Targeting viral reservoirs: ability of antiretroviral therapy to stop viral replication

: Antiretroviral drug therapy has significantly improved the prognosis and life expectancy of People Living with HIV over the years. But this progress comes with an important caveat that antiretroviral regimens generally require adherence to life-long, daily dosing, to keep viral multiplication under check. Non-adherence to such dosing leads to decreased efficacy and increased drug resistance against antiretroviral drugs. Besides, poor drug penetration to certain tissues like CNS and lymph nodes leads to build-up of viral reservoirs in these sites. To combat some of these challenges and improve patient compliance, long-acting antiretroviral drugs, are a new weapon in the arsenal, in fight against HIV. Few long acting preparations have been approved, and several others are in various clinical and preclinical stages of development. However, longacting formulations also have their share of clinical issues like limited drug distribution, long term adverse drug reactions, drug-drug interactions, and gradual development of drug resistance. Modern technological premises are being tested to mitigate some of these problems. One such promising approach involves nanotechnological methods, which are being used to develop ultra-long acting formulations and drug delivery systems, targeting tissues with residual HIV concentration. LongActing Slow Effective Release Antiretroviral Therapy aka LASER ART, also builds on nanotechnology and prodrug modifications to design preparations with tailor-made favorable pharmacokinetics and wider drug distribution. These recent advances are fueling the progression of antiretroviral therapy towards eliminating the disease.

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Neuro-AIDS: Current status and Challenges to Antiretroviral Drug Therapy (ART) for Its Treatment.

Current Drug Therapy ◽

10.2174/1574885515666200604123046 ◽

2020 ◽

Vol 15 ◽

Cited By ~ 1

Author(s):

Smita P. Kakad ◽

Sanjay J. Kshirsagar

Keyword(s):

Nervous System ◽

Antiretroviral Therapy ◽

Highly Active Antiretroviral Therapy ◽

Sensory Neuropathy ◽

Current Status ◽

Viral Reservoir ◽

Viral Reservoirs ◽

Highly Active ◽

Aids Therapy ◽

The Brain

Introduction: The infiltration of HIV into the brain alters the functions of the nervous system known as NeuroAIDS. It leads to neuronal defects clinically manifested by motor and cognitive dysfunctions. Materials/Methods: Current antiretroviral therapy can prevent viral replication but cannot cure the disease completely. HAART-Highly active antiretroviral therapy used for the treatment of HIV infection. Challenges in neuro-AIDS therapy are as shown in the graphical abstract. One of the challenges is latent viral reservoirs like the brain; which acts as a sanctuary site for viruses. Nearly ~50% of HIV patients show neuropathological signs. Nervous system related disorders including AIDS dementia, sensory neuropathy, and myelopathy have a 25% of prevalence in patients having access to a highly active combination antiretroviral therapy. Results/Conclusions: Brain is one of the viral sanctuary sites for HIV. The current need of neuro-AIDS therapy is to target the brain as a viral reservoir. Drugs should cross or bypass the blood-brain barrier to reach the brain with effective concentrations. Current research on novel drug delivery approaches may prove helpful to treat neuro-AIDS and related disorders effectively.

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Antigen-driven CD4+ T cell and HIV-1 dynamics: Residual viral replication under highly active antiretroviral therapy

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.96.26.15167 ◽

1999 ◽

Vol 96 (26) ◽

pp. 15167-15172 ◽

Cited By ~ 51

Author(s):

N. M. Ferguson ◽

F. deWolf ◽

A. C. Ghani ◽

C. Fraser ◽

C. A. Donnelly ◽

...

Keyword(s):

T Cell ◽

Antiretroviral Therapy ◽

Viral Replication ◽

Highly Active Antiretroviral Therapy ◽

Cd4 T Cell ◽

Highly Active ◽

Hiv 1

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HIV-1 Reservoirs and Residual Viral Replication during Highly Active Antiretroviral Therapy

Cell Death During HIV Infection ◽

10.1201/9781420038156.ch26 ◽

2005 ◽

pp. 457-474

Author(s):

Roger Pomerantz ◽

Giuseppe Nunnari

Keyword(s):

Antiretroviral Therapy ◽

Viral Replication ◽

Highly Active Antiretroviral Therapy ◽

Highly Active ◽

Hiv 1

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Transient viral replication during analytical treatment interruptions in SIV infected macaques can alter the rebound-competent viral reservoir

PLoS Pathogens ◽

10.1371/journal.ppat.1009686 ◽

2021 ◽

Vol 17 (6) ◽

pp. e1009686

Author(s):

Taina T. Immonen ◽

Christine M. Fennessey ◽

Leslie Lipkey ◽

Abigail Thorpe ◽

Gregory Q. Del Prete ◽

...

Keyword(s):

Antiretroviral Therapy ◽

Viral Replication ◽

Rhesus Macaques ◽

Treatment Strategies ◽

Viral Reservoir ◽

Virus Population ◽

Analytical Treatment ◽

Treatment Interruptions ◽

The Impact ◽

Hiv 1

Analytical treatment interruptions (ATIs) of antiretroviral therapy (ART) play a central role in evaluating the efficacy of HIV-1 treatment strategies targeting virus that persists despite ART. However, it remains unclear if ATIs alter the rebound-competent viral reservoir (RCVR), the virus population that persists during ART and from which viral recrudescence originates after ART discontinuation. To assess the impact of ATIs on the RCVR, we used a barcode sequence tagged SIV to track individual viral lineages through a series of ATIs in Rhesus macaques. We demonstrate that transient replication of individual rebounding lineages during an ATI can lead to their enrichment in the RCVR, increasing their probability of reactivating again after treatment discontinuation. These data establish that the RCVR can be altered by uncontrolled replication during ATI.

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A New Perspective on HIV Diagnostics: Reinterpretation in the Age of Early Treatment

Journal of Clinical Microbiology ◽

10.1128/jcm.00978-19 ◽

2019 ◽

Vol 57 (10) ◽

Author(s):

Sheila M. Keating

Keyword(s):

Antiretroviral Therapy ◽

Hiv Infection ◽

Viral Replication ◽

Early Treatment ◽

Clinical Microbiology ◽

Link Type ◽

New Perspective ◽

Hiv Diagnostics ◽

The Impact

ABSTRACT Early treatment of HIV infection with antiretroviral therapy in recently identified HIV-infected individuals reduces viral replication and decreases the risk of transmission. The screening and supplemental, confirmatory assays used to identify infection are influenced by early treatment and may obscure a clear diagnosis of HIV infection. In this issue of the Journal of Clinical Microbiology, Manak et al. demonstrate the impact of antiretroviral therapy on the evolution of biomarkers that have traditionally been used for identifying HIV infection (M. M. Manak, L. L. Jagodzinski, A. Shutt, J. A. Malia, et al., J Clin Microbiol 57:e00757-19, 2019, https://doi.org/10.1128/JCM.00757-19).

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Immune Activation and Viral Replication after Vaccination with an Influenza A H1N1 2009 Vaccine in HIV-Infected Children Receiving Antiretroviral Therapy

Disease Markers ◽

10.1155/2013/276547 ◽

2013 ◽

Vol 35 ◽

pp. 221-227 ◽

Cited By ~ 1

Author(s):

Nattawat Onlamoon ◽

Petai Unpol ◽

Michittra Boonchan ◽

Kasama Sukapirom ◽

Orasri Wittawatmongkol ◽

...

Keyword(s):

T Cells ◽

Antiretroviral Therapy ◽

Viral Replication ◽

Cd8 T Cells ◽

Immune Activation ◽

Influenza A ◽

Haemagglutination Inhibition ◽

Hla Dr ◽

Influenza A H1n1 ◽

The Impact

Immunization with a pandemic influenza A H1N1 2009 was recommended for HIV-infected patients. However, there is limited information concerning the impact of immunization with this vaccine on immune activation and HIV viral replication. In this study, 45 HIV-infected children and adolescents receiving antiretroviral therapy were immunized with a 2-dose series of nonadjuvated monovalent influenza A H1N1 2009 vaccine upon enrollment and approximately 1 month later. Immunogenicity was determined by haemagglutination inhibition assay. The level of immune activation was determined by identification of CD38 and HLA-DR on CD8+ T cells. Patients were divided into 2 groups which include patients who had an undetectable HIV viral load (HIV detectable group) and patients who show virological failure (HIV nondetectable group). The results showed seroconversion rate of 55.2% in HIV nondetectable group, whereas 31.3% was found in HIV detectable group. Both groups of patients showed no major increase in immune activation after immunization. Interestingly, a decrease in the frequency of CD8+ T cells that coexpressed CD38 and HLA-DR was observed after immunization in both groups of patients. We suggested that immunization with influenza A H1N1 2009 vaccine can induce immune response to the pandemic virus without major impact on HIV viral replication and immune activation.

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