Bioavailability of dissolved and crushed single tablets of bictegravir, emtricitabine, tenofovir alafenamide in healthy adults: the SOLUBIC randomized crossover study.

Background: Crushing or dissolving bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) tablets is not recommended because there are no data supporting this practice.

Methods: A crossover, randomized trial in healthy adults (NCT04244448) investigated the bioavailability of two off-label uses of BIC/TAF/FTC (50/200/25 mg), dissolved in water or crushed in apple compote, compared with the solid tablet. Pharmacokinetic (PK) parameters were estimated from sequential intensive plasma antiretroviral concentrations over a 72 h period post dose.

EVG/COBI/FTC/TAF Bioequivalence Comparing Whole Tablets with Tablets Dissolved in Tap Water.

Medication adherence can be challenging for persons with difficulty swallowing tablets. We investigated the bioequivalence of a dissolved tablet when compared with that of a whole tablet of the fixed-dose combination elvitegravir (EVG)/cobicistat (COBI)/emtricitabine (FTC)/tenofovir (TFV) alafenamide fumarate (TAF). A within-subject fixed-order two-period open-label study was conducted in 12 HIV-negative research participants after obtaining informed consent.

Bictegravir/emtricitabine/tenofovir alafenamide in older individuals with HIV: Results of a 96-week, phase 3b, open-label, switch trial in virologically suppressed people ≥65 years of age.

Objectives: Bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) is an effective treatment for HIV-1 infection; however, clinical trial data in older people living with HIV (PLWH) are lacking. The primary 24-week and secondary 48-week analyses of study GS-US-380-4449 (NCT03405935), which assessed the efficacy and safety of switching to B/F/TAF in older PLWH, have been published. Here we report the results of the final 96-week analyses from the study.

High efficacy of switching to bictegravir/emtricitabine/tenofovir alafenamide in people with suppressed HIV and preexisting M184V/I.

Objective: We investigated the prevalence of preexisting M184V/I and associated risk factors among clinical trial participants with suppressed HIV and evaluated the impact of M184V/I on virologic response after switching to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF).

Design: Participant data were pooled from six clinical trials investigating the safety and efficacy of switching to B/F/TAF in virologically suppressed people with HIV.

Methods: Preexisting drug resistance was assessed by historical genotypes and/or baseline proviral DNA genotyping.

Brief Report: Efficacy and Safety of Bictegravir/Emtricitabine/Tenofovir Alafenamide in Females Living With HIV: An Integrated Analysis of 5 Trials.

Background: We characterized the efficacy and safety of bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) in a broad population of pediatric/adolescent/adult/elderly females living with HIV (FWH).

Setting: Integrated analysis.

Methods: Available data from 5 trials were integrated.

Pilot comparison of the ease of swallowing of single tablet antiretroviral regimens.

Daily adherence to lifelong antiretroviral therapy (ART) is required to achieve long term treatment success. However, patient preferences for ART tablet size have not been well studied. Our study assessed factors associated with the ease of swallowing (EoS) and tolerability of two placebo tablets representing and matching B/F/TAF (BPT) and DTG/ABC/3TC (DPT).

Bictegravir/Emtricitabine/Tenofovir Alafenamide in Virologically Suppressed People with HIV Aged ≥ 65 Years: Week 48 Results of a Phase 3b, Open-Label Trial.

Introduction: We report the 48-week results of an ongoing study to assess the efficacy and safety of switching older people with HIV to bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF).

Methods: This was a 96-week, phase 3b, open-label, single-arm study (GS-US-380-4449; NCT03405935). Virologically suppressed individuals aged ≥ 65 years receiving elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide or a tenofovir disoproxil fumarate-based regimen were switched to B/F/TAF.

Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide in Adults With HIV and M184V/I Mutation.

Background: The ability of elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) to maintain virologic suppression in participants with M184V and/or M184I resistance mutations from historical genotypic reports when switching from a tenofovir disoproxil fumarate-based or abacavir (ABC)-based regimen was investigated.

Setting: Phase IIIb, 48-week, open-label, single-arm, multicenter, clinical trial (NCT02616029).

Methods: Virologically suppressed adults with HIV and documented M184V/I on historical genotypic records switched to E/C/F/TAF from a tenofovir disoproxil fumarate-based or ABC-based regimen.

Differential detection of M184V/I between plasma historical HIV genotypes and HIV proviral DNA from PBMCs.

Background: The M184V/I reverse transcriptase mutation, which confers major resistance to lamivudine and emtricitabine, is still quite frequent in people living with HIV. The underlying presence of the M184V/I mutation may undermine virological outcomes of ART, particularly in the context of proposed treatment with two-drug combinations that include drugs affected by M184V, such as lamivudine. In suppressed patients for whom historical data are seldom available, resistance assays evaluating integrated viral DNA can help select a fully active switch regimen.

Bone mineral density in virologically suppressed people aged 60 years or older with HIV-1 switching from a regimen containing tenofovir disoproxil fumarate to an elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide single-tablet regimen: a multicentre, open-label, phase 3b, randomised trial.

Background: Tenofovir alafenamide is associated with less renal and bone toxicity than tenofovir disoproxil fumarate and might improve the long-term safety of antiretroviral therapy. We aimed to investigate the effect on bone mineral density of switching from a regimen containing tenofovir disoproxil fumarate to one containing tenofovir alafenamide in participants aged 60 years and older.

Methods: We did a prospective, open-label, multicentre, randomised trial in 36 European centres.

Analysis of drug-drug interactions among patients receiving antiretroviral regimens using data from a large open-source prescription database.

Purpose: Results of a study of contraindicated concomitant medication use among recipients of preferred antiretroviral therapy (ART) regimens are reported.

Methods: A retrospective study was conducted to evaluate concomitant medication use in a cohort of previously treatment-naive, human immunodeficiency virus (HIV)-infected U.S.

A Pharmacist-Led Program to Evaluate and Reduce Polypharmacy and Potentially Inappropriate Prescribing in Older HIV-Positive Patients.

Objective: The goal of this pharmacist-led study was to utilize two validated instruments, Beers Criteria and Screening Tool of Older Persons' Potentially Inappropriate Prescriptions (STOPP), to assess potentially inappropriate prescribing (PIP) in older patients infected with the human immunodeficiency virus (HIV) and evaluate pharmacist interventions.

Design: Prospective randomized interventional trial.

Setting: Large urban clinic providing interdisciplinary primary and HIV care for ~2700 HIV-positive publicly insured patients.

Drug Interactions with Cobicistat- or Ritonavir-Boosted Elvitegravir.

Cobicistat and ritonavir are structurally distinct compounds that both potently inhibit cytochrome P450 (CYP) 3A, the metabolizing enzyme primarily responsible for the elimination of several antiretroviral medications, and, as such, are pharmacokinetic boosters for antiretroviral agents that require longer dosing intervals. Recently, cobicistat was approved for the treatment of HIV-1 infection in treatment-naive adults as a component of a single-tablet regimen consisting of cobicistat-boosted elvitegravir plus emtricitabine and tenofovir disoproxil fumarate. While studies have demonstrated that boosting with either cobicistat or ritonavir results in comparable plasma exposure of the target antiretroviral agent, a better understanding of drug-drug interactions between cobicistat- and ritonavir-boosted antiretrovirals and other medications will inform treatment decisions in HIV-infected patients.

Adherence and HIV RNA Suppression in the Current Era of Highly Active Antiretroviral Therapy.

Background: We examined trends in adherence to highly active antiretroviral therapy (HAART) and HIV RNA suppression and estimated the minimum cutoff of adherence to newer HAART formulations needed for HIV RNA suppression by regimen type.

Methods: We used Veterans Affairs pharmacy dispensing data from the Veterans Aging Cohort Study Virtual Cohort between October 2000 and September 2010 and defined adherence as the duration of time the patient had the medications available, relative to the total number of days between refills for all antiretrovirals in a year. Temporal trends in adherence and viral load suppression were examined by the patient's most frequently used HAART regimen in the year.

Polypharmacy, drug-drug interactions, and potentially inappropriate medications in older adults with human immunodeficiency virus infection.

Objectives: To describe the frequency of medication-related problems in older adults with human immunodeficiency virus (HIV) infection.

Design: Retrospective chart review.

Setting: Community.

The next therapeutic challenge in HIV: polypharmacy.

With the adoption of combination antiretroviral therapy (ART), most HIV-infected individuals in care are on five or more medications and at risk of harm from polypharmacy, a risk that likely increases with number of medications, age, and physiologic frailty. Established harms of polypharmacy include decreased medication adherence and increased serious adverse drug events, including organ system injury, hospitalization, geriatric syndromes (falls, fractures, and cognitive decline) and mortality. The literature on polypharmacy among those with HIV infection is limited, and the literature on polypharmacy among non-HIV patients requires adaptation to the special issues facing those on chronic ART.

Does once-daily etravirine have a role in the management of HIV-1 infection?

When individualizing therapy for HIV-positive patients and for those in whom the 'preferred regimens' of the US Department of Health and Human Services HIV treatment guidelines are not appropriate, a once-daily non-nucleoside with a fixed-dose combination of two nucleosides may be considered in patients who are adherence challenged, intolerant to other regimens but with no viral resistance, or in those in whom the pill burden or actual pill size was too great to accept. Despite having a 30- to 40-h elimination half-life, etravirine was never considered for once-daily dosing during development due to an unacceptably high pill burden in phase II trials. However, a recently published study, SENSE, enrolled 157 HIV-positive patients in a multinational, randomized, placebo-controlled, double-blind trial that investigated 400 mg etravirine once daily with two nucleosides versus a comparator arm that included efavirenz and two nucleosides.

Coinfection with human immunodeficiency virus and hepatitis C virus: challenges and therapeutic advances. Insights from the Society of Infectious Diseases Pharmacists.

In the United States, approximately 30% of all human immunodeficiency virus (HIV)-positive patients are also infected with hepatitis C virus (HCV). Both viruses share similar routes of transmission. Unlike HIV or hepatitis B virus, HCV is curable if treated and the patient achieves a sustained virologic response.

Etravirine and rilpivirine: nonnucleoside reverse transcriptase inhibitors with activity against human immunodeficiency virus type 1 strains resistant to previous nonnucleoside agents.

Etravirine and rilpivirine are two new nonnucleoside reverse transcriptase inhibitors (NNRTIs) that have the distinct advantage of being able to be used in patients with exposure to previous NNRTIs (e.g., nevirapine or efavirenz).

On the horizon: promising investigational antiretroviral agents.

Human immunodeficiency virus (HIV) infection affects close to 40 million individuals worldwide. Since 1981 when the first case reports of individuals dying from a then rare opportunistic infection were published, twenty million people have died from this epidemic. With 3 or more antiretrovirals as the standard of care, the prevalence of single, double and triple-class resistant HIV strains has increased significantly over the last 5 years due to the tremendous replicative capacity of HIV and selective drug pressure.

Enfuvirtide: first fusion inhibitor for treatment of HIV infection.

Purpose: The mechanism of action, pharmacokinetics, clinical efficacy, adverse effects, and availability of enfuvirtide are discussed.

Summary: To date, 20 antiretrovirals have been approved by FDA for the treatment of HIV infection. The recent approval of enfuvirtide offers a new and fourth class of antiretroviral agents called fusion inhibitors.