Doravirine/islatravir for the treatment of HIV.

Introduction: HIV is a global disease affecting millions of people. While treatments have improved over the past decades, treatment failure remains a significant issue for treatment experienced patients. Doravirine/islatravir is a new dual-therapy regimen with a promising resistance profile and reductions in central nervous system effects.

Drug-drug interactions in HIV-infected patients receiving chemotherapy.

Introduction: Coadministration of antiretrovirals and anti-cancer medications may present many complex clinical scenarios. This is characterized by the potential for drug-drug interactions (DDIs) and the challenges that arise in patient management. In this article, we investigate the potential for DDIs between antiretrovirals, including protease inhibitors (PIs), non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors (NRTIs), integrase strand transfer inhibitors (INSTIs), and anti-cancer medications.

Expanding therapeutic options: lenacapavir + bictegravir as a potential treatment for HIV.

Introduction: Treatment for people with HIV/AIDS has radically evolved since the introduction of the first antiretrovirals. One newly approved antiretroviral is lenacapavir, which targets the viral capsid. Lenacapavir is currently approved as a therapeutic addition for subjects who are treatment-experienced, and who have developed resistance to multiple antiretrovirals.

Substances of abuse and their effect on SAR-CoV-2 pathogenesis.

Following the emergence of SARS-CoV-2, various reports suggest that there has been a significant increase in substance abuse due to social distancing and related issues. Several reports have suggested the impact of chronic substance use on individuals' physiological and psychological health. Therefore, there is a need to know the impact of SARS-CoV-2 on persons with substance use disorders.

Drug-drug interactions between COVID-19 therapeutics and antiretroviral treatment: the evidence to date.

Introduction: With new effective treatments for SARS-CoV-2, patient outcomes have greatly improved. However, new medications bring a risk of drug interactions with other medications. People living with HIV (PLWH) are at particular risk for these interactions due to heightened risk of immunosuppression, polypharmacy, and overlap in affected organs.

Senescent macrophages alter fibroblast fibrogenesis in response to SARS-CoV-2 infection.

SARS-CoV-2 has, since its emergence in 2019, become a global pandemic. Disease outcomes are worsened in older patients who are infected. The causes for this is multifactorial, but one potential cause for this disparity is increased rates of cellular senescence in older individuals, particularly in immune cells.

An evaluation of long-acting cabotegravir + rilpivirine for the treatment of virologically suppressed adults living with HIV.

Introduction: HIV is a global disease that has seen significant improvements in care over the past decades. Despite improvements, treatments for maintaining suppression are complex for patients and include two to three oral medications. The approval of intramuscular cabotegravir (CAB) and rilpivirine (RPV) offers a new therapeutic modality with the opportunity of a longer dosing frequency.

The Importance of Tissue Sanctuaries and Cellular Reservoirs of HIV-1.

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.

Metformin Suppresses Monocyte Immunometabolic Activation by SARS-CoV-2 Spike Protein Subunit 1.

A hallmark of COVID-19 is a hyperinflammatory state associated with severity. Monocytes undergo metabolic reprogramming and produce inflammatory cytokines when stimulated with SARS-CoV-2. We hypothesized that binding by the viral spike protein mediates this effect, and that drugs which regulate immunometabolism could inhibit the inflammatory response.

An evaluation of ledipasvir + sofosbuvir for the treatment of chronic hepatitis C infection.

: Hepatitis C (HCV) is viral disease with a global impact. Over the last 10 years, the treatment of this disease has evolved. Treatment guidelines have evolved to adopt new medications for HCV.

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

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 multidrug resistance-associated protein 1.

Opioid Use Disorders in People Living with HIV/AIDS: A Review of Implications for Patient Outcomes, Drug Interactions, and Neurocognitive Disorders.

The opioid epidemic has had a significant, negative impact in the United States, and people living with HIV/AIDS (PLWHA) represent a vulnerable sub-population that is at risk for negative sequela from prolonged opioid use or opioid use disorder (OUD). PLWHA are known to suffer from HIV-related pain and are commonly treated with opioids, leading to subsequent addictive disorders. PLWHA and OUD are at an increased risk for attrition in the HIV care continuum, including suboptimal HIV laboratory testing, delayed entry into HIV care, and initiation or adherence to antiretroviral therapy.

An update on drug-drug interactions between antiretroviral therapies and drugs of abuse in HIV systems.

Introduction: While considerable progress has been made in the fight against HIV/AIDS, to date there has not been a cure, and millions of people around the world are currently living with HIV/AIDS. People living with HIV/AIDS have substance abuse disorders at higher rates than non-infected individuals, which puts them at an increased risk of drug-drug interactions.

Areas Covered: Potential drug-drug interactions are reviewed for a variety of potential drugs of abuse, both licit and illicit.

Extracellular Vesicles in Viral Replication and Pathogenesis and Their Potential Role in Therapeutic Intervention.

Extracellular vesicles (EVs) have shown their potential as a carrier of molecular information, and they have been involved in physiological functions and diseases caused by viral infections. Virus-infected cells secrete various lipid-bound vesicles, including endosome pathway-derived exosomes and microvesicles/microparticles that are released from the plasma membrane. They are released via a direct outward budding and fission of plasma membrane blebs into the extracellular space to either facilitate virus propagation or regulate the immune responses.

Differential packaging of inflammatory cytokines/ chemokines and oxidative stress modulators in U937 and U1 macrophages-derived extracellular vesicles upon exposure to tobacco constituents.

Smoking, which is highly prevalent in HIV-infected populations, has been shown to exacerbate HIV replication, in part via the cytochrome P450 (CYP)-induced oxidative stress pathway. Recently, we have shown that extracellular vesicles (EVs), derived from tobacco- and/or HIV-exposed macrophages, alter HIV replication in macrophages by cell-cell interactions. We hypothesize that cigarette smoke condensate (CSC) and/or HIV-exposed macrophage-derived EVs carry relatively high levels of pro-oxidant and pro-inflammatory cargos and/or low levels of antioxidant and anti-inflammatory cargos, which are key mediators for HIV pathogenesis.

Evaluating emtricitabine + rilpivirine + tenofovir alafenamide in combination for the treatment of HIV-infection.

Antiretroviral therapy (ART) is recommended for all people who are living with HIV to suppress viral load and to stop the progression and transmission of HIV-1. Fixed-dose combinations of antiretrovirals largely reduce pill burden. The authors first provide an overview of the use of non-nucleoside reverse transcriptase inhibitor (NNRTI) based therapy in HIV care.

Nanotechnology approaches for delivery of cytochrome P450 substrates in HIV treatment.

: Antiretroviral therapy (ART) has led to a significant reduction in HIV-1 morbidity and mortality. Many antiretroviral drugs (ARVs) are metabolized by cytochrome P450 (CYP) pathway, and the majority of these drugs are also either CYP inhibitors or inducers and few possess both activities. These CYP substrates, when used for HIV treatment in the conventional dosage form, have limitations such as low systemic bioavailability, potential drug-drug interactions, and short half-lives.

Azithromycin Polarizes Macrophages to an M2 Phenotype via Inhibition of the STAT1 and NF-κB Signaling Pathways.

Azithromycin is effective at controlling exaggerated inflammation and slowing the long-term decline of lung function in patients with cystic fibrosis. We previously demonstrated that the drug shifts macrophage polarization toward an alternative, anti-inflammatory phenotype. In this study we investigated the immunomodulatory mechanism of azithromycin through its alteration of signaling via the NF-κB and STAT1 pathways.

Pharmacokinetics and pharmacodynamics of cytochrome P450 inhibitors for HIV treatment.

Drugs used in HIV treatment; all protease inhibitors, some non-nucleoside reverse transcriptase inhibitors, and pharmacoenhancers ritonavir and cobicistat can inhibit cytochrome P450 (CYP) enzymes. CYP inhibition can cause clinically significant drug-drug interactions (DDI), leading to increased drug exposure and potential toxicity. Areas covered: A complete understanding of pharmacodynamics and CYP-mediated DDI is crucial to prevent adverse side effects and to achieve optimal efficacy.

Mannose-decorated hybrid nanoparticles for enhanced macrophage targeting.

Our goal was to design nanocarriers that specifically target and deliver therapeutics to polarized macrophages. Mannose receptors are highly overexpressed on polarized macrophages. In this study, we constructed Pluronic® -F127 polymer and tannic acid (TA) based nanoparticles (F127-TA core nanoparticles) with varying mannose densities.

Tobacco and Antiretrovirals Modulate Transporter, Metabolic Enzyme, and Antioxidant Enzyme Expression and Function in Polarized Macrophages.

Background: Cigarette smoking increases systemic oxidative stress, inflammation, and viral replication in individuals with HIV. Macrophages are infected during HIV infection and serve as an important reservoir throughout the process. Macrophages exist in two phenotypes, the classically activated M1 macrophage and alternatively activated M2 macrophage.

The role of cytochrome P450 2E1 on ethanol-mediated oxidative stress and HIV replication in human monocyte-derived macrophages.

Background: Alcohol consumption is considered to be a major health problem among people living with HIV/AIDS. Our previous reports have shown that ethanol reduced intracellular concentrations of antiretroviral drugs elvitegravir and darunavir in the HIV-1-infected U1 cell line. Ethanol also increased HIV-1 replication despite the presence of elvitegravir.

The dawn of precision medicine in HIV: state of the art of pharmacotherapy.

Introduction: Combination antiretroviral therapy (ART) reduces viral load to under the limit of detection, successfully decreasing HIV-related morbidity and mortality. Due to viral mutations, complex drug combinations and different patient response, there is an increasing demand for individualized treatment options for patients.

Areas Covered: This review first summarizes the pharmacokinetic and pharmacodynamic profile of clinical first-line drugs, which serves as guidance for antiretroviral precision medicine.

Sofosbuvir + velpatasvir + voxilaprevir for the treatment of hepatitis C infection.

Hepatitis C is a disease with a significant global impact. Over the last several years, the treatment of the disease has been revolutionized. Therapy has transformed over the last several years with the approval of second generation direct acting antivirals, and currently utilized medications for the treatment of hepatitis C are significantly more efficacious with better safety profiles than previously approved treatments.