RESUMEN
People living with HIV on antiretroviral therapy often have undetectable virus levels by standard assays, but "latent" HIV still persists in viral reservoirs. Eliminating these reservoirs is the goal of HIV cure research. The quantitative viral outgrowth assay (QVOA) is commonly used to estimate the reservoir size, that is, the infectious units per million (IUPM) of HIV-persistent resting CD4+ T cells. A new variation of the QVOA, the ultra deep sequencing assay of the outgrowth virus (UDSA), was recently developed that further quantifies the number of viral lineages within a subset of infected wells. Performing the UDSA on a subset of wells provides additional information that can improve IUPM estimation. This paper considers statistical inference about the IUPM from combined dilution assay (QVOA) and deep viral sequencing (UDSA) data, even when some deep sequencing data are missing. Methods are proposed to accommodate assays with wells sequenced at multiple dilution levels and with imperfect sensitivity and specificity, and a novel bias-corrected estimator is included for small samples. The proposed methods are evaluated in a simulation study, applied to data from the University of North Carolina HIV Cure Center, and implemented in the open-source R package SLDeepAssay.
Asunto(s)
Infecciones por VIH , VIH-1 , Humanos , Latencia del Virus , VIH-1/genética , Linfocitos T CD4-Positivos , Simulación por Computador , Carga ViralRESUMEN
Improving adherence to antiretroviral therapy (ART) is essential for limiting HIV disease progression among young sexual minority men living with HIV. Daily diaries allow for a detailed examination of how fluctuations in psychosocial factors are associated with adherence over time. Across three cities in the United States, this study collected 60 days of quantitative data from 44 young men (between 16 and 24 years of age) living with HIV who have sex with men. Lagged transition models explored the associations of mood, stress, social support, substance use, and condomless intercourse with daily ART adherence. Baseline levels of illicit substance use and condomless intercourse, and a higher proportion of days with stress or marijuana use, were associated with lower ART adherence. Lapses in adherence predicted non-adherence the following day. Findings suggest prospective data collection may identify different predictors of adherence compared to retrospective recall. Lapse-management strategies are needed to improve adherence following a missed dose.
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Infecciones por VIH , Minorías Sexuales y de Género , Trastornos Relacionados con Sustancias , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Infecciones por VIH/psicología , Humanos , Masculino , Cumplimiento de la Medicación/psicología , Estudios Retrospectivos , Trastornos Relacionados con Sustancias/complicaciones , Trastornos Relacionados con Sustancias/epidemiología , Estados Unidos/epidemiologíaAsunto(s)
Índice de Masa Corporal , Glutatión Transferasa/genética , Lipopolisacáridos/farmacología , Neutrófilos/efectos de los fármacos , Esputo/efectos de los fármacos , gamma-Tocoferol/farmacología , Adulto , Estudios Cruzados , Método Doble Ciego , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Esputo/citología , Adulto JovenRESUMEN
Background: The Accelerating COVID-19 Therapeutic Interventions and Vaccines-4c (ACTIV-4c) trial investigated prophylactic apixaban for 30 days following hospitalization for COVID-19. The overall incidence of early postdischarge death or thromboembolism was low, and the trial was closed early. Objectives: To identify a high-risk patient population who might benefit from postdischarge thromboprophylaxis through subgroup analyses stratified by age, race/ethnicity, obesity, D-dimer elevation, World Health Organization score, and modified International Medical Prevention Registry on Venous Thromboembolism score on 30-day composite outcome of all-cause death, arterial thromboembolism (ATE), and venous thromboembolism (VTE). Methods: Cumulative incidences of all-cause death, ATE, and VTE within 30 days were described for each subgroup. Time to death, ATE, or VTE by 30 days was analyzed using Cox proportional hazard models with interaction testing for each subgroup. Results: Among 1217 patients randomized to apixaban or placebo group, 32% were >60 years old. Modified International Medical Prevention Registry on Venous Thromboembolism score was ≥4 in 2% and 2 or 3 with an elevated D-dimer in an additional 9% of participants. The overall incidence of the primary endpoint was 2.13% in the apixaban group and 2.31% in the placebo group. At day 30, similar rates of the primary endpoint occurred within subgroups, except for participants aged >60 years. No benefit of thromboprophylaxis was seen in any subgroup. Conclusion: The combined incidence of 30-day death, ATE, and VTE was low in patients who survived COVID-19 hospitalization, except in patients over age 60 years. Due to the limited number of events, the findings remain inconclusive; nonetheless, the study did not identify a high-risk subgroup that would derive benefits from extended thromboprophylaxis.
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Background: Availability of PrEP-providing clinics is low in the Southern U.S., a region at the center of the U.S. HIV epidemic with significant HIV disparities among minoritized populations, but little is known about state-level differences in PrEP implementation in the region. We explored state-level clustering of organizational constructs relevant to PrEP implementation in family planning (FP) clinics in the Southern U.S. Methods: We surveyed providers and administrators of FP clinics not providing PrEP in 18 Southern states (Feb-Jun 2018, N = 414 respondents from 224 clinics) on these constructs: readiness to implement PrEP, PrEP knowledge/attitudes, implementation climate, leadership engagement, and available resources. We analyzed each construct using linear mixed models. A principal component analysis identified six principal components, which were inputted into a K-means clustering analysis to examine state-level clustering. Results: Three clusters (C1-3) were identified with five, three, and four states, respectively. Canonical variable 1 separated C1 and C2 from C3 and was primarily driven by PrEP readiness, HIV-specific implementation climate, PrEP-specific leadership engagement, PrEP attitudes, PrEP knowledge, and general resource availability. Canonical variable 2 distinguished C2 from C1 and was primarily driven by PrEP-specific resource availability, PrEP attitudes, and general implementation climate. All C3 states had expanded Medicaid, compared to 1 C1 state (none in C2). Conclusion: Constructs relevant for PrEP implementation exhibited state-level clustering, suggesting that tailored strategies could be used by clustered states to improve PrEP provision in FP clinics. Medicaid expansion was a common feature of states within C3, which could explain the similarity of their implementation constructs. The role of Medicaid expansion and state-level policies on PrEP implementation warrants further exploration.
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Fármacos Anti-VIH , Infecciones por VIH , Profilaxis Pre-Exposición , Estados Unidos , Humanos , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Infecciones por VIH/tratamiento farmacológico , Servicios de Planificación Familiar , Fármacos Anti-VIH/uso terapéutico , MedicaidRESUMEN
Self-report surveys are subject to measurement error associated with variation in the methodology employed. The current analysis uses data from the Campus Climate Survey Validation Study (CCSVS) to examine the impact that measurement decisions have on estimates. The findings demonstrate that asking victims to provide detailed information in an effort to properly place incidents in time and classify incidents by type resulted in relatively minor decreases in estimate magnitude. Ultimately, asking respondents to provide or confirm additional incident-level information for proper classification resulted in more complete information with very little impact on estimates.
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Acoso Escolar , Víctimas de Crimen , Delitos Sexuales , Humanos , Estudiantes , Encuestas y Cuestionarios , UniversidadesRESUMEN
BACKGROUND: We evaluated features of HIV transmission networks involving persons diagnosed during incident HIV infection (IHI) to assess network-based opportunities to curtail onward transmission. METHODS: Transmission networks were constructed using partial pol sequences reported to North Carolina surveillance among persons with recent (2014-2018) and past (<2014) HIV diagnoses. IHI were defined as documented acute infections or seroconversion. Demographic and virologic features of HIV genetic clusters (<1.5% pairwise genetic distance) involving ≥ 1 IHI were assessed. Persons with viral genetic links and who had diagnoses >90 days prior to an IHI were further characterized. We assessed named partner outcomes among IHI index persons using contact tracing data. FINDINGS: Of 4,405 HIV diagnoses 2014-2018 with sequences, there were 323 (7%) IHI index persons; most were male (88%), Black (65%), young (68% <30 years), and reported sex with men (MSM) risk (79%). Index persons were more likely to be cluster members compared to non-index persons diagnosed during the same period (72% vs. 49%). In total, 162 clusters were identified involving 233 IHI, 577 recent diagnoses, and 163 past diagnoses. Most IHI cases (53%) had viral linkages to ≥1 previously diagnosed person without evidence of HIV viral suppression in the year prior to the diagnosis of the IHI index. In contact tracing, only 53% IHI cases named an HIV-positive contact, resulting in 0.5 previously diagnosed persons detected per IHI investigated. When combined with viral analyses, the detection rate of viremic previously diagnosed persons increased to 1.3. INTERPRETATION: Integrating public health with molecular epidemiology, revealed that more than half of IHI have viral links to persons with previously diagnosed unsuppressed HIV infection which was largely unrecognized by traditional contact tracing. Enhanced partner services to support engagement and retention in HIV care and improved case finding supported by rapid phylogenetic analysis are tools to substantially reduce onward HIV transmission.