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1.
J Infect Dis ; 2024 Sep 03.
Artículo en Inglés | MEDLINE | ID: mdl-39225478

RESUMEN

Coronavirus disease 2019 (COVID-19) vaccines reduce severe disease and mortality and may lessen transmission, measured by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral load (VL). Evaluating vaccine associations in VL at COVID-19 diagnosis in 4 phase 3 randomized, placebo-controlled vaccine trials, July 2020 to July 2021, VL reductions were 2.78 log10 copies/mL (95% confidence interval [CI], 1.38-4.18; n = 60 placebo, 11 vaccine) and 2.12 log10 copies/mL (95% CI, 1.44-2.80; n = 594 placebo, 36 vaccine) for NVX-CoV2373 and mRNA-1273, respectively. Associations were not significant for AZD1222 (0.59 log10 copies/mL; 95% CI, -.19 to 1.36; n = 90 placebo, 78 vaccine) or Ad26.COV2.S (0.23 log10 copies/mL; 95% CI, -.01 to .47; n = 916 placebo, 424 vaccine). Thus, vaccines potentially decreased transmission when ancestral SARS-CoV-2 predominated. Clinical Trials Registration. NCT04470427, NCT04505722, NCT04516746, NCT04611802.

2.
Artículo en Inglés | MEDLINE | ID: mdl-39264541

RESUMEN

BACKGROUND: Vaccine hesitancy has been a significant concern throughout the COVID-19 pandemic. Vaccine hesitancy can be attributed to lack of confidence in vaccines, complacency about the health threat, or lack of convenience of vaccination. To date, few studies have used methods designed to include populations underrepresented in research when identifying factors associated with vaccine hesitancy. METHODS: Between January and July 2021, potential participants were recruited from community venues selected through time-location sampling in 15 defined communities in the United States. Study staff administered a questionnaire on demographics, COVID-19 behaviors and attitudes, and vaccination status or intention to consenting individuals. Vaccine hesitancy was analyzed among those age 18 years and older from nine of the 15 sites and was defined as self-reported neutral, unlikely, or very unlikely vaccine intention. Logistic regression modeling, adjusted for site, identified factors associated with vaccine hesitancy. RESULTS: Among 11,559 individuals, vaccine hesitancy by site ranged from 8.7 to 31.1%. Vaccine hesitancy was associated with being Black compared to White, being White compared to Asian, younger age, unstable housing, being unemployed, lower income, having a disability, providing care in home, not reporting inability to visit sick or elderly relatives during the pandemic, not reporting increased anxiety during the pandemic, and not spending more time with loved ones during the pandemic. CONCLUSIONS: In these selected US communities, early in vaccine rollout, there were significant racial disparities in vaccine hesitancy. Additionally, individuals who were more marginalized due to their socioeconomic status were more likely to report vaccine hesitancy. Vaccine campaigns should make efforts to remove barriers to vaccination, by improving convenience.

3.
Vaccine ; 42(26): 126260, 2024 Sep 11.
Artículo en Inglés | MEDLINE | ID: mdl-39265456

RESUMEN

BACKGROUND: Minoritized communities in the United States have had higher COVID-19 mortality and lower vaccine uptake. The influence of previous SARS-CoV-2 infection, initial disease severity, and persistent symptoms on COVID-19 vaccine uptake in Black and Latinx communities has not been examined. OBJECTIVE: To investigate whether initial COVID-19 severity, persistent symptoms, and other correlates affected vaccine uptake in a predominantly minoritized cohort hospitalized for COVID-19 during the early pandemic in New York City. DESIGN: In this historical cohort study, we abstracted electronic health record data on demographics, comorbidities, hospital oxygen requirements, symptoms at 3 and 6 months post-admission, COVID-19 vaccinations through November 2022, and influenza vaccinations during the 2018-2019 through 2021-2022 seasons. Unadjusted and adjusted odds ratios were estimated through logistic regression analyses of correlates of COVID-19 vaccination, on-time vaccination, and boosting. PARTICIPANTS: Survivors among the first 1186 adult patients hospitalized for COVID-19 between March 1 and April 8, 2020 at a large quaternary care medical center in Northern Manhattan. MAIN MEASURES: Uptake of at least one COVID-19 vaccine dose, uptake of at least one booster, and on-time vaccination. KEY RESULTS: The 890 surviving individuals were predominantly Latinx (54%) and Non-Hispanic Black (15%). Most had one or more comorbidities (67%), and received at least one COVID-19 vaccine dose (78%). Among those vaccinated, 57% received at least one booster, and 31% delayed vaccination. 67% experienced persistent symptoms. Multiple logistic regression showed no association between vaccine uptake and disease severity or symptom persistence. However, older age and influenza vaccination during the COVID-19 era were associated with increased vaccination, booster uptake, and on-time vaccination. CONCLUSIONS: Pinpointing drivers of vaccine uptake and hesitancy is critical to increasing and sustaining COVID-19 vaccination as the field transitions to annual boosters. The association between influenza vaccination and increased vaccine uptake suggests that bundling vaccines for adults may be an effective delivery strategy.

4.
Front Reprod Health ; 6: 1366262, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-39119145

RESUMEN

Introduction: Violence against women is a prevalent, preventable public health crisis. COVID-19 stressors and pandemic countermeasures may have exacerbated violence against women. Cisgender college women are particularly vulnerable to violence. Thus, we examined the prevalence and correlates of verbal/physical violence experienced and perpetrated among cisgender women enrolled at a New York City college over one year during the COVID-19 pandemic. Methods: From a prospective cohort study, we analyzed data self-reported quarterly (T1, T2, T3, T4) between December 2020 and December 2021. Using generalized estimated equations (GEE) and logistic regression, we identified correlates of experienced and perpetrated violence among respondents who were partnered or cohabitating longitudinally and at each quarter, respectively. Multivariable models included all variables with unadjusted parameters X 2 p-value ≤0.05. Results: The prevalence of experienced violence was 52% (T1: N = 513), 30% (T2: N = 305), 33% (T3: N = 238), and 17% (T4: N = 180); prevalence of perpetrated violence was 38%, 17%, 21%, and 9%. Baseline correlates of experienced violence averaged over time (GEE) included race, living situation, loneliness, and condom use; correlates of perpetrated violence were school year, living situation, and perceived social support. Quarter-specific associations corroborated population averages: living with family members and low social support were associated with experienced violence at all timepoints except T4. Low social support was associated with higher odds of perpetrated violence at T1/T3. Other/Multiracial identity was associated with higher odds of violence experience at T3. Conclusions: Living situation was associated with experienced and perpetrated violence in all analyses, necessitating further exploration of household conditions, family dynamics, and interpersonal factors. The protective association of social support with experienced and perpetrated violence also warrants investigation into forms of social engagement and cohesion. Racial differences in violence also require examination. Our findings can inform university policy development on violence and future violence research. Within or beyond epidemic conditions, universities should assess and strengthen violence prevention and support systems for young women by developing programming to promote social cohesion.

5.
Vaccines (Basel) ; 12(8)2024 Aug 03.
Artículo en Inglés | MEDLINE | ID: mdl-39204009

RESUMEN

A better understanding of the long-term safety, efficacy, and immunogenicity of COVID-19 vaccines is needed. This phase 3, randomized, placebo-controlled study for AZD1222 (ChAdOx1 nCoV-19) primary-series vaccination enrolled 32,450 participants in the USA, Chile, and Peru between August 2020 and January 2021 (NCT04516746). Endpoints included the 2-year follow-up assessment of safety, efficacy, and immunogenicity. After 2 years, no emergent safety signals were observed for AZD1222, and no cases of thrombotic thrombocytopenia syndrome were reported. The assessment of anti-SARS-CoV-2 nucleocapsid antibody titers confirmed the durability of AZD1222 efficacy for up to 6 months, after which infection rates in the AZD1222 group increased over time. Despite this, all-cause and COVID-19-related mortality remained low through the study end, potentially reflecting the post-Omicron decoupling of SARS-CoV-2 infection rates and severe COVID-19 outcomes. Geometric mean titers were elevated for anti-SARS-CoV-2 neutralizing antibodies at the 1-year study visit and the anti-spike antibodies were elevated at year 2, providing further evidence of increasing SARS-CoV-2 infections over long-term follow-up. Overall, this 2-year follow-up of the AZD1222 phase 3 study confirms that the long-term safety profile remains consistent with previous findings and supports the continued need for COVID-19 booster vaccinations due to waning efficacy and humoral immunity.

6.
Res Sq ; 2024 Jun 14.
Artículo en Inglés | MEDLINE | ID: mdl-38947062

RESUMEN

Background: Rising hepatitis C and B virus (HCV and HBV) rates have been reported in men who have sex with men (MSM) and transgender women (TGW). This study characterizes HCV and HBV infections longitudinally among 2,496 MSM/TGW aged 18-50 years and at risk for HIV acquisition enrolled in an HIV-1 vaccine trial in 18 U.S. cities between 2009-2013. Methods: Participants completed behavioral surveys, HIV testing, and blood collection over 24 months. Of the 2,397 participants who consented for future testing, 1,792 (74.8%) had available paired stored blood samples at baseline and a later timepoint (Month 24 [N = 999]; if unavailable, M12 [N = 775] or M15 [N = 18]). Results: Among 1,792 participants, 98.1% were MSM, 0.8% were TGW, and the median age was 30 years (IQR 24, 40). Participants reported a median number of 3 male sex partners (IQR 1,5) within the past 3 months. Condomless insertive anal sex was reported by 55.8% and condomless receptive anal sex by 46.7%.1.3% reported injection drug use. During follow-up, 1.4% reported pre-exposure prophylaxis (PrEP) use. At baseline 11/1792 (0.61%) participants had HCV infection (HCV AB positive, RNA detectable), with all having persistent detectable RNA and chronic HCV infection at follow-up. Phylogenetic analysis showed no clusters of HCV infection. 8 participants had HCV AB positive, RNA undetectable at baseline and follow-up, representing past HCV infection with clearance; only 2 acquired HCV, which cleared over 12-24 months. At baseline, 2 participants (2/1792 = 0.11%) had positive HBsAg, indicating chronic HBV infection. Over 12-24 months, 4 (4/1790, 0.22%) developed HBsAg positivity; these participants had HBcAB positivity at baseline, thereby likely representing reactivation. There were no new HBV infections during follow-up. Conclusion: Among 1,792 men who have sex with men and transgender women aged 18-50 years and at risk for HIV acquisition enrolled in a U.S. HIV-1 vaccine trial, incident hepatitis C infection rates were extremely low, with no cases of incident hepatitis B infection. These rates of incident HCV infection and HBSAg positivity are lower than previously reported among MSM/TGW.

7.
Front Immunol ; 15: 1401728, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38827749

RESUMEN

Background: Immunity to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is now widespread; however, the degree of cross-immunity between SARS-CoV-2 and endemic, seasonal human coronaviruses (HCoVs) remains unclear. Methods: SARS-CoV-2 and HCoV cross-immunity was evaluated in adult participants enrolled in a US sub-study in the phase III, randomized controlled trial (NCT04516746) of AZD1222 (ChAdOx1 nCoV-19) primary-series vaccination for one-year. Anti-HCoV spike-binding antibodies against HCoV-229E, HCoV-HKU1, HCoV-OC43, and HCoV-NL63 were evaluated in participants following study dosing and, in the AZD1222 group, after a non-study third-dose booster. Timing of SARS-CoV-2 seroconversion (assessed via anti-nucleocapsid antibody levels) and incidence of COVID-19 were evaluated in those who received AZD1222 primary-series by baseline anti-HCoV titers. Results: We evaluated 2,020/21,634 participants in the AZD1222 group and 1,007/10,816 in the placebo group. At the one-year data cutoff (March 11, 2022) mean duration of follow up was 230.9 (SD: 106.36, range: 1-325) and 94.3 (74.12, 1-321) days for participants in the AZD1222 (n = 1,940) and placebo (n = 962) groups, respectively. We observed little elevation in anti-HCoV humoral titers post study-dosing or post-boosting, nor evidence of waning over time. The occurrence and timing of SARS-CoV-2 seroconversion and incidence of COVID-19 were not largely impacted by baseline anti-HCoV titers. Conclusion: We found limited evidence for cross-immunity between SARS-CoV-2 and HCoVs following AZD1222 primary series and booster vaccination. Susceptibility to future emergence of novel coronaviruses will likely persist despite a high prevalence of SARS-CoV-2 immunity in global populations.


Asunto(s)
Anticuerpos Antivirales , Vacunas contra la COVID-19 , COVID-19 , ChAdOx1 nCoV-19 , Inmunidad Humoral , SARS-CoV-2 , Humanos , COVID-19/inmunología , COVID-19/prevención & control , ChAdOx1 nCoV-19/inmunología , Adulto , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , SARS-CoV-2/inmunología , Masculino , Femenino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Persona de Mediana Edad , Inmunidad Humoral/efectos de los fármacos , Reacciones Cruzadas/inmunología , Estaciones del Año , Adulto Joven , Vacunación , Método Doble Ciego
8.
J Antimicrob Chemother ; 79(8): 1877-1884, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38831614

RESUMEN

BACKGROUND: Candidaemia is associated with poor outcomes including high mortality rates. Controversy remains regarding whether fluconazole or an echinocandin is the optimal choice for initial candidaemia treatment, particularly among high-risk patients such as the immunocompromised or critically ill. OBJECTIVES: To understand optimal initial treatment of candidaemia. METHODS: We conducted a retrospective study of immunocompromised or ICU adult patients with candidaemia from 2010 to 2014. Patients who received ≥3 consecutive days of initial treatment with fluconazole or micafungin were included. The primary outcome was complete response at day 14, defined as clinical improvement and blood culture sterilization. Secondary outcomes included microbiological and clinical success, survival and recurrent candidaemia. RESULTS: A total of 197 patients were included; 76 received fluconazole and 121 received micafungin. There was no difference in complete response between the fluconazole and micafungin groups (ICU: 38% versus 40%, P = 0.87; immunocompromised: 57% versus 59%, P = 0.80). Secondary outcomes including survival were also similar. In multivariable analysis, among ICU patients, Pitt bacteraemia score < 4 (P = 0.002) and time to antifungal (P = 0.037) were associated with meeting the primary outcome; white blood cell count > 11 cells × 103/µL on day 0 (P < 0.001) and Candida isolated from a non-blood site (P = 0.025) were associated with not meeting the primary outcome. Among immunocompromised patients, white blood cells > 11 × 103/µL (P = 0.003) and Candida isolated from a non-blood site (P = 0.026) were associated with not meeting the primary outcome. CONCLUSIONS: These data suggest that among ICU or immunocompromised patients, severity of illness rather than initial antifungal choice drove clinical outcomes.


Asunto(s)
Antifúngicos , Candidemia , Enfermedad Crítica , Equinocandinas , Fluconazol , Huésped Inmunocomprometido , Micafungina , Humanos , Micafungina/uso terapéutico , Micafungina/administración & dosificación , Antifúngicos/uso terapéutico , Masculino , Estudios Retrospectivos , Femenino , Persona de Mediana Edad , Resultado del Tratamiento , Candidemia/tratamiento farmacológico , Candidemia/mortalidad , Anciano , Fluconazol/uso terapéutico , Fluconazol/administración & dosificación , Equinocandinas/uso terapéutico , Equinocandinas/administración & dosificación , Adulto , Lipopéptidos/uso terapéutico , Lipopéptidos/administración & dosificación , Análisis de Supervivencia
9.
PLoS Med ; 21(6): e1004329, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38913710

RESUMEN

BACKGROUND: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. We conducted a multicenter, randomized, partially blinded Phase I clinical trial to evaluate the safety and serum concentrations of VRC07-523LS, administered in multiple doses and routes to healthy adults without HIV. METHODS AND FINDINGS: Participants were recruited between 2 February 2018 and 9 October 2018. A total of 124 participants were randomized to receive 5 VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), subcutaneous (SC) (T4: 2.5 mg/kg, T5: 5 mg/kg), or intramuscular (IM) (T6: 2.5 mg/kg or P6: placebo) routes at 4-month intervals. Participants and site staff were blinded to VRC07-523LS versus placebo for the IM group, while all other doses and routes were open-label. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum PK. Neutralization activity was measured in a TZM-bl assay and antidrug antibodies (ADAs) were assayed using a tiered bridging assay testing strategy. Injections and infusions were well tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusion reactions were reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals [95% CIs]) following the first administration were 29.0 µg/mL (25.2, 33.4), 58.5 µg/mL (49.4, 69.3), and 257.2 µg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 µg/mL (8.8, 13.3) and 22.8 µg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 µg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM (95% CIs) concentrations immediately prior to the second administration were 3.4 µg/mL (2.5, 4.6), 6.5 µg/mL (5.6, 7.5), and 27.2 µg/mL (23.9, 31.0) with IV dosing; 0.97 µg/mL (0.65, 1.4) and 3.1 µg/mL (2.2, 4.3) with SC dosing, and 2.6 µg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titers, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titer ADA at a lone time point. VRC07-523LS has an estimated mean half-life of 42 days across all doses and routes (95% CI: 40.5, 43.5), over twice as long as VRC01 (15 days). CONCLUSIONS: VRC07-523LS was safe and well tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens. TRIAL REGISTRATION: ClinicalTrials.gov/ NCT03387150 (posted on 21 December 2017).


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Anti-VIH , Humanos , Masculino , Femenino , Adulto , Anticuerpos Neutralizantes/sangre , Anticuerpos Anti-VIH/sangre , Persona de Mediana Edad , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/inmunología , VIH-1/inmunología , Adulto Joven , Anticuerpos ampliamente neutralizantes/administración & dosificación , Anticuerpos ampliamente neutralizantes/efectos adversos , Adolescente , Inyecciones Intramusculares
10.
Open Forum Infect Dis ; 11(6): ofae297, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38911948

RESUMEN

Introduction: HIV preexposure prophylaxis (PrEP), a key strategy for preventing HIV transmission, requires awareness and access to PrEP services. Although all patients should be made aware of HIV PrEP; the diagnosis of bacterial sexually transmitted infections (STIs) is an important indicator of potential HIV PrEP need. In a previous evaluation of Get2PrEP (G2P), we found that an electronic medical record laboratory comments did not increase the frequency of PrEP discussions between patients and providers. In Get2PrEP2 (G2P2), we hypothesized that active, personalized messaging to providers about HIV PrEP would increase the documentation of PrEP discussions, referrals, and/or provision of HIV PrEP to individuals diagnosed with an STI. Methods: G2P2 was a parallel 3-arm, unblinded, randomized controlled design. Participants were allocated 2:1 to intervention or control. Participants in the intervention arm were further allocated to receive provider messaging through the electronic medical record chat message or e-mail. Results: The 191 randomized encounters resulted in a modest 7.8% (odds ratio, 1.078; confidence interval, 1.02-1.13) increase in documented PrEP discussions in intervention encounters versus none in the standard care group. There was no statistical difference by intervention modality. All documented discussions occurred in the outpatient or emergency department and were more frequent in women and those aged <25 years. Discussion: An e-mail or electronic medical record chat message sent to providers of patients testing positive for an STI had a small but significant effect on documented patient-provider PrEP discussions. Further investigation is required to determine whether provider messaging can increase PrEP uptake among eligible patients and longer-term outcomes.

11.
Pharmaceutics ; 16(5)2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38794258

RESUMEN

Monoclonal antibodies are commonly engineered with an introduction of Met428Leu and Asn434Ser, known as the LS mutation, in the fragment crystallizable region to improve pharmacokinetic profiles. The LS mutation delays antibody clearance by enhancing binding affinity to the neonatal fragment crystallizable receptor found on endothelial cells. To characterize the LS mutation for monoclonal antibodies targeting HIV, we compared pharmacokinetic parameters between parental versus LS variants for five pairs of anti-HIV immunoglobin G1 monoclonal antibodies (VRC01/LS/VRC07-523LS, 3BNC117/LS, PGDM1400/LS PGT121/LS, 10-1074/LS), analyzing data from 16 clinical trials of 583 participants without HIV. We described serum concentrations of these monoclonal antibodies following intravenous or subcutaneous administration by an open two-compartment disposition, with first-order elimination from the central compartment using non-linear mixed effects pharmacokinetic models. We compared estimated pharmacokinetic parameters using the targeted maximum likelihood estimation method, accounting for participant differences. We observed lower clearance rate, central volume, and peripheral volume of distribution for all LS variants compared to parental monoclonal antibodies. LS monoclonal antibodies showed several improvements in pharmacokinetic parameters, including increases in the elimination half-life by 2.7- to 4.1-fold, the dose-normalized area-under-the-curve by 4.1- to 9.5-fold, and the predicted concentration at 4 weeks post-administration by 3.4- to 7.6-fold. Results suggest a favorable pharmacokinetic profile of LS variants regardless of HIV epitope specificity. Insights support lower dosages and/or less frequent dosing of LS variants to achieve similar levels of antibody exposure in future clinical applications.

12.
JAMA Netw Open ; 7(5): e2412835, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38780941

RESUMEN

Importance: SARS-CoV-2 viral load (VL) in the nasopharynx is difficult to quantify and standardize across settings, but it may inform transmission potential and disease severity. Objective: To characterize VL at COVID-19 diagnosis among previously uninfected and unvaccinated individuals by evaluating the association of demographic and clinical characteristics, viral variant, and trial with VL, as well as the ability of VL to predict severe disease. Design, Setting, and Participants: This secondary cross-protocol analysis used individual-level data from placebo recipients from 4 harmonized, phase 3 COVID-19 vaccine efficacy trials sponsored by Moderna, AstraZeneca, Janssen, and Novavax. Participants were SARS-CoV-2 negative at baseline and acquired COVID-19 during the blinded phase of the trials. The setting included the US, Brazil, South Africa, Colombia, Argentina, Peru, Chile, and Mexico; start dates were July 27, 2020, to December 27, 2020; data cutoff dates were March 26, 2021, to July 30, 2021. Statistical analysis was performed from November 2022 to June 2023. Main Outcomes and Measures: Linear regression was used to assess the association of demographic and clinical characteristics, viral variant, and trial with polymerase chain reaction-measured log10 VL in nasal and/or nasopharyngeal swabs taken at the time of COVID-19 diagnosis. Results: Among 1667 participants studied (886 [53.1%] male; 995 [59.7%] enrolled in the US; mean [SD] age, 46.7 [14.7] years; 204 [12.2%] aged 65 years or older; 196 [11.8%] American Indian or Alaska Native, 150 [9%] Black or African American, 1112 [66.7%] White; 762 [45.7%] Hispanic or Latino), median (IQR) log10 VL at diagnosis was 6.18 (4.66-7.12) log10 copies/mL. Participant characteristics and viral variant explained only 5.9% of the variability in VL. The independent factor with the highest observed differences was trial: Janssen participants had 0.54 log10 copies/mL lower mean VL vs Moderna participants (95% CI, 0.20 to 0.87 log10 copies/mL lower). In the Janssen study, which captured the largest number of COVID-19 events and variants and used the most intensive post-COVID surveillance, neither VL at diagnosis nor averaged over days 1 to 28 post diagnosis was associated with COVID-19 severity. Conclusions and Relevance: In this study of placebo recipients from 4 randomized phase 3 trials, high variability was observed in SARS-CoV-2 VL at the time of COVID-19 diagnosis, and only a fraction was explained by individual participant characteristics or viral variant. These results suggest challenges for future studies of interventions seeking to influence VL and elevates the importance of standardized methods for specimen collection and viral load quantitation.


Asunto(s)
COVID-19 , Nasofaringe , SARS-CoV-2 , Carga Viral , Humanos , Nasofaringe/virología , Carga Viral/estadística & datos numéricos , Masculino , Femenino , Adulto , Persona de Mediana Edad , Vacunas contra la COVID-19/uso terapéutico , Ensayos Clínicos Controlados Aleatorios como Asunto , Estados Unidos , Anciano
13.
AIDS Behav ; 28(9): 2850-2862, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-38801501

RESUMEN

With the rise of new and emerging Pre-Exposure Prophylaxis (PrEP) modalities, greater attention is needed to better understand how people who could benefit from PrEP make decisions to initiate, stop, pause, or switch PrEP regimens. In this study we borrow from the field of consumer research to create a consumer-derived PrEP Consumer Journey Model that describes key decision-making touchpoints a PrEP consumer moves through within and outside of a clinical context. Using in-depth interviews (n = 29) with gay and bisexual men who have sex with men, we evaluate which system 1 (emotional) and system 2 (cognitive) attributes are used for decision-making at different touchpoints along the PrEP Consumer Journey. Our results suggest system 1 attributes, such as feeling protected, reducing anxiety, enhancing pleasure, social norms, and taking ownership over health were more salient when consumers moved from pre-contemplation to information gathering, as well as evaluating post-uptake experience. System 2 attributes, including cost, side effects, dosing schedule, and sexual frequency, were present throughout the PrEP Consumer Journey, but particularly influential in the information gathering stage and when pausing, switching, or opting out of PrEP. We contend the PrEP Consumer Journey, and our findings related to decision-making, can help orient medical providers to anticipated patient concerns around PrEP use and ultimately provide more supportive and engaging PrEP counseling and services.


Asunto(s)
Toma de Decisiones , Infecciones por VIH , Homosexualidad Masculina , Profilaxis Pre-Exposición , Humanos , Masculino , Infecciones por VIH/prevención & control , Adulto , Homosexualidad Masculina/psicología , Fármacos Anti-VIH/administración & dosificación , Entrevistas como Asunto , Persona de Mediana Edad , Minorías Sexuales y de Género/psicología , Investigación Cualitativa
14.
BMJ Glob Health ; 9(5)2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38770814

RESUMEN

INTRODUCTION: Some African countries plan to introduce and scale-up new long-acting pre-exposure prophylaxis methods (LA-PrEP), like the monthly dapivirine vaginal ring (PrEP ring) and injectable cabotegravir. National costed implementation plans, roadmaps for successful product implementation, are often overlooked. International stakeholders engaged in oral PrEP planning, introduction and scale-up are an information resource of lessons learned to advise LA-PrEP planning. We consulted such international stakeholders and synthesised oral PrEP lessons to inform the development of a costed rollout plan template for LA-PrEP. METHODS: From selected global health organisations (five international nongovernmental, four donor, four university/research and two multilateral), we interviewed 27 representatives based in America, Europe, Asia and Africa about strategic content and approaches for LA-PrEP policy, programming and implementation. We conducted a thematic analysis of the interview data for implementation considerations. RESULTS: From the consultations, we identified six implementation themes for LA-PrEP introduction and scale-up: (1) ethically increasing choice and avoiding coercion; (2) de-stigmatising PrEP by focusing on preference rather than risk-based eligibility; (3) integrating LA-PrEP into services that are more woman-oriented, couple-oriented and family-oriented, and providing private spaces for LA-PrEP delivery; (4) de-medicalising delivery of relatively safe products (eg, PrEP ring); (5) constructing multilevel, nuanced communication strategies to address measured and perceived product efficacy and effectiveness; and (6) devising product-agnostic, modular approaches to service delivery. Despite the widespread emphasis on integration, few stakeholders offered empirical examples of successful integration approaches and frameworks. CONCLUSIONS: Lessons learnt from stakeholder participants suggest standardised and modular processes can improve efficiencies in LA-PrEP planning and implementation. Tiered communication strategies addressing product efficacy and effectiveness will improve clients' and providers' efficacy in making informed decisions. Integration is important for LA-PrEP delivery, but data on empirical integration approaches and frameworks is minimal: further research in this discipline is needed.


Asunto(s)
Países en Desarrollo , Infecciones por VIH , Profilaxis Pre-Exposición , Investigación Cualitativa , Humanos , Femenino , Infecciones por VIH/prevención & control , Dispositivos Anticonceptivos Femeninos , Administración Oral , Fármacos Anti-VIH/uso terapéutico , Fármacos Anti-VIH/administración & dosificación
15.
medRxiv ; 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38562833

RESUMEN

Background: HIV-1 vaccine development is a global health priority. Broadly neutralizing antibodies (bnAbs) which target the HIV-1 gp41 membrane-proximal external region (MPER) have some of the highest neutralization breadth. An MPER peptide-liposome vaccine has been found to expand bnAb precursors in monkeys. Methods: The HVTN133 phase 1 clinical trial (NCT03934541) studied the MPER-peptide liposome immunogen in 24 HIV-1 seronegative individuals. Participants were recruited between 15 July 2019 and 18 October 2019 and 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. Results: The trial was stopped prematurely due to an anaphylaxis reaction in one participant ultimately attributed to vaccine-associated polyethylene glycol. The immunogen induced robust immune responses, including MPER+ serum and blood CD4+ T-cell responses in 95% and 100% of vaccinees, respectively, and 35% (7/20) of vaccine recipients had blood IgG memory B cells with MPER-bnAb binding phenotype. Affinity purification of plasma MPER+ IgG demonstrated tier 2 HIV-1 neutralizing activity in two of five participants after 3 immunizations. Conclusions: MPER-peptide liposomes induced gp41 serum neutralizing epitope-targeted antibodies and memory B-cell responses in humans despite the early termination of the study. These results suggest that the MPER region is a promising target for a candidate HIV vaccine.

16.
Clin Infect Dis ; 79(2): 364-374, 2024 Aug 16.
Artículo en Inglés | MEDLINE | ID: mdl-38598658

RESUMEN

BACKGROUND: Although the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are highly efficacious at preventing severe disease in the general population, current data are lacking regarding vaccine efficacy (VE) for individuals with mild immunocompromising conditions. METHODS: A post hoc, cross-protocol analysis of participant-level data from the blinded phase of four randomized, placebo-controlled, coronavirus disease 2019 (COVID-19) vaccine phase 3 trials (Moderna, AstraZeneca, Janssen, and Novavax) was performed. We defined a "tempered immune system" (TIS) variable via a consensus panel based on medical history and medications to determine VE against symptomatic and severe COVID-19 cases in TIS participants versus non-TIS individuals starting at 14 days after completion of the primary series through the blinded phase for each of the 4 trials. An analysis of participants living with well-controlled human immunodeficiency virus was conducted using the same methods. RESULTS: A total of 3852/30 351 (12.7%) Moderna participants, 3088/29 868 (10.3%) Novavax participants, 3549/32 380 (11.0%) AstraZeneca participants, and 5047/43 788 (11.5%) Janssen participants were identified as having a TIS. Most TIS conditions (73.9%) were due to metabolism and nutritional disorders. Vaccination (vs placebo) significantly reduced the likelihood of symptomatic and severe COVID-19 for all participants for each trial. VE was not significantly different for TIS participants versus non-TIS for either symptomatic or severe COVID-19 for each trial, nor was VE significantly different in the symptomatic endpoint for participants with human immunodeficiency virus. CONCLUSIONS: For individuals with mildly immunocompromising conditions, there is no evidence of differences in VE against symptomatic or severe COVID-19 compared with those with non-TIS in the 4 COVID-19 vaccine randomized controlled efficacy trials.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Eficacia de las Vacunas , Humanos , COVID-19/prevención & control , COVID-19/inmunología , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/administración & dosificación , Masculino , Femenino , SARS-CoV-2/inmunología , Persona de Mediana Edad , Adulto , Huésped Inmunocomprometido , Anciano , Ensayos Clínicos Controlados Aleatorios como Asunto
17.
Epidemics ; 47: 100768, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38643547

RESUMEN

While rapid development and roll out of COVID-19 vaccines is necessary in a pandemic, the process limits the ability of clinical trials to assess longer-term vaccine efficacy. We leveraged COVID-19 surveillance data in the U.S. to evaluate vaccine efficacy in U.S. Government-funded COVID-19 vaccine efficacy trials with a three-step estimation process. First, we used a compartmental epidemiological model informed by county-level surveillance data, a "population model", to estimate SARS-CoV-2 incidence among the unvaccinated. Second, a "cohort model" was used to adjust the population SARS-CoV-2 incidence to the vaccine trial cohort, taking into account individual participant characteristics and the difference between SARS-CoV-2 infection and COVID-19 disease. Third, we fit a regression model estimating the offset between the cohort-model-based COVID-19 incidence in the unvaccinated with the placebo-group COVID-19 incidence in the trial during blinded follow-up. Counterfactual placebo COVID-19 incidence was estimated during open-label follow-up by adjusting the cohort-model-based incidence rate by the estimated offset. Vaccine efficacy during open-label follow-up was estimated by contrasting the vaccine group COVID-19 incidence with the counterfactual placebo COVID-19 incidence. We documented good performance of the methodology in a simulation study. We also applied the methodology to estimate vaccine efficacy for the two-dose AZD1222 COVID-19 vaccine using data from the phase 3 U.S. trial (ClinicalTrials.gov # NCT04516746). We estimated AZD1222 vaccine efficacy of 59.1% (95% uncertainty interval (UI): 40.4%-74.3%) in April, 2021 (mean 106 days post-second dose), which reduced to 35.7% (95% UI: 15.0%-51.7%) in July, 2021 (mean 198 days post-second-dose). We developed and evaluated a methodology for estimating longer-term vaccine efficacy. This methodology could be applied to estimating counterfactual placebo incidence for future placebo-controlled vaccine efficacy trials of emerging pathogens with early termination of blinded follow-up, to active-controlled or uncontrolled COVID-19 vaccine efficacy trials, and to other clinical endpoints influenced by vaccination.


Asunto(s)
Vacunas contra la COVID-19 , COVID-19 , SARS-CoV-2 , Eficacia de las Vacunas , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , COVID-19/prevención & control , COVID-19/epidemiología , Vacunas contra la COVID-19/administración & dosificación , Vacunas contra la COVID-19/uso terapéutico , Estudios de Seguimiento , Incidencia , Vigilancia de la Población/métodos , SARS-CoV-2/inmunología , Estados Unidos/epidemiología , Eficacia de las Vacunas/estadística & datos numéricos
19.
medRxiv ; 2024 Jan 11.
Artículo en Inglés | MEDLINE | ID: mdl-38260276

RESUMEN

Background: Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the only bnAb HIV prevention efficacy studies to date, the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. Greater efficacy is required before passively administered bnAbs become a viable option for HIV prevention; furthermore subcutaneous (SC) or intramuscular (IM) administration may be preferred. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. Methods: Participants were recruited between 02 February 2018 and 09 October 2018. 124 healthy participants without HIV were randomized to receive five VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), SC (T4: 2.5 mg/kg, T5: 5 mg/kg) or IM (T6: 2.5 mg/kg or P6: placebo) routes at four-month intervals. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA after the first dose through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum pharmacokinetics. Neutralization activity was measured in a TZM-bl assay and anti-drug antibodies (ADA) were assayed using a tiered bridging assay testing strategy. Results: Injections were well-tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusions were generally well-tolerated, with infusion reactions reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals) following the first administration were 29.0 µg/mL (25.2, 33.4), 58.5 µg/mL (49.4, 69.3), and 257.2 µg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 µg/mL (8.8, 13.3) and 22.8 µg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 µg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM concentrations immediately prior to the second administration were 3.4 µg/mL (2.5, 4.6), 6.5 µg/mL (5.6, 7.5), and 27.2 µg/mL (23.9, 31.0) with IV dosing; 0.97 µg/mL (0.65, 1.4) and 3.1 µg/mL (2.2, 4.3) with SC dosing, and 2.6 µg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titres, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titre ADA at a lone timepoint. VRC07-523LS has an estimated mean half-life of 42 days (95% CI: 40.5, 43.5), approximately twice as long as VRC01. Conclusions: VRC07-523LS was safe and well-tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens.

20.
Emerg Infect Dis ; 30(2): 245-254, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38270128

RESUMEN

During January-August 2021, the Community Prevalence of SARS-CoV-2 Study used time/location sampling to recruit a cross-sectional, population-based cohort to estimate SARS-CoV-2 seroprevalence and nasal swab sample PCR positivity across 15 US communities. Survey-weighted estimates of SARS-CoV-2 infection and vaccine willingness among participants at each site were compared within demographic groups by using linear regression models with inverse variance weighting. Among 22,284 persons >2 months of age and older, median prevalence of infection (prior, active, or both) was 12.9% across sites and similar across age groups. Within each site, average prevalence of infection was 3 percentage points higher for Black than White persons and average vaccine willingness was 10 percentage points lower for Black than White persons and 7 percentage points lower for Black persons than for persons in other racial groups. The higher prevalence of SARS-CoV-2 infection among groups with lower vaccine willingness highlights the disparate effect of COVID-19 and its complications.


Asunto(s)
COVID-19 , Vacunas , Adulto , Niño , Humanos , COVID-19/epidemiología , SARS-CoV-2 , Estudios Transversales , Prevalencia , Estudios Seroepidemiológicos
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