scholarly journals HIV Proviral Burden, Genetic Diversity, and Dynamics in Viremic Controllers Who Subsequently Initiated Suppressive Antiretroviral Therapy

mBio ◽  
2021 ◽  
Author(s):  
F. Harrison Omondi ◽  
Hanwei Sudderuddin ◽  
Aniqa Shahid ◽  
Natalie N. Kinloch ◽  
Bradley R. Jones ◽  
...  

HIV therapy is lifelong because integrated, replication-competent viral copies persist within long-lived cells. To cure HIV, we need to understand when these viral reservoirs form, how large and genetically diverse they are, and how long they endure.

2009 ◽  
Vol 20 (2) ◽  
pp. 63-78 ◽  
Author(s):  
Christina Gavegnano ◽  
Raymond F Schinazi

HIV type-1 (HIV-1) accounts for more than 25 million deaths and nearly 40 million people are infected worldwide. A significant obstacle in clearing virus from infected individuals is latently infected viral reservoirs. Latent HIV-1 can emerge with recrudescence as a productive infection later in disease progression and could provide a source for the emergence of resistant HIV-1. It is widely recognized that macrophages represent a latently infected viral reservoir and are a significant and critical HIV-1 target cell in vivo. Macrophages can be divided into multiple subsets of macrophage-like cells, all of which are susceptible to HIV-1 infection, including dendritic cells, Langerhans cells, alveolar macrophages, mucosal macrophages and microglial cells. Current antiretroviral therapy (ART) often displays differential antiviral activity in macrophages relative to CD4+ T-lymphocytes. Significant work has been performed to establish antiviral activity of many clinically approved ART in macrophages; however, a direct link between antiviral activity and specific mechanisms responsible for these antiviral effects are incompletely understood. This review identifies many understudied areas of research, along with topics for further research in the field of HIV therapy and eradication. Discussion focuses upon the known cellular pharmacology and antiviral activity of antiretroviral agents in macrophages and its relationship to latency, chronic HIV-1 infection and therapeutic strategies to eradicate systemic HIV-1 infection.


2020 ◽  
Vol 18 ◽  
Author(s):  
Rajpushpa Labh ◽  
Rachna Gupta

: 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.


2020 ◽  
Vol 15 ◽  
Author(s):  
Smita P. Kakad ◽  
Sanjay J. Kshirsagar

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.


2018 ◽  
Vol 52 ◽  
pp. 62 ◽  
Author(s):  
Felipe Campos Vale ◽  
Ernani Tiaraju de Santa-Helena ◽  
Maria Altenfelder Santos ◽  
Wania Maria do Espirito Santo Carvalho ◽  
Paulo Rossi Menezes ◽  
...  

OBJECTIVE: To present the development and validation of the WebAd-Q Questionnaire, a self-report instrument to monitor adherence to antiretroviral therapy in HIV/AIDS centers in Brazil. METHODS: The WebAd-Q is an electronic questionnaire that has three questions about the use of antiretrovirals in the last week. It was constructed from interviews and focus groups with 38 patients. Its validity was tested in a study with a sample of 90 adult patients on antiretroviral therapy for at least three months. We used electronic monitoring bottles, pill counting, and self-report interview to compare adherence. The WebAd-Q was answered on the sixtieth day, twice, with at least one hour of interval. The viral load of the patients was obtained from the service records. We have analyzed the agreement between the answers to the WebAd-Q, the associations, and the correlations with viral load and performance compared to other measures of adherence. RESULTS: Among the invited patients, 74 (82.2%) answered the WebAd-Q. No difficulties were reported to answer the questionnaire. The average answer time was 5 min 47 sec. The set of three questions of the WebAd-Q obtained agreement of 89.8%, with Kappa of 0.77 (95%CI 0.61–0.94). The non-adherence answers of the WebAd-Q were associated with detectable viral load. We obtained moderate viral load correlations with the non-adherence scale according to the WebAd-Q. For the three questions of the WebAd-Q, patients with non-adherence answers were also reported as less adherent according to the other measures of adherence. CONCLUSIONS: The WebAd-Q answered all the issues considered relevant in the validation of questionnaires, was well understood by patients, was associated with viral load, and obtained good agreement and good performance compared to the other measures. The feasibility analysis of its implementation still depends on a national study on its applicability.


F1000Research ◽  
2017 ◽  
Vol 6 ◽  
pp. 759 ◽  
Author(s):  
Eric S. Daar

There are approximately 35 million people infected by human immunodeficiency virus (HIV), with an estimated 2 million incident infections annually across the globe. While HIV infection was initially associated with high rates of morbidity and mortality, advances in therapy have transformed it into a chronic and manageable disease. In addition, there is very strong evidence that those on antiretroviral therapy are much less likely to transmit infection to their partners. The success rates for maintaining viral suppression in treated patients has dramatically increased owing to the development of agents that are potent and well tolerated and can often be co-formulated into single pills for simplification. This review will outline advances in treatment over the last several years as well as new strategies that may shift the existing treatment paradigm in the near future.


Cholesterol ◽  
2010 ◽  
Vol 2010 ◽  
pp. 1-13 ◽  
Author(s):  
Sara Melzi ◽  
Laura Carenzi ◽  
Maria Vittoria Cossu ◽  
Simone Passerini ◽  
Amedeo Capetti ◽  
...  

Many infections favor or are directly implicated with lipid metabolism perturbations and/or increased risk of coronary heart disease (CHD). HIV itself has been shown to increase lipogenesis in the liver and to alter the lipid profile, while the presence of unsafe habits, addiction, comorbidities, and AIDS-related diseases increases substantially the risk of cardiovascular disease (CVD) in the HIV-infected population. Antiretroviral therapy reduces such stimuli but many drugs have intrinsic toxicity profiles impacting on metabolism or potential direct cardiotoxicity. In a moment when the main guidelines of HIV therapy are predating the point when to start treating, we mean to highlight the contribution of HIV-1 to lipid alteration and inflammation, the impact of antiretroviral therapy, the decisions on what drugs to use to reduce the probability of having a cardiovascular event, the increasing use of statins and fibrates in HIV-1 infected subjects, and finally the switch strategies, that balance effectiveness and toxicity to move the decision to change HIV drugs. Early treatment might reduce the negative effect of HIV on overall cardiovascular risk but may also evidence the impact of drugs, and the final balance (reduction or increase in CHD and lipid abnormalities) is not known up to date.


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