Investigations of Long-Acting Formulations in Children, Adolescents, and Pregnant Women: A Systematic Review.

Long-acting and extended-release drug delivery strategies have greatly improved treatment for a variety of medical conditions. Special populations, specifically infants, children, young people, and pregnant and postpartum women, could greatly benefit from access to these strategies but are often excluded from clinical trials. We conducted a systematic review of all clinical studies involving the use of a long-acting intramuscular injection or implant in infants, children, young people, and pregnant and postpartum people.

Preferences and Feasibility of Long-Acting Technologies for the Treatment of Hepatitis C Virus: A Survey of Patients in Diverse Low- and Middle-Income Countries.

Despite available curative treatments, global rates of hepatitis C virus (HCV) infection persist with significant burden in low- and middle-income countries (LMICs). Long-acting (LA) antiviral products are in development. This study explored the challenges and opportunities in LA-HCV treatment across three LMICs: Egypt, Ethiopia and India.

Strategic use of salvage long-acting antiretrovirals in the setting of resistance.

Purpose: Long-acting cabotegravir/rilpivirine (LA-CAB/RPV) was approved for use in virally suppressed patients with human immunodeficiency virus (HIV) in January 2021. While this was a paradigm shift for many patients living with HIV, as LA-CAB/RPV was the first injectable complete regimen for the treatment of HIV, several patient populations, including those lacking virologic suppression, have not been able to easily access this advance in science and care.

Summary: In this article, we provide an update on 2 patients from our previous report and describe one further patient who experienced treatment failure following initiation of LA-CAB/RPV.

Pharmacokinetics of tenofovir alafenamide, emtricitabine, and dolutegravir in a patient on peritoneal dialysis.

Introduction: Peritoneal dialysis (PD) is an effective renal replacement modality in people with HIV (PWH) with end-stage kidney disease (ESKD), particularly those with residual kidney function. Data on pharmacokinetics (PK) of antiretrovirals in patients on peritoneal dialysis are limited.

Methods: A single-participant study was performed on a 49-year-old gentleman with ESKD on PD and controlled HIV on once daily dolutegravir (DTG) 50 mg + tenofovir alafenamide (TAF) 25 mg / emtricitabine (FTC) 200 mg.

Preferences and feasibility of long-acting technologies for treatment of hepatitis C virus in low- and middle-income countries: A survey of providers and policymakers.

Long-acting technologies (LATs) for hepatitis C virus (HCV) are under development as a strategy to improve linkage to care, treatment adherence and outcomes. We conducted a survey of HCV treatment prescribers and HCV policymakers in low- and middle-income countries (LMICs) regarding acceptability and feasibility of HCV LATs. We included one-time intramuscular injection, subdermal implant and transdermal patch as potential LAT options.

Predicted Pharmacokinetic Interactions Between Hormonal Contraception and Single or Intermittently Dosed Rifampicin.

The scale-up of rifampicin-based prevention regimens is an essential part of the global leprosy strategy. Daily rifampicin may reduce the effectiveness of the oral contraceptive pill (OCP), but little is known about the effects of rifampicin at the less frequent dosing intervals used for leprosy prophylaxis. As many women of reproductive age rely on OCP for family planning, evaluating the interaction with less-than-daily rifampicin regimens would enhance the scalability and acceptability of leprosy prophylaxis.

Your Outpatient has Coronavirus Disease 2019: What Are the Treatment Options in the Current Severe Acute Respiratory Syndrome Coronavirus 2 Variant Climate?

Mutations accumulated by novel Severe Acute Respiratory Syndrome Coronavirus 2 Omicron sublineages contribute to evasion of previously effective monoclonal antibodies for treatment or prevention of Coronavirus Disease 2019 (COVID-19). Other authorized or approved antiviral drugs such as nirmatrelvir/ritonavir, remdesivir, and molnupiravir are, however, predicted to maintain activity against these sublineages and are key tools to reduce severe COVID-19 outcomes in vulnerable populations. A stepwise approach may be taken to target the appropriate antiviral drug to the appropriate patient, beginning with identifying whether a patient is at high risk for hospitalization or other complications of COVID-19.

Development and validation of a liquid chromatographic-tandem mass spectrometric assay for the quantification of cabotegravir and rilpivirine from dried blood spots.

Background: Dried blood spots (DBS) have been utilized as a blood plasma alternative for therapeutic drug monitoring and pharmacologic analysis. There are analytical and physiochemical considerations in bridging drug concentrations from plasma to DBS. Recently, the long-acting antiretroviral cabotegravir (CAB) has been approved for HIV prevention, and a co-packaged regimen of long-acting CAB and rilpivirine (RPV) has been approved for HIV treatment.

Realizing the promise of long-acting antiretroviral treatment strategies for individuals with HIV and adherence challenges: an illustrative case series.

Background: Adherence to antiretroviral treatment (ART) remains the cornerstone of optimal HIV outcomes, including viral suppression (VS), immune recovery, and decreased transmission risk. For many people with HIV (PWH), particularly those with early-acquired HIV, structural, behavioral, and cognitive barriers to adherence and competing priorities related to life events may be difficult to overcome, resulting in nonadherence. Long-acting injectable antiretroviral therapies (LAI-ART) may be a useful strategy to overcome some of these barriers.

A population pharmacokinetic model based on HPTN 077 of long-acting injectable cabotegravir for HIV PrEP.

Aims: Cabotegravir delivered as a long-acting intramuscular injection has shown superior efficacy to oral tenofovir-emtricitabine as pre-exposure prophylaxis (PrEP) for HIV. Cabotegravir pharmacokinetics (PK), like those of other long-acting depot preparations, exhibit variability between individuals and between injection occasions. The aim of this study is to describe the population pharmacokinetics of long-acting cabotegravir (CAB-LA).

Clinical outcomes after IL-6 blockade in patients with COVID-19 and HIV: a case series.

Background: In hospitalized people with HIV (PWH) there is an increased risk of mortality from COVID-19 among hospitalized PWH as compared to HIV-negative individuals. Evidence suggests that tocilizumab-a humanized monoclonal interleukin (IL)-6 receptor inhibitor (IL-6ri) antibody-has a modest mortality benefit when combined with corticosteroids in select hospitalized COVID-19 patients who are severely ill. Data on clinical outcomes after tocilizumab use in PWH with severe COVID-19 are lacking.

Preferences of Persons With or at Risk for Hepatitis C for Long-Acting Treatments.

Background: Whereas safe, curative treatments for hepatitis C virus (HCV) have been available since 2015, there are still 58 million infected persons worldwide, and global elimination may require new paradigms. We sought to understand the acceptability of approaches to long-acting HCV treatment.

Methods: A cross-sectional, 43-question survey was administered to 1457 individuals with or at risk of HCV at 28 sites in 9 countries to assess comparative interest in a variety of long-acting strategies in comparison with oral pills.

Ethical issues in therapeutic use and research in pregnant and breastfeeding women.

Pregnant or potentially pregnant women have historically been excluded from clinical trials of new medications. However, it is increasingly recognised that it is imperative to generate evidence from the population in whom the drugs are likely to be used to inform safe, evidence-based shared clinical decision making. Reluctance by researchers and regulators to perform such studies often relates to concerns about risk, particularly to the foetus.

Examining the Safety, Pharmacokinetics, and Pharmacodynamics of a Rectally Administered IQP-0528 Gel for HIV Pre-Exposure Prophylaxis: A First-In-Human Study.

A lubricating microbicide gel designed for rectal and vaginal use would provide a behaviorally congruent strategy to enhance pre-exposure prophylaxis adherence and reduce HIV infection risk. In this study, we report the first-in-human evaluation of such a gel containing 1% IQP-0528, an investigational antiretroviral. Seven HIV-1-negative participants received one 10 mL rectal dose of radiolabeled 1% IQP-0528 gel.

Long-acting implants to treat and prevent HIV infection.

Purpose Of Review: Subcutaneous implants are a promising technology to enable long-acting parenteral delivery of antiretroviral drugs (ARV) because they may be able to provide protective drugs concentrations for a year or longer following a single implant. The present review covers the current status of preclinical and clinical development of antiretroviral implants.

Recent Findings: Over the past three decades, subcutaneous implants have been widely used for long-acting hormonal contraception and the treatment of hormonally-driven malignancies.

Conceptual Design of a Universal Donor Screening Approach for Vaginal Microbiota Transplant.

The success of fecal microbiota transplant (FMT) in treating recurrent infection has led to growing excitement about the potential of using transplanted human material as a therapy for a wide range of diseases and conditions related to microbial dysbiosis. We anticipate that the next frontier of microbiota transplantation will be vaginal microbiota transplant (VMT). The composition of the vaginal microbiota has broad impact on sexual and reproductive health.