Safety Data Timelines for Pregnant Individuals with HIV on Antiretroviral Therapy.

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); median delay was six years.

Mental Bandwidth is Associated with HIV and Viral Suppression Among Low-Income Women in Philadelphia.

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. Pregnancy was not associated with any decision-making factors. Viral suppression was associated with greater mental bandwidth (one of two measures), and antenatal care engagement with lower future discounting. Anti-poverty interventions may be particularly beneficial to improve health behaviors in the context of HIV.

Bictegravir Use During Pregnancy: A Multi-Center Retrospective Analysis Evaluating HIV Viral Suppression and Perinatal Outcomes.

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

Case Series of People With HIV on the Long-Acting Combination of Lenacapavir and Cabotegravir: Call for a Trial.

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. Methods: We assembled a case series from 4 US academic medical centers where patients with adherence challenges were prescribed LEN subcutaneously every 26 weeks/CAB (+/- RPV) intramuscularly every 4 or 8 weeks. Descriptive statistics, including viral load (VL) outcomes, were summarized. Results: All patients (n = 34: 76% male; 24% cis/trans female; 41% Black; 38% Latino/a; median age [range], 47 [28-75] years; 29% and 71% on CAB every 4 or 8 weeks) reported challenges adhering to oral ART. The reasons for using LEN/CAB with or without RPV were documented or suspected NNRTI mutations (n = 21, 59%), integrase mutations (n = 5, 15%), high VL (n = 6, 18%), or continued viremia on CAB/RPV alone (n = 4, 12%). Injection site reactions on LA LEN were reported in 44% (32% grade I, 12% grade 2). All patients but 2 (32/34; 94%) were suppressed (VL <75 copies/mL) after starting LEN at a median (range) of 8 (4-16) weeks, with 16/34 (47%) suppressed at baseline. Conclusions: In this case series of 34 patients on LEN/CAB, high rates of virologic suppression (94%) were observed. Reasons for using LEN/CAB included adherence challenges and underlying resistance, mostly to NNRTIs. These data support a clinical trial of LEN/CAB among persons with NNRTI resistance.

A Risk Profile Using Simple Hematologic Parameters to Assess Benefits From Baricitinib in Patients Hospitalized With COVID-19: A Post Hoc Analysis of the Adaptive COVID-19 Treatment Trial-2.

BACKGROUND: The ACTT risk profile, which was developed from ACTT-1 (Adaptive COVID-19 Treatment Trial-1), demonstrated that hospitalized patients with COVID-19 in the high-risk quartile (characterized by low absolute lymphocyte count [ALC], high absolute neutrophil count [ANC], and low platelet count at baseline) benefited most from treatment with the antiviral remdesivir. It is unknown which patient characteristics are associated with benefit from treatment with the immunomodulator baricitinib. OBJECTIVE: To apply the ACTT risk profile to the ACTT-2 cohort to investigate potential baricitinib-related treatment effects by risk quartile. DESIGN: Post hoc analysis of ACTT-2, a randomized, double-blind, placebo-controlled trial. (ClinicalTrials.gov: NCT04401579). SETTING: Sixty-seven trial sites in 8 countries. PARTICIPANTS: Adults hospitalized with COVID-19 (n = 999; 85% U.S. participants). INTERVENTION: Baricitinib+remdesivir versus placebo+remdesivir. MEASUREMENTS: Mortality, progression to invasive mechanical ventilation (IMV) or death, and recovery, all within 28 days; ALC, ANC, and platelet count trajectories. RESULTS: In the high-risk quartile, baricitinib+remdesivir was associated with reduced risk for death (hazard ratio [HR], 0.38 [95% CI, 0.16 to 0.86]; P = 0.020), decreased progression to IMV or death (HR, 0.57 [CI, 0.35 to 0.93]; P = 0.024), and improved recovery rate (HR, 1.53 [CI, 1.16 to 2.02]; P = 0.002) compared with placebo+remdesivir. After 5 days, participants receiving baricitinib+remdesivir had significantly larger increases in ALC and significantly larger decreases in ANC compared with control participants, with the largest effects observed in the high-risk quartile. LIMITATION: Secondary analysis of data collected before circulation of current SARS-CoV-2 variants. CONCLUSION: The ACTT risk profile identifies a subgroup of hospitalized patients who benefit most from baricitinib treatment and captures a patient phenotype of treatment response to an immunomodulator and an antiviral. Changes in ALC and ANC trajectory suggest a mechanism whereby an immunomodulator limits severe COVID-19. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

Incidence and Predictors of Pregnancy in Women Enrolled in Large Multinational HIV Treatment Trials of the AIDS Clinical Trials Group.

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. METHODS: We included data from multicountry HIV treatment trials conducted during the period 2005-2019 by the AIDS Clinical Trials Group that included females with HIV who were of reproductive potential, did not intend to become pregnant, and agreed to use effective contraception during study treatment. We extracted data from all female participants of age 18-55 years, including occurrence and dates of pregnancy on-study; however, only a few incident pregnancy predictor variables were available for analysis. RESULTS: One thousand six hundred twenty-six women from 4 trials were included. Over a median of 28 months (6461 person-years) of follow-up, 143 (9%) women became pregnant, for an overall incidence of 2.2 pregnancies/100 person-years (range 0.5-3/100 person-years, by study). In multivariable analysis including baseline age, type of regimen, and country as predictor variables, younger age remained the strongest predictor of incident pregnancy ( P < 0.0001 adjusted for country and antiretroviral treatment regimen). CD4 and HIV-1 RNA were not associated with pregnancy incidence. CONCLUSIONS: Pregnancy incidence was 2.2/100 person-years in female participants of HIV treatment trials. Rather than leading to exclusion of young women from trials, this finding should prompt appropriate adaptations in study design and analysis for earlier generation of pregnancy safety information for drugs.

Evaluating Demographic Representation in Clinical Trials: Use of the Adaptive Coronavirus Disease 2019 Treatment Trial (ACTT) as a Test Case.

Background: Clinical trials initiated during emerging infectious disease outbreaks must quickly enroll participants to identify treatments to reduce morbidity and mortality. This may be at odds with enrolling a representative study population, especially when the population affected is undefined. Methods: We evaluated the utility of the Centers for Disease Control and Prevention's COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), the COVID-19 Case Surveillance System (CCSS), and 2020 United States (US) Census data to determine demographic representation in the 4 stages of the Adaptive COVID-19 Treatment Trial (ACTT). We compared the cumulative proportion of participants by sex, race, ethnicity, and age enrolled at US ACTT sites, with respective 95% confidence intervals, to the reference data in forest plots. Results: US ACTT sites enrolled 3509 adults hospitalized with COVID-19. When compared with COVID-NET, ACTT enrolled a similar or higher proportion of Hispanic/Latino and White participants depending on the stage, and a similar proportion of African American participants in all stages. In contrast, ACTT enrolled a higher proportion of these groups when compared with US Census and CCSS. The proportion of participants aged ≥65 years was either similar or lower than COVID-NET and higher than CCSS and the US Census. The proportion of females enrolled in ACTT was lower than the proportion of females in the reference datasets. Conclusions: Although surveillance data of hospitalized cases may not be available early in an outbreak, they are a better comparator than US Census data and surveillance of all cases, which may not reflect the population affected and at higher risk of severe disease.

Temporal Improvements in COVID-19 Outcomes for Hospitalized Adults: A Post Hoc Observational Study of Remdesivir Group Participants in the Adaptive COVID-19 Treatment Trial.

BACKGROUND: The COVID-19 standard of care (SOC) evolved rapidly during 2020 and 2021, but its cumulative effect over time is unclear. OBJECTIVE: To evaluate whether recovery and mortality improved as SOC evolved, using data from ACTT (Adaptive COVID-19 Treatment Trial). DESIGN: ACTT is a series of phase 3, randomized, double-blind, placebo-controlled trials that evaluated COVID-19 therapeutics from February 2020 through May 2021. ACTT-1 compared remdesivir plus SOC to placebo plus SOC, and in ACTT-2 and ACTT-3, remdesivir plus SOC was the control group. This post hoc analysis compared recovery and mortality between these comparable sequential cohorts of patients who received remdesivir plus SOC, adjusting for baseline characteristics with propensity score weighting. The analysis was repeated for participants in ACTT-3 and ACTT-4 who received remdesivir plus dexamethasone plus SOC. Trends in SOC that could explain outcome improvements were analyzed. (ClinicalTrials.gov: NCT04280705 [ACTT-1], NCT04401579 [ACTT-2], NCT04492475 [ACTT-3], and NCT04640168 [ACTT-4]). SETTING: 94 hospitals in 10 countries (86% U.S. participants). PARTICIPANTS: Adults hospitalized with COVID-19. INTERVENTION: SOC. MEASUREMENTS: 28-day mortality and recovery. RESULTS: Although outcomes were better in ACTT-2 than in ACTT-1, adjusted hazard ratios (HRs) were close to 1 (HR for recovery, 1.04 [95% CI, 0.92 to 1.17]; HR for mortality, 0.90 [CI, 0.56 to 1.40]). Comparable patients were less likely to be intubated in ACTT-2 than in ACTT-1 (odds ratio, 0.75 [CI, 0.53 to 0.97]), and hydroxychloroquine use decreased. Outcomes improved from ACTT-2 to ACTT-3 (HR for recovery, 1.43 [CI, 1.24 to 1.64]; HR for mortality, 0.45 [CI, 0.21 to 0.97]). Potential explanatory factors (SOC trends, case surges, and variant trends) were similar between ACTT-2 and ACTT-3, except for increased dexamethasone use (11% to 77%). Outcomes were similar in ACTT-3 and ACTT-4. Antibiotic use decreased gradually across all stages. LIMITATION: Unmeasured confounding. CONCLUSION: Changes in patient composition explained improved outcomes from ACTT-1 to ACTT-2 but not from ACTT-2 to ACTT-3, suggesting improved SOC. These results support excluding nonconcurrent controls from analysis of platform trials in rapidly changing therapeutic areas. PRIMARY FUNDING SOURCE: National Institute of Allergy and Infectious Diseases.

Debulking different Corona (SARS-CoV-2 delta, omicron, OC43) and Influenza (H1N1, H3N2) virus strains by plant viral trap proteins in chewing gums to decrease infection and transmission.

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 0.925 µg of CTB-ACE2 (p = 0.0001). Among 20 delta or omicron NP samples, 17 had virus load reduced below the detection level of spike protein in the RAPID assay, after incubation with the CTB-ACE2 gum powder. A dose-dependent 50% plaque reduction with 50-100 ng FRIL or 600-800 µg FRIL gum against Influenza strains H1N1, H3N2, and Coronavirus HCoV-OC43 was observed with both purified FRIL, lablab bean powder or gum. In electron micrographs, large/densely packed clumps of overlapping influenza particles and FRIL protein were observed. Chewing simulator studies revealed that CTB-ACE2 release was time/dose-dependent and release was linear up to 20 min chewing. Phase I/II placebo-controlled, double-blinded clinical trial (IND 154897) is in progress to evaluate viral load in saliva before or after chewing CTB-ACE2/placebo gum. Collectively, this study advances the concept of chewing gum to deliver proteins to debulk oral viruses and decrease infection/transmission.

Integrating ART adherence support technologies in the care of pregnant and postpartum people with HIV: a qualitative study.

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. The interview instrument was guided by the Consolidated Framework for Implementation Research and included questions on the implementation climate, barriers, and facilitators to the clinical integration of the adherence approach and strategies that could be used to maximize this integration. The order of adherence support technologies was randomized to minimize bias. We used a modified grounded theory to develop the coding structure and two coders applied the codebook to the transcripts after establishing strong inter-rater reliability with 20% of interviews (kappa = 0.82). RESULTS: Between March and December 2020, we conducted 26 in-depth, semi-structured interviews with providers who weighed several factors when considering each approach, including the approach's effect on patient-provider interaction in and outside of the clinic visit, timing for and duration of the approach's utility, threat of disclosing status, and added burden to providers (e.g., needing to act on generated information) or to patients (e.g., needing to hide the signaling pills, responding to text messages). Providers' most preferred approach was text-messages, and the least preferred was the signaling pill. Barriers to acceptability varied by approach and included perceived surveillance, violation of privacy, added time demand for providers, potential inaccuracy of the adherence data generated, and negative impact on the patient-provider relationship, particularly if the approach was perceived as coercive. Payers anticipated regulatory hurdles with unfamiliar approaches, particularly the signaling pill and signaling pill bottle. Facilitators included strengthened therapeutic alliance, predictable reminder mechanisms, and options for customization according to patient preference. CONCLUSIONS: Our study elucidates barriers and facilitators to integrating technology-based adherence support approaches in clinical care to support adherence of pregnant and postpartum people with HIV.

Unraveling the Treatment Effect of Baricitinib on Clinical Progression and Resource Utilization in Hospitalized COVID-19 Patients: Secondary Analysis of the Adaptive COVID-19 Treatment Randomized Trial-2.

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. We estimated the effect of BCT on cumulative incidence of clinical improvement and deterioration using competing risks models. We developed multistate models to estimate the effect of BCT on clinical improvement and deterioration and on utilization of respiratory therapies. Results: BCT resulted in more linear improvement and lower incidence of clinical deterioration compared with RMT (hazard ratio [HR], 0.74; 95% CI, 0.58 to 0.95). The benefit was pronounced among participants enrolled on high-flow oxygen or noninvasive positive-pressure ventilation. In this group, BCT sped clinical improvement (HR, 1.21; 95% CI, 0.99 to 1.51) while slowing clinical deterioration (HR, 0.71; 95% CI, 0.48 to 1.02), which reduced the expected days in ordinal score (OS) 6 per 100 patients by 74 days (95% CI, -8 to 154 days) and the expected days in OS 7 per 100 patients by 161 days (95% CI, 46 to 291 days) compared with RMT. BCT did not benefit participants who were mechanically ventilated at enrollment. Conclusions: Compared with RMT, BCT reduces the clinical burden and utilization of intensive respiratory therapies for patients requiring low-flow oxygen or noninvasive positive-pressure ventilation compared with RMT and may thereby improve care for this patient population.

Implementation of an HIV Pre-exposure Prophylaxis Strategy Into Abortion and Early Pregnancy Loss Care.

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. METHODS: We used a multifaceted implementation strategy directed toward family planning providers comprised of educational sessions, an electronic medical record-prompted verbal assessment of HIV risk, electronic medical record shortcuts for PrEP prescription, and support of a PrEP navigator. We assessed penetration of the intervention by calculating the penetration of a PrEP offer, measured as the proportion of encounters in which PrEP was offered to PrEP-eligible individuals. We evaluated feasibility, acceptability, and appropriateness of the intervention using belief elicitation interviews with providers. RESULTS: From November 2018 to April 2019, the proportion of PrEP eligible patients who were offered PrEP, was 87.9% (29/33). Providers found the intervention acceptable and appropriate, but reported barriers including time constraints, and disappointment if patients did not adhere to PrEP. Providers liked that PrEP provision in abortion care settings felt innovative, and that they could contribute to HIV prevention. CONCLUSION: Family planning providers in an academic center found HIV risk assessment and PrEP provision to be feasible, acceptable, and appropriate. Further research should evaluate implementation outcomes of PrEP care strategies in additional abortion care contexts, including clinics offering reproductive health care outside of academia.

Metrics of HIV Pre-exposure Prophylaxis (PrEP) Implementation Before and After a Multidisciplinary Task Force at an Academic Institution.

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. Participants were adults prescribed PrEP for greater than or equal to 30 days at 9 clinical sites across a university health system. Metrics of PrEP implementation were compared over 12-month intervals before and after the creation of the task force. RESULTS: An increased proportion of participants had HIV testing within 7 days of new PrEP prescriptions (92% vs 63%, P < .001) and were prescribed PrEP in increments of 90 days or shorter (74% vs 56%, P < .001) after the creation of the task force. There were higher rates of testing for bacterial sexually transmitted infections in men who had sex with men and transgender women in the post-intervention compared with pre-intervention period. CONCLUSIONS: A multidisciplinary team that focuses on optimizing PrEP delivery along each step of the care continuum may facilitate PrEP scale-up and best practices in an academic setting.

Baricitinib versus dexamethasone for adults hospitalised with COVID-19 (ACTT-4): a randomised, double-blind, double placebo-controlled trial.

BACKGROUND: Baricitinib and dexamethasone have randomised trials supporting their use for the treatment of patients with COVID-19. We assessed the combination of baricitinib plus remdesivir versus dexamethasone plus remdesivir in preventing progression to mechanical ventilation or death in hospitalised patients with COVID-19. METHODS: In this randomised, double-blind, double placebo-controlled trial, patients were enrolled at 67 trial sites in the USA (60 sites), South Korea (two sites), Mexico (two sites), Singapore (two sites), and Japan (one site). Hospitalised adults (≥18 years) with COVID-19 who required supplemental oxygen administered by low-flow (≤15 L/min), high-flow (>15 L/min), or non-invasive mechanical ventilation modalities who met the study eligibility criteria (male or non-pregnant female adults ≥18 years old with laboratory-confirmed SARS-CoV-2 infection) were enrolled in the study. Patients were randomly assigned (1:1) to receive either baricitinib, remdesivir, and placebo, or dexamethasone, remdesivir, and placebo using a permuted block design. Randomisation was stratified by study site and baseline ordinal score at enrolment. All patients received remdesivir (≤10 days) and either baricitinib (or matching oral placebo) for a maximum of 14 days or dexamethasone (or matching intravenous placebo) for a maximum of 10 days. The primary outcome was the difference in mechanical ventilation-free survival by day 29 between the two treatment groups in the modified intention-to-treat population. Safety analyses were done in the as-treated population, comprising all participants who received one dose of the study drug. The trial is registered with ClinicalTrials.gov, NCT04640168. FINDINGS: Between Dec 1, 2020, and April 13, 2021, 1047 patients were assessed for eligibility. 1010 patients were enrolled and randomly assigned, 516 (51%) to baricitinib plus remdesivir plus placebo and 494 (49%) to dexamethasone plus remdesivir plus placebo. The mean age of the patients was 58·3 years (SD 14·0) and 590 (58%) of 1010 patients were male. 588 (58%) of 1010 patients were White, 188 (19%) were Black, 70 (7%) were Asian, and 18 (2%) were American Indian or Alaska Native. 347 (34%) of 1010 patients were Hispanic or Latino. Mechanical ventilation-free survival by day 29 was similar between the study groups (Kaplan-Meier estimates of 87·0% [95% CI 83·7 to 89·6] in the baricitinib plus remdesivir plus placebo group and 87·6% [84·2 to 90·3] in the dexamethasone plus remdesivir plus placebo group; risk difference 0·6 [95% CI -3·6 to 4·8]; p=0·91). The odds ratio for improved status in the dexamethasone plus remdesivir plus placebo group compared with the baricitinib plus remdesivir plus placebo group was 1·01 (95% CI 0·80 to 1·27). At least one adverse event occurred in 149 (30%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 179 (37%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·5% [1·6 to 13·3]; p=0·014). 21 (4%) of 503 patients in the baricitinib plus remdesivir plus placebo group had at least one treatment-related adverse event versus 49 (10%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 6·0% [2·8 to 9·3]; p=0·00041). Severe or life-threatening grade 3 or 4 adverse events occurred in 143 (28%) of 503 patients in the baricitinib plus remdesivir plus placebo group and 174 (36%) of 482 patients in the dexamethasone plus remdesivir plus placebo group (risk difference 7·7% [1·8 to 13·4]; p=0·012). INTERPRETATION: In hospitalised patients with COVID-19 requiring supplemental oxygen by low-flow, high-flow, or non-invasive ventilation, baricitinib plus remdesivir and dexamethasone plus remdesivir resulted in similar mechanical ventilation-free survival by day 29, but dexamethasone was associated with significantly more adverse events, treatment-related adverse events, and severe or life-threatening adverse events. A more individually tailored choice of immunomodulation now appears possible, where side-effect profile, ease of administration, cost, and patient comorbidities can all be considered. FUNDING: National Institute of Allergy and Infectious Diseases.

Preexposure Prophylaxis Acceptability Among Pregnant Individuals and Implications for Human Immunodeficiency Virus Prevention.

OBJECTIVE: To understand perspectives on and preferences for preexposure prophylaxis (PrEP) for pregnant individuals who are at risk for human immunodeficiency virus (HIV) infection. METHODS: In this qualitative study, we purposively sampled and conducted in-depth interviews with pregnant participants at risk of HIV infection (indicated by a recent sexually transmitted infection [STI]) from a U.S. urban obstetrics clinic. Interview questions focused on perceived HIV risk, knowledge and perceptions of PrEP, and preferences for different PrEP formulations. We coded data using deductive and inductive codes, created matrices to explore patterns in findings, and wrote memos to interpret emergent themes. RESULTS: Twenty patients were enrolled. Median age of the participants was 24 years (interquartile range 19-26 years), 95.0% were African American, 65.0% were high school graduates, and 70.0% had unplanned pregnancies. Participants had low knowledge of PrEP and most saw themselves at low to no risk of HIV acquisition, despite their recent STI. Further, participants' low HIV risk perception and medication safety concerns reduced PrEP acceptability. Moreover, very few had discussed PrEP with their obstetrician-gynecologists (ob-gyns) during antenatal care, which further affected perceived acceptability. However, participants who did discuss PrEP with their ob-gyns had favorable perceptions of it. These participants indicated that they would choose a formulation based on individual preferences, which were largely shaped by perceived ease of use, acceptability, and prior experience with other medication regimens. CONCLUSION: Obstetrician-gynecologists may play an important role in increasing pregnant individuals' knowledge of and access to PrEP during pregnancy among those who are at risk of HIV acquisition. To maximize uptake and adherence during this time, PrEP formulations should be tailored to individual preferences. Prevention of HIV during this critical life transition is important not only for the long-term health and well-being of pregnant individuals and their infants, but to the plan to end the HIV epidemic in the United States by 2030.

Incorporating HIV Pre-Exposure Prophylaxis Care for Patients Seeking Induced Abortion and Pregnancy Loss Management.

BACKGROUND: Family planning clinical encounters are important opportunities for HIV prevention. Our objectives were to 1) estimate the proportion of patients seeking induced abortion and early pregnancy loss management eligible for HIV pre-exposure prophylaxis (PrEP) and 2) compare PrEP eligibility and uptake between patients with unintended and intended pregnancy. METHODS: We conducted a cross-sectional survey and a nested prospective cohort study of patients seeking an induced abortion or early pregnancy loss management. We assessed pregnancy intendedness, PrEP awareness, HIV risk and risk perception, desire for same-day PrEP start, and PrEP continuation at 30 days. We used the χ2 and Fisher's exact tests to assess differences between the participants with intended and unintended pregnancy. We had 80% power to detect a 14% difference in PrEP eligibility between the groups. RESULTS: We enrolled 250 women. Fifty-six percent (139) had an unintended pregnancy and 44% (110) had an intended pregnancy. PrEP eligibility did not differ significantly between the patients with intended and unintended pregnancy (16% vs. 10%; p = .18). More than one-half (54%, 135/250) were unaware of PrEP before their study visit, and 93% (232/250) considered themselves unlikely to acquire HIV. Of 33 women who were PrEP eligible, 11 accepted same-day start and 1 continued PrEP at 30 days. CONCLUSIONS: Intendedness of pregnancy was unrelated to PrEP eligibility in women seeking induced abortion and early pregnancy loss management. Most patients seeking these services are unaware of PrEP. Integrating PrEP into family planning care is likely to increase awareness and uptake of PrEP in women.

Clinic screening for adverse childhood experiences in people living with HIV to Improve Care Delivery.

Adverse childhood experiences (ACEs) are associated with negative health outcomes; however, screening for ACEs is not routinely performed among people living with HIV (PLWH). We conducted a single-center, cross-sectional pilot study to define the (1) prevalence of ACEs in PLWH and (2) acceptability of ACEs screening in routine out-patient clinical care. One hundred participants completed screening: median age of participants was 49 years (interquartile range: 38.5-59.5), 73% male, 66% Non-Hispanic Black/African American, and 47% gay/lesbian. Clinically significant ACEs score, defined as ≥4, was reported in 51%. High ACEs score was more common among participants <50 years old (64.7% vs. 36.7%; p < 0.01), but the prevalence of ACEs ≥4 did not differ by gender, race, ethnicity, or sexual orientation. Among participants with ≥4 ACEs, 44.4% screened negative on both PHQ-9 and PC-PTSD screens. The majority of participants (89%) reported a positive experience with ACEs screening. The prevalence of clinically significant ACEs in this clinic population of PLWH was more than twice that reported in the general population. Routine ACEs screening can improve delivery of trauma-informed care in the HIV primary care setting.

Remdesivir for the Prevention of Invasive Mechanical Ventilation or Death in Coronavirus Disease 2019 (COVID-19): A Post Hoc Analysis of the Adaptive COVID-19 Treatment Trial-1 Cohort Data.

This post hoc analysis of the Adaptive Coronavirus Disease 2019 (COVID-19) Treatment Trial-1 (ACTT-1) shows a treatment effect of remdesivir (RDV) on progression to invasive mechanical ventilation (IMV) or death. Additionally, we create a risk profile that better predicts progression than baseline oxygen requirement alone. The highest risk group derives the greatest treatment effect from RDV.

A randomized controlled study of convalescent plasma for individuals hospitalized with COVID-19 pneumonia.

BackgroundAntibody-based strategies for COVID-19 have shown promise in prevention and treatment of early disease. COVID-19 convalescent plasma (CCP) has been widely used but results from randomized trials supporting its benefit in hospitalized patients with pneumonia are limited. Here, we assess the efficacy of CCP in severely ill, hospitalized adults with COVID-19 pneumonia.MethodsWe performed a randomized control trial (PennCCP2), with 80 adults hospitalized with COVID-19 pneumonia, comparing up to 2 units of locally sourced CCP plus standard care versus standard care alone. The primary efficacy endpoint was comparison of a clinical severity score. Key secondary outcomes include 14- and 28-day mortality, 14- and 28-day maximum 8-point WHO ordinal score (WHO8) score, duration of supplemental oxygenation or mechanical ventilation, respiratory SARS-CoV-2 RNA, and anti-SARS-CoV-2 antibodies.ResultsEighty hospitalized adults with confirmed COVID-19 pneumonia were enrolled at median day 6 of symptoms and day 1 of hospitalization; 60% were anti-SARS-CoV-2 antibody seronegative. Participants had a median of 3 comorbidities, including risk factors for severe COVID-19 and immunosuppression. CCP treatment was safe and conferred significant benefit by clinical severity score (median [MED] and interquartile range [IQR] 10 [5.5-30] vs. 7 [2.75-12.25], P = 0.037) and 28-day mortality (n = 10, 26% vs. n = 2, 5%; P = 0.013). All other prespecified outcome measures showed weak evidence toward benefit of CCP.ConclusionTwo units of locally sourced CCP administered early in hospitalization to majority seronegative participants conferred a significant benefit in clinical severity score and 28-day mortality. Results suggest CCP may benefit select populations, especially those with comorbidities who are treated early.Trial RegistrationClinicalTrials.gov NCT04397757.FundingUniversity of Pennsylvania.