CD4+CD25+CD127 regulatory cells play multiple roles in maintaining HIV-1 p24 production in patients on long-term treatment: HIV-1 p24-producing cells and suppression of anti-HIV immunity

Abstract BACKGROUND Tenofovir disoproxil fumarate (TDF) has a strong antiviral effect, but TDF is known to cause renal dysfunction. Therefore, we are investigating preventing renal dysfunction by replacing TDF with tenofovir alafenamide fumarate (TAF), which is known to be relatively safe to the kidneys. However, the changes in renal function under long-term use of TAF are not known. In this study, we evaluated renal function in Japanese HIV-1-positive patients switching to TAF after long-term treatment with TDF.METHODS A single-center observational study was conducted in Japanese HIV-1-positive patients. TDF was switched to TAF after at least 48 weeks of treatment so we could evaluate the long-term use of TDF. The primary endpoint was the estimated glomerular filtration rate (eGFR) at 144 weeks of TAF administration. In addition, we predicted the factors that would lead to changes in eGFR after long-term use of TAF.RESULTS Of the 125 HIV-1-positive patients who were prescribed TAF at our hospital during the study period, 70 fulfilled the study criteria. The eGFR at the time of switching from TDF to TAF was 81.4 ± 21.1 mL/min/1.73 m2. eGFR improved significantly after 12 weeks of taking TAF but significantly decreased at 96 and 144 weeks. At 144 weeks of taking TAF, the factors significantly correlated with the difference in eGFR from baseline were the difference in eGFR at 48 weeks of taking TAF and age at the start of TAF.CONCLUSIONS In this study, Japanese HIV-1-positive patients who had been taking TDF for a long period of time showed a decrease in eGFR after switching to long-term use of TAF. Japanese HIV-1-positive patients are expected to take TAF for a long time. Depending on age, laboratory values related to renal function need to be monitored carefully.

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Long-term treatment of patients with HIV-1: the role of atazanavir

HIV/AIDS - Research and Palliative Care ◽

10.2147/hiv.s5069 ◽

2010 ◽

pp. 157

Author(s):

José Fernández-Montero

Keyword(s):

Term Treatment ◽

Long Term Treatment ◽

Hiv 1

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Network Pharmacology: Exploring the Resources and Methodologies

Current Topics in Medicinal Chemistry ◽

10.2174/1568026618666180330141351 ◽

2018 ◽

Vol 18 (12) ◽

pp. 949-964 ◽

Cited By ~ 12

Author(s):

Junaid Muhammad ◽

Abbas Khan ◽

Arif Ali ◽

Li Fang ◽

Wang Yanjing ◽

...

Keyword(s):

Single Gene ◽

Acquired Resistance ◽

Term Treatment ◽

Network Pharmacology ◽

Gene Target ◽

Target Interaction ◽

Long Term Treatment ◽

Cellular Components ◽

Hiv 1

Multi-target and combinatorial therapies have been focused for the past several decades. These approaches achieved considerable therapeutic efficacy by modulating the activities of the targets in complex diseases such as HIV-1 infection, cancer and diabetes disease. Most of the diseases cannot be treated efficiently in terms of single gene target, because it involves the cessation of the coordinated function of distinct gene groups. Most of the cellular components work efficiently by interacting with other cellular components and all these interactions together represent interactome. This interconnectivity shows that a defect in a single gene may not be restricted to the gene product itself, but may spread along the network. So, drug development must be based on the network-based perspective of disease mechanisms. Many systematic diseases like neurodegenerative disorders, cancer and cardiovascular cannot be treated efficiently by the single gene target strategy because these diseases involve the complex biological machinery. In clinical trials, many mono-therapies have been found to be less effective. In mono-therapies, the long term treatment, for the systematic diseases make the diseases able to acquired resistance because of the disease nature of the natural evolution of feedback loop and pathway redundancy. Multi-target drugs might be more efficient. Multi-target therapeutics might be less vulnerable because of the inability of the biological system to resist multiple actions. In this study, we will overview the recent advances in the development of methodologies for the identification of drug target interaction and its application in the poly-pharmacology profile of the drug.

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No evidence of autoimmune disorders in antiretroviral-experienced HIV-1-infected subjects after long-term treatment with raltegravir

Antiviral Therapy ◽

10.3851/imp2433 ◽

2012 ◽

Vol 18 (3) ◽

pp. 321-327 ◽

Cited By ~ 3

Author(s):

Silvia Baroncelli ◽

Ivano Mezzaroma ◽

Alessandra Fantauzzi ◽

Maria Clementina Galluzzo ◽

Anna Degli Antoni ◽

...

Keyword(s):

Autoimmune Disorders ◽

Term Treatment ◽

Long Term Treatment ◽

Hiv 1

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Evaluation of long-term treatment with glycyrrhizin and of combination therapy with glycyrrhizin and AZT or DDI on HIV-1 carriers

Antiviral Research ◽

10.1016/0166-3542(96)80279-8 ◽

1996 ◽

Vol 30 (1) ◽

pp. A33 ◽

Cited By ~ 2

Author(s):

N. Ikegami ◽

S. Kinoshita ◽

T. Kanesaki ◽

K. Uno ◽

K. Akatani ◽

...

Keyword(s):

Combination Therapy ◽

Term Treatment ◽

Long Term Treatment ◽

Hiv 1

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TSAO Derivatives the First Non-Peptide Inhibitors of HIV-1 RT Dimerization

Antiviral Chemistry and Chemotherapy ◽

10.1177/095632020501600301 ◽

2005 ◽

Vol 16 (3) ◽

pp. 147-153 ◽

Cited By ~ 4

Author(s):

María-José Camarasa ◽

Sonsoles Velázquez ◽

Ana San-Félix ◽

María-Jesús Pérez-Pérez

Keyword(s):

Specific Interaction ◽

Standard Of Care ◽

Term Treatment ◽

New Drugs ◽

Treatment Modalities ◽

Long Term Treatment ◽

Hiv Drugs ◽

Rt Inhibitors ◽

Anti Hiv ◽

Hiv 1

The combination of different anti-HIV agents has become the standard of care for AIDS or HIV-infected individuals. Important progress has been made in the development of drugs for the clinical treatment of HIV infection. To date, 20 drugs have been approved for the treatment of AIDS. However, viral rebound during therapy, the emergence of HIV drug resistance and the need for long-term treatment modalities are the main causes for the failure of current antiretroviral therapy. There is still a need for the development of new drugs that are either less toxic, active against the growing number of drug-resistant HIV strains or directed to novel targets in the viral life cycle. Eleven of the approved anti-HIV drugs target the reverse transcriptase (RT). Among the so-called non-nucleoside RT inhibitors (NNRTIs) TSAO derivatives are an unusual class of compounds that exert their unique selectivity for HIV-1 through a specific interaction with the p51 subunit of HIV-1 RT. They are the only NNRTIs for which amino acids at both subunits (p66 and p51) of HIV-1 RT are needed for optimal interaction with the enzyme. Moreover, the TSAO compounds are the first non-peptide molecules that interfere with the dimerization of the enzyme.

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Genotype and Phenotype Patterns of Human Immunodeficiency Virus Type 1 Resistance to Enfuvirtide during Long-Term Treatment

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.48.9.3253-3259.2004 ◽

2004 ◽

Vol 48 (9) ◽

pp. 3253-3259 ◽

Cited By ~ 59

Author(s):

Stefano Menzo ◽

Antonella Castagna ◽

Alessia Monachetti ◽

Hamid Hasson ◽

Anna Danise ◽

...

Keyword(s):

Human Immunodeficiency Virus ◽

Human Immunodeficiency Virus Type ◽

Virus Type ◽

Term Treatment ◽

Heptad Repeat ◽

Long Term Treatment ◽

Immunodeficiency Virus ◽

Hiv 1

ABSTRACT The human immunodeficiency virus type 1 (HIV-1) fusion inhibitor enfuvirtide has recently been introduced into clinical practice and has exhibited efficient anti-HIV-1 activity in combination with other antiretroviral agents. In the present study, we addressed the effect of long-term treatment with enfuvirtide on the intrahost evolution of HIV-1. The genotype and phenotype patterns and the relative replication capacity (rRC) of enfuvirtide-resistant HIV-1 mutants were evaluated in samples from 11 subjects (7 virological nonresponders and 4 responders) who received the compound for more than 1 year in combination with different regimens. Selection of one or more mutations clustering in a sequence (amino acids 36 to 45) of the gp41 N-terminal heptad repeat was observed in samples from the seven virological nonresponders but not in those from responders. In two subjects who discontinued enfuvirtide, reversion of the resistant genotype was detected within 3 months. Recombinant clones bearing mutated gp41 sequences displayed reduced susceptibilities to enfuvirtide, with the 50% inhibitory concentrations (IC50s) ranging from 0.6 to 12.8 μg/ml, whereas the IC50 for isolates with baseline sequences was 0.013 ± 0.010 μg/ml. Interestingly, long-term monitoring of resistant variants provided evidence that ongoing adaptation to the drug is paralleled by phenotypic changes. A limited drop in the rRC in the absence of drug was observed for clones from four of the seven nonresponders bearing mutations associated with resistance. Overall, the data indicate that the different genotype patterns associated with a detectable degree of HIV-1 resistance to enfuvirtide generated during long-term treatments are characterized by a substantially low genetic barrier, possible ongoing adaptation with increased degrees of resistance, and limited influence on the viral rRC.

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