Inflammatory Biomarker Reduction With Fostemsavir Over 96 Weeks in Heavily Treatment-Experienced Adults With Multidrug-Resistant HIV-1 in the BRIGHTE Study.

Background: Fostemsavir, a first-in-class attachment inhibitor that binds to the viral envelope protein gp120, is approved for heavily treatment-experienced persons with HIV-1 with limited treatment options. We explored changes in immunologic and coagulopathy parameters in the BRIGHTE study: a phase 3 trial that evaluated fostemsavir plus optimized background therapy in heavily treatment-experienced adults with multidrug-resistant HIV-1.

Methods: CD4+ T-cell count, CD4+/CD8+ ratio, soluble CD14, soluble CD163, and D-dimer levels were measured through 96 weeks in participants with 1 or 2 fully active antiretroviral agents available at screening.

The impact of diabetes mellitus on HIV virologic control: results of the MACS/WIHS combined cohort study.

Objective: Diabetes mellitus (DM) is associated with lower antiretroviral (ART) drug exposure among persons with HIV (PWH) compared to PWH without DM. The association between DM and virologic control in PWH, however, remains unknown.

Methods: We included participants in the Multicenter AIDS Cohort Study/Women's Interagency HIV Study Combined Cohort Study (MWCCS) who had initiated ART between 1999 and 2020 and had a suppressed HIV viral load (≤200 copies/ml) within 1 year of ART initiation.

Depression: an individual-level early warning indicator of virologic failure in HIV patients in South Africa.

Objective: To identify individual-level early warning indicators of virologic failure in HIV patients receiving antiretroviral therapy (ART) in South Africa.

Design: A matched case-control study of individuals with and without virologic failure (VF) (>5 months on ART and HIV-1 plasma viral load >1,000 copies/mL) was conducted between June 2014 and June 2018. Of the 1,000 participants enrolled in the parent cohort, 96 experienced VF, and 199 additional controls were identified from the parent cohort and matched 1:2 (some matched 1:3) for sex, age, ART duration, and site.

Tenofovir-Diphosphate and Emtricitabine-Triphosphate Adherence Benchmarks in Dried Blood Spots for Persons With HIV Receiving Tenofovir Alafenamide and Emtricitabine-Based Antiretroviral Therapy (QUANTI-TAF).

Background: QUANTI-TAF aimed to establish tenofovir-diphosphate (TFV-DP)/emtricitabine-triphosphate (FTC-TP) adherence benchmarks in dried blood spots (DBS) for persons with human immunodeficiency virus (PWH) receiving tenofovir alafenamide/emtricitabine (TAF/FTC)-based antiretroviral therapy (ART).

Methods: For 16 weeks, PWH received TAF/FTC-based ART co-encapsulated with an ingestible sensor to directly measure cumulative (enrollment to final visit) and 10-day adherence. At monthly visits, intraerythrocytic concentrations of TFV-DP and FTC-TP in DBS were quantified and summarized at steady-state (week 12 or 16) as median (interquartile range).

Viral and host mediators of non-suppressible HIV-1 viremia.

Non-suppressible HIV-1 viremia (NSV) is defined as persistent low-level viremia on antiretroviral therapy (ART) without evidence of ART non-adherence or significant drug resistance. Unraveling the mechanisms behind NSV would broaden our understanding of HIV-1 persistence. Here we analyzed plasma virus sequences in eight ART-treated individuals with NSV (88% male) and show that they are composed of large clones without evidence of viral evolution over time in those with longitudinal samples.

Tenofovir diphosphate in dried blood spots and HIV-1 resistance in South Africa.

Background: Suboptimal antiretroviral (ART) adherence can lead to virologic failure with consequent HIV-1 resistance. Tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) is a powerful biomarker of cumulative adherence, predictive of future viremia. It has been associated with resistance in Persons With HIV (PWH) in South Africa and the US.

Food Insecurity Is Associated With Low Tenofovir Diphosphate in Dried Blood Spots in South African Persons With HIV.

Background: Food insecurity has been linked to suboptimal antiretroviral therapy (ART) adherence in persons with HIV (PWH). This association has not been evaluated using tenofovir diphosphate (TFV-DP) in dried blood spots (DBSs), a biomarker of cumulative ART adherence and exposure.

Methods: Within a prospective South African cohort of treatment-naive PWH initiating ART, a subset of participants with measured TFV-DP in DBS values was assessed for food insecurity status.

Measuring ART Adherence Among Young Adults with Perinatally Acquired HIV: Comparison Between Self-report, Telephone-Based Pill Count, and Objective Pharmacologic Measures.

Tenofovir diphosphate (TVF-DP) can be quantified in red blood cells (RBCs) and dried blood spots (DBS) and can objectively measure ART adherence and predict viral suppression. Data on the association of TFV-DP with viral load are very limited in adolescents and young adults (AYA) living with perinatally-acquired HIV (PHIV), as are data comparing TFV-DP to other measures of ART adherence, such as self-report and unannounced telephone pill count. Viral load and ART adherence (self-report, TFV-DP and unannounced telephone pill count) were assessed and compared among 61 AYAPHIV recruited from an ongoing longitudinal study (CASAH) in New York City.

Outcomes of a Career Development Award (Pre-K) Mock Review Program for Postdoctoral Fellows and Early-Career Faculty.

Purpose: Securing research funding for early-career investigators remains challenging. The authors present the results of a presubmission career development award (Pre-K) review program for postdoctoral fellows and early-career faculty.

Method: The Pre-K program is designed to help mentored postdoctoral fellows and early-career faculty write successful career development awards by assigning expert reviewers to score each application and provide written and oral critiques before a mock study section.

Beyond Undetectable: Modeling the Clinical Benefit of Improved Antiretroviral Adherence in Persons With Human Immunodeficiency Virus With Virologic Suppression.

Background: Incomplete antiretroviral therapy (ART) adherence has been linked to deleterious immunologic, inflammatory, and clinical consequences, even among virally suppressed (<50 copies/mL) persons with human immunodeficiency virus (PWH). The impact of improving adherence in the risk of severe non-AIDS events (SNAEs) and death in this population is unknown.

Methods: We estimated the reduction in the risk of SNAEs or death resulting from an increase in ART adherence by (1) applying existing data on the association between adherence with high residual inflammation/coagulopathy in virally suppressed PWH, and (2) using a Cox proportional hazards model derived from changes in plasma interleukin 6 (IL-6) and D-dimer from 3 randomized clinical trials.

Acceptability and Feasibility of Providing Adherence Feedback Based on Tenofovir Diphosphate in Dried Blood Spots: Results from a Pilot Study Among Patients and Providers in Cape Town, South Africa.

Tenofovir diphosphate (TFV-DP) concentrations in dried blood spots (DBS) predict viral breakthrough, but their use remains understudied in real-world clinic settings. This pilot study examined acceptability, feasibility, and initial adherence outcomes of providing adherence feedback using TFV-DP concentrations on patient- and provider-levels in Cape Town, South Africa. We enrolled 60 persons with HIV (PWH) receiving tenofovir-containing ART attending a primary health clinic.

Viral and Host Mediators of Non-Suppressible HIV-1 Viremia.

Non-suppressible HIV-1 viremia (NSV) can occur in persons with HIV despite adherence to combination antiretroviral therapy (ART) and in the absence of significant drug resistance. Here, we show that plasma NSV sequences are comprised primarily of large clones without evidence of viral evolution over time. We defined proviruses that contribute to plasma viremia as "producer", and those that did not as "non-producer".

Comparing Predictive Ability of Two Objective Adherence Measures in a Community-Based Cohort on Antiretroviral Therapy in South Africa: Tenofovir Diphosphate Concentrations and Electronic Adherence Monitors.

Background: Electronic adherence (EA) and tenofovir diphosphate (TFV-DP) in dried blood spots (DBS) are objective measures of antiretroviral therapy (ART) adherence. We characterized the association between these measures in a prospective cohort of persons with HIV (PWH) on ART.

Setting: Four primary health clinics in Cape Town, South Africa.

Incomplete Antiretroviral Therapy Adherence Is Associated with Lower CD4-CD8 Ratio in Virally Suppressed Patients with HIV Infection in Mexico.

Suboptimal adherence to antiretroviral therapy (ART) in people with HIV, even during sustained viral suppression, is associated with persistent inflammation, immune activation, and coagulopathy. Persistently low CD4-CD8 Ratio has been also associated with residual inflammation, is a good predictor of increased risk of death and more widely available than inflammatory biomarkers. We tested the hypothesis that the CD4-CD8 Ratio is associated with ART adherence during periods of complete viral suppression.

Improving the accuracy of adherence data collected using medication monitoring technology in clinical research.

Ambiguous adherence data adversely effects the statistical analyses, study conclusions, and generalizability of research findings for clinical trials. Fortunately, technology-based measures of drug dosing provide more objective measures of medication adherence. While adherence data obtained through monitoring technology avoids the well documented shortcomings of self-reported adherence data, there are important limitations and nuances with use of these technologies that should be considered at study inception, conduct, and analysis.

Adherence challenges with daily oral pre-exposure prophylaxis during pregnancy and the postpartum period in South African women: a cohort study.

Introduction: Daily oral pre-exposure prophylaxis (PrEP) can reduce HIV acquisition. However, prevention effectiveness requires daily adherence prior to and during periods of sexual activity. Little is known about pharmacologic measures of PrEP adherence during pregnancy and postpartum and the factors related to optimal adherence during periods of sexual activity in this population.

Demographic and Clinical Characteristics of Persons with HIV with Viral Load:Adherence Mismatch Who Are at Risk of Future Viremia.

The potency of modern antiretroviral therapy (ART) allows for greater forgiveness to missed doses while still achieving, and maintaining, viral suppression. However, imperfect ART adherence, even if sufficient to maintain viral suppression, has been associated with adverse clinical outcomes. ART adherence can be objectively quantified using tenofovir diphosphate (TFV-DP) in dried blood spots (DBS), a biomarker of cumulative adherence that is predictive of future viremia-even among persons with HIV (PWH) with an undetectable HIV viral load (VL).

Statins Utilization in Adults With HIV: The Treatment Gap and Predictors of Statin Initiation.

Background: We characterized trends in statin eligibility and subsequent statin initiation among people with HIV (PWH) from 2001 to 2017 and identified predictors of statin initiation between 2014 and 2017.

Setting: PWH participating in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) enrolled in 12 US cohorts collecting data on statin eligibility criteria/prescriptions from 2001 to 2017.

Methods: We determined the annual proportion eligible for statins, initiating statins, and median waiting time (from statin eligibility to initiation).

Cumulative tenofovir diphosphate exposure in persons with HIV taking single- vs. multiple-tablet regimens.

Background: We assessed cumulative antiretroviral exposure-using tenofovir diphosphate (TFV-DP) in dried blood spots (DBS)-in persons with HIV (PWH) receiving tenofovir disoproxil fumarate (TDF)-based antiretroviral therapy (ART) as single-tablet regimens (STR) or multiple-tablet regimens (MTR).

Methods: Blood for DBS was prospectively collected in PWH on TDF during 1144 person visits (n = 523). Linear mixed-effects models, adjusted for baseline characteristics, were used to compare TFV-DP in STR versus MTR.

The use of technology-based adherence monitoring in the treatment of hepatitis C virus.

Direct-acting antivirals (DAAs) achieve high hepatitis C virus (HCV) cure rates and are forgiving to missed doses, but adherence-efficacy relationships have not been well defined. Traditional adherence measures (e.g.

Prospective telehealth analysis of functional performance, frailty, quality of life, and mental health after COVID-19 hospitalization.

Background: COVID-19 is a global pandemic with poorly understood long-term consequences. Determining the trajectory of recovery following COVID-19 hospitalization is critical for prioritizing care, allocating resources, facilitating prognosis, and informing rehabilitation. The purpose of this study was to prospectively evaluate recovery following COVID-19 hospitalization.

Predictors of 007 triphosphate concentrations in dried blood spots in persons with hepatitis C and active drug or alcohol use.

Background: Sofosbuvir is converted to its active form, 007 triphosphate (007-TP), within cells. To date, the association between treatment adherence and 007-TP in dried blood spots (DBS) and factors that influence this relationship remain unknown.

Objectives: To examine relationships between adherence and 007-TP concentrations in DBS and identify factors that influence 007-TP in DBS.

Miniature mass spectrometer-based point-of-care assay for cabotegravir and rilpivirine in whole blood.

HIV prevention and treatment with injectable cabotegravir and/or rilpivirine administered once every 4 to 8 weeks is an attractive alternative to daily therapy. Prescribed dosage and drug concentrations in plasma are based on patient data collected in clinical trials, but actual patients are expected to exhibit more variability in drug concentrations, which is important to quantify. Here, we demonstrate the first quantitative point-of-care assay with a miniature mass spectrometer to assess these drug concentrations in whole blood.