In the US, COVID-19 has caused 7+ million deaths since 2020; influenza caused roughly 28,000–52,000 deaths between 2023–2024, and RSV caused about 33,000 in-hospital deaths in older adults annually. Vaccines for these viruses are highly effective in reducing illness and death. Evidence suggests that discrimination may influence vaccine uptake. In predominantly Black and Latinx communities in New York City, we measured Experiences of Discrimination (EOD), examined social determinants and measured their association with COVID-19, influenza, and RSV vaccination.Sociodemographic characteristics and COVID-19, influenza, and RSV vaccination. This cross-sectional study recruited adults 18+ living near Columbia Medical Center. From Sep 2023 – Aug 2024, participants completed an online questionnaire collecting demographics, medical history, vaccine status, and EOD. We tabulated descriptive statistics for continuous and categorical variables and logistic regression analyses to estimate associations with vaccination.Figure 1Percentage of COVID-19, influenza, and RSV vaccine doses and uptake. Among 2033 participants, the mean age was 38.3 years and 58% were female. Nearly half identified as Hispanic (48.7%) and 14.9% identified as Non-Hispanic Black (Table 1). Most had received 1–4 COVID-19 vaccine doses (84.5%), 42.7% reported 1–4 influenza vaccinations in the past 5 years and 2.7% of those aged 60+ received the RSV vaccine (Figure 1). Self-reported major and everyday discrimination were low (Table 2, 3). In unadjusted tests, age, sex, gender, education, income and health insurance status were associated with vaccination (Table 1). In adjusted models, family caregivers had lower odds of receiving the COVID-19 (OR=0.14, 0.02-0.98, p=0.0363) or influenza (OR=0.18, 0.04-0.83, p=0.0276) vaccines compared to employed participants. Those with less than high school education had lower odds of influenza vaccination than those with college degrees (OR=0.32, 0.42, 1.41, p=0.004). Although most participants were vaccinated against COVID-19 and a many against influenza, RSV uptake was low. We also observed unexpectedly low levels of discrimination. The relatively high levels of vaccination and low levels of self-reported discrimination in this sample of predominantly minoritized, lower income individuals warrant further investigation and triangulation with other recent data from these communities. Lawrence Purpura, III, MD, MPH&TM, Regeneron: Grant/Research Support

Background:The isolation of many HIV broadly neutralizing antibodies (bnAbs) from people living with HIV (PLWH) and rigorous characterization of their ontogeny has promoted the goal of reverse engineering their natural development as a strategy for achieving an effective preventive HIV vaccine. We previously described the developmental process of CH103, a CD4-binding site (CD4bs)-specific monoclonal antibody, and the associated evolution of HIV Envelopes (Envs) within the person (CH505) from whom it was isolated. A series of monomeric gp120 protein subunit immunogens representing the transmitted founder (TF) and Envs that evolved during infection and optimally reacted with lineage members at each step of the CH103 clone maturation path were evaluated in this placebo controlled randomized vaccine trial to test-- for the first time in humans-- the concept of whether sequential immunization with gp120 monomeric proteins can recapitulate the development of CD4bs B-cell clonal lineages, including CH103. Methods:HIV Vaccine Trials Network 115 (HVTN 115) was a randomized placebo-controlled vaccine trial at US clinical research sites. We tested the safety and immunogenicity of CH505TF gp120 + GLA-SE (Part A), and then the ability of sequential CH505 gp120 proteins (corresponding to CH505's weeks 53 and 78 Envs) + GLA-SE immunizations to induce CD4bs-specific neutralizing antibodies (Part B). We assessed binding and neutralizing antibody responses, antibody dependent cellular cytotoxicity, antibody dependent cellular phagocytosis, T-cell responses and B-cell phenotyping. Results:We enrolled 42 participants between October 2017 and May 2018 for Part A, and 65 participants from December 2020 to October 2022 for Part B. Immunization with the CH505 gp120 proteins adjuvanted with GLA-SE was well tolerated and induced CD4bs-specific B cells and Env-specific plasma antibodies. The plasma neutralizing antibody response was limited to primarily tier 1 autologous and heterologous HIV-1 strains. Blood-derived B-cell repertoire analyses identified CD4bs antibodies that preferentially bound to open-occluded trimeric Envs that exist in an intermediate state between prefusion-closed to CD4-bound open confirmations, consistent with tier 1 HIV neutralizing activity. Conclusions:Together, these results suggest that the low-affinity CH505TF gp120 monomer elicited CD4bs antibodies in the sera and B-cell repertoires of humans. However, our findings also indicate that gp120 monomers are insufficient to induce detectable bnAb precursors to epitopes on native Env trimers. Nonetheless, our data provide a benchmark for comparison with ongoing clinical trials testing high-affinity CH505 Env trimers for induction of CD4bs bnAb precursors.

Background. Postacute sequelae of COVID-19 (PASC), also known as long COVID, and postacute COVID-19 vaccination syndrome (PACVS) present overlapping but distinct clinical challenges. We hypothesize that PASC and PACVS share clinical features but differ in symptom patterns and biomarker profiles. This study aims to identify differences in presentation and distinguish immunologic biomarkers relevant to general clinical practice. Methods. This cross-sectional study analyzed 181 patients from a PASC clinic at Columbia University Irving Medical Center. Patients were divided into PASC with myalgic encephalomyelitis/chronic fatigue syndrome (MECFS), PASC without MECFS (LC), and PACVS groups. Prevalence and severity of self-reported symptoms, as well as immunologic abnormalities, were compared across groups. Results. Fatigue was the most common symptom (Total: 88.95%; MECFS: 100.00%; PACVS: 92.86%; LC: 78.05%). The MECFS group generally reported more symptoms across all organ systems. The PACVS group reported higher rates of atypical chief complaints such as peripheral neuropathy (17.9%), tinnitus (7.1%), and rash (10.7%) compared to the other groups (P = <.01). Functional impairment was comparable between the MECFS and PACVS groups and less severe in the LC group. All groups had high rates of autoantibody positivity and cytokine elevation. The PACVS group showed significantly higher rates of anticardiolipin IgM (PACVS 42.9%, LC 11.6%; P = .02) and anti-U1-RNP (PACVS 21.4%, LC 2.3%; P = .04) positivity compared to the LC group. Conclusions. PASC and PACVS share symptom overlap but exhibit distinct biomarker patterns, particularly elevated autoantibody levels in PACVS. These findings suggest autoimmune involvement, warranting further investigation for targeted therapies.

Post-acute sequelae of COVID-19 (PASC), and post-COVID-19 vaccination syndrome (PVS) present overlapping but distinct clinical challenges. Immunologic biomarker abnormalities have previously been established in PASC but less so in PVS. This study aims to distinguish immunologic biomarker patterns in PASC and PVS.Figure 1Clinical lab abnormality level, as defined by percent of patients with abnormal lab result at anytime (initial visit or follow-up), compared between the long covid positive for MECFS (MECFS), post-vaccination syndrome (PVS), and long covid negative for MECFS (LC) groups and previously reported positivity rates in healthy populations. Histamine: plasma histamine level, Tryptase: plasma tryptase level, IL 2 receptor: interleukin 2 receptor (CD25), IL 10: interleukin 10, IL 13: interleukin 13, TNF-alpha: tumor necrosis factor alpha, CD4+ T Cells: quantitative CD3+/CD4 lymphocytes, CD8+ T Cells: quantitative CD8+ lymphocytes, HSP70: heat shock protein-70 IgG western blot, ACL: quantitative anticardiolipin IgM, Anti U1-RNP: quantitative ribonucleic protein extranuclear antibody IgG. Reference ranges: Histamine: 0-8 mmol/L, Tryptase: <=10.9 ug/L, IL 2 receptor 175.3-858.2 pg/mL, IL 10: <=2.8 pg/mL, IL 13 <=2.3 pg/mL. TNF-alpha <=7.2 pg/mL, CD4+ T Cells: 393-1489 cells/uL, CD8+ T Cells: 148-788 cells/uL, HSP70: Negative, ACL: <=12 MPL, Anti U1-RNP: <1.0 U This cross-sectional study analyzed 78 participants from a Long COVID clinic divided into PASC with myalgic encephalomyelitis/chronic fatigue syndrome (MECFS, n = 28), PASC without MECFS (LC, n = 38), and PVS (n = 12) groups. The proportion of laboratory abnormality for each group was defined as the number of participants with a result greater than laboratory reference range at any point in their clinic course, over the total number of participants in the group. Statistical significance was determined using logistic regression controlling for age, sex, race, ethnicity, and history of autoimmunity. The groups did not differ significantly in all demographic factors aside from median age (MECFS 38, PVS 58, LC 48; p = 0.04). All groups showed a high proportion of anti-HSP-70 antibody positivity (MECFS 17.9%, PVS 41.7%, LC 21.1%) greater than previously reported in healthy populations (8%). The PVS group showed a significantly higher proportion of anti-cardiolipin IgM (PVS 50.0%, LC 7.9%; p = 0.04) and anti U1-RNP (PVS 25.0%, LC 0.0%; p = 0.004) autoantibody positivity compared to the LC group. In all groups, elevations in IL 2 receptor, IL 10, IL 13, and TNF-α were common (Figure 1). The proportion of absolute CD8+ T-cell above normal ( > 788 cells/µL) appeared to be higher in the MECFS group (MECFS 21.4%, PVS 16.7%, LC 5.3%), although not significant (Figure 1). The high level of autoantibody positivity in the PVS group suggests a potential role of autoimmunity. Few studies have reported the presence of HSP-70 autoantibody in PASC or PVS, yet positivity was high in all groups, warranting further investigation into its potential role in pathogenesis. PVS and PASC show overlapping patterns of cytokine and T cell levels; however, future studies should investigate functional T cell markers as a measure of immune activation. Overall, this study is limited by small sample size and lack of control group. Future studies are needed to validate these results. Lawrence Purpura, III, MD, MPH&TM, Regeneron: Grant/Research Support

The association between vaccine efficacy (VE) and force of infection (FoI) remains incompletely understood. Previous analyses have been primarily based on trial-level summary data—not accounting for the effect of time and constrained by the number of trials. Here, we leverage individual-level data from three phase 3 randomized, placebo-controlled COVID-19 vaccine trials—the COVE trial (Moderna, CoVPN3001), the AZD1222 trial (AstraZeneca, CoVPN3002), and the ENSEMBLE trial (Janssen/Johnson & Johnson, CoVPN3003)—and contemporaneous geographic-location-specific SARS-CoV-2 surveillance data from the start of the pandemic through November 14, 2021 (including the blinded follow-up periods of the trials) to conduct five cohort- and vaccine-specific analyses: COVE (U.S.), AZD1222 overall (U.S. + non-U.S.), AZD1222 U.S., ENSEMBLE overall (U.S. + non-U.S.), and ENSEMBLE U.S. In AZD1222 U.S., higher VE was associated with higher FoI (p = 0.01). In ENSEMBLE overall, lower VE was marginally associated with higher FoI (p = 0.21), further supported by a region-specific analysis. In COVE, AZD1222 overall, and ENSEMBLE U.S., no VE-FoI association was found. These findings highlighted a new perspective: the VE–FoI association appears complex, potentially influenced by FoI levels, with patterns suggesting an inverted U-shaped relationship, showing a positive association at low FoI levels and a negative association at high levels.

Abstract Long-acting pre-exposure prophylaxis (PrEP) expands HIV prevention options for women. However, PrEP impact depends on addressing persistent gaps in awareness, access, and use. Artificial intelligence (AI) tools, including conversational agents, are being explored to advance PrEP uptake, but comfort with AI may influence their impact. Thus, we examined women’s comfort with AI and its association with PrEP awareness. We analyzed self-reported data from women aged ≥ 18 years in a cross-sectional survey conducted in New York City from August 2023 to August 2024. We performed descriptive analyses, applied latent class analysis to identify AI knowledge/comfort profiles, and estimated unadjusted and adjusted odds ratios to assess associations between profile membership and PrEP awareness. Among 306 respondents without a diagnosis of HIV who completed AI-related survey items, the median age was 36. Most women identified as Hispanic/Latina (60%) or Non-Hispanic Black (18%), had not completed college (53%), and spoke only English or were bilingual (81%). Latent class analysis identified four AI knowledge/comfort profiles that differed by PrEP awareness, race/ethnicity, borough, prior drug use, and technology utilization. Women with varied AI knowledge, broad AI discomfort, and comfort with clinicians maintaining privacy had lower odds of PrEP awareness (OR: 0.35, 95% CI: 0.16-0.75), but this association did not persist after statistical adjustment. PrEP awareness and AI knowledge were limited, yet many women expressed openness to AI-enabled tools when privacy was assured. AI-enabled HIV prevention tools should prioritize trust, transparency, confidentiality, and the lived contexts of the women they intend to serve.

BACKGROUND:Quarterly sexually transmitted infection (STI) screening is recommended for gay, bisexual, and other men who have sex with men (gbMSM) using HIV pre-exposure prophylaxis (PrEP). However, frequent in-person testing can pose engagement barriers and increase costs, prompting interest in risk-based screening strategies to individualize testing frequency. METHODS:We evaluated the extent to which two common sexual risk assessment tools, the I Want the Kit (IWTK) survey and the HIV Incidence Risk Index for MSM (HIRI-MSM), predict bacterial STI acquisition among gbMSM using PrEP. Participants were recruited from a free sexual health clinic in New York City and enrolled in Stick2PrEP2.0 (2018-2020) or Stick2PrEP3.0 (2021-2023). Risk scores were assessed at enrollment and compared with gonorrhea and chlamydia nucleic acid amplification test results at enrollment and during follow-up at three and six months. RESULTS:Among 298 gbMSM PrEP users, 25% had at least one positive gonorrhea or chlamydia test within one year. Most participants were classified as high-risk by IWTK (53%) or HIRI-MSM (87%). Higher IWTK scores were modestly associated with STI positivity within three months, but neither tool reliably predicted STI acquisition beyond this interval. Low-risk cutoff scores that maintained sensitivity would have applied to only a small minority of participants, limiting clinical utility. CONCLUSIONS:Risk-based screening tools demonstrated limited ability to predict bacterial STI acquisition among gbMSM using PrEP. Reliance on these tools to reduce screening frequency could result in missed STI diagnoses and onward transmission. Until more accurate STI risk models are developed, universal and routine laboratory screening remains essential.

Broadly neutralizing antibodies (bnAbs) are a promising tool for HIV prevention and treatment. Here we conducted a first-in-human, phase 1 trial of the bispecific 10E8.4/iMab antibody, which consists of a 10E8.4 arm binding the HIV-1 envelope glycoprotein membrane-proximal external region and an ibalizumab (iMab) arm binding the human CD4 molecule. 10E8.4/iMab was administered intravenously (IV) or subcutaneously (SC). Safety/tolerability within 2 weeks of 10E8.4/iMab administration (primary outcome) and the pharmacokinetics (PK), antiviral activity, induction of anti-10E8.4/iMab antibodies, longitudinal CD4+ and CD8+ T cell counts and long-term safety (secondary outcomes) were evaluated. 54 participants living with HIV (PLWH) or without HIV (PLWoH) received 10E8.4/iMab or placebo. In arm 1, PLWoH received 10E8.4/iMab 0.3 mg kg-1 IV, 1 mg kg-1 SC, or 1 mg kg-1 IV (n = 3 each). In arm 2, PLWoH received 10E8.4/iMab 3 mg kg-1 IV, 10 mg kg-1 IV or 30 mg kg-1 IV (n = 6 each). In arms 3/3a, PLWH received 10E8.4/iMab 10 mg kg-1 IV (n = 3) or 30 mg kg-1 IV (n = 6). In arm 4, PLWoH were randomized to receive 10E8.4/iMab or placebo 2.5 mg kg-1 SC or 10 mg kg-1 SC (n = 9 each). Participants in arms 1-3 were not randomized. No treatment-related serious adverse events (AEs) or AEs ≥ grade 3 were reported. The most common solicited AEs were tenderness (10/54, 18.5%), fatigue (18/54, 33.3%) and headache (12/54, 22.2%). Related grade 2 local and systemic solicited AEs occurred in one and six participants, respectively. Three of nine PLWH developed a generalized rash 8-12 days after infusion that resolved within 9-16 days. The primary objective of the study to evaluate the safety/tolerability of 10E8.4/iMab was met. These data support further study of 10E8.4/iMab to expand HIV treatment and prevention options. ClinicalTrials.gov: NCT03875209 .

Background The COVID-19 Prevention Network (CoVPN) co-conducted six COVID-19 phase 3 vaccine efficacy (VE) trials that featured harmonized immunogenicity analyses using validated antibody assays. These trials enabled a uniquely comprehensive characterization of immunogenicity produced by different vaccine platforms and regimens in individuals with and without prior SARS-CoV-2 acquisition. Methods Comparisons of serum binding antibody concentration and serum neutralization antibody ID50 titers were performed across three strata: vaccine immunity (vaccination in SARS-CoV-2-naïve individuals), natural immunity (placebo with prior SARS-CoV-2 acquisition), and hybrid immunity (vaccination after prior SARS-CoV-2 acquisition). We compared immunogenicity across immunity strata for each trial and each dose, adjusting for age, sex assigned at birth, and body mass index. Antibody levels were also examined in relation to VE. Results Antibody levels in response to a single vaccine dose varied across trials and generally increased most substantially after a second dose in naïve participants. Fold rise in antibody levels after a single dose were more pronounced in participants with hybrid immunity: a single dose of any of the tested vaccine yielded responses comparable to or exceeding the post-dose-two (peak) response of any two-dose vaccine in naïve participants. Population-level antibody levels demonstrated high concordance with VE across trials and immunity strata. Conclusions In SARS-CoV-2-naïve individuals, a two-dose vaccine regimen is needed to provide antibody levels correlated with protection against disease caused by the cognate virus strain. In contrast, in individuals with prior SARS-CoV-2 acquisition, a single dose of any of the tested vaccines/platforms (mRNA/protein/vector) provides comparably high antibody levels.

OBJECTIVE:To examine predictors, correlates, and trajectories of food insecurity (FI) among students during COVID-19. PARTICIPANTS:Undergraduates. METHODS:Between 2020-2021, students completed quarterly (T1-T4) self-administered questionnaires. FI comprised food not lasting or not affording balanced meals. Trajectories were created using cumulative FI reports. RESULTS:Across time, FI varied (T1 = 21%, T2 = 25%, T3 = 17%, T4 = 19%). FI predictors included preexisting FI, need-based aid, low social support, alcohol use, COVID-19 care-seeking behaviors, violence experience, transgender/gender non-conforming [TGNC] identity, and unsafe home perceptions. FI trajectories spanned Never (69%), Rarely (12% FI once), Frequently (14% FI twice/thrice), and Persistently (5%). Along with low social support, Persistently FI students had high psychological distress, need-based aid, unsafe home perceptions, smoking/vaping, drug use, TGNC representation, violence experience, and COVID-19 care-seeking behaviors. CONCLUSIONS:FI was associated with sociodemographic, residential, interpersonal, psychosocial, behavioral, and healthcare-related factors. In routine campus operations and emergency situations, universities must develop multi-component interventions to address multi-factorial stressors.

In the phase 3 AZD1222 COVID-19 vaccine trial, anti-Spike (vaccine-matched and Delta) binding IgG antibody concentration and neutralizing antibody (nAb) titer (vaccine-matched+D614G and Delta), measured four weeks post-dose two (D57), were assessed as correlates of risk of severe COVID-19 and Delta COVID-19 over ~4 to ~13 months (severe) or ~11 months (Delta) post-D57. Using a case-control design, antibodies were measured in baseline SARS-CoV-2-negative per-protocol ChAdOx1 nCoV-19 recipients (19 severe COVID-19 cases, 57 Delta COVID-19 cases, 111 controls). The hazard ratio (HR) of severe COVID-19 per 10-fold vaccine-matched D57 marker increase was 0.16 (95% CI: 0.05, 0.54; p = 0.004) for Spike IgG and 0.13 (0.03, 0.59; p = 0.009) for nAb titer. D57 Delta antibodies were weak correlates of Delta COVID-19: HR per 10-fold increase 0.70 (0.14, 3.47; p = 0.66) for Delta Spike IgG; 0.46 (0.14, 1.47; p = 0.19) for Delta nAb titer. Binding and nAb levels strongly predicted severe COVID-19, even with antibody waning.

BACKGROUND:Realizing the potential of HIV prevention options requires understanding product tolerability across diverse groups vulnerable to HIV acquisition. Gender minority (GM) individuals are understudied in clinical trials. SETTING:HVTN 704/HIV Prevention Trials Network 085, a phase 2b randomized HIV prevention trial, enrolled MSM and transgender participants from Brazil, Peru, Switzerland, and the United States to receive an infusion every 8 weeks (10 total) of VRC01 30 mg/kg, VRC01 10 mg/kg, or placebo. Solicited adverse events (AEs) were recorded for 3 days after each infusion. METHODS:Gender was defined by self-report and sex assigned-at-birth. Multivariate mixed logistic models were used to estimate the association between gender (cisgender men [CM] vs. GM participants [transgender women, transgender men, or another gender]) and solicited AE frequency and severity. RESULTS:GM participants reported more solicited AEs than CM among all participants (adjusted OR 1.59, 95% CI: 1.20 to 2.10, P = 0.001) and among placebo recipients (1.72, 1.05 to 2.81, P = 0.031). The severity of solicited AEs (occurrence of grade 2 and higher event) did not significantly differ overall (1.83, 0.79 to 4.20, P = 0.174) or among placebo recipients (3.05, 0.76 to 12.32, P = 0.112). Grade 2 events were reported after 1% and 2% of total infusions among CM and GM participants, respectively. Grade 3-4 events were rare overall (<0.1%). Completion of 10 infusions was high (78.6%) and slightly higher in CM (79.2%) than GM participants (73%). CONCLUSIONS:This is the first report of associations between gender and solicited AEs after monoclonal antibody infusion. GM participants reported more events; severity was low. HIV prevention trials must engage and support GM individuals to best evaluate tolerability of novel agents.

mRNA technology might accelerate development of an urgently needed preventive human immunodeficiency virus (HIV) vaccine. We evaluated the safety and immunogenicity of three mRNA-encoded envelope trimers, including two doses of soluble and membrane-anchored forms, in a randomized, open-label, phase 1 clinical trial. Vaccines were generally well tolerated, although 6.5% (7 of 108) of participants developed urticaria, a higher proportion than seen with other mRNA vaccines. mRNA-encoded trimers induced strong envelope-specific B and T cell responses. Immunization with membrane-anchored trimers, intended to obscure epitopes at the trimer base targeted by nonneutralizing antibodies, reduced the frequency of base-binding serum antibodies in comparison with soluble trimers. Three immunizations elicited autologous tier 2 serum neutralizing antibodies in 80% of vaccinees receiving the membrane-anchored trimers, in contrast to only 4% receiving the soluble trimer. Thus, with demonstration of more favorable safety, mRNA-encoded membrane-anchored HIV envelope trimers represent a promising platform for HIV vaccine clinical development.

Broadly neutralizing antibodies (bnAbs) that target the HIV gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand MPER bnAb precursors in monkeys. The HVTN133 phase 1 clinical trial (NCT03934541) studied the MPER peptide-liposome immunogen in 24 HIV-1 seronegative individuals. Participants were randomized in a dose-escalation design to either 500 mcg or 2000 mcg of the MPER-peptide liposome or placebo. Four intramuscular injections were planned at months 0, 2, 6, and 12. The trial was stopped prematurely due to an anaphylaxis reaction in one participant attributed to vaccine-associated polyethylene glycol. The immunogen induced MPER-specific serum antibodies and CD4+ T-cell responses in 95% and 85% of vaccinees, respectively, and 35% of vaccine recipients had circulating IgG+ memory B cells with an MPER-bnAb binding phenotype. Affinity purification of plasma MPER-specific IgG demonstrated tier 2 HIV-1 neutralizing activity in two of five participants after 3 immunizations and tier 2 HIV-1 neutralizing B cell clonal lineages were isolated from MPER-reactive B cells. These results demonstrate that the HIV gp41 MPER region is a promising target for induction of heterologous neutralizing antibodies by a candidate HIV vaccine. Trial Registration:http://www.clinicaltrials.gov/ Identifier: NCT03934541.

The COVID-19 pandemic may have exacerbated mental health conditions by introducing and/or modifying stressors, particularly in university populations. We examined longitudinal patterns, time-varying predictors, and contemporaneous correlates of moderate-severe psychological distress (MS-PD) among college students. During 2020–2021, participants completed self-administered questionnaires quarterly (T1 = 562, T2 = 334, T3 = 221, and T4 = 169). MS-PD reflected Kessler-6 scores ≥ 8. At T1 (baseline), most participants were cisgender women [96% vs. 4% transgender/gender non-conforming (TGNC)]. MS-PD prevalence was over 50% at all timepoints. MS-PD predictors included low self-rated health and perceptions of local pandemic control, verbal/physical violence experience, food insecurity, cohabitation dynamics, geographic location, and loneliness. Unique MS-PD correlates encompassed drug use and TGNC identity. Trajectories comprised Persistently (40%), Highly (24% MS-PD twice/thrice), Minimally (15% MS-PD once), and Never (21%) Distressed. Persistently Distressed students had low social support and self-rated health; high food insecurity, drug use, physical/verbal violence experience, need-based financial aid, and TGNC representation; and fluctuating self-rated health amid increasing COVID-19 symptomatology. In this sample, MS-PD prevalence was high, persistent, and associated with financial, behavioral, structural, experiential, and intra- and inter-personal factors. Given its complexity, improving and preserving college students’ mental health necessitates comprehensive, multi-component activities to change adjustable stressors while attenuating the adverse effects of immutable influences.

This prospective cohort study evaluated the real-world effectiveness of doxycycline postexposure prophylaxis use in reducing bacterial sexually transmitted infections (STIs) within a diverse urban sexual health program. Propensity-matched analyses showed significant STI reductions, particularly in rectal Chlamydia trachomatis infections, among early adopters. Uptake was disproportionately higher in non-Hispanic White individuals and those more engaged in care. Findings emphasize the need for targeted outreach to improve care engagement and equitable access to this STI prevention strategy. (Am J Public Health. 2025;115(10):1584-1588. https://doi.org/10.2105/AJPH.2025.308209).

BACKGROUND:Pharmacokinetic (PK) modelling and simulations have been used to support label changes of dosing levels or strategies for multiple marketed therapeutic monoclonal antibodies (mAbs). Using data from early-phase clinical trials in adults without HIV-1, we compared fixed and weight-based dosing strategies for three HIV-1 broadly neutralising mAbs planned for prevention efficacy evaluation: PGDM1400LS, PGT121.414.LS, and VRC07-523LS. METHODS:We used a two-compartment population PK model to describe overall trends and inter-individual variability in post-administration serum concentrations over time from individuals administered PGDM1400LS (n = 95), PGT121.414.LS (n = 113), or VRC07-523LS (n = 251) subcutaneously or intravenously. We evaluated the effect of body weight on various PK parameters, including clearance rate, and simulated mAb concentrations after fixed and weight-based dosing administrations using sex-specific weights observed in participants from two recent HIV-1 mAb efficacy trials. We compared magnitudes and inter-individual variabilities of concentrations at specific post-administration timepoints, areas under the time-concentration curves (AUC), and predicted neutralisation titres against representative HIV-1 virus strains. FINDINGS:For all three mAbs, we observed a modest effect of body weight on clearance rate and volumes of the central and peripheral compartments. The population-level magnitude and variability in time-specific concentrations, AUC, and predicted neutralisation titres were comparable between the two dosing strategies for both sexes. The relationship between body weight and concentrations differed between the two dosing strategies with a positive correlation for weight-based dosing and a negative correlation for fixed dosing. For individuals with body weight below the 15th or above the 85th percentiles, fixed dosing resulted in <3% difference in median AUC compared to the overall population. For lower weight individuals, fixed dosing improved AUC, potentially correcting the underdosing seen in the previous weight-based mAb efficacy trials. For higher weight individuals (e.g., >100 kg), body weight-based dosing or a higher fixed dose may be preferred. INTERPRETATION:For HIV-1 prophylactic mAbs, a fixed-dose approach, possibly banded by weight categories may be advantageous over weight-based dosing, as it offers increased operational efficiency while maintaining comparable pharmacokinetics and inter-individual consistency. FUNDING:NIAID.

Background Multiple broadly neutralising monoclonal antibodies (mAbs) are in development for HIV-1 prevention. The aim of this trial was to test the PGT121.414.LS and VRC07-523LS mAbs for safety and pharmacokinetics in adults. Methods In this first-in-human phase 1 trial (HVTN 136/HPTN 092), adults without HIV were enrolled at six university-affiliated clinical research sites in the USA. Part A evaluated escalating single intravenous doses or subcutaneous infusion of PGT121.414.LS, in four groups: 3 mg/kg intravenous (treatment group 1; n=3), 10 mg/kg intravenous (treatment group 2; n=4), 30 mg/kg intravenous (treatment group 3; n=3), and 5 mg/kg subcutaneous (treatment group 4; n=3). Part B evaluated repeated sequential intravenous administrations of 20 mg/kg PGT121.414.LS plus 20 mg/kg VRC07-523LS (treatment group 5; n=10) and sequential subcutaneous administrations of 5 mg/kg PGT121.414.LS plus 5 mg/kg VRC07-523LS (treatment group 6; n=10) on days 0, 112, and 224. Participants in treatment groups 1 and 2 were enrolled sequentially, with participants enrolled and randomly assigned to treatment groups 3 and 4 after a review of safety data. Participants in treatment groups 5 and 6 were randomly assigned in blocks after a review of safety data from treatment groups 1-4. The primary endpoints were safety and tolerability of mAbs, serum concentrations and pharmacokinetics of mAbs, and serum neutralising activity, assessed in participants who received all scheduled product administrations. Serum concentrations of each mAb were measured via multiplex assay, and neutralisation activity against multiple HIV viruses was measured via the TZM-bl assay. Serum concentrations were estimated via an open, two-compartment model with first-order elimination from the central compartment. This study was registered with ClinicalTrials.gov (NCT04212091) and has been completed. Findings Between Nov 10, 2020, and Oct 5, 2021, we enrolled 33 participants without HIV: median age was 31 years (range 22-48); 19 were assigned female sex at birth and 11 were assigned male sex at birth. Three participants and four participants were sequentially assigned to treatment groups 1 and 2, respectively, and, after safety review, six participants were randomly assigned to treatment groups 3 (n=3) and 4 (n=3); after safety review, 20 participants were randomly assigned to treatment groups 5 (n=10) and 6 (n=10). Intravenous and subcutaneous infusions were safe and well tolerated, without serious adverse events or dose-limiting toxicities. Dose escalation of PGT121.414.LS from 3 mg/kg to 30 mg/kg (intravenous) resulted in a dose-proportional increase in serum concentration of PGT121.414.LS, whether administered alone or in combination with VRC07-523LS. The estimated elimination half-life of PGT121.414.LS was 71 days (95% CI 66-75), three times that of its parental form, PGT121. The estimated subcutaneous (vs intravenous) bioavailability of PGT121.414.LS was 861% (95% CI 640-955). Neutralisation activities were greater in the higher dose and dual combination intravenous groups than in the subcutaneous administration groups. Interpretation These findings support further evaluation of PGT121.414.LS in combination with other mAbs for HIV-1 prevention. Copyright (c) 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

Background:Clients seeking sexual health care often need concurrent mental healthcare services, which were disrupted during the COVID-19 pandemic. Using data from two studies conducted before and after the onset of COVID-19, we examined changes in self-reported depression and anxiety scores among clients in a sexual health clinic in New York City (NYC). Methods:We enrolled 144 participants pre-COVID-19 and 319 post-COVID-19 pandemic onset. Participants completed questionnaires assessing demographics, sexual behaviors, and mental health status. Primary mental outcomes included depression (Patient Health Questionnaire [PHQ-9]) and anxiety (Generalized Anxiety Disorder Scale [GAD-7]). We conducted descriptive analyses and used generalized linear mixed models (GLMM) to estimate predictors of mental health changes. Results:Cohorts were comparable by age, self-identified gender, race/ethnicity, income, HIV, and sexually transmitted infection assessment scores. Post-COVID-19 participants reported significantly higher mean PHQ-9 and GAD-7 scores compared with pre-COVID-19 participants (3.6 ± 4.2 vs 5.7 ± 5.3, P < .001; 3.9 ± 4.3 vs 5.1 ± 5.0; P = .019). Post-COVID-19 participants were also more likely to be uninsured or on Medicaid (2.7% vs 20%, 18% vs 30%, P < .001), and to report intimate partner violence victimization (24% vs 45%, P = .003). Adjusted GLMM showed post-COVID-19 was associated with a 1.55 (95% CI: .07, 3.03, P < .04) mean increase in PHQ-9 scores, but not GAD-7. Conclusions:Depression and anxiety scores increased after the onset of the COVID-19 pandemic in this NYC sexual health clinic sample. The sustained impact of the COVID-19 pandemic on depression calls for integrated, accessible mental health services within sexual health care settings.