustained suppression of viral replication.[1]. Antiretroviral drugs may be substrates, inhibitors or inducers of ATP-binding cassette transporters(ABC transporters) which function as drug efflux pumps with possible implications for the intracellular concentrations of antiretrovirals.[9]
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