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BACKGROUND: A trial found that a community health worker (CHW) strategy using "Health Scouts" improved HIV care uptake and ART coverage. To better understand outcomes and areas for improvement, we conducted an implementation science evaluation. METHODS: Using the RE-AIM framework, quantitative methods included analyses of a community-wide survey (n = 1903), CHW log books, and phone application data. Qualitative methods included in-depth interviews (n = 72) with CHWs, clients, staff, and community leaders. RESULTS: Thirteen Health Scouts logged 11,221 counseling sessions; 2532 unique clients were counseled. 95.7% (1789 of 1891) of residents reported awareness of the Health Scouts. Overall, reach (self-reported receipt of counseling) was 30.7% (580 of 1891). Unreached residents were more likely to be male and HIV seronegative ( P < 0.05). Qualitative themes included the following: (1) reach was promoted by perceived usefulness but deterred by busy client lifestyles and stigma, (2) effectiveness was enabled through good acceptability and consistency with the conceptual framework, (3) adoption was facilitated by positive impacts on HIV service engagement, and (4) implementation fidelity was initially promoted by the CHW phone application but deterred by mobility. Maintenance showed consistent counseling sessions over time. The findings suggested the strategy was fundamentally sound but had suboptimal reach. Future iterations could consider adaptations to improve reach to priority populations, testing the need for mobile health support, and additional community sensitization to reduce stigma. CONCLUSIONS: A CHW strategy to promote HIV services was implemented with moderate success in an HIV hyperendemic setting and should be considered for adoption and scale-up in other communities as part of comprehensive HIV epidemic control efforts. TRIAL REGISTRATION: ClinicalTrials.gov Trial Number NCT02556957.
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Agentes Comunitarios de Salud , Infecciones por VIH , Femenino , Humanos , Masculino , Agentes Comunitarios de Salud/psicología , Consejo , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Ciencia de la Implementación , Uganda/epidemiologíaRESUMEN
Development of and increased access to generic oral medications to treat high-burden diseases including human immunodeficiency virus (HIV), tuberculosis, viral hepatitis, and malaria have had a major impact on reducing global morbidity and mortality. However, access and adherence to these life-saving treatments remains limited for some of the most vulnerable and underserved populations, for whom stigma, control, and discretion are critical to decisions around care. Current efforts to develop long-acting formulations to treat and prevent these conditions could overcome many of these barriers. However, generic manufacturing of these innovative products will be required to ensure affordable access to the communities and patients in greatest need. Strategic investments in new infrastructure will be required even before markets and manufacturing costs are clear, to ensure that access to these new products is not delayed, particularly for patients in low- and middle-income countries. Unlike conventional oral medications, long-acting products require greater investment for formulation, packaging, and delivery. The requirement for long-term bioequivalence studies will introduce additional delays in regulatory approval of generic long-acting products, and expedited approval pathways must be developed. Lessons learned from the development of long-acting hormonal contraceptives and long-acting antiretroviral products may provide a way forward.
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Infecciones por VIH , Tuberculosis , Humanos , Medicamentos Genéricos/uso terapéutico , Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/prevención & control , Tuberculosis/tratamiento farmacológico , ComercioRESUMEN
BACKGROUND: Medical schools in Sub-Saharan Africa have adopted competency based medical education (CBME) to improve the quality of graduates trained. In 2015, Makerere University College of Health Sciences (MaKCHS) implemented CBME for the Bachelor of Medicine and Bachelor of Surgery (MBChB) programme in order to produce doctors with the required attributes to address community health needs. However, no formal evaluation of the curriculum has been conducted to determine whether all established competencies are being assessed. OBJECTIVE: To evaluate whether assessment methods within the MBChB curriculum address the stated competencies. METHODS: The evaluation adopted a cross-sectional study design in which the MBChB curriculum was evaluated using an Essential Course Evidence Form (ECEF) that was developed to collect information about each assessment used for each course. Information was collected on: (1) Assessment title, (2) Description, (3) Competency domain (4) Sub-competency addressed, (5) Student instructions, and (6) Grading method/details. Data were entered into a structured Access data base. In addition, face-to-face interviews were conducted with faculty course coordinators. RESULTS: The MBChB curriculum consisted of 62 courses over 5 years, focusing on preclinical skills in years 1-2 and clinical skills in years 3-5. Fifty-nine competencies were identified and aggregated into 9 domains. Fifty-eight competencies were assessed at least one time in the curriculum. Faculty cited limited training in assessment as well as large student numbers as hindrances to designing robust assessments for the competencies. CONCLUSION: CBME was successfully implemented evidenced by all but one of the 59 competencies within the nine domains established being assessed within the MBChB curriculum at MaKCHS. Faculty interviewed were largely aware of it, however indicated the need for more training in competency-based assessment to improve the implementation of CBME.
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Curriculum , Facultades de Medicina , Competencia Clínica , Educación Basada en Competencias/métodos , Estudios Transversales , HumanosRESUMEN
Background and Objectives: Current clinical guidelines recommend thromboprophylaxis for adults hospitalized with coronavirus disease 2019 (COVID-19), yet it is unknown whether higher doses of thromboprophylaxis offer benefits beyond standard doses. Methods: We studied electronic health records from 50 091 adults hospitalized with COVID-19 in the United States between February 2020 and February 2021. We compared standard (enoxaparin 30 or 40 mg/day, fondaparinux 2.5 mg, or heparin 5000 units twice or thrice per day) versus intermediate (enoxaparin 30 or 40 mg twice daily, or up to 1.2 mg/kg of body weight daily, heparin 7500 units thrice per day or heparin 10 000 units twice or thrice per day) thromboprophylaxis. We separately examined risk of escalation to therapeutic anticoagulation, severe disease (first occurrence of high-flow nasal cannula, noninvasive positive pressure ventilation or invasive mechanical ventilation), and death. To summarize risk, we present hazard ratios (HRs) with 95% confidence intervals (CIs) using adjusted time-dependent Cox proportional hazards regression models. Results: People whose first dose was high intensity were younger, more often obese, and had greater oxygen support requirements. Intermediate dose thromboprophylaxis was associated with increased risk of therapeutic anticoagulation (HR, 3.39; 95% CI, 3.22-3.57), severe disease (HR, 1.22; 95% CI, 1.17-1.28), and death (HR, 1.37; 95% CI, 1.21-1.55). Increased risks associated with intermediate-dose thromboprophylaxis persisted in subgroup and sensitivity analyses varying populations and definitions of exposures, outcomes, and covariates. Conclusions: Our findings do not support routine use of intermediate-dose thromboprophylaxis to prevent clinical worsening, severe disease, or death among adults hospitalized with COVID-19.
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INTRODUCTION: Poeple living with HIV have higher prevalence of diabetes mellitus and metabolic perturbations compared to non-HIV populations. Diabetes and metabolic syndrome co-morbidities add significant burden to HIV care. Currently, WHO recommends integrase strand transfer inhibitors (INSTIs) as the first or second line therapy in people with HIV due to overall good tolerability and safety profile. However, whether INSTI use increases the risk of incident diabetes (with or without metabolic syndrome) compared to other anti-retroviral therapies (ART) is controversial. In this systematic review and meta-analysis, we aim to examine this risk in HIV-positive populations receiving INSTIs compared to other ART regimens (not containing INSTIs). METHODS AND ANALYSIS: The study will be reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) statement and the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. This protocol adheres to the Standard Protocol Items for reporting systematic reviews and meta-analyses checklist. Eligibility criteria will be original peer-reviewed published articles and conference abstracts with no language or geographical restriction; that report the ocurrence of diabetes mellitus as a discrete outcome or part of metabolic syndrome, in adult PLWHIV receiving INSTIs compared to other ART regimens. PubMed/ Medline, Web of Science, Embase and Cochrane Database of Systematic Reviews will be searched from 1st- January-2000 to 31st-January-2022. Per our a priori, screening, inclusion and data extraction will be conducted separately by two investigators, and a senior researcher will be consulted in case of disagreement. The quality of included studies will be assessed by the Newcastle-Ottawa Scale (NOS) for cohort and case-control studies and the revised Cochrane risk-of-bias tool (ROB2) for randomized controlled trials. The quantitative synthesis of the study outcomes will be explored in different subgroups and sensitivity analyses. Meta regression will also be performed to further test the predictors of the outcome. ETHICS AND DISSEMINATION: Ethical approval is waived as the study is a review of published litterature. The analyses will be presented in conferences and published as a scientific article. TRIAL REGISTRARTION: PROSPERO registration number is; CRD42021273040.
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Diabetes Mellitus , Infecciones por VIH , Resistencia a la Insulina , Síndrome Metabólico , Diabetes Mellitus/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Integrasas , Metaanálisis como Asunto , Síndrome Metabólico/complicaciones , Proyectos de Investigación , Revisiones Sistemáticas como AsuntoRESUMEN
BACKGROUND: There is an urgent need to understand the real-world effectiveness of remdesivir in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: This was a retrospective comparative effectiveness study. Individuals hospitalized in a large private healthcare network in the United States from 23 February 2020 through 11 February 2021 with a positive test for SARS-CoV-2 and ICD-10 diagnosis codes consistent with symptomatic coronavirus disease 2019 (COVID-19) were included. Remdesivir recipients were matched to controls using time-dependent propensity scores. The primary outcome was time to improvement with a secondary outcome of time to death. RESULTS: Of 96 859 COVID-19 patients, 42 473 (43.9%) received at least 1 remdesivir dose. The median age of remdesivir recipients was 65 years, 23 701 (55.8%) were male, and 22 819 (53.7%) were non-White. Matches were found for 18 328 patients (43.2%). Remdesivir recipients were significantly more likely to achieve clinical improvement by 28 days (adjusted hazard ratio [aHR] 1.19, 95% confidence interval [CI], 1.16-1.22). Remdesivir patients on no oxygen (aHR 1.30, 95% CI, 1.22-1.38) or low-flow oxygen (aHR 1.23, 95% CI, 1.19-1.27) were significantly more likely to achieve clinical improvement by 28 days. There was no significant impact on the likelihood of mortality overall (aHR 1.02, 95% CI, .97-1.08). Remdesivir recipients on low-flow oxygen were significantly less likely to die than controls (aHR 0.85, 95% CI, .77-.92; 28-day mortality 8.4% [865 deaths] for remdesivir patients, 12.5% [1334 deaths] for controls). CONCLUSIONS: These results support the use of remdesivir for hospitalized COVID-19 patients on no or low-flow oxygen. Routine initiation of remdesivir in more severely ill patients is unlikely to be beneficial.
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Tratamiento Farmacológico de COVID-19 , Adenosina Monofosfato/análogos & derivados , Adulto , Anciano , Alanina/análogos & derivados , Antivirales/uso terapéutico , Femenino , Humanos , Masculino , Estudios Retrospectivos , SARS-CoV-2 , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: The utility of interferon-gamma release assays (IGRAs) for latent tuberculosis infection (LTBI) screening among health-care workers (HCWs) in low- and middle-income countries (LMICs) remains unclear. METHODS: This was a prospective cohort study among HCW trainees undergoing annual LTBI screening via tuberculin skin test (TST) and QuantiFERON® TB Gold Test-in-tube (QFT-GIT) in Pune, India. TST induration ≥ 10 mm and QFT-GIT ≥ 0.35 IU/ml were considered positive. Test concordance was evaluated at entry among the entire cohort and at 1 year among baseline TST-negative participants with follow-up testing. Overall test agreement was evaluated at both timepoints using the kappa statistic: fair (k < 0.40), good (0.41 ≥ k ≤0.60), or strong (k > 0.60). RESULTS: Of 200 participants, prevalent LTBI was detected in 42 (21%) via TST and 45 (23%) via QFT-GIT; QFT-GIT was positive in 27/42 (64%) TST-positive and 18/158 (11%) TST-negative trainees. Annual TST conversion was 28% (40/142) and included 11 trainees with baseline TST-/IGRA+; QFT-GIT was positive in 17/40 (43%) TST-positive and 5/102 (5%) TST-negative trainees. Overall test concordance was 84% (k = 0.52; 95% confidence interval [CI]: 0.38-0.66) and 80% (k = 0.44; 95% CI: 0.29-0.59) at baseline and 12 months, respectively. CONCLUSIONS: We observed good overall agreement between TST and QFT-GIT, and QFT-GIT detected additional LTBI cases among TST-negative trainees with possible early detection of LTBI conversion. Overall, our results support the use of IGRA for annual LTBI screening among HCWs in a high burden LMIC setting.
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BACKGROUND: Men in Sub-Saharan Africa are less engaged than women in accessing HIV testing and treatment and, consequently, experience higher HIV-related mortality. Reaching men with HIV testing services is challenging, thus, increasing the need for innovative ways to engage men with low access and those at higher risk. In this study, we explore men's perceptions of drivers and barriers of workplace-based HIV self-testing in Uganda. METHODS: An exploratory study involving men working in private security companies employing more than 50 men in two districts, in central and western Uganda. Focus group discussions and key informant interviews were conducted. Data were analyzed using inductive content analysis. RESULTS: Forty-eight (48) men from eight private security companies participated in 5 focus group discussions and 17 key informant interviews. Of the 48 men, 14(29.2%) were ages 26-35 years. The majority 31(64.6%) were security guards. The drivers reported for workplace-based HIV self-testing included convenience, autonomy, positive influence from work colleagues, the need for alternative access for HIV testing services, incentives, and involvement of employers. The barriers reported were the prohibitive cost of HIV tests, stigma, lack of testing support, the fear of discrimination and isolation, and concerns around decreased work productivity in the event of a reactive self-test. CONCLUSIONS: We recommend the involvement of employers in workplace-based HIV self-testing to encourage participation by employees. There is need for HIV self-testing support both during and after the testing process. Both employers and employees recommend the use of non-monetary incentives, and regular training about HIV self-testing to increase the uptake and acceptability of HIV testing services at the workplace.
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Infecciones por VIH , Lugar de Trabajo , Adulto , África del Sur del Sahara , Femenino , Infecciones por VIH/diagnóstico , Humanos , Masculino , Investigación Cualitativa , Autoevaluación , UgandaRESUMEN
BACKGROUND: Effective implementation strategies are needed to increase engagement in HIV services in hyperendemic settings. We conducted a pragmatic cluster-randomized trial in a high-risk, highly mobile fishing community (HIV prevalence: approximately 38%) in Rakai, Uganda, to assess the impact of a community health worker-delivered, theory-based (situated Information, Motivation, and Behavior Skills), motivational interviewing-informed, and mobile phone application-supported counseling strategy called "Health Scouts" to promote engagement in HIV treatment and prevention services. METHODS AND FINDINGS: The study community was divided into 40 contiguous, randomly allocated clusters (20 intervention clusters, n = 1,054 participants at baseline; 20 control clusters, n = 1,094 participants at baseline). From September 2015 to December 2018, the Health Scouts were deployed in intervention clusters. Community-wide, cross-sectional surveys of consenting 15 to 49-year-old residents were conducted at approximately 15 months (mid-study) and at approximately 39 months (end-study) assessing the primary programmatic outcomes of self-reported linkage to HIV care, antiretroviral therapy (ART) use, and male circumcision, and the primary biologic outcome of HIV viral suppression (<400 copies/mL). Secondary outcomes included HIV testing coverage, HIV incidence, and consistent condom use. The primary intent-to-treat analysis used log-linear binomial regression with generalized estimating equation to estimate prevalence risk ratios (PRR) in the intervention versus control arm. A total of 2,533 (45% female, mean age: 31 years) and 1,903 (46% female; mean age 32 years) residents completed the mid-study and end-study surveys, respectively. At mid-study, there were no differences in outcomes between arms. At end-study, self-reported receipt of the Health Scouts intervention was 38% in the intervention arm and 23% in the control arm, suggesting moderate intervention uptake in the intervention arm and substantial contamination in the control arm. At end-study, intention-to-treat analysis found higher HIV care coverage (PRR: 1.06, 95% CI: 1.01 to 1.10, p = 0.011) and ART coverage (PRR: 1.05, 95% CI: 1.01 to 1.10, p = 0.028) among HIV-positive participants in the intervention compared with the control arm. Male circumcision coverage among all men (PRR: 1.05, 95% CI: 0.96 to 1.14, p = 0.31) and HIV viral suppression among HIV-positive participants (PRR: 1.04, 95% CI: 0.98 to 1.12, p = 0.20) were higher in the intervention arm, but differences were not statistically significant. No differences were seen in secondary outcomes. Study limitations include reliance on self-report for programmatic outcomes and substantial contamination which may have diluted estimates of effect. CONCLUSIONS: A novel community health worker intervention improved HIV care and ART coverage in an HIV hyperendemic setting but did not clearly improve male circumcision coverage or HIV viral suppression. This community-based, implementation strategy may be a useful component in some settings for HIV epidemic control. TRIAL REGISTRATION: ClinicalTrials.gov NCT02556957.
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Agentes Comunitarios de Salud , Infecciones por VIH/prevención & control , Promoción de la Salud/métodos , Aplicaciones Móviles , Entrevista Motivacional , Adolescente , Adulto , Fármacos Anti-VIH/uso terapéutico , Circuncisión Masculina , Condones , Femenino , Infecciones por VIH/epidemiología , Humanos , Incidencia , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Prevalencia , Uganda/epidemiologíaRESUMEN
Background: Strengthening health research is essential to inform public health policies. However, few research training programs have systematically measured their impact on capacity building and most evaluations have been limited to reporting of individual trainee metrics. Hence, we conducted an evaluation of the impact of a five-year training program focused on building both trainee and institutional research capacity at a public medical college in India. Methods: Quantitative and qualitative methods were used to assess the individual and institutional research capacity building of a five-year HIV-TB research training program at Byramjee Jeejeebhoy Government Medical College in Pune, India, supported by the US National Institutes of Health, Fogarty International Center. In addition to documentation of the number of trainee research projects initiated, the number of research papers produced by the Fogarty Scholars (FSs) available on PubMed was calculated. The institutional impact of this program was assessed by documentation of research training activities conducted by the FSs, as well as by surveys and in-depth interviews conducted at the beginning and end of the program. Results: Twenty-one mid-level BJGMC faculty were provided training in HIV-TB research competencies. Between 1 April 2014 and 1 April 2019, 13 of these FSs designed and implemented new IRB-approved research studies and contributed to 49 PubMed listed research papers, including 11 first-authored manuscripts. FSs also conducted 36 journal club discussions, mentored 58 student research projects and conducted 5 institutional research method workshops. Pre- and-post-program surveys and in-depth interviews documented a perceived increase in institutional research capacity, particularly in TB research (epidemiology, clinical research, laboratory research). The impact of the Fogarty Training Program on institutional scientific output was perceived to be marginally improved. Conclusion: The Fogarty Training Program had a significant impact on building individual research capacity. To sustain this impact beyond the five years of Fogarty support, additional governmental and institutional resources, the establishment of dedicated space for faculty research and protected faculty time for research are needed. These findings can inform the design and implementation of future health research capacity building initiatives.
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Investigación Biomédica/educación , Creación de Capacidad , Docentes Médicos/educación , Infecciones por VIH , Humanos , India , Evaluación de Programas y Proyectos de Salud , Edición , Facultades de Medicina , TuberculosisRESUMEN
INTRODUCTION: India's national AIDS Control Organization implemented World Health Organization's option B+ HIV prevention of mother-to-child transmission (PMTCT) guidelines in 2013. However, scalable strategies to improve uptake of new PMTCT guidelines to reduce new infection rates are needed. This study assessed impact of Mobile Health-Facilitated Behavioral Intervention on the uptake of PMTCT services. METHODS: A cluster-randomized trial of a mobile health (mHealth)-supported behavioural training intervention targeting outreach workers (ORWs) was conducted in four districts of Maharashtra, India. Clusters (one Integrated Counselling and Testing Center (ICTC, n = 119), all affiliated ORWs (n = 116) and their assigned HIV-positive pregnant/postpartum clients (n = 1191)) were randomized to standard-of-care (SOC) ORW training vs. the COMmunity home Based INDia (COMBIND) intervention - specialized behavioural training plus a tablet-based mHealth application to support ORW-patient communication and patient engagement in HIV care. Impact on uptake of maternal antiretroviral therapy at delivery, exclusive breastfeeding at six months, infant nevirapine prophylaxis, and early infant diagnosis at six months was assessed using multi-level random-effects logistic regression models. RESULTS: Of 1191 HIV-positive pregnant/postpartum women, 884 were eligible for primary outcome assessment; 487 were randomized to COMBIND. Multivariable analyses identified no statistically significant differences in any primary outcome by study arm. COMBIND was associated with higher uptake of exclusive breastfeeding at two months (adjusted Odds Ratio (aOR), 2.10; 95% CI 1.06 to 4.15) and early infant diagnosis at six weeks (aOR, 2.19; 95% CI 1.05 to 3.98) than SOC. CONCLUSIONS: The COMBIND intervention was easily integrated into India's existing PMTCT programme and improved early uptake of two PMTCT components that require self-motivated health-seeking behaviour, thus providing preliminary evidence to support COMBIND as a potentially scalable PMTCT strategy. Further study would identify modifications needed to optimize other PMTCT outcomes.
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Terapia Conductista , Lactancia Materna , Agentes Comunitarios de Salud/educación , Infecciones por VIH/diagnóstico , Telemedicina , Adulto , Fármacos Anti-VIH/uso terapéutico , Análisis por Conglomerados , Consejo , Diagnóstico Precoz , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/transmisión , Humanos , India , Lactante , Recién Nacido , Transmisión Vertical de Enfermedad Infecciosa , Nevirapina/uso terapéutico , EmbarazoRESUMEN
The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4-6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8-19). HIV infection (aIRR = 29.08, 95% CI: 2.38-355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89-20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.
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Vivienda , Tuberculosis Pulmonar/prevención & control , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Incidencia , India/epidemiología , Masculino , Persona de Mediana Edad , Factores de Riesgo , Tuberculosis Pulmonar/epidemiología , Tuberculosis Pulmonar/transmisión , Adulto JovenRESUMEN
OBJECTIVE: Though several genetic variants have been recognized to be associated with susceptibility to Tuberculosis (TB) infection and disease, a recent observation on the association of TIRAP C975T (S180L) variants with TB disease severity in mice model prompted us to assess their relevance in humans. In addition, TIRAP variants have also been reported to be associated with varied circulating Interferon-gamma induced protein (IP-10) levels. We investigated the association of TIRAP variants with severity of TB disease and IP-10 production in humans, which may be useful in predicting poor clinical outcome. METHODS: Culture positive symptomatic adult pulmonary TB (PTB) patients enrolled between August 2014 and October 2017 were included in this investigation. Allelic discrimination PCR and conventional IP-10 quantification methods were employed for genotyping and IP-10 measurement followed by statistical investigations to analyse patients' variables. RESULTS: Among 211 participants, C/C allele was identified in 70% (nâ¯=â¯147); 26% (nâ¯=â¯55) and 4% (nâ¯=â¯9) had C/T and T/T alleles respectively. There was no significant association between TIRAP variants and smear grade, chest-X-ray score, symptom severity score and circulating IP-10 levels. However, significant association was observed between i) circulating IP-10 levels and time to Mycobacterium Growth Indicator Tube (MGIT) culture conversion (pâ¯=0.032); ii) smear grade among active TB patients and circulating IP-10 levels (pâ¯=0â¯.032). CONCLUSIONS: Although mice experiments showed promising results with more severe disease in C/C and T/T individuals, we did not observe any such association in humans.
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Quimiocina CXCL10/sangre , Glicoproteínas de Membrana/genética , Polimorfismo de Nucleótido Simple , Receptores de Interleucina-1/genética , Tuberculosis Pulmonar/genética , Adulto , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Humanos , Masculino , Persona de Mediana Edad , Mycobacterium tuberculosis/aislamiento & purificación , Índice de Severidad de la Enfermedad , Tuberculosis Pulmonar/inmunología , Tuberculosis Pulmonar/microbiologíaRESUMEN
The first long-acting formulations of HIV drugs are undergoing regulatory review for use in maintenance of viral suppression in people with HIV. Although these novel drug formulations could contribute greatly to HIV treatment and prevention efforts, their lack of activity against hepatitis B virus (HBV) could limit their global impact, particularly in populations with high burdens of both HIV and HBV. An urgent need for greater investment in research and development of long-acting drugs with dual activity against HIV and HBV exists. Access to long-acting HIV drug formulations with dual activity against HBV would be transformative and have a great impact on efforts to prevent, treat, and eradicate both of these important global epidemics.
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Antivirales/farmacología , Infecciones por VIH/tratamiento farmacológico , Hepatitis B/tratamiento farmacológico , Antivirales/uso terapéutico , Coinfección , Preparaciones de Acción Retardada , Salud Global , Infecciones por VIH/prevención & control , VIH-1/efectos de los fármacos , Hepatitis B/prevención & control , Virus de la Hepatitis B/efectos de los fármacos , Humanos , Inyecciones , Carga Viral/efectos de los fármacosRESUMEN
BACKGROUND: Various individual biomarkers of inflammation and micronutrient status, often correlated with each other, are associated with adverse treatment outcomes in human immunodeficiency virus (HIV)-infected adults. The objective of this study was to conduct exploratory factor analysis (EFA) on multiple inflammation and micronutrient biomarkers to identify biomarker groupings (factors) and determine their association with HIV clinical treatment failure (CTF) and incident active tuberculosis (TB). METHODS: Within a multicountry randomized trial of antiretroviral therapy (ART) efficacy (PEARLS) among HIV-infected adults, we nested a case-control study (n = 290; 124 cases, 166 controls) to identify underlying factors, based on EFA of 23 baseline (pre-ART) biomarkers of inflammation and micronutrient status. The EFA biomarker groupings results were used in Cox proportional hazards models to study the association with CTF (primary analysis where cases were incident World Health Organization stage 3, 4 or death by 96 weeks of ART) or incident active TB (secondary analysis). RESULTS: In the primary analysis, based on eigenvalues> 1 in the EFA, three factors were extracted: (1) carotenoids), (2) other nutrients, and (3) inflammation. In multivariable-adjusted models, there was an increased hazard of CTF (adjusted hazard ratio (aHR) 1.47, 95% confidence interval (CI)1.17-1.84) per unit increase of inflammation factor score. In the secondary incident active TB case-control analysis, higher scores of the high carotenoids and low interleukin-18 factor was protective against incident active TB (aHR 0.48, 95% CI 0.26-0.87). CONCLUSION: Factors identified through EFA were associated with adverse outcomes in HIV-infected individuals. Strategies focused on reducing adverse HIV outcomes through therapeutic interventions that target the underlying factor (e.g., inflammation) rather than focusing on an individual observed biomarker might be more effective and warrant further investigation.
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Biomarcadores/sangre , Infecciones por VIH , Inflamación/sangre , Micronutrientes/sangre , Tuberculosis/complicaciones , Adulto , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Estudios de Casos y Controles , Femenino , Infecciones por VIH/sangre , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Oligoelementos/sangre , Insuficiencia del Tratamiento , Tuberculosis/tratamiento farmacológico , Adulto JovenRESUMEN
BACKGROUND: The Prevention of Mother-to-Child Transmission of HIV (PMTCT) program in India is one of the largest in the world. It uses outreach workers (ORWs) to facilitate patient uptake of services, however, the challenges faced by the ORWs, and their views about the effectiveness of this program are unknown. METHODS: The COMmunity-Home Based INDia (COMBIND) Prevention of Mother to Child Transmission of HIV study evaluated an integrated mobile health and behavioral intervention to enhance the capacity of ORWs in India. To understand the challenges faced by ORWs, and their perceptions of opportunities for program improvement, four group discussions were conducted among 60 ORW from four districts of Maharashtra, India, as part of the baseline assessment for COMBIND. Data were qualitatively analyzed using a thematic approach. RESULTS: Numerous personal-, social-, and structural-level challenges existed for ORW as they engaged with their patients. Personal-level challenges for ORWs included disclosure of their own HIV status and travelling costs for home visits. Personal-level challenges for patients included financial costs of travelling to ART centers, non-adherence to ART, loss of daily wages, non-affordability of infant formula, lack of awareness of the baby's needs, financial dependence on family, four time points (6weeks, 6 months, 12 months and 18 months) for HIV tests, and need for nevirapine (NVP) prophylaxis. Social-level challenges included lack of motivation by patients and/or health care staff, social stigma, and rude behavior of health care staff and their unwillingness to provide maternity services to women in the PMTCT programme. Structural-level challenges included cultural norms around infant feeding, shortages of HIV testing kits, shortages of antiretroviral drugs and infant NVP prophylaxis, and lack of training/knowledge related to PMTCT infant feeding guidelines by hospital staff. The consensus among ORWs was that there was a critical need for tools and training to improve their capacity to effectively engage with patients, and deliver appropriate care, and for motivation through periodic feedback. CONCLUSIONS: Given the significant challenges in PMTCT programme implementation reported by ORW, novel strategies to address these challenges are urgently needed to improve patient engagement, and access to and retention in care.
Asunto(s)
Infecciones por VIH , Transmisión Vertical de Enfermedad Infecciosa , Programas Nacionales de Salud , Servicios Preventivos de Salud , Adulto , Antirretrovirales/administración & dosificación , Antirretrovirales/economía , Costos y Análisis de Costo , Femenino , Infecciones por VIH/economía , Infecciones por VIH/epidemiología , Infecciones por VIH/prevención & control , Humanos , India/epidemiología , Transmisión Vertical de Enfermedad Infecciosa/economía , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Programas Nacionales de Salud/economía , Programas Nacionales de Salud/organización & administración , Embarazo , Servicios Preventivos de Salud/economía , Servicios Preventivos de Salud/organización & administraciónRESUMEN
Background: Preterm birth (PTB) rates are high in human immunodeficiency virus (HIV)-infected populations, even when on treatment. Still, only a subset of all births in HIV-infected pregnant women result in PTB, suggesting that risk factors other than HIV infection itself are also important. Inflammation is a known risk factor in uninfected populations, but its role in HIV-infected population have not been studied; in addition, the immune pathways involved are not clear and noninvasive immune markers with predictive value are lacking. Our objective was to determine the association of select markers of inflammation with PTB in HIV-1-infected pregnant women. Methods: Within a randomized trial of pregnant women receiving nevirapine (Six-Week Extended-Dose Nevirapine [SWEN] trial), we nested a case-control study (n = 107; 26 cases, 81 controls) to determine the association of maternal inflammation with PTB. Cases were defined as PTB (<37 weeks' gestational age). We assessed inflammation by measuring plasma levels of markers of general inflammation (C-reactive protein [CRP]), intestinal barrier dysfunction (intestinal fatty acid binding protein [I-FABP]), and microbial translocation/monocyte activation (soluble CD14 [sCD14] and CD163 [sCD163]). Multivariable logistic regression was used to determine the odds of PTB per log2 increase of each marker. Results: In multivariable models, there was increased odds of PTB per unit increase of log2 sCD14 (adjusted odds ratio [aOR], 2.45; 95% confidence interval [CI], 1.24-4.86), log2 sCD163 (aOR, 3.87; 95% CI, 1.43-10.49), and log2 I-FABP (aOR, 2.28; 95% CI, 1.18-4.41) but not log2 CRP (aOR, 0.72; 95% CI, .48-1.09). Conclusions: Our results show that select immune markers can identify women at higher risk for PTB in HIV-1-infected populations and suggest that modulating gut barrier integrity and microbial translocation may affect PTB. Clinical Trials Registration: NCT00061321.
Asunto(s)
Traslocación Bacteriana , Infecciones por VIH/complicaciones , Mucosa Intestinal/patología , Complicaciones Infecciosas del Embarazo , Nacimiento Prematuro/etiología , Adulto , Fármacos Anti-VIH/uso terapéutico , Estudios de Casos y Controles , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Recién Nacido , Embarazo , Adulto JovenRESUMEN
BACKGROUND: Gender-based violence (GBV) is a major global public health concern and is a risk factor for adverse health outcomes. Early identification of GBV is crucial for improved health outcomes. Interactions with health care providers may provide a unique opportunity for routine GBV screening, if a safe, confidential environment can be established. METHODS: Between November 2014 and February 2015, a cross-sectional, observational study was conducted where women were interviewed about their opinions concerning GBV screening in a tertiary health care setting in Pune, India. Trained counsellors interviewed 300 women at different out-patient and in-patient departments using a semi-structured questionnaire. RESULTS: Twenty-three percent of these women reported experiencing GBV in their life. However, 90% of women said they had never been asked about GBV in a health care setting. Seventy-two percent expressed willingness to be asked about GBV by their health care providers, with the preferred provider being nurses or counsellors. More than half (53%) women reported face-to-face interview as the most preferred method for screening. There were no major differences in these preferences by GBV history status. CONCLUSIONS: Our study provides evidence for preferred GBV screening methods and optimal provider engagement as perceived by women attending a public hospital.