Dataset Information

Macrophage folate receptor-targeted antiretroviral therapy facilitates drug entry, retention, antiretroviral activities and biodistribution for reduction of human immunodeficiency virus infections.

ABSTRACT: Macrophages serve as vehicles for the carriage and delivery of polymer-coated nanoformulated antiretroviral therapy (nanoART). Although superior to native drug, high drug concentrations are required for viral inhibition. Herein, folate-modified ritonavir-boosted atazanavir (ATV/r)-encased polymers facilitated macrophage receptor targeting for optimizing drug dosing. Folate coating of nanoART ATV/r significantly enhanced cell uptake, retention and antiretroviral activities without altering cell viability. Enhanced retentions of folate-coated nanoART within recycling endosomes provided a stable subcellular drug depot. Importantly, up to a five-fold enhanced plasma and tissue drug levels followed folate-coated formulation injection in mice. Folate polymer encased ATV/r improves nanoART pharmacokinetics bringing the technology one step closer to human use.This team of authors describes a novel method for macrophage folate receptor-targeted antiretroviral therapy. Atazanvir entry, retention, and antiretroviral activities were superior using the presented method, and so was its biodistribution, enabling a more efficient way to address human immunodeficiency virus infections, with a hoped for clinical application in the near future.

SUBMITTER: Puligujja P

PROVIDER: S-EPMC3779529 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature

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Macrophage folate receptor-targeted antiretroviral therapy facilitates drug entry, retention, antiretroviral activities and biodistribution for reduction of human immunodeficiency virus infections.

Puligujja Pavan P McMillan Joellyn J Kendrick Lindsey L Li Tianyuzi T Balkundi Shantanu S Smith Nathan N Veerubhotla Ram S RS Edagwa Benson J BJ Kabanov Alexander V AV Bronich Tatiana T Gendelman Howard E HE Liu Xin-Ming XM

Nanomedicine : nanotechnology, biology, and medicine 20130513 8

Macrophages serve as vehicles for the carriage and delivery of polymer-coated nanoformulated antiretroviral therapy (nanoART). Although superior to native drug, high drug concentrations are required for viral inhibition. Herein, folate-modified ritonavir-boosted atazanavir (ATV/r)-encased polymers facilitated macrophage receptor targeting for optimizing drug dosing. Folate coating of nanoART ATV/r significantly enhanced cell uptake, retention and antiretroviral activities without altering cell v ...[more]

PMID: 23680933

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Project description:BackgroundIn August 2016, Ethiopia endorsed a universal "test and treat" strategy for people living with human immunodeficiency virus (PLHIV) based on World Health Organization recommendation. However, there is limited evidence on the routine application of the same-day "test and treat" recommendation in low-income settings. This study assessed the effect of same-day treatment initiation on individual-level retention at 6- and 12-months follow-up.MethodsA multicenter facility-based retrospective cohort study was conducted to compare retention-in-care between PLHIV who started antiretroviral therapy (ART) on the same-day and those started ART > 7 days following HIV diagnoses. Participants were at least 15 years-old and were newly diagnosed and started on ART between October 2016 and July 2018 in 11 health facilities in the Amhara region of Ethiopia. Multivariable logistic regression controlling for potential confounders and Kaplan-Meier survival analysis were used to assess differences in outcomes between the groups.ResultsIn total, 433 PLHIV started ART on the same-day of diagnosis and 555 PLHIV who started ART > 7 days after HIV diagnosis were included in the study. At 6-months, 82.0% (355) in the same-day group vs 89.4% (496) in the > 7 days group were retained-in-care (absolute risk difference (RD) = 7.4%; 95% confidence interval (CI): 2.9-11.8%). At 12-months, 75.8% (328) in the same-day group vs 82.0% (455) in the > 7 days group were retained-in-care (absolute RD = 6.2%; 95% CI: 1.1, 11.4%). The major drop in retention was in the first 30 days following ART initiation among same-day group. After adjusting for baseline and non-baseline covariates, the same-day group was less likely to be retained-in-care at 6- and 12-months (adjusted risk ratio (RR) = 0.89; 95% CI: 0.87, 0.90 and adjusted RR = 0.86; 95% CI: 0.83, 0.89, respectively).ConclusionsReduced retention-in-care can threaten the benefit of the same-day "test and treat" policy. The policy needs to be implemented cautiously with greater emphasis on assessment and preparation of PLHIV for ART to ensure treatment readiness before starting them on same-day ART and close monitoring of patients during early follow-up periods.

Dataset Information

Macrophage folate receptor-targeted antiretroviral therapy facilitates drug entry, retention, antiretroviral activities and biodistribution for reduction of human immunodeficiency virus infections.

Publications

Macrophage folate receptor-targeted antiretroviral therapy facilitates drug entry, retention, antiretroviral activities and biodistribution for reduction of human immunodeficiency virus infections.

Similar Datasets

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