Factors Associated with HIV-1 Proviral DNA Loads in Patients with Undetectable Plasma RNA Load

Choi, Jun Yong; Song, Young Goo; Kim, Young Hwa; Kim, Chang Oh; Kim, Myoung Soo; Chin, Bum Sik; Han, Sang Hoon; Choi, Sang Zin; Lee, Han Sung; Jeong, Su Jin; Choi, Heekyoung; Kim, June Myung

doi:10.3346/jkms.2009.24.1.152

Cited by 3 publications

(3 citation statements)

References 12 publications

(20 reference statements)

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“…17,18,23,25 Our results confirm and further extend these studies showing a negative correlation between the frequency of CD4 T cells carrying HIV-1 proviral DNA and CD4/CD8 ratio or CD4 T cells, in infected individuals receiving ART and in whom plasma viremia had been suppressed below the limit of detection for prolonged periods of time.…”

Section: Discussionsupporting

confidence: 91%

“…These results are in concordance with recent findings showing that levels of HIV-1 proviral DNA in PBMC or CD4 T cells were not associated with ART duration or aviremia period after several years of suppressive therapy. 17,18 However, our results differ from those reported by Koelsch et al, showing an inverse association between levels of HIV-1 proviral DNA in CD4 T cells and treatment duration. This may be attributable to the small number of participants in their study with 42% of patients having started ART within 6 months after seroconversion.…”

Section: Discussioncontrasting

confidence: 85%

See 1 more Smart Citation

CD4 T cell nadir independently predicts the magnitude of the HIV reservoir after prolonged suppressive antiretroviral therapy

Boulassel

Chomont

Pai

et al. 2012

Journal of Clinical Virology

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Section: Discussionsupporting

confidence: 91%

Section: Discussioncontrasting

confidence: 85%

CD4 T cell nadir independently predicts the magnitude of the HIV reservoir after prolonged suppressive antiretroviral therapy

Boulassel

Chomont

Pai

et al. 2012

Journal of Clinical Virology

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“…The use of combination highly active antiretroviral therapy (ART) can achieve levels of HIV-1-RNA in plasma (viral load) that are undetectable by conventional assays in the vast majority of HIV-1-infected individuals [1–3]. In spite of this factor, there is growing evidence for residual viral replication in patients on suppressive ART [4 ▪ ,5].…”

Section: Introductionmentioning

confidence: 99%

Overcoming pharmacologic sanctuaries

Cory

Schacker

Stevenson

et al. 2013

Current Opinion in HIV and AIDS

135

100

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Purpose of review Current antiretroviral treatment regimens represent significant improvements in the management of HIV-1 infection; however, these regimens have not achieved a functional or sterilizing cure. One barrier to achieving a cure may be suboptimal antiretroviral concentrations in sanctuary sites throughout the body, including the central nervous system, gut-associated lymphoid tissue, lymph nodes, and tissue macrophages. This review will focus on the problems associated with achieving effective concentrations in these restricted sanctuary sites, and potential strategies to overcome these barriers. Recent findings Sufficient data exist to conclude that antiretroviral drug distribution is not uniform throughout the body. Low tissue/reservoir concentrations may be associated with viral replication. Multiple means to increase drug concentrations in sanctuary sites are being investigated, including modification of currently utilized drugs, blockade of transporters and enzymes that affect drug metabolism and pharmacokinetics, and local drug administration. Accumulating data suggest these methods increase antiretroviral concentrations in reservoirs of viral replication. No method has yet resulted in the complete clearance of HIV. Summary New strategies for increasing antiretroviral concentrations in predominant sites of viral replication may provide more effective means for elimination of viral sanctuaries. Additional research is necessary to optimize antiretroviral tissue distribution in order to inhibit virus replication fully, and avoid resistance and replenishment of viral reservoirs that may persist in the face of antiretroviral therapy.

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Suppression of HIV-1 Viral Replication by Inhibiting Drug Efflux Transporters in Activated Macrophages

2021

CHR

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Background: Ethanol has been shown to increase oxidative stress, drug efflux transporter expression, and promote HIV progression. Macrophages, which express drug efflux transporters, serve as an essential sanctuary site for HIV. The antiretroviral drug lopinavir, a protease inhibitor, is a substrate of the drug efflux transporters P-glycoprotein and multi-drug resistance-associated protein 1. The NF-κB signaling pathway is associated with inflammation and drug efflux transporter expression. Objective: Examine the effects of ethanol on drug efflux transporters and HIV replication of macrophages. Develop strategies to increase efficacy of protease inhibitor. Methods: The expression of PGP and MRP1 was examined with western blot. The NF- κB inhibition was assessed with nuclear western blot. LC-MS/MS and p24 ELISA were used to assess intracellular LPV and viral replication. Results: Ethanol at 40mM slightly increased drug efflux transporter PGP and MRP1 expression in activated macrophages. IKK-16, a NF- κB inhibitor, counteracted the increased transporter expression caused by ethanol exposure. MK571, a MRP1 inhibitor, and IKK-16 significantly increased intracellular LPV concentration with or without ethanol treatment. MK571 significantly increased LPV efficacy in suppressing viral replication with or without ethanol treatment. A decreasing trend and a significant decrease were observed with IKK-16+LPV treatment compared with LPV alone in the no ethanol treatment and ethanol treatment groups, respectively. Conclusion: In activated macrophages, inhibiting drug efflux transporter MRP1 activity and reducing its expression may represent a promising approach to suppress viral replication by increasing intracellular antiretroviral concentrations. However, different strategies may be required for ethanol-related vs. untreated groups.

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Factors Associated with HIV-1 Proviral DNA Loads in Patients with Undetectable Plasma RNA Load

Cited by 3 publications

References 12 publications

CD4 T cell nadir independently predicts the magnitude of the HIV reservoir after prolonged suppressive antiretroviral therapy

CD4 T cell nadir independently predicts the magnitude of the HIV reservoir after prolonged suppressive antiretroviral therapy

Overcoming pharmacologic sanctuaries

Suppression of HIV-1 Viral Replication by Inhibiting Drug Efflux Transporters in Activated Macrophages

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