Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 388
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
N Engl J Med ; 388(14): 1296-1306, 2023 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-37018493

RESUMO

BACKGROUND: Interventions to reduce sexually transmitted infections (STIs) among men who have sex with men (MSM) are needed. METHODS: We conducted an open-label, randomized study involving MSM and transgender women who were taking preexposure prophylaxis (PrEP) against human immunodeficiency virus (HIV) infection (PrEP cohort) or living with HIV infection (persons living with HIV infection [PLWH] cohort) and who had had Neisseria gonorrhoeae (gonorrhea), Chlamydia trachomatis (chlamydia), or syphilis in the past year. Participants were randomly assigned in a 2:1 ratio to take 200 mg of doxycycline within 72 hours after condomless sex (doxycycline postexposure prophylaxis) or receive standard care without doxycycline. STI testing was performed quarterly. The primary end point was the incidence of at least one STI per follow-up quarter. RESULTS: Of 501 participants (327 in the PrEP cohort and 174 in the PLWH cohort), 67% were White, 7% Black, 11% Asian or Pacific Islander, and 30% Hispanic or Latino. In the PrEP cohort, an STI was diagnosed in 61 of 570 quarterly visits (10.7%) in the doxycycline group and 82 of 257 quarterly visits (31.9%) in the standard-care group, for an absolute difference of -21.2 percentage points and a relative risk of 0.34 (95% confidence interval [CI], 0.24 to 0.46; P<0.001). In the PLWH cohort, an STI was diagnosed in 36 of 305 quarterly visits (11.8%) in the doxycycline group and 39 of 128 quarterly visits (30.5%) in the standard-care group, for an absolute difference of -18.7 percentage points and a relative risk of 0.38 (95% CI, 0.24 to 0.60; P<0.001). The incidences of the three evaluated STIs were lower with doxycycline than with standard care; in the PrEP cohort, the relative risks were 0.45 (95% CI, 0.32 to 0.65) for gonorrhea, 0.12 (95% CI, 0.05 to 0.25) for chlamydia, and 0.13 (95% CI, 0.03 to 0.59) for syphilis, and in the PLWH cohort, the relative risks were 0.43 (95% CI, 0.26 to 0.71), 0.26 (95% CI, 0.12 to 0.57), and 0.23 (95% CI, 0.04 to 1.29), respectively. Five grade 3 adverse events and no serious adverse events were attributed to doxycycline. Of the participants with gonorrhea culture available, tetracycline-resistant gonorrhea occurred in 5 of 13 in the doxycycline groups and 2 of 16 in the standard-care groups. CONCLUSIONS: The combined incidence of gonorrhea, chlamydia, and syphilis was lower by two thirds with doxycycline postexposure prophylaxis than with standard care, a finding that supports its use among MSM with recent bacterial STIs. (Funded by the National Institutes of Health; DoxyPEP ClinicalTrials.gov number, NCT03980223.).


Assuntos
Anti-Infecciosos , Doxiciclina , Prevenção Primária , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Feminino , Humanos , Masculino , Infecções por Chlamydia/prevenção & controle , Doxiciclina/administração & dosagem , Doxiciclina/uso terapêutico , Gonorreia/prevenção & controle , Infecções por HIV/prevenção & controle , Homossexualidade Masculina , Profilaxia Pré-Exposição , Infecções Sexualmente Transmissíveis/prevenção & controle , Infecções Sexualmente Transmissíveis/transmissão , Sífilis/epidemiologia , Sífilis/prevenção & controle , Prevenção Primária/métodos , Anti-Infecciosos/administração & dosagem , Anti-Infecciosos/uso terapêutico , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Pessoas Transgênero
2.
Proc Natl Acad Sci U S A ; 120(11): e2218960120, 2023 03 14.
Artigo em Inglês | MEDLINE | ID: mdl-36877848

RESUMO

HIV post-treatment controllers (PTCs) are rare individuals who maintain low levels of viremia after stopping antiretroviral therapy (ART). Understanding the mechanisms of HIV post-treatment control will inform development of strategies aiming at achieving HIV functional cure. In this study, we evaluated 22 PTCs from 8 AIDS Clinical Trials Group (ACTG) analytical treatment interruption (ATI) studies who maintained viral loads ≤400 copies/mL for ≥24 wk. There were no significant differences in demographics or frequency of protective and susceptible human leukocyte antigen (HLA) alleles between PTCs and post-treatment noncontrollers (NCs, n = 37). Unlike NCs, PTCs demonstrated a stable HIV reservoir measured by cell-associated RNA (CA-RNA) and intact proviral DNA assay (IPDA) during analytical treatment interruption (ATI). Immunologically, PTCs demonstrated significantly lower CD4+ and CD8+ T cell activation, lower CD4+ T cell exhaustion, and more robust Gag-specific CD4+ T cell responses and natural killer (NK) cell responses. Sparse partial least squares discriminant analysis (sPLS-DA) identified a set of features enriched in PTCs, including a higher CD4+ T cell% and CD4+/CD8+ ratio, more functional NK cells, and a lower CD4+ T cell exhaustion level. These results provide insights into the key viral reservoir features and immunological profiles for HIV PTCs and have implications for future studies evaluating interventions to achieve an HIV functional cure.


Assuntos
Linfócitos T CD8-Positivos , Infecções por HIV , Humanos , Células Matadoras Naturais , Ativação Linfocitária , RNA , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , Viremia
3.
Clin Infect Dis ; 2024 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-39367871

RESUMO

BACKGROUND: We previously demonstrated at the Ward 86 HIV clinic in San Francisco that long-acting cabotegravir/rilpivirine (LA-CAB/RPV) can rapidly lead to viral suppression (VS) in people with HIV (PWH) with viremia due to adherence challenges. We now evaluate VS durability in this population. METHODS: We conducted a retrospective cohort study of PWH who started LA-CAB/RPV with viremia (HIV RNA viral load [VL]≥50 copies/mL) before December 2022. Our primary outcome was VS (VL<50 copies/mL) with LA-CAB/RPV persistence (not discontinued or late by >14 days) at 48 weeks, using the closest VL to 48+/-8 weeks. We also describe viral failure (VF), defined as <2-log VL decline at 4 weeks or VL≥200 copies/mL after initial VS with emergent CAB- or RPV-associated resistance mutations; and overall 48-week VS including those switched to alternative ART. RESULTS: Fifty nine PWH initiated LA-CAB/RPV with viremia and were included in analysis; 49% had CD4<200 cells/µL and median baseline VL was 42,900 copies/mL (Q1-Q3 5,272-139,038). At 48 weeks, 47 met the primary outcome of VS with LA-CAB/RPV persistence (80%; 95%CI 67-89%). Five had VF with resistance (three with RPV-associated mutations, two with CAB and RPV-associated mutations) and one was lost-to-follow-up. At week 48, two of those with VF were suppressed on alternative regimens (lenacapavir+BIC/TAF/FTC and CAB+lenacapavir). Overall week 48 VS on either LA-CAB/RPV or alternative ART was 92% (54/59). CONCLUSIONS: In PWH initiating LA-CAB/RPV with initial viremia, 48-week VS (<50 copies/mL) was 92%. Long-acting ART can be an important tool for improving VS among patients who face adherence challenges to oral ART.

4.
Clin Infect Dis ; 2024 Jun 02.
Artigo em Inglês | MEDLINE | ID: mdl-38824440

RESUMO

Data on alcohol use and incident Tuberculosis (TB) infection are needed. In adults aged 15+ in rural Uganda (N=49,585), estimated risk of incident TB infection was 29.2% with alcohol use vs. 19.2% without (RR: 1.49; 95%CI: 1.40-1.60). There is potential for interventions to interrupt transmission among people who drink alcohol.

5.
Clin Infect Dis ; 78(6): 1601-1607, 2024 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-38226445

RESUMO

BACKGROUND: Human immunodeficiency virus (HIV) treatment reduces tuberculosis (TB) disease and mortality; however, the population-level impact of universal HIV-test-and-treat interventions on TB infection and transmission remain unclear. METHODS: In a sub-study nested in the SEARCH trial, a community cluster-randomized trial (NCT01864603), we assessed whether a universal HIV-test-and-treat intervention reduced population-level incident TB infection in rural Uganda. Intervention communities received annual, population-level HIV testing and patient-centered linkage. Control communities received population-level HIV testing at baseline and endline. We compared estimated incident TB infection by arms, defined by tuberculin skin test conversion in a cohort of persons aged 5 and older, adjusting for participation and predictors of infection, and accounting for clustering. RESULTS: Of the 32 trial communities, 9 were included, comprising 90 801 participants (43 127 intervention and 47 674 control). One-year cumulative incidence of TB infection was 16% in the intervention and 22% in the control; SEARCH reduced the population-level risk of incident TB infection by 27% (adjusted risk ratio = 0.73; 95% confidence interval [CI]: .57-.92, P = .005). In pre-specified analyses, the effect was largest among children aged 5-11 years and males. CONCLUSIONS: A universal HIV-test-and-treat intervention reduced incident TB infection, a marker of population-level TB transmission. Investments in community-level HIV interventions have broader population-level benefits, including TB reductions.


Assuntos
Infecções por HIV , População Rural , Tuberculose , Humanos , Uganda/epidemiologia , Masculino , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Infecções por HIV/prevenção & controle , Tuberculose/epidemiologia , Tuberculose/prevenção & controle , Tuberculose/transmissão , Tuberculose/diagnóstico , Adulto , Pré-Escolar , Criança , Adulto Jovem , Adolescente , Incidência , Pessoa de Meia-Idade , Teste de HIV , Análise por Conglomerados , Programas de Rastreamento/métodos
6.
Biostatistics ; 24(2): 502-517, 2023 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-34939083

RESUMO

Cluster randomized trials (CRTs) randomly assign an intervention to groups of individuals (e.g., clinics or communities) and measure outcomes on individuals in those groups. While offering many advantages, this experimental design introduces challenges that are only partially addressed by existing analytic approaches. First, outcomes are often missing for some individuals within clusters. Failing to appropriately adjust for differential outcome measurement can result in biased estimates and inference. Second, CRTs often randomize limited numbers of clusters, resulting in chance imbalances on baseline outcome predictors between arms. Failing to adaptively adjust for these imbalances and other predictive covariates can result in efficiency losses. To address these methodological gaps, we propose and evaluate a novel two-stage targeted minimum loss-based estimator to adjust for baseline covariates in a manner that optimizes precision, after controlling for baseline and postbaseline causes of missing outcomes. Finite sample simulations illustrate that our approach can nearly eliminate bias due to differential outcome measurement, while existing CRT estimators yield misleading results and inferences. Application to real data from the SEARCH community randomized trial demonstrates the gains in efficiency afforded through adaptive adjustment for baseline covariates, after controlling for missingness on individual-level outcomes.


Assuntos
Avaliação de Resultados em Cuidados de Saúde , Projetos de Pesquisa , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Probabilidade , Viés , Análise por Conglomerados , Simulação por Computador
7.
BMC Health Serv Res ; 24(1): 313, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38454501

RESUMO

BACKGROUND: Isoniazid preventive therapy (IPT) works to prevent tuberculosis (TB) among people living with HIV (PLHIV), but uptake remains low in Sub-Saharan Africa. In this analysis, we sought to identify barriers mid-level managers face in scaling IPT in Uganda and the mechanisms by which the SEARCH-IPT trial intervention influenced their abilities to increase IPT uptake. METHODS: The SEARCH-IPT study was a cluster randomized trial conducted from 2017-2021. The SEARCH-IPT intervention created collaborative groups of district health managers, facilitated by local HIV and TB experts, and provided leadership and management training over 3-years to increase IPT uptake in Uganda. In this qualitative study we analyzed transcripts of annual Focus Group Discussions and Key Informant Interviews, from a subset of SEARCH-IPT participants from intervention and control groups, and participant observation field notes. We conducted the analysis using inductive and deductive coding (with a priori codes and those derived from analysis) and a framework approach for data synthesis. RESULTS: When discussing factors that enabled positive outcomes, intervention managers described feeling ownership over interventions, supported by the leadership and management training they received in the SEARCH-IPT study, and the importance of collaboration between districts facilitated by the intervention. In contrast, when discussing factors that impeded their ability to make changes, intervention and control managers described external funders setting agendas, lack of collaboration in meetings that operated with more of a 'top-down' approach, inadequate supplies and staffing, and lack of motivation among frontline providers. Intervention group managers mentioned redistribution of available stock within districts as well as between districts, reflecting efforts of the SEARCH-IPT intervention to promote between-district collaboration, whereas control group managers mentioned redistribution within their districts to maximize the use of available IPT stock. CONCLUSIONS: In Uganda, mid-level managers' perceptions of barriers to scaling IPT included limited power to set agendas and control over funding, inadequate resources, lack of motivation of frontline providers, and lack of political prioritization. We found that the SEARCH-IPT intervention supported managers to design and implement strategies to improve IPT uptake and collaborate between districts. This may have contributed to the overall intervention effect in increasing the uptake of IPT among PLHIV compared to standard practice. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03315962 , Registered 20 October 2017.


Assuntos
Infecções por HIV , Tuberculose , Humanos , Antituberculosos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/prevenção & controle , Isoniazida/uso terapêutico , Pesquisa Qualitativa , Ensaios Clínicos Controlados Aleatórios como Assunto , Tuberculose/prevenção & controle , Tuberculose/tratamento farmacológico , Uganda
8.
Ann Intern Med ; 176(7): 969-974, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37399555

RESUMO

BACKGROUND: Intramuscular cabotegravir (CAB) and rilpivirine (RPV) is the only long-acting antiretroviral therapy (LA-ART) regimen approved for people with HIV (PWH). Long-acting ART holds promise for improving outcomes among populations with barriers to adherence but is only approved for PWH who have virologic suppression with use of oral ART before initiating injectables. OBJECTIVE: To examine LA-ART in a population of PWH that includes those with viremia. DESIGN: Observational cohort study. SETTING: Urban academic safety-net HIV clinic. PATIENTS: Publicly insured adults living with HIV with and without viral suppression, high rates of unstable housing, mental illness, and substance use. INTERVENTION: Demonstration project of long-acting injectable CAB-RPV. MEASUREMENTS: Descriptive statistics summarizing cohort outcomes to date, based on pharmacy team logs and electronic medical record data. RESULTS: Between June 2021 and November 2022, 133 PWH at the Ward 86 HIV Clinic were started on LA-ART, 76 of whom had virologic suppression while using oral ART and 57 of whom had viremia. The median age was 46 years (IQR, 25 to 68 years); 117 (88%) were cisgender men, 83 (62%) had non-White race, 56 (42%) were experiencing unstable housing or homelessness, and 45 (34%) had substance use. Among those with virologic suppression, 100% (95% CI, 94% to 100%) maintained suppression. Among PWH with viremia, at a median of 33 days, 54 of 57 had viral suppression, 1 showed the expected 2-log10 reduction in HIV RNA level, and 2 experienced early virologic failure. Overall, 97.5% (CI, 89.1% to 99.8%) were projected to achieve virologic suppression by a median of 33 weeks. The current virologic failure rate of 1.5% in the cohort is similar to that across registrational clinical trials at 48 weeks. LIMITATION: Single-site study. CONCLUSION: This project demonstrates the ability of LA-ART to achieve virologic suppression among PWH, including those with viremia and challenges to adherence. Further data on the ability of LA-ART to achieve viral suppression in people with barriers to adherence are needed. PRIMARY FUNDING SOURCE: National Institutes of Health, City and County of San Francisco, and Health Resources and Services Administration.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adulto , Masculino , Humanos , Pessoa de Meia-Idade , Fármacos Anti-HIV/uso terapêutico , Viremia/tratamento farmacológico , Infecções por HIV/epidemiologia , Rilpivirina/uso terapêutico , Estudos de Coortes , Carga Viral
9.
Clin Infect Dis ; 76(3): e645-e651, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35913500

RESUMO

BACKGROUND: Long-acting injectable antiretroviral therapy (LAI-ART) is approved for treatment-naive or experienced people with human immunodeficiency virus (HIV; PWH) based on trials that only included participants with viral suppression. We performed the first LAI-ART demonstration project to include PWH unable to achieve or maintain viral suppression due to challenges adhering to oral ART. METHODS: Ward 86 is a large HIV clinic in San Francisco that serves publicly insured and underinsured patients. We started patients on LAI-ART via a structured process of provider referral, multidisciplinary review (MD, RN, pharmacist), and monitoring for on-time injections. Inclusion criteria were willingness to receive monthly injections and a reliable contact method. RESULTS: Between June 2021 and April 2022, 51 patients initiated LAI-ART, with 39 receiving at least 2 follow-up injections by database closure (median age, 46 years; 90% cisgender men, 61% non-White, 41% marginally housed, 54% currently using stimulants). Of 24 patients who initiated injections with viral suppression (median CD4 cell count, 706 cells/mm3), 100% (95% confidence interval [CI], 86%-100%) maintained viral suppression. Of 15 patients who initiated injections with detectable viremia (median CD4 cell count, 99 cells/mm3; mean log10 viral load, 4.67; standard deviation, 1.16), 12 (80%; 95% CI, 55%-93%) achieved viral suppression, and the other 3 had a 2-log viral load decline by a median of 22 days. CONCLUSIONS: This small demonstration project of LAI-ART in a diverse group of patients with high levels of substance use and marginal housing demonstrated promising early treatment outcomes, including in those with detectable viremia due to adherence challenges. More data on LAI-ART in hard-to-reach populations are needed.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Masculino , Humanos , Pessoa de Meia-Idade , HIV , Fármacos Anti-HIV/uso terapêutico , Viremia/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Resultado do Tratamento , Contagem de Linfócito CD4 , Carga Viral
10.
Clin Infect Dis ; 76(4): 600-608, 2023 02 18.
Artigo em Inglês | MEDLINE | ID: mdl-36219705

RESUMO

BACKGROUND: Malaria in pregnancy has been associated with worse cognitive outcomes in children, but its association with behavioral outcomes and the effectiveness of malaria chemoprevention on child neurodevelopment are not well characterized. METHODS: To determine if more effective malaria chemoprevention in mothers and their children results in better neurodevelopment, 305 pregnant women were randomly assigned to 3 doses of sulfadoxine-pyrimethamine, 3 doses of dihydroartemisinin-piperaquine (DP), or monthly DP during pregnancy, and their 293 children were assigned to DP every 3 months or monthly DP from 2 to 24 months of age. Cognition, language, and motor function were assessed at 12, 24. and 36 months of age, and attention, memory, behavior, and executive function were assessed at 24 and 36 months of age. RESULTS: Children of mothers with versus without malaria in pregnancy had worse scores on cognitive, behavioral, and executive function outcomes at 24 months. Clinical malaria in children within the first 12 months was similarly associated with poorer scores in behavior and executive function at 24 months, language at 24 and 36 months, and motor function scores at 36 months. However, more effective malaria chemoprevention in the mothers and children was not associated with better outcomes. CONCLUSIONS: Malaria in pregnancy was associated with worse cognitive, behavioral, and executive function scores in affected children, but more effective malaria chemoprevention measures did not result in better outcomes. Malaria chemoprevention prior to and early in gestation and with even higher efficacy in mothers and children may be required to prevent neurodevelopmental impairment in children. Clinical Trials Registration. NCT02557425.


Assuntos
Antimaláricos , Artemisininas , Malária , Quinolinas , Criança , Feminino , Gravidez , Humanos , Antimaláricos/uso terapêutico , Malária/tratamento farmacológico , Pirimetamina/uso terapêutico , Sulfadoxina/uso terapêutico , Artemisininas/uso terapêutico , Combinação de Medicamentos , Quinolinas/uso terapêutico , Quimioprevenção/métodos
11.
Clin Infect Dis ; 76(3): e902-e909, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-35982635

RESUMO

BACKGROUND: Social network analysis can elucidate tuberculosis transmission dynamics outside the home and may inform novel network-based case-finding strategies. METHODS: We assessed the association between social network characteristics and prevalent tuberculosis infection among residents (aged ≥15 years) of 9 rural communities in Eastern Uganda. Social contacts named during a census were used to create community-specific nonhousehold social networks. We evaluated whether social network structure and characteristics of first-degree contacts (sex, human immunodeficiency virus [HIV] status, tuberculosis infection) were associated with revalent tuberculosis infection (positive tuberculin skin test [TST] result) after adjusting for individual-level risk factors (age, sex, HIV status, tuberculosis contact, wealth, occupation, and Bacillus Calmette-Guérin [BCG] vaccination) with targeted maximum likelihood estimation. RESULTS: Among 3 335 residents sampled for TST, 32% had a positive TST results and 4% reported a tuberculosis contact. The social network contained 15 328 first-degree contacts. Persons with the most network centrality (top 10%) (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.1]) and the most (top 10%) male contacts (1.5 [1.3-1.9]) had a higher risk of prevalent tuberculosis, than those in the remaining 90%. People with ≥1 contact with HIV (adjusted risk ratio, 1.3 [95% confidence interval, 1.1-1.6]) and ≥2 contacts with tuberculosis infection were more likely to have tuberculosis themselves (2.6 [ 95% confidence interval: 2.2-2.9]). CONCLUSIONS: Social networks with higher centrality, more men, contacts with HIV, and tuberculosis infection were positively associated with tuberculosis infection. Tuberculosis transmission within measurable social networks may explain prevalent tuberculosis not associated with a household contact. Further study on network-informed tuberculosis case finding interventions is warranted.


Assuntos
Infecções por HIV , Tuberculose Latente , Mycobacterium tuberculosis , Tuberculose , Adulto , Masculino , Humanos , Feminino , Uganda/epidemiologia , População Rural , Teste Tuberculínico , Tuberculose/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia
12.
AIDS Care ; 35(1): 41-47, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36473203

RESUMO

The uptake of HIV prevention services is lower among youth than adults in sub-Saharan Africa. Existing youth livelihood trainings offer a potential entry point to HIV prevention services. We determined feasibility and preliminary effectiveness of integrating HIV prevention into youth clubs implementing an empowerment and livelihood for adolescents (ELA) intervention in rural Uganda. Staff conducted community mobilization for youth (15-24 years) over one month. Clubs met (3×/week) over six months, with local peer mentors trained to teach life-skills and sexual/reproductive health education. We integrated mentor-led education on HIV prevention, including pre- and post-exposure prophylaxis (PrEP/PEP). Clubs offered on-site HIV testing, a field trip to a local clinic and PrEP referrals after one month and six months. Surveys were conducted at baseline and six months. Forty-two participants (24 adolescent girls/young women (AGYW) and 18 adolescent boys/young men (ABYM)) joined the clubs. At baseline, no participants accepted referral for PrEP, whereas 5/18 (28%) sexually active, HIV-negative AGYW requested PrEP referral at follow-up. One ABYM requested PEP referral. Integration of HIV prevention services into an established ELA curriculum at mentor-led youth clubs in rural Uganda was feasible. PrEP uptake increased among sexually active AGYW. Evaluation of this approach for HIV prevention among youth merits further study.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Profilaxia Pré-Exposição , Adulto , Masculino , Humanos , Adolescente , Feminino , Infecções por HIV/prevenção & controle , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Uganda , Estudos de Viabilidade , Homens
13.
AIDS Care ; 35(1): 95-105, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35578398

RESUMO

Youth living with HIV in sub-Saharan Africa have poor HIV care outcomes. We determined the association of recent significant life-events with HIV antiretroviral treatment (ART) initiation and HIV viral suppression in youth aged 15-24 years living with HIV in rural Kenya and Uganda. This was a cross-sectional analysis of 995 youth enrolled in the SEARCH Youth study. At baseline, providers assessed recent (within 6 months) life-events, defined as changes in schooling/employment, residence, partnerships, sickness, incarceration status, family strife or death, and birth/pregnancy, self-reported alcohol use, being a parent, and HIV-status disclosure. We examined the frequencies of events and their association with ART status and HIV viral suppression (<400 copies/ul). Recent significant life-events were prevalent (57.7%). Having >2 significant life-events (aOR = 0.61, 95% CI:0.45-0.85) and consuming alcohol (aOR = 0.61, 95% CI:0.43-0.87) were associated with a lower odds of HIV viral suppression, while disclosure of HIV-status to partner (aOR = 2.39, 95% CI:1.6-3.5) or to family (aOR = 1.86, 95% CI:1.3-2.7), being a parent (aOR = 1.8, 95% CI:1.2-2.5), and being single (aOR = 1.6, 95% CI:1.3-2.1) had a higher odds. This suggest that two or more recent life-events and alcohol use are key barriers to ART initiation and achievement of viral suppression among youth living with HIV in rural East Africa.Trial registration: ClinicalTrials.gov identifier: NCT03848728..


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Adolescente , Feminino , Humanos , Gravidez , Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Estudos Transversais , Infecções por HIV/tratamento farmacológico , Quênia/epidemiologia , Uganda/epidemiologia , Carga Viral
14.
Ann Intern Med ; 175(5): 682-690, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35286144

RESUMO

BACKGROUND: SARS-CoV-2 rapid antigen tests are an important public health tool. OBJECTIVE: To evaluate field performance of the BinaxNOW rapid antigen test (Abbott) compared with reverse transcriptase polymerase chain reaction (RT-PCR) for detecting infection with the Omicron variant of SARS-CoV-2. DESIGN: Cross-sectional surveillance study. SETTING: Free, walk-up, outdoor, urban community testing and vaccine site led by Unidos en Salud, serving a predominantly Latinx community highly impacted by COVID-19. PARTICIPANTS: Persons seeking COVID-19 testing in January 2022. MEASUREMENTS: Simultaneous BinaxNOW and RT-PCR from nasal, cheek, and throat swabs, including cycle threshold (Ct) measures; a lower Ct value is a surrogate for higher amounts of virus. RESULTS: Among 731 persons tested with nasal swabs, there were 296 (40.5%) positive results on RT-PCR; 98.9% were the Omicron variant. BinaxNOW detected 95.2% (95% CI, 91% to 98%) of persons who tested positive on RT-PCR with a Ct value below 30, 82.1% (CI, 77% to 87%) of those who tested positive on RT-PCR with a Ct value below 35, and 65.2% (CI, 60% to 71%) of all who were positive on RT-PCR. Among 75 persons with simultaneous nasal and cheek swabs, BinaxNOW using a cheek swab failed to detect 91% (20 of 22) of specimens that were positive on BinaxNOW with a nasal swab. Among persons with simultaneous nasal and throat swabs who were positive on RT-PCR with a Ct value below 30, 42 of 49 (85.7%) were detected by nasal BinaxNOW, 23 of 49 (46.9%) by throat BinaxNOW, and 44 of 49 (89.8%) by either. LIMITATION: Participants were a cross-sectional sample from a community-based sentinel surveillance site, precluding study of viral or symptom dynamics. CONCLUSION: BinaxNOW detected persons with high SARS-CoV-2 levels during the Omicron surge, enabling rapid responses to positive test results. Cheek or throat swabs should not replace nasal swabs. As currently recommended, high-risk persons with an initial negative BinaxNOW result should have repeated testing. PRIMARY FUNDING SOURCE: University of California, San Francisco.


Assuntos
COVID-19 , SARS-CoV-2 , Antígenos Virais/análise , COVID-19/diagnóstico , Teste para COVID-19 , Estudos Transversais , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa , SARS-CoV-2/genética , Sensibilidade e Especificidade
15.
J Infect Dis ; 226(Suppl 3): S353-S362, 2022 10 07.
Artigo em Inglês | MEDLINE | ID: mdl-35759251

RESUMO

BACKGROUND: People with HIV experiencing homelessness have low rates of viral suppression, driven by sociostructural barriers and traditional care system limitations. Informed by the capability-opportunity-motivation-behavior (COM-B) model and patient preference research, we developed POP-UP, an integrated drop-in (nonappointment-based) HIV clinic with wrap-around services for persons with housing instability and viral nonsuppression in San Francisco. METHODS: We report HIV viral suppression (VS; <200 copies/mL), care engagement, and mortality at 12 months postenrollment. We used logistic regression to determine participant characteristics associated with VS. RESULTS: We enrolled 112 patients with viral nonsuppression and housing instability: 52% experiencing street-homelessness, 100% with a substance use disorder, and 70% with mental health diagnoses. At 12 months postenrollment, 70% had ≥1 visit each 4-month period, although 59% had a 90-day care gap; 44% had VS, 24% had viral nonsuppression, 23% missing, and 9% died (6 overdose, 2 AIDS-associated, 2 other). No baseline characteristics were associated with VS. CONCLUSIONS: The POP-UP low-barrier HIV care model successfully reached and retained some of our clinic's highest-risk patients. It was associated with VS improvement from 0% at baseline to 44% at 12 months among people with housing instability. Care gaps and high mortality from overdose remain major challenges to achieving optimal HIV treatment outcomes in this population.


Assuntos
Overdose de Drogas , Infecções por HIV , Pessoas Mal Alojadas , Transtornos Relacionados ao Uso de Substâncias , Infecções por HIV/complicações , Pessoas Mal Alojadas/psicologia , Humanos , Atenção Primária à Saúde , Transtornos Relacionados ao Uso de Substâncias/complicações , Resultado do Tratamento
16.
J Infect Dis ; 225(11): 1909-1914, 2022 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-34979030

RESUMO

The wide spectrum of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants with phenotypes impacting transmission and antibody sensitivity necessitates investigation of immune responses to different spike protein versions. Here, we compare neutralization of variants of concern, including B.1.617.2 (delta) and B.1.1.529 (omicron), in sera from individuals exposed to variant infection, vaccination, or both. We demonstrate that neutralizing antibody responses are strongest against variants sharing certain spike mutations with the immunizing exposure, and exposure to multiple spike variants increases breadth of variant cross-neutralization. These findings contribute to understanding relationships between exposures and antibody responses and may inform booster vaccination strategies.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Formação de Anticorpos , Humanos , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética
17.
Clin Infect Dis ; 75(1): e303-e306, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35037050

RESUMO

While SARS-CoV-2 vaccines prevent severe disease effectively, postvaccination "breakthrough" COVID-19 infections and transmission among vaccinated individuals remain ongoing concerns. We present an in-depth characterization of transmission and immunity among vaccinated individuals in a household, revealing complex dynamics and unappreciated comorbidities, including autoimmunity to type 1 interferon in the presumptive index case.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Imunidade
18.
Clin Infect Dis ; 75(1): e947-e954, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-35245934

RESUMO

BACKGROUND: After coronavirus disease 2019 (COVID-19) shelter-in-place (SIP) orders, viral suppression (VS) rates initially decreased within a safety-net human immunodeficiency virus (HIV) clinic in San Francisco, particularly among people living with HIV (PLWH) who are experiencing homelessness. We sought to determine if proactive outreach to provide social services, scaling up of in-person visits, and expansion of housing programs could reverse this decline. METHODS: We assessed VS 24 months before and 13 months after SIP using mixed-effects logistic regression followed by interrupted time series (ITS) analysis to examine changes in the rate of VS per month. Loss to follow-up (LTFU) was assessed via active clinic tracing. RESULTS: Data from 1816 patients were included; the median age was 51 years, 12% were female, and 14% were experiencing unstable housing/homelessness. The adjusted odds of VS increased 1.34 fold following institution of the multicomponent strategies (95% confidence interval [CI], 1.21-1.46). In the ITS analysis, the odds of VS continuously increased 1.05 fold per month over the post-intervention period (95% CI, 1.01-1.08). Among PLWH who previously experienced homelessness and successfully received housing support, the odds of VS were 1.94-fold higher (95% CI, 1.05-3.59). The 1-year LTFU rate was 2.8 per 100 person-years (95% CI, 2.2-3.5). CONCLUSIONS: The VS rate increased following institution of the multicomponent strategies, with a lower LFTU rate compared with prior years. Maintaining in-person care for underserved patients, with flexible telemedicine options, along with provision of social services and permanent expansion of housing programs, will be needed to support VS among underserved populations during the COVID-19 pandemic.


Assuntos
COVID-19 , Infecções por HIV , Pessoas Mal Alojadas , Feminino , HIV , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Análise de Séries Temporais Interrompida , Masculino , Pessoa de Meia-Idade , Pandemias
19.
Clin Infect Dis ; 74(1): 32-39, 2022 01 07.
Artigo em Inglês | MEDLINE | ID: mdl-33788923

RESUMO

BACKGROUND: Sequencing of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral genome from patient samples is an important epidemiological tool for monitoring and responding to the pandemic, including the emergence of new mutations in specific communities. METHODS: SARS-CoV-2 genomic sequences were generated from positive samples collected, along with epidemiological metadata, at a walk-up, rapid testing site in the Mission District of San Francisco, California during 22 November to 1 December, 2020, and 10-29 January 2021. Secondary household attack rates and mean sample viral load were estimated and compared across observed variants. RESULTS: A total of 12 124 tests were performed yielding 1099 positives. From these, 928 high-quality genomes were generated. Certain viral lineages bearing spike mutations, defined in part by L452R, S13I, and W152C, comprised 54.4% of the total sequences from January, compared to 15.7% in November. Household contacts exposed to the "California" or "West Coast" variants (B.1.427 and B.1.429) were at higher risk of infection compared to household contacts exposed to lineages lacking these variants (0.36 vs 0.29, risk ratio [RR] = 1.28; 95% confidence interval [CI]: 1.00-1.64). The reproductive number was estimated to be modestly higher than other lineages spreading in California during the second half of 2020. Viral loads were similar among persons infected with West Coast versus non-West Coast strains, as was the proportion of individuals with symptoms (60.9% vs 64.3%). CONCLUSIONS: The increase in prevalence, relative household attack rates, and reproductive number are consistent with a modest transmissibility increase of the West Coast variants. Summary: We observed a growing prevalence and modestly elevated attack rate for "West Coast" severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants in a community testing setting in San Francisco during January 2021, suggesting its modestly higher transmissibility.


Assuntos
COVID-19 , SARS-CoV-2 , Genômica , Humanos , Incidência , São Francisco/epidemiologia
20.
N Engl J Med ; 381(3): 219-229, 2019 07 18.
Artigo em Inglês | MEDLINE | ID: mdl-31314966

RESUMO

BACKGROUND: Universal antiretroviral therapy (ART) with annual population testing and a multidisease, patient-centered strategy could reduce new human immunodeficiency virus (HIV) infections and improve community health. METHODS: We randomly assigned 32 rural communities in Uganda and Kenya to baseline HIV and multidisease testing and national guideline-restricted ART (control group) or to baseline testing plus annual testing, eligibility for universal ART, and patient-centered care (intervention group). The primary end point was the cumulative incidence of HIV infection at 3 years. Secondary end points included viral suppression, death, tuberculosis, hypertension control, and the change in the annual incidence of HIV infection (which was evaluated in the intervention group only). RESULTS: A total of 150,395 persons were included in the analyses. Population-level viral suppression among 15,399 HIV-infected persons was 42% at baseline and was higher in the intervention group than in the control group at 3 years (79% vs. 68%; relative prevalence, 1.15; 95% confidence interval [CI], 1.11 to 1.20). The annual incidence of HIV infection in the intervention group decreased by 32% over 3 years (from 0.43 to 0.31 cases per 100 person-years; relative rate, 0.68; 95% CI, 0.56 to 0.84). However, the 3-year cumulative incidence (704 incident HIV infections) did not differ significantly between the intervention group and the control group (0.77% and 0.81%, respectively; relative risk, 0.95; 95% CI, 0.77 to 1.17). Among HIV-infected persons, the risk of death by year 3 was 3% in the intervention group and 4% in the control group (0.99 vs. 1.29 deaths per 100 person-years; relative risk, 0.77; 95% CI, 0.64 to 0.93). The risk of HIV-associated tuberculosis or death by year 3 among HIV-infected persons was 4% in the intervention group and 5% in the control group (1.19 vs. 1.50 events per 100 person-years; relative risk, 0.79; 95% CI, 0.67 to 0.94). At 3 years, 47% of adults with hypertension in the intervention group and 37% in the control group had hypertension control (relative prevalence, 1.26; 95% CI, 1.15 to 1.39). CONCLUSIONS: Universal HIV treatment did not result in a significantly lower incidence of HIV infection than standard care, probably owing to the availability of comprehensive baseline HIV testing and the rapid expansion of ART eligibility in the control group. (Funded by the National Institutes of Health and others; SEARCH ClinicalTrials.gov number, NCT01864603.).


Assuntos
Antirretrovirais/uso terapêutico , Serviços de Saúde Comunitária , Infecções por HIV/tratamento farmacológico , Administração Massiva de Medicamentos , Programas de Rastreamento , Infecções Oportunistas Relacionadas com a AIDS/diagnóstico , Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , Adolescente , Adulto , Feminino , Infecções por HIV/diagnóstico , Infecções por HIV/epidemiologia , Infecções por HIV/mortalidade , Humanos , Incidência , Quênia/epidemiologia , Masculino , Pessoa de Meia-Idade , Assistência Centrada no Paciente , Prevalência , Fatores Socioeconômicos , Tuberculose/diagnóstico , Tuberculose/epidemiologia , Uganda/epidemiologia , Carga Viral , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA