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Indian Heart Journal 2019Antiretrovirals have immensely increased the average life expectancy of HIV-positive patients. However, the incidence of QT interval prolongation and other arrhythmias... (Review)
Review
INTRODUCTION
Antiretrovirals have immensely increased the average life expectancy of HIV-positive patients. However, the incidence of QT interval prolongation and other arrhythmias has also increased.
METHODS
Pubmed and Google Scholar were searched for relevant literature published between 1990 and 2019.
RESULTS AND DISCUSSION
HIV-positive patients with high viral load, low CD4 count, chronic inflammation, and autonomic neuropathy can develop QT interval prolongation. Another factor prolonging QT interval includes exposure to the HIV transactivator protein, which inhibits hERG K (+) channels controlling IKr K (+) currents in cardiomyocytes. Protease inhibitors inhibiting the CYP3A4 enzyme can also lead to QT interval prolongation. QT interval prolongation can potentially be exacerbated by opioids, antipsychotics, antibiotics, and antifungals, the adjunct medications often used in HIV-positive patients. Hepatic insufficiency in seropositive patients on antiretrovirals may also increase the risk of QT interval prolongation.
CONCLUSION
Baseline and follow-up EKG in the susceptible population is suggested.
Topics: Analgesics, Opioid; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Arrhythmias, Cardiac; Autonomic Nervous System Diseases; CD4 Lymphocyte Count; Electrocardiography; HIV Infections; HIV Protease Inhibitors; Hepatitis B, Chronic; Hepatitis C, Chronic; Humans; Inflammation; Methadone; Opiate Substitution Treatment; Viral Load
PubMed: 32248914
DOI: 10.1016/j.ihj.2019.11.259 -
HIV Medicine May 2019Theoretical and untested interactions between antiretrovirals and direct-acting oral anticoagulants have limited the use of this new class of anticoagulant in people...
OBJECTIVES
Theoretical and untested interactions between antiretrovirals and direct-acting oral anticoagulants have limited the use of this new class of anticoagulant in people with HIV infection. This case series, the first of its kind, reports on the successful concurrent use of the direct-acting oral anticoagulant dabigatran and antiretroviral therapy.
METHODS
This series involved 14 patients requiring anticoagulation for management of atrial fibrillation, who were either unable or unwilling to take warfarin, and who were receiving concurrent treatment for HIV infection. Participants were treated with dabigatran with dose monitoring to establish the safety and efficacy of concurrent use with antiretrovirals. All were commenced on 110 mg twice daily, increased to 150 mg twice daily if the trough level was < 69.3 ng/mL.
RESULTS
In the 14 patients treated with dabigatran and antiretrovirals, there were no thromboembolic or bleeding complications. Dabigatran treatment was discontinued in one patient because of undetectable dabigatran levels despite dose escalation. Dabigatran levels fell within the fivefold variance seen in the Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study at a dose of either 110 or 150 mg twice daily.
CONCLUSIONS
This case series represents the largest published population to date successfully receiving antiretroviral and direct-acting oral anticoagulant therapy. Given the significant health care burden faced by people living with HIV, the availability of safe anticoagulant therapy without the requirement for monitoring is an important option in this patient population.
Topics: Aged; Aged, 80 and over; Anti-Retroviral Agents; Atrial Fibrillation; Comorbidity; Dabigatran; Drug Administration Schedule; Drug Interactions; Factor Xa Inhibitors; HIV Infections; Humans; Male; Middle Aged; Treatment Outcome
PubMed: 30924585
DOI: 10.1111/hiv.12722 -
Cells Apr 2024Endothelial cell activation, injury, and dysfunction underlies the pathophysiology of vascular diseases and infections associated with vascular dysfunction, including... (Review)
Review
Endothelial cell activation, injury, and dysfunction underlies the pathophysiology of vascular diseases and infections associated with vascular dysfunction, including human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome. Despite viral suppression with combination antiretroviral therapy (ART), people living with HIV (PLWH) are prone to many comorbidities, including neurological and neuropsychiatric complications, cardiovascular and metabolic diseases, premature aging, and malignancies. HIV and viral proteins can directly contribute to the development of these comorbidities. However, with the continued high prevalence of these comorbidities despite viral suppression, it is likely that ART or some antiretroviral (ARVs) drugs contribute to the development and persistence of comorbid diseases in PLWH. These comorbid diseases often involve vascular activation, injury, and dysfunction. The purpose of this manuscript is to review the current literature on ARVs and the vascular endothelium in PLWH, animal models, and in vitro studies. I also summarize evidence of an association or lack thereof between ARV drugs or drug classes and the protection or injury/dysfunction of the vascular endothelium and vascular diseases.
Topics: Animals; Humans; Anti-HIV Agents; Anti-Retroviral Agents; Endothelium, Vascular; HIV Infections
PubMed: 38667287
DOI: 10.3390/cells13080672 -
Expert Review of Anti-infective Therapy Jun 2016As the population of people living with HIV ages, the increase in non-AIDs morbidities is expected to increase in parallel. Maintaining bone health in those with HIV... (Review)
Review
INTRODUCTION
As the population of people living with HIV ages, the increase in non-AIDs morbidities is expected to increase in parallel. Maintaining bone health in those with HIV will be an important area of focus for the HIV clinician to prevent the morbidity and mortality associated with fragility fractures, the principal clinical sequela of low bone mineral density (BMD). Rates of fractures and prevalence of low bone mineral density, a risk factor for future fragility fractures, are already increased in the HIV positive population.
AREAS COVERED
This review examines the strategies to maintain bone health in those living with HIV from screening through to managing those with established low BMD or fracture, including the role for choice of or modification of antiretroviral therapy to maintain bone health. Expert commentary: The increasing complexity of managing bone health in the age of succesful antiretroviral therapy and an aging patient population as well as future perspectives which may help achieve the long term aim of minimising the impact of low BMD in those with HIV are discussed and explored.
Topics: Absorptiometry, Photon; Anti-Retroviral Agents; Bone Density; Bone Density Conservation Agents; Cholecalciferol; Ergocalciferols; Fractures, Bone; HIV Infections; Humans; Osteoporosis; Risk Factors
PubMed: 27189695
DOI: 10.1080/14787210.2016.1184570 -
Current Opinion in HIV and AIDS Jul 2017
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Global Health; HIV Infections; Humans
PubMed: 28486340
DOI: 10.1097/COH.0000000000000390 -
HIV Medicine Apr 2019Three-drug combination antiretroviral therapy (ART) became available in 1996, dramatically improving the prognosis of people living with HIV. The clinical benefits of... (Review)
Review
Three-drug combination antiretroviral therapy (ART) became available in 1996, dramatically improving the prognosis of people living with HIV. The clinical benefits of ART are due to the sustained viral load suppression and CD4 T cell gains. Major drawbacks of the first ART regimens were adverse events, and high pill burden, which led to the reduction of drug adherence resulting in frequent treatment discontinuations and the development of drug resistance. Due to increased viral potency of new antiretroviral drugs consideration of a two-drug combination therapy repositioning occurred in an effort to reduce adverse events, drug-drug interactions and cost, while maintaining a sustained antiviral effect. Various combinations of two-drug regimens have been studied, and non-inferiority compared to a three-drug regimen has been shown only for some of them. In addition, a two-drug combination regimen may not be suitable for every patient, especially those who are pregnant, those with tuberculosis or coexisting HBV infection. Furthermore no information has been generated concerning the secondary transmission of HIV from patients who have undetectable plasma viral load on two-drug regimens. Additional studies of two-drug combinations are also necessary to evaluate the debated existence of low viral replication in tissues and on immune activation. While there is no urgent need to routinely switch patients to two-drug combination therapy, due to the availability of drug combinations without significant toxicities, dual regimens represent a suitable option that deserve long-term evaluation before being introduced to clinical practice.
Topics: Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; CD4 Lymphocyte Count; Drug Substitution; Drug-Related Side Effects and Adverse Reactions; HIV Infections; Humans; Sustained Virologic Response
PubMed: 30821898
DOI: 10.1111/hiv.12716 -
Current HIV Research Aug 2022There have been significant developments in the treatment of people living with HIV-1/AIDS with current antiretroviral therapies; however, these developments have not... (Review)
Review
PURPOSE OF REVIEW
There have been significant developments in the treatment of people living with HIV-1/AIDS with current antiretroviral therapies; however, these developments have not been able to achieve a functional or sterilizing cure for HIV-1. While there are multiple barriers, one such barrier is the existence of pharmacological sanctuaries and viral reservoirs where the concentration of antiretrovirals is suboptimal, which includes the gut-associated lymphoid tissue, central nervous system, lymph nodes, and myeloid cells. This review will focus on illustrating the significance of these sanctuaries, specific barriers to optimal antiretroviral concentrations in each of these sites, and potential strategies to overcome these barriers.
RECENT FINDINGS
Research and studies have shown that a uniform antiretroviral distribution is not achieved with current therapies. This may allow low-level replication associated with low antiretroviral concentrations in these sanctuaries/reservoirs. Many methods are being investigated to increase antiretroviral concentrations in these sites, such as blocking transporting enzymes functions, modulating transporter expression and nanoformulations of current antiretrovirals. While these methods have been shown to increase antiretroviral concentrations in the sanctuaries/reservoirs, no functional or sterilizing cure has been achieved due to these approaches.
SUMMARY
New methods of increasing antiretroviral concentrations at the specific sites of HIV-1 replication has the potential to target cellular reservoirs. In order to optimize antiretroviral distribution into viral sanctuaries/reservoirs, additional research is needed.
Topics: Anti-Retroviral Agents; Disease Reservoirs; HIV Infections; HIV Seropositivity; HIV-1; Humans; Virus Latency
PubMed: 34961449
DOI: 10.2174/1570162X20666211227161237 -
Journal of Pharmaceutical Sciences Dec 2016The human immunodeficiency virus has infected millions of people and the epidemic continues to grow rapidly in some parts of the world. Antiretroviral (ARV) therapy has... (Review)
Review
The human immunodeficiency virus has infected millions of people and the epidemic continues to grow rapidly in some parts of the world. Antiretroviral (ARV) therapy has provided improved treatment and prolonged the life expectancy of patients. Moreover, there is growing interest in using ARVs to protect against new infections. Hence, ARVs have emerged as our primary strategy in combating the virus. Unfortunately, several challenges limit the optimal performance of these drugs. First, ARVs often require life-long use and complex dosing regimens. This results in low patient adherence and periods of lapsed treatment manifesting in drug resistance. This has prompted the development of alternate dosage forms such as vaginal rings and long-acting injectables that stand to improve patient adherence. Another problem central to therapeutic failure is the inadequate penetration of drugs into infected tissues. This can lead to incomplete treatment, development of resistance, and viral rebound. Several strategies have been developed to improve drug penetration into these drug-free sanctuaries. These include encapsulation of drugs in nanoparticles, use of pharmacokinetic enhancers, and cell-based drug delivery platforms. In this review, we discuss issues surrounding ARV therapy and their impact on drug efficacy. We also describe various drug delivery-based approaches developed to overcome these issues.
Topics: Animals; Anti-HIV Agents; Anti-Retroviral Agents; Antiretroviral Therapy, Highly Active; Contraceptive Devices, Female; Dosage Forms; Drug Delivery Systems; Forecasting; HIV Infections; Humans
PubMed: 27771050
DOI: 10.1016/j.xphs.2016.09.015 -
Current Opinion in HIV and AIDS Jul 2015Long-acting injectable antiretroviral therapy (ART) formulations hold great promise in helping to close the significant gap between efficacy and effectiveness in HIV... (Review)
Review
PURPOSE OF REVIEW
Long-acting injectable antiretroviral therapy (ART) formulations hold great promise in helping to close the significant gap between efficacy and effectiveness in HIV treatment by eliminating the requirement for lifelong daily pills. However, significant systems-level and individual challenges to implementation of long-acting ART in HIV treatment are anticipated.
RECENT FINDINGS
Studies of long-acting ART formulations are burgeoning, but the drugs are still in early phases of investigation and key knowledge gaps in pharmacokinetics and pharmacodynamics, as well as their effectiveness in settings with the largest burden of HIV disease and in key populations, remain. Extrapolating from the literature on implementation barriers to using long-acting contraception on a global scale, we explore the implementation barriers to rolling-out long-acting ART, including country approval and endorsements; prioritization of patient populations for preferred use, clinic infrastructure requirements, steady supply chains, decentralization of care, provider and patient training programs, and laboratory monitoring; and the need to examine patient preferences and conduct rigorous implementation science research to effectively scale-up this intervention.
SUMMARY
Long-acting ART for HIV treatment harbors exciting potential to shift treatment paradigms. Current knowledge gaps in the use of these agents remain, leading to multiple anticipated systems-level and individual-level barriers to implementation. Addressing these gaps and barriers will help fulfill the promise of these agents against the pandemic.
Topics: Anti-HIV Agents; Anti-Retroviral Agents; Delayed-Action Preparations; HIV Infections; Humans
PubMed: 26049955
DOI: 10.1097/COH.0000000000000158 -
The Annals of Pharmacotherapy Feb 2024To review the efficacy, safety, and role of lenacapavir (LEN) in the treatment of HIV-1 infection. (Review)
Review
OBJECTIVE
To review the efficacy, safety, and role of lenacapavir (LEN) in the treatment of HIV-1 infection.
DATA SOURCES
A literature search was performed using PubMed and Google Scholar (through March 2023) with the search term LEN and GS-6207. Other resources included abstracts presented at recent conferences, the manufacturer's Web site, and prescribing information.
STUDY SELECTION AND DATA EXTRACTION
All relevant articles, trial updates, and conference abstracts in the English language were included.
DATA SYNTHESIS
Lenacapavir represents a new class of antiretrovirals (ARVs) with a novel mechanism of action as a capsid inhibitor and a unique twice-a-year subcutaneous administration schedule. Lenacapavir when combined with other ARVs has proven to benefit heavily treatment-experienced (HTE) patients with HIV-1 infection in achieving viral suppression and immune restoration.
RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE IN COMPARISON WITH EXISTING DRUGS
Lenacapavir is a new treatment option that patients who are HTE can consider adding as part of an ARV regimen.
CONCLUSIONS
Lenacapavir is an effective and well-tolerated option for HTE patients which is a valuable addition to the arsenal of ARVs.
Topics: Humans; Capsid; Anti-HIV Agents; HIV Infections; Anti-Retroviral Agents
PubMed: 37138515
DOI: 10.1177/10600280231171375