Publications by authors named "William Short"

Background: Ethical patient outreach is critical for engaging patients with HIV in HIV cure-directed research. We sought to examine HIV clinical providers' awareness of current HIV cure-directed research strategies investigated through the Martin Delaney Collaboratories (MDC) and providers' attitudes toward patient outreach for HIV cure-directed research and to identify opportunities for clinical provider education on MDC research strategies.

Methods: We conducted a 1-time, cross-sectional, web-based survey with 64 HIV clinical providers (physicians, physician assistants, and nurses) in Philadelphia.

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Lowering viral load during pregnancy is regarded as the most important method of reducing human immunodeficiency virus 1 (HIV-1) vertical transmission risk, and minimizing fetal exposure to drugs is a guiding principle during pregnancy. Dolutegravir/lamivudine (DTG/3TC) has demonstrated high efficacy, a high barrier to resistance, and a good safety profile in non-pregnant individuals; however, DTG/3TC is not recommended by perinatal HIV treatment guidelines for initial therapy in pregnant people living with HIV-1 because of limited data on use of the 2-drug regimen during pregnancy. Efficacy and pharmacokinetic data from pregnant individuals using DTG and/or 3TC are reviewed and used to extrapolate anticipated DTG/3TC efficacy in pregnancy.

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Background: The first long-acting injectable antiretroviral, cabotegravir/rilpivirine (LA-CAB/RPV), was FDA approved in January 2021 for persons with HIV suppressed on their current regimen. Body mass index (BMI) ≥30 kg/m2 has been identified as a risk factor for virologic failure, however data is limited due to small sample sizes. The aim of this study was to evaluate the impact of BMI on the efficacy of LA-CAB/RPV in a real-world setting.

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Behavioral economics research suggests poverty may influence behavior by reducing mental bandwidth, increasing future discounting, and increasing risk aversion. It is plausible these decision-making processes are further impaired in the context of HIV or pregnancy. In this cross-sectional study of 86 low-income women in Philadelphia, HIV was associated with lower mental bandwidth (one of two measures) and lower risk aversion.

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Advances in antiretroviral therapy (ART) have made it possible for persons with human immunodeficiency virus (HIV) to live a lifespan approaching that of people without HIV, without progressing to AIDS or transmitting HIV to sexual partners or infants. There is, therefore, increasing emphasis on maintaining health throughout the lifespan. To receive optimal medical care and achieve desired outcomes, persons with HIV must be consistently engaged in care and able to access uninterrupted treatment, including ART.

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Article Synopsis
  • Integrase strand transfer inhibitor (InSTI)-based antiretroviral therapies can lead to increased weight gain in people with HIV, prompting the DEFINE study to explore if switching to a protease inhibitor (PI)-based regimen could reverse this trend.
  • The study involved 103 adults who were either switched to a specific PI regimen (darunavir/cobicistat/emtricitabine/TAF) or continued their current treatment for the first half before the switch, with weight change measured primarily at 24 weeks.
  • Results showed no significant weight change at 24 weeks between the two groups, but a potential trend toward weight loss was noted at 48 weeks, particularly in subgroups with higher weight gain risk, suggesting
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Pregnant persons with chronic health conditions often require pharmacotherapy to remain healthy. The Antiretroviral Pregnancy Registry is a prospective, international, voluntary, and exposure registry that collects information on antiretroviral (ARV) exposure; however, a minority of providers use the registry, leaving critical gaps to guide prescribing in this population. The Task Force for the Elimination of Perinatal HIV Transmission in the United States, funded by the Centers for Disease Control and Prevention, has identified the monitoring of ARV safety as a paramount concern in the ongoing mission to eliminate perinatal human immunodeficiency virus (HIV) transmission.

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Article Synopsis
  • There are limited treatment options for people with HIV-1 who have already tried many medicines and have drug-resistant HIV-1.
  • Since 2018, three new medications have been approved to help these patients: ibalizumab, fostemsavir, and lenacapavir.
  • Experts created guidelines to help doctors use these new medicines better and suggested more areas to study for future research.
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Antiretrovirals are often approved by the Food and Drug Administration without sufficient safety data regarding their use in pregnancy. To quantify this delay, we calculated the interval from the approval date to their inclusion in the Antiretroviral Pregnancy Registry prospective analysis (≥200 first-trimester exposures); the median delay was 6 years.

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This study describes the largest cohort to date (n = 147) of pregnant patients with human immunodeficiency virus (HIV) on bictegravir (BIC). BIC in pregnancy was associated with high levels of viral suppression and perinatal outcomes similar to those in the published literature. These findings support consideration for the use of BIC in managing HIV during pregnancy.

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Background: Injectable cabotegravir (CAB)/rilpivirine (RPV) is the only combination long-acting (LA) antiretroviral regimen approved for HIV. RPV may not be effective among individuals with non-nucleoside reverse transcriptase inhibitor (NNRTI) resistance, which has >10% prevalence in many countries. Lenacapavir (LEN) is an LA capsid inhibitor given every 6 months, but has not been studied in combination with other LA agents.

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Behavioral economics research suggests poverty may influence behavior by reducing mental bandwidth, increasing future discounting, and increasing risk aversion. It is plausible that these decision-making processes are further impaired in the context of HIV or pregnancy. In this cross-sectional study of 86 low-income women in Philadelphia, multivariable models showed that HIV was associated with decreased mental bandwidth (one of two measures) and lower risk aversion.

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Article Synopsis
  • The study investigates the effectiveness of the immunomodulator baricitinib when combined with remdesivir for hospitalized COVID-19 patients, focusing on those identified as high-risk based on specific blood count metrics.
  • In the high-risk group, the combination therapy showed significant benefits, including a lower risk of death, reduced likelihood of needing invasive ventilation, and improved recovery rates compared to the placebo group.
  • The findings suggest that baricitinib+remdesivir can enhance treatment outcomes for high-risk COVID-19 patients, although it is noted that the analysis is based on data prior to the emergence of newer SARS-CoV-2 variants.
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Objectives: Women are under-represented in clinical trials and must often commit to using contraception to enroll. We sought to determine the incidence and predictors of pregnancy in women participating in HIV treatment trials.

Design: Individual participant data meta-analysis.

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Article Synopsis
  • Clinical trials during infectious disease outbreaks like COVID-19 often face challenges in quickly enrolling a representative study population, which can impact treatment identification against morbidity and mortality.
  • The study assessed participant demographics in the Adaptive COVID-19 Treatment Trial (ACTT) by comparing enrolled data against COVID-19 surveillance networks and US Census information, focusing on sex, race, ethnicity, and age.
  • Results showed that while ACTT's demographic makeup somewhat aligned with COVID-NET data, it highlighted discrepancies such as a lower proportion of females enrolled compared to reference datasets, indicating that using surveillance data is more relevant than census data in understanding the affected population.
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Objectives: Women make up nearly a fifth of new human immunodeficiency virus (HIV) infections yearly in the United States, more than half of which could have been prevented with broader use of HIV pre-exposure prophylaxis (PrEP). We aimed to qualitatively assess (1) acceptability of an HIV risk screening strategy and PrEP provision in a family planning setting, and (2) the influence of family planning visit type (abortion, pregnancy loss management, or contraception) on HIV risk screening acceptability.

Study Design: Guided by the P3 (practice-, provider-, and patient-level) model for preventive care interventions, we conducted three focus group discussions including patients who had experienced induced abortion, early pregnancy loss (EPL), or contraception care.

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Objective: The aim of this study was to assess the susceptibility of HIV to two HIV monoclonal antibodies (bnAbs), 3BNC117 and 10-1074, in individuals with chronically antiretroviral therapy (ART) suppressed HIV infection.

Design: The susceptibility of bnAbs was determined using the PhenoSense mAb Assay, which is a cell-based infectivity assay designed to assess the susceptibility of luciferase-reporter pseudovirions. This assay is the only Clinical Laboratory Improvement Ammendment (CLIA)/College of American Pathologist (CAP) compliant screening test specifically developed for evaluating bnAb susceptibility in people with HIV infection.

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Article Synopsis
  • The study assessed the progression of COVID-19 treatment standards (SOC) and their impact on patient recovery and mortality rates during 2020-2021, using data from the Adaptive COVID-19 Treatment Trial (ACTT).
  • Results indicated that outcomes improved significantly from ACTT-2 to ACTT-3, with notable reductions in mortality and intubation rates, although the improvements from ACTT-1 to ACTT-2 were less pronounced.
  • The analysis also explored various factors that could explain these trends, including changes in SOC, surges in COVID-19 cases, and the emergence of different virus variants, highlighting an increase in the use of dexamethasone in later trials.
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Because oral transmission of SARS-CoV-2 is 3-5 orders of magnitude higher than nasal transmission, we investigated debulking of oral viruses using viral trap proteins (CTB-ACE2, FRIL) expressed in plant cells, delivered through the chewing gum. In omicron nasopharyngeal (NP) samples, the microbubble count (based on N-antigen) was significantly reduced by 20 μg of FRIL (p < 0.0001) and 0.

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Background: We have a limited understanding on how to best integrate technologies to support antiretroviral therapy (ART) adherence in routine HIV care.

Methods: We conducted semi-structured interviews with multidisciplinary providers caring for pregnant and postpartum people with HIV and asked providers about their perspectives on utilizing adherence support technologies such as text messages, video check-ins with providers or automated with facial recognition for directly-observed-therapy, signaling pill bottle, and signaling pill to support ART adherence. Each approach generated an adherence report.

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Background: The Adaptive COVID Treatment Trial-2 (ACTT-2) found that baricitinib in combination with remdesivir therapy (BCT) sped recovery in hospitalized coronavirus disease 2019 (COVID-19) patients vs remdesivir monotherapy (RMT). We examined how BCT affected progression throughout hospitalization and utilization of intensive respiratory therapies.

Methods: We characterized the clinical trajectories of 891 ACTT-2 participants requiring supplemental oxygen or higher levels of respiratory support at enrollment.

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Background And Objectives: There is a paucity of guidance on HIV pre-exposure prophylaxis (PrEP) implementation in an academic medical center. The objectives of this study were to describe interventions by a multidisciplinary PrEP task force at an academic medical center and compare metrics of PrEP implementation pre- and post-creation of this entity.

Methods: The interventions of the task force are described within the rubric of the PrEP care continuum.

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Background: Family planning and abortion clinics routinely address sexual health. We sought to evaluate implementation outcomes of an HIV pre-exposure prophylaxis (PrEP) care strategy for patients seeking management of induced abortion and pregnancy loss.

Setting: Single-center, urban, academic, hospital-based family planning service.

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