An article published this year in “PlosOne” using one of our products, “7AAD”, by our customers from Department of Internal Medicine, AHEPA University Hospital, Aristotle University Medical School, Thessaloniki, Greece., in the analysis of how Prevalence and correlates of persistent intracellular HIV transcription in individuals on efavirenz versus atazanavir-based regimens: A prospective cohort study. Congrats and Thanks.
Summay:
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] The establishment of HIV latency in a population of long lived
memory CD4+ T cells is perceived as the major barrier for the eradication of
HIV infection.[2] Several lines of evidence support the notion of persistent
low level viral replication on cART at least in a subgroup of patients.[3–6]
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] There is
limited evidence derived from raltegravir intensification studies that residual
viral replication as evidenced by increases in 2-long terminal repeat circles
may affect to a lesser extent patients on non-nucleoside transcriptase
inhibitors(NNRTIs) versus protease inhibitors (PIs).[3,4] For drugs with steep
dose-response curves such as PIs, small decreases in intracellular
concentrations may diminish significantly the viral inhibition providing a
plausible explanation for this observation.[8] 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] In our prospective
study, we used a method which combines immunophenotyping with
ultrasensitive-FISH to detect unspliced HIV-1 gag-pol in relevant cell
populations in order to compare HIVpt in virologically suppressed patients on
efavirenz(EFV) or atazanavir/ritonavir (ATV/r) and a backbone of
emtricitabine-tenofovir(FTC-TDF).[7,10,11] We followed prospectively our
patient cohort for one year and investigated the impact of HIVpt on virological
outcomes and CD4+ T-cell recovery. Finally, we tested for differences in the
mRNA expression of two widely studied ABC transporters (P-glycoprotein,
P-gp/ABCB1 and multidrug resistance-associated protein-1, MRP1/ABCC1) in
peripheral blood mononuclear cells(PBMCs) between patients with and without
HIVpt by treatment regimen.
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