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1.
Biostatistics ; 25(2): 323-335, 2024 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-37475638

RESUMO

The rich longitudinal individual level data available from electronic health records (EHRs) can be used to examine treatment effect heterogeneity. However, estimating treatment effects using EHR data poses several challenges, including time-varying confounding, repeated and temporally non-aligned measurements of covariates, treatment assignments and outcomes, and loss-to-follow-up due to dropout. Here, we develop the subgroup discovery for longitudinal data algorithm, a tree-based algorithm for discovering subgroups with heterogeneous treatment effects using longitudinal data by combining the generalized interaction tree algorithm, a general data-driven method for subgroup discovery, with longitudinal targeted maximum likelihood estimation. We apply the algorithm to EHR data to discover subgroups of people living with human immunodeficiency virus who are at higher risk of weight gain when receiving dolutegravir (DTG)-containing antiretroviral therapies (ARTs) versus when receiving non-DTG-containing ARTs.


Assuntos
Registros Eletrônicos de Saúde , Infecções por HIV , Compostos Heterocíclicos com 3 Anéis , Piperazinas , Piridonas , Humanos , Heterogeneidade da Eficácia do Tratamento , Oxazinas , Infecções por HIV/tratamento farmacológico
2.
J Infect Dis ; 2024 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-39041648

RESUMO

BACKGROUND: Human immunodeficiency virus type 1 (HIV-1) acquired drug resistance (ADR) compromises antiretroviral therapy (ART). METHODS: We aggregated all HIV-1 protease-reverse transcriptase-integrase sequences over 2004-2021 at the largest HIV center in Rhode Island and evaluated ADR extent, trends, and impact using Stanford Database tools. Trends were measured with Mann-Kendall statistic, and multivariable regressions evaluated resistance predictors. RESULTS: Sequences were available for 914 ART-experienced persons. Overall ADR to any drug decreased from 77% to 49% (-0.66 Mann-Kendall statistic); nucleoside reverse transcriptase inhibitors 65% to 32%, nonnucleoside reverse transcriptase inhibitors 53% to 43%, and protease inhibitors 28% to 7% (2004-2021), and integrase strand transfer inhibitors 16% to 13% (2017-2021). Multiclass resistance decreased from 44% to 12% (2-class) and 12% to 6% (3-class). In 2021, 94% had at least one 3-drug or 2-drug one-pill-once-daily (OPOD) option. Males and those exposed to more ART regimens were more likely to have ≥2-class resistance, and higher regimen exposure was also associated with fewer OPOD options. CONCLUSIONS: Comprehensive analyses within a densely-sampled HIV epidemic over 2004-2021 demonstrated decreasing ADR. Continued ADR monitoring is important to maintain ART success, particularly with rising INSTI use in all lines of therapy and 2-drug and long-acting formulations.

3.
AIDS Behav ; 28(11): 3809-3818, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39126558

RESUMO

Sexually minoritized men (SMM) with HIV who use stimulants experience difficulties achieving and maintaining an undetectable viral load (VL). Home-based VL monitoring could augment HIV care by supporting interim, early identification of detectable VL. We describe implementation challenges associated with a home-collection device for laboratory-based VL testing among SMM with HIV who use stimulants. From March-May 2022, cisgender SMM with HIV reporting moderate-to-severe stimulant use disorder and suboptimal (< 90%) past-month antiretroviral therapy (ART) adherence were recruited via a consent-to-contact participant registry. Eligible men completed teleconference-based informed consent and were mailed a HemaSpot-HD blood collection device (volume capacity 160 µL; lower limit of detection 839 copies/mL) with detailed instructions for home blood self-collection and return shipment. Implementation process measures included estimated blood volume and VL quantification. Among 24 participants, 21 (88%) returned specimens with a median duration of 23 days (range: 10-71 days) between sending devices to participants and receiving specimens. Of these, 13/21 (62%) included enough blood (≥ 40 µL) for confidence in detectable/undetectable results; 10/13 (77%) had detectable VL, with 4/10 (40%) were quantifiable at ≥ 839 copies/mL. The remaining 8/21 had low blood volume (< 40 µL), but 3/8 (38%) still had detectable VL, with 1/3 (33%) quantifiable at ≥ 839 copies/mL. Home blood collection of ≥ 40 µL using HemaSpot-HD was feasible among this high-priority population, with > 50% having a VL detected. However, interim VL monitoring using HemaSpot-HD among those experiencing difficulties with ART adherence may be strengthened by building rapport via teleconferencing and providing detailed instructions to achieve adequate sample volume.


Assuntos
Infecções por HIV , HIV-1 , Carga Viral , Humanos , Masculino , Infecções por HIV/tratamento farmacológico , Adulto , HIV-1/isolamento & purificação , Adesão à Medicação , Coleta de Amostras Sanguíneas/métodos , Pessoa de Meia-Idade , Minorias Sexuais e de Gênero/psicologia , Homossexualidade Masculina/psicologia , Transtornos Relacionados ao Uso de Substâncias
4.
PLoS Med ; 20(9): e1004293, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37738247

RESUMO

• Human immunodeficiency virus (HIV) drug resistance has implications for antiretroviral treatment strategies and for containing the HIV pandemic because the development of HIV drug resistance leads to the requirement for antiretroviral drugs that may be less effective, less well-tolerated, and more expensive than those used in first-line regimens. • HIV drug resistance studies are designed to determine which HIV mutations are selected by antiretroviral drugs and, in turn, how these mutations affect antiretroviral drug susceptibility and response to future antiretroviral treatment regimens. • Such studies collectively form a vital knowledge base essential for monitoring global HIV drug resistance trends, interpreting HIV genotypic tests, and updating HIV treatment guidelines. • Although HIV drug resistance data are collected in many studies, such data are often not publicly shared, prompting the need to recommend best practices to encourage and standardize HIV drug resistance data sharing. • In contrast to other viruses, sharing HIV sequences from phylogenetic studies of transmission dynamics requires additional precautions as HIV transmission is criminalized in many countries and regions. • Our recommendations are designed to ensure that the data that contribute to HIV drug resistance knowledge will be available without undue hardship to those publishing HIV drug resistance studies and without risk to people living with HIV.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , HIV-1 , Humanos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Filogenia , HIV-1/genética , Farmacorresistência Viral/genética , Antirretrovirais/uso terapêutico , Mutação , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico
5.
AIDS Behav ; 27(8): 2751-2762, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36723769

RESUMO

Characterizing HIV-related stigma and its impacts are important for interventions toward their elimination. A cross-sectional study was conducted in 2016 to evaluate enacted and internalized stigma among adult people living with HIV (PLWH) across four cities in Myanmar using the India Stigma Index questionnaire. Multivariable regression analyses were performed to determine differences in measured enacted and internalized stigma outcomes. Among 1,006 participants, 89% reported any stigma indicator, 47% enacted stigma, and 87% internalized stigma. In regression analysis, city and duration of illness were associated with higher enacted stigma, and younger age was associated with higher internalized stigma. Those with HIV duration > 7.4 years had mean enacted stigma nearly 2 units higher than the overall mean. Internalized stigma increased with duration of illness and leveled off at 5 years. PLWH from smaller cities experienced lower stigma. In Myanmar, nearly 90% of PLWH experience stigma, results that reflect a unique transition point.


Assuntos
Infecções por HIV , Adulto , Humanos , Estudos Transversais , Mianmar , Infecções por HIV/epidemiologia , Estigma Social , Cidades
6.
AIDS Care ; 34(6): 762-770, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-33749465

RESUMO

In Myanmar, an Asian country with one of the highest HIV-1 prevalence rates, counseling prior to initiating antiretroviral therapy (ART) is standard care, either by a healthcare worker (standard counselor, SC) or trained counselor who is also living with HIV (peer counselor, PC). PC is commonly utilized in Myanmar and other resource-limited settings. However, its benefit over SC is unclear. We conducted a cross-sectional survey of people living with HIV (PLWH), who completed either only PC or only SC before treatment initiation across four cities in Myanmar. Participants were evaluated for HIV knowledge, stigma, antiretroviral adherence, barriers to care, social support satisfaction and attitudes regarding both counseling processes. Bivariate analyses and multivariable mixed effects modeling were conducted to compare differences in these measures among PC and SC participants. Among 1006 participants (49% PC; 51% SC), 52% were females and median age was 37 years in those receiving PC and 40 years in those receiving SC. More than 70% of participants in both groups achieved up to grade school education. The average duration since HIV diagnosis was 4.6 years for PC and 5.7 years for SC participants. HIV knowledge and attitudes regarding counseling were good in both groups and more PC participants credited their HIV counselor for knowledge (75% vs 63%, p < 0.001). Compared to SC, PC participants had lower enacted stigma (Incidence Rate Ratio (IRR) 0.75, Confidence Interval (CI) [0.65, 0.86]), mean internalized stigma (-0.24, CI [-0.34, -0.14]), and risk of antiretroviral therapy non-adherence (Odds Ratio 0.59, CI [0.40, 0.88]), while reporting higher levels of barriers to care (9.63, CI [8.20, 11.75]). Our findings demonstrate potential benefits of PC compared to SC, and support the utilization of PC to enhance HIV health outcomes within the unique societal and geographical context of Myanmar, and possibly beyond.


Assuntos
Infecções por HIV , Adulto , Antirretrovirais/uso terapêutico , Aconselhamento , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Adesão à Medicação/psicologia , Mianmar
7.
BMC Public Health ; 22(1): 1122, 2022 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-35658924

RESUMO

INTRODUCTION: Adolescents living with HIV (ALHIV, ages 10-19) experience complex barriers to care engagement. Challenges surrounding HIV status disclosure or non-disclosure to adolescents may contribute to adolescent disengagement from HIV care or non-adherence to ART. We performed a qualitative study to investigate the contribution of disclosure challenges to adolescent disengagement from HIV care. METHODS: This was a qualitative study performed with disengaged ALHIV and their caregivers, and with healthcare workers (HCW) in the Academic Model Providing Access to Healthcare (AMPATH) program in western Kenya. Inclusion criteria for ALHIV were ≥1 visit within the 18 months prior to data collection at one of two clinical sites and nonattendance ≥60 days following their last scheduled appointment. HCW were recruited from 10 clinics. Analysis was conducted by multiple independent coders, and narratives of disclosure and care disengagement were closely interrogated. Overarching themes were elucidated and summarized. RESULTS: Interviews were conducted with 42 disengaged ALHIV, 32 caregivers, and 28 HCW. ALHIV were average age 17.0 (range 12.9-20.9), and 95% indicated awareness of their HIV diagnosis. Issues surrounding disclosure to ALHIV presented important barriers to HIV care engagement. Themes centered on delays in HIV status disclosure; hesitancy and reluctance among caregivers to disclose; struggles for adolescents to cope with feelings of having been deceived prior to full disclosure; pervasive HIV stigma internalized in school and community settings prior to disclosure; and inadequate and unstructured support after disclosure, including for adolescent mental health burdens and for adolescent-caregiver relationships and communication. Both HCW and caregivers described feeling inadequately prepared to optimally handle disclosure and to manage challenges that may arise after disclosure. CONCLUSIONS: Complex challenges surrounding HIV status disclosure to adolescents contribute to care disengagement. There is need to enhance training and resources for HCW, and to empower caregivers to support children and adolescents before, during, and after HIV status disclosure. This should include counseling caregivers on how to provide children with developmentally-appropriate and accurate information about their health from an early age, and to support adolescent-caregiver communication and relationships. Optimally integrating peer support can further promote ALHIV wellbeing and retention in care.


Assuntos
Revelação , Infecções por HIV , Adolescente , Adulto , Cuidadores , Criança , Infecções por HIV/diagnóstico , Infecções por HIV/psicologia , Infecções por HIV/terapia , Humanos , Quênia , Pesquisa Qualitativa , Estigma Social , Adulto Jovem
8.
Bioinformatics ; 35(12): 2029-2035, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-30407489

RESUMO

MOTIVATION: Next-generation deep sequencing of viral genomes, particularly on the Illumina platform, is increasingly applied in HIV research. Yet, there is no standard protocol or method used by the research community to account for measurement errors that arise during sample preparation and sequencing. Correctly calling high and low-frequency variants while controlling for erroneous variants is an important precursor to downstream interpretation, such as studying the emergence of HIV drug-resistance mutations, which in turn has clinical applications and can improve patient care. RESULTS: We developed a new variant-calling pipeline, hivmmer, for Illumina sequences from HIV viral genomes. First, we validated hivmmer by comparing it to other variant-calling pipelines on real HIV plasmid datasets. We found that hivmmer achieves a lower rate of erroneous variants, and that all methods agree on the frequency of correctly called variants. Next, we compared the methods on an HIV plasmid dataset that was sequenced using Primer ID, an amplicon-tagging protocol, which is designed to reduce errors and amplification bias during library preparation. We show that the Primer ID consensus exhibits fewer erroneous variants compared to the variant-calling pipelines, and that hivmmer more closely approaches this low error rate compared to the other pipelines. The frequency estimates from the Primer ID consensus do not differ significantly from those of the variant-calling pipelines. AVAILABILITY AND IMPLEMENTATION: hivmmer is freely available for non-commercial use from https://github.com/kantorlab/hivmmer. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Assuntos
Infecções por HIV , Sequenciamento de Nucleotídeos em Larga Escala , Genoma Viral , Humanos , Mutação
9.
Stat Med ; 38(11): 2002-2012, 2019 05 20.
Artigo em Inglês | MEDLINE | ID: mdl-30609090

RESUMO

Binary classification rules based on covariates typically depend on simple loss functions such as zero-one misclassification. Some cases may require more complex loss functions. For example, individual-level monitoring of HIV-infected individuals on antiretroviral therapy requires periodic assessment of treatment failure, defined as having a viral load (VL) value above a certain threshold. In some resource limited settings, VL tests may be limited by cost or technology, and diagnoses are based on other clinical markers. Depending on scenario, higher premium may be placed on avoiding false-positives, which brings greater cost and reduced treatment options. Here, the optimal rule is determined by minimizing a weighted misclassification loss/risk. We propose a method for finding and cross-validating optimal binary classification rules under weighted misclassification loss. We focus on rules comprising a prediction score and an associated threshold, where the score is derived using an ensemble learner. Simulations and examples show that our method, which derives the score and threshold jointly, more accurately estimates overall risk and has better operating characteristics compared with methods that derive the score first and the cutoff conditionally on the score especially for finite samples.


Assuntos
Biomarcadores/análise , Modelos Estatísticos , Algoritmos , Neoplasias da Mama , Contagem de Linfócito CD4 , Infecções por HIV , Humanos , Reprodutibilidade dos Testes , Falha de Tratamento , Carga Viral/classificação
10.
J Antimicrob Chemother ; 73(8): 2152-2161, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29800305

RESUMO

Objectives: Examine HIV-1 plasma viral load (PVL) and genital tract (GT) viral load (GVL) and drug resistance in India. Methods: At the YRG Centre for AIDS Research and Education, Chennai, we tested: PVL in women on first-line ART for ≥6 months; GVL when PVL >2000 copies/mL; and plasma, genital and proviral reverse transcriptase drug resistance when GVL >2000 copies/mL. Wilcoxon rank-sum and Fisher's exact tests were used to identify failure and resistance associations. Pearson correlations were calculated to evaluate PVL-GVL associations. Inter-compartmental resistance discordance was evaluated using generalized estimating equations. Results: Of 200 women, 37% had detectable (>400 copies/mL) PVL and 31% had PVL >1000 copies/mL. Of women with detectable PVL, 74% had PVL >2000 copies/mL, of which 74% had detectable GVL. Higher PVL was associated with higher GVL. Paired plasma and genital sequences were available for 21 women; mean age of 34 years, median ART duration of 33 months, median CD4 count of 217 cells/mm3, median PVL of 5.4 log10 copies/mL and median GVL of 4.6 log10 copies/mL. Drug resistance was detected in 81%-91% of samples and 67%-76% of samples had dual-class resistance. Complete three-compartment concordance was seen in only 10% of women. GT-proviral discordance was significantly larger than plasma-proviral discordance. GT or proviral mutations discordant from plasma led to clinically relevant resistance in 24% and 30%, respectively. Conclusions: We identified high resistance and high inter-compartmental resistance discordance in Indian women, which might lead to unrecognized resistance transmission and re-emergence compromising treatment outcomes, particularly relevant to countries like India, where sexual HIV transmission is predominant.


Assuntos
Sangue/virologia , Farmacorresistência Viral , Genitália/virologia , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Adolescente , Adulto , Idoso , Feminino , Genótipo , Técnicas de Genotipagem , Transcriptase Reversa do HIV/genética , HIV-1/classificação , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Índia , Pessoa de Meia-Idade , Falha de Tratamento , Carga Viral , Adulto Jovem
11.
J Infect Dis ; 216(suppl_9): S816-S819, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-28968824

RESUMO

In diverse global regions with significant human immunodeficiency virus (HIV) burden, programmatic, cultural, and provider-, patient-, and virus-related factors may result in HIV drug resistance, with global implications. This article reviews such common and unique challenges in Russia, Latin America and the Caribbean, China, and India, to suggest potential solutions.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV/efeitos dos fármacos , Região do Caribe/epidemiologia , China/epidemiologia , Países em Desenvolvimento , Farmacorresistência Viral , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Índia/epidemiologia , América Latina/epidemiologia , Federação Russa/epidemiologia , Carga Viral
12.
J Infect Dis ; 216(suppl_9): S824-S828, 2017 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-29040621

RESUMO

Healthcare delivery has advanced due to the implementation of point-of-care testing, which is often performed within minutes to hours in minimally equipped laboratories or at home. Technologic advances are leading to point-of-care kits that incorporate nucleic acid-based assays, including polymerase chain reaction, isothermal amplification, ligation, and hybridization reactions. As a limited number of single-nucleotide polymorphisms are associated with clinically significant human immunodeficiency virus (HIV) drug resistance, assays to detect these mutations have been developed. Early versions of these assays have been used in research. This review summarizes the principles underlying each assay and discusses strategic needs for their incorporation into the management of HIV infection.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV/efeitos dos fármacos , Testes Imediatos , Farmacorresistência Viral , HIV/genética , Infecções por HIV/virologia , Humanos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
14.
Clin Infect Dis ; 60(9): 1426-35, 2015 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-25637585

RESUMO

BACKGROUND: Drug resistance development in the human immunodeficiency virus (HIV)-infected pediatric population in the United States can impact long-term antiretroviral therapy (ART) efficacy. Limited formularies and adherence constraints in children jeopardize lifelong-needed ART. METHODS: We examined treatment failure, drug resistance, and their correlates in ART-naive and ART-experienced children attending the pediatric HIV clinic in Rhode Island between 1991 and 2012. Pol sequences were obtained for phylogenetic, subtype, and resistance analyses. Associations between selected covariates and virologic failure and resistance were evaluated using generalized additive models and Fisher exact tests. RESULTS: Data were available for all 56 clinic-attending children. At diagnosis, 33% were aged <1 year, 31% aged 1-4 years, and 37% aged ≥ 5 years; 54% were male, 73% black or Hispanic, 55% US-born, 20% refugees, and 64% perinatally infected. Of 44 ART-experienced children, 57% had virologic failure, most never virologically suppressed. Failure was associated with missed appointments (P = .05) and missed doses (P < .01). Of 40 children with available genotypes, 35% were infected with non-B subtypes; 6% of ART-naive children had resistance; and 73% of ART-experienced children had ≥ 1 major mutation: (16% conferring triple-class, 47% dual-class, and 37% single-class resistance). An epidemiologically confirmed resistance transmission from a perinatally infected teenage male to a newly infected teenage female was demonstrated. CONCLUSIONS: We report high HIV type 1 diversity, extensive drug resistance among ART-experienced children, and horizontal transmission of resistance in the Rh ode Island pediatric HIV clinic. As HIV-infected children mature into adulthood, close monitoring of ART, adherence, and diagnosis disclosure are essential to optimize patient care.


Assuntos
Farmacorresistência Viral/genética , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , Adolescente , Assistência Ambulatorial , Terapia Antirretroviral de Alta Atividade , Criança , Pré-Escolar , Feminino , Variação Genética , HIV-1/fisiologia , Humanos , Lactente , Masculino , Mutação , Pediatria , Filogenia , Rhode Island/epidemiologia , Fatores de Tempo , Falha de Tratamento , Carga Viral
15.
Clin Infect Dis ; 60(10): 1541-9, 2015 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-25681380

RESUMO

BACKGROUND: Evaluation of pretreatment HIV genotyping is needed globally to guide treatment programs. We examined the association of pretreatment (baseline) drug resistance and subtype with virologic failure in a multinational, randomized clinical trial that evaluated 3 antiretroviral treatment (ART) regimens and included resource-limited setting sites. METHODS: Pol genotyping was performed in a nested case-cohort study including 270 randomly sampled participants (subcohort), and 218 additional participants failing ART (case group). Failure was defined as confirmed viral load (VL) >1000 copies/mL. Cox proportional hazards models estimated resistance-failure association. RESULTS: In the representative subcohort (261/270 participants with genotypes; 44% women; median age, 35 years; median CD4 cell count, 151 cells/µL; median VL, 5.0 log10 copies/mL; 58% non-B subtypes), baseline resistance occurred in 4.2%, evenly distributed among treatment arms and subtypes. In the subcohort and case groups combined (466/488 participants with genotypes), used to examine the association between resistance and treatment failure, baseline resistance occurred in 7.1% (9.4% with failure, 4.3% without). Baseline resistance was significantly associated with shorter time to virologic failure (hazard ratio [HR], 2.03; P = .035), and after adjusting for sex, treatment arm, sex-treatment arm interaction, pretreatment CD4 cell count, baseline VL, and subtype, was still independently associated (HR, 2.1; P = .05). Compared with subtype B, subtype C infection was associated with higher failure risk (HR, 1.57; 95% confidence interval [CI], 1.04-2.35), whereas non-B/C subtype infection was associated with longer time to failure (HR, 0.47; 95% CI, .22-.98). CONCLUSIONS: In this global clinical trial, pretreatment resistance and HIV-1 subtype were independently associated with virologic failure. Pretreatment genotyping should be considered whenever feasible. CLINICAL TRIALS REGISTRATION: NCT00084136.


Assuntos
Farmacorresistência Viral , Genótipo , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , HIV-1/classificação , HIV-1/efeitos dos fármacos , Adolescente , Adulto , Idoso , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Técnicas de Genotipagem , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como Assunto , Falha de Tratamento , Carga Viral , Adulto Jovem , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
16.
J Antimicrob Chemother ; 70(4): 1146-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25525199

RESUMO

OBJECTIVES: The aim of this study was to prospectively survey transmitted drug resistance (TDR) among recently infected individuals (mostly MSM). METHODS: TDR was determined in prospective annual cohorts of recently HIV-1-infected individuals consecutively recruited from 2008 to 2010. Resistance interpretation was carried out using Stanford Database tools and the WHO surveillance drug resistance mutation list. Kruskal-Wallis and Fisher's exact tests were used to compare demographic and laboratory outcomes. RESULTS: A total of 299 subjects were enrolled, with 89% MSM. Median viral load was significantly higher in 2010 than in 2008 (P=0.004). Of the 284 analysable reverse transcriptase/protease sequences, TDR to any drug was found in 14/284 (4.9%); 4.0% in 2008, 5.9% in 2009 and 5.3% in 2010, with an increasing trend of TDR to NRTIs and NNRTIs from 2008 to 2010 (P=0.07). Good correlation was found between our data and the WHO threshold surveillance method. Only rilpivirine had significantly higher (P<0.05) predicted resistance in 2010 than in 2008 and 2009. CONCLUSIONS: A trend towards an increase in TDR in Thailand where the major epidemic is among MSM was observed, but did not reach the WHO-defined high-level threshold (>15%). Attention to prevent the development and spread of drug resistance is needed.


Assuntos
Farmacorresistência Viral , Infecções por HIV/transmissão , Infecções por HIV/virologia , HIV-1/isolamento & purificação , Adolescente , Adulto , Instituições de Assistência Ambulatorial , Estudos de Coortes , Monitoramento Epidemiológico , Feminino , Genótipo , Infecções por HIV/epidemiologia , HIV-1/classificação , HIV-1/efeitos dos fármacos , HIV-1/genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Prevalência , Estudos Prospectivos , Cruz Vermelha , Tailândia/epidemiologia , Adulto Jovem
17.
J Acquir Immune Defic Syndr ; 97(1): 48-54, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39116331

RESUMO

BACKGROUND: The use of molecular HIV cluster analysis to supplement public health contact tracing has shown promise in addressing HIV outbreaks. However, the potential of HIV cluster analysis as an adjunct to daily, person-by-person HIV prevention efforts remains unknown. We documented lessons learned within a unique public health-academic partnership while guiding workaday HIV prevention efforts with near-real-time molecular cluster analysis. SETTING: A public health-academic partnership in the State of Rhode Island, the United States. METHODS: We recorded perceptions of our team of academicians and public health practitioners that were encountered in an 18-month study evaluating the integration of molecular cluster analysis with HIV contact tracing for public health benefit. The focus was on monthly conferences where molecular clustering of each new statewide diagnosis was discussed to facilitate targeted interventions and on attempted reinterviews of all newly HIV-diagnosed persons statewide whose HIV sequences clustered to increase partner naming. RESULTS: Three main themes emerged: First, multidisciplinary conferences are substantially beneficial for gleaning actionable inferences from integrating molecular cluster analysis and public health data. Second, universal reinterviews were perceived to potentially have negative consequences but may be selectively beneficial. Third, the translation of cluster analysis into public health action is hampered by jurisdictional surveillance boundaries and within-jurisdictional data silos, across which data sharing is problematic. CONCLUSIONS: Insights from a statewide public health-academic partnership support integration of molecular HIV cluster analyses with public health efforts, which can guide public health activities to prevent transmission while identifying substantial barriers to integration, informing continued research.


Assuntos
Busca de Comunicante , Infecções por HIV , Humanos , Infecções por HIV/prevenção & controle , Infecções por HIV/epidemiologia , Análise por Conglomerados , Rhode Island/epidemiologia , Prática de Saúde Pública , Saúde Pública
18.
Viruses ; 16(10)2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39459846

RESUMO

BACKGROUND: The extent of the SARS-CoV-2 short-term evolution under Remdesivir (RDV) exposure and whether it varies across different upper respiratory compartments are not fully understood. METHODS: Patients hospitalized for COVID-19, with or without RDV therapy, were enrolled and completed up to three visits, in which they provided specimens from four respiratory compartments. Near full-length genome SARS-CoV-2 sequences were obtained from viral RNA, standard lineage and variant assignments were performed, and viral mutations in the RNA-dependent RNA polymerase (RdRp) region-the RDV target gene-were detected and compared between participants with and without RDV, across the four compartments, within participants across visits, and versus a larger sequence dataset. The statistical analysis used a generalized linear mixed-effects model. RESULTS: A total of 139 sequences were obtained from 37 out of the 44 (84%) enrolled participants. The genotyping success varied across respiratory compartments, which ranged from 42% with oropharyngeal specimens to 67% with nasopharyngeal specimens and showed improvement with higher viral loads. No RdRp mutations known to be associated with RDV resistance were identified, and for 34 detected mutations at 32 amino acid positions that are not known as RDV-associated, there was no evidence of any associations with the RDV exposure, respiratory compartment, or time. At least 1 of these 34 mutations were detected in all participants, and some differed from the larger sequence dataset. CONCLUSIONS: This study highlighted the SARS-CoV-2 short-term genomic stability within hosts and across upper respiratory compartments, which suggests a lack of evolution of RDV resistance over time. This contributes to our understanding of SARS-CoV-2 genomic dynamics.


Assuntos
Monofosfato de Adenosina , Alanina , Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Mutação , SARS-CoV-2 , Humanos , Alanina/análogos & derivados , SARS-CoV-2/genética , SARS-CoV-2/efeitos dos fármacos , Monofosfato de Adenosina/análogos & derivados , Monofosfato de Adenosina/farmacologia , Feminino , Masculino , Pessoa de Meia-Idade , Antivirais/farmacologia , Antivirais/uso terapêutico , COVID-19/virologia , Adulto , Evolução Molecular , Idoso , Nasofaringe/virologia , RNA-Polimerase RNA-Dependente de Coronavírus/genética , RNA Polimerase Dependente de RNA/genética , Orofaringe/virologia , Carga Viral/efeitos dos fármacos , RNA Viral/genética , Genoma Viral , Farmacorresistência Viral/genética
19.
Lancet HIV ; 10(3): e202-e208, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36610438

RESUMO

HIV drug resistance is a major global hurdle to successful and sustained antiretroviral therapy. Global guidelines recommend testing for antiretroviral drug resistance and results are used to inform treatment regimen design for patients at different stages of therapy. Several clinical trials investigated optimal regimens after failure of first-line antiretroviral therapy, yielding data that advanced knowledge and informed care. However, further interpretation of data from these studies questioned the benefit of antiretroviral drug resistance testing for cases in which first-line treatment is not effective and, furthermore, that relying on the results of antiretroviral drug resistance testing could be misleading and unnecessary. In this Viewpoint, which is largely focused on high-income settings, we review these data, reflect on the potential problems with their interpretation, and call for caution in their extrapolation. Without negating the importance of the data, and recognising the varied circumstances related to HIV drug resistance testing in different global settings, we advise caution before changing current practice and recommendations. We believe that we should not universally stop considering HIV drug resistance testing at failure of first-line antiretroviral therapy.


Assuntos
Fármacos Anti-HIV , Infecções por HIV , Humanos , Infecções por HIV/tratamento farmacológico , Fármacos Anti-HIV/uso terapêutico , Farmacorresistência Viral , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Antirretrovirais/uso terapêutico , Falha de Tratamento , Carga Viral
20.
J Empir Res Hum Res Ethics ; 18(5): 346-362, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37872659

RESUMO

Research engaging children and adolescents living with HIV (CALWH) is critical for youth-friendly services and HIV care, and researchers need to ensure that such engagement is ethical. We conducted a systematic review to identify key ethical considerations for the engagement of CALWH in research. The review focused on primary research articles conducted in African countries that examined ethical issues in CALWH engaged in research. Ten studies met the inclusion criteria; the following seven key domains were extracted: 1) justifications for engaging CALWH in research; 2) community involvement; 3) informed consent/assent; 4) caregiver involvement; 5) perceptions of benefits; 6) perception of the risks of involvement; and 7) confidentiality. These domains can inform the ethical engagement of CALWH in research.


Assuntos
Participação da Comunidade , Infecções por HIV , Humanos , Adolescente , Criança , Consentimento Livre e Esclarecido , Pesquisadores , Inquéritos e Questionários
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