Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 25
Filtrar
1.
J Clin Microbiol ; 58(9)2020 Aug 24.
Artículo en Inglés | MEDLINE | ID: mdl-32522826

RESUMEN

HIV drug resistance (HIVDR) is a barrier to sustained virologic suppression in low- and middle-income countries (LMICs). Point mutation assays targeting priority drug resistance mutations (DRMs) are being evaluated to improve access to HIVDR testing. In a cross-sectional study (June 2018 to September 2019), we evaluated the diagnostic accuracy of a simple and rapid HIVDR assay (the pan-degenerate amplification and adaptation [PANDAA] assay targeting the mutations K65R, K103NS, M184VI, Y181C, and G190A) compared to Sanger sequencing and next-generation sequencing (NGS). Plasma samples from adolescents and young adults (aged 10 to 24 years) failing antiretroviral therapy (viral load, >1,000 copies/ml on 2 consecutive occasions 1 month apart) were analyzed. Sensitivity and specificity of the PANDAA assay were determined by a proprietary application designed by Aldatu Biosciences. Agreement between genotyping methods was evaluated using Cohen's kappa coefficient. One hundred fifty samples previously characterized by Sanger sequencing were evaluated using PANDAA. For all DRMs detected, PANDAA showed a sensitivity and specificity of 98% and 94%, respectively. For nucleotide reverse transcriptase inhibitor DRMs, sensitivity and specificity were 98% (95% confidence interval [CI], 92% to 100%) and 100% (94% to 100%), respectively. For non-nucleotide reverse transcriptase inhibitor DRMs, sensitivity and specificity were 100% (97% to 100%) and 76% (61% to 87%), respectively. PANDAA showed strong agreement with Sanger sequencing for K65R, K103NS, M184VI, and G190A (kappa > 0.85) and substantial agreement for Y181C (kappa = 0.720). Of the 21 false-positive samples genotyped by PANDAA, only 6 (29%) were identified as low-abundance variants by NGS. With the high sensitivity and specificity to detect major DRMs, PANDAA could represent a simple and rapid alternative HIVDR assay in LMICs.

3.
AIDS ; 33(11): 1729-1737, 2019 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-31361272

RESUMEN

OBJECTIVES: The integrase strand inhibitor dolutegravir (DTG) combined with tenofovir and lamivudine (TLD) is a single tablet regimen recommended for 1st, 2nd and 3rd-line public health antiretroviral therapy (ART). We determined drug resistance mutations (DRMs) and evaluated the predictive efficacy of a TLD containing regimen for viremic adolescents and young adults in Harare, Zimbabwe. METHODS: We sequenced plasma viral RNA from HIV-1-infected adolescents and young adults on 1st and 2nd-line ART with confirmed virologic failure (viral load >1000 copies/ml) and calculated total genotypic susceptibility scores to current 2nd, 3rd line and DTG regimens. RESULTS: A total of 160 participants were genotyped; 112 (70%) on 1st line and 48 (30%) on 2nd line, median (interquartile range) age 18 (15-19) and duration of ART (interquartile range) was 6 (4-8) years. Major DRMs were present in 94 and 67% of 1st and 2nd-line failures, respectively (P < 0.001). Dual class resistance to nucleotide reverse transcriptase inhibitors and nonnucleotide reverse transcriptase inhibitors was detected in 96 (60%) of 1st-line failures; protease inhibitor DRMs were detected in a minority (10%) of 2nd-line failures. A total genotypic susceptibility score of 2 or less may risk protease inhibitor or DTG monotherapy in 11 and 42% of 1st-line failures switching to 2nd-line protease inhibitor and TLD respectively. CONCLUSION: Among adolescents and young adults, current protease inhibitor-based 2nd-line therapies are poorly tolerated, more expensive and adherence is poor. In 1st-line failure, implementation of TLD for many adolescents and young adults on long-term ART may require additional active drug(s). Drug resistance surveillance and susceptibility scores may inform strategies for the implementation of TLD.


Asunto(s)
Farmacorresistencia Viral/genética , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/uso terapéutico , Compuestos Heterocíclicos con 3 Anillos/uso terapéutico , Adolescente , Estudios Transversales , Combinación de Medicamentos , Femenino , Genotipo , Infecciones por VIH/sangre , Inhibidores de la Proteasa del VIH , VIH-1/efectos de los fármacos , VIH-1/genética , Humanos , Lamivudine/uso terapéutico , Masculino , Cumplimiento de la Medicación , Oxazinas , Piperazinas , Piridonas , Tenofovir/uso terapéutico , Insuficiencia del Tratamiento , Carga Viral , Adulto Joven , Zimbabwe
4.
AIDS Res Ther ; 16(1): 12, 2019 06 06.
Artículo en Inglés | MEDLINE | ID: mdl-31171021

RESUMEN

BACKGROUND: Data on chronic kidney disease development in HIV infection is important towards building a comprehensive knowledge of HIV, ageing and polypharmacy in Africa. Several previous studies on tenofovir-associated kidney disease in Africa have shown conflicting results. This review summarises what is known about the development of kidney disease in HIV-positive African patients on tenofovir disoproxil fumarate (TDF)-containing ART. We set out to document the occurrence of kidney disease in HIV-positive Africans on TDF-containing ART in population-based studies and to evaluate the renal safety of TDF in Africans. METHODS: We conducted a systemic review using published studies which were identified through a computerized search of original research using the Medline/PubMed database, EMBASE, EBM Reviews, Proquest Google Scholar and Global Health reported from inception until 5 October 2017. Two reviewers independently abstracted the data and performed quality assessment of the included studies. We screened 595 articles and included 31 in the qualitative analysis performed. RESULTS: A total of 106 406 patients (of whom 66,681 were on Tenofovir) were involved in these 31 studies with sample sizes ranging from 30 to 62,230. Duration on tenofovir-containing ART ranged from those initiating ART at baseline to those who received TDF for up to 9 years. All but one of the studies involved only patients 16 years and older. The studies had differing definitions of kidney dysfunction and were of variable study design quality. The documented outcomes had substantial discrepancies across the studies, most likely due to methodological differences, study size and disparate outcome definitions. CONCLUSIONS: Our review identified studies in Africans reporting statistically significant renal function decline associated with TDF use but the clinical significance of this effect was not enough to contraindicate its continued use in ART regimens. Consistent with studies in other populations, patients are at greater risk if they have pre-existing renal disease and are more advanced in age. More research is needed on paediatric populations under 16 years of age. Trial registration This review was registered on Prospero (registration number CRD42018078717).


Asunto(s)
Fármacos Anti-VIH/efectos adversos , Infecciones por VIH/tratamiento farmacológico , Enfermedades Renales/inducido químicamente , Riñón/efectos de los fármacos , Tenofovir/efectos adversos , África , Infecciones por VIH/etnología , Humanos , Enfermedades Renales/virología , Insuficiencia Renal/inducido químicamente
5.
BMJ Open ; 9(4): e026288, 2019 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-30940760

RESUMEN

INTRODUCTION: Cryptococcal meningitis is responsible for around 15% of all HIV-related deaths globally. Conventional treatment courses with amphotericin B require prolonged hospitalisation and are associated with multiple toxicities and poor outcomes. A phase II study has shown that a single high dose of liposomal amphotericin may be comparable to standard treatment. We propose a phase III clinical endpoint trial comparing single, high-dose liposomal amphotericin with the WHO recommended first-line treatment at six sites across five counties. An economic analysis is essential to support wide-scale implementation. METHODS AND ANALYSIS: Country-specific economic evaluation tools will be developed across the five country settings. Details of patient and household out-of-pocket expenses and any catastrophic healthcare expenditure incurred will be collected via interviews from trial patients. Health service patient costs and related household expenditure in both arms will be compared over the trial period in a probabilistic approach, using Monte Carlo bootstrapping methods. Costing information and number of life-years survived will be used as the input to a decision-analytic model to assess the cost-effectiveness of a single, high-dose liposomal amphotericin to the standard treatment. In addition, these results will be compared with a historical cohort from another clinical trial. ETHICS AND DISSEMINATION: The AMBIsome Therapy Induction OptimisatioN (AMBITION) trial has been evaluated and approved by the London School of Hygiene and Tropical Medicine, University of Botswana, Malawi National Health Sciences, University of Cape Town, Mulago Hospital and Zimbabwe Medical Research Council research ethics committees. All participants will provide written informed consent or if lacking capacity will have consent provided by a proxy. The findings of this economic analysis, part of the AMBITION trial, will be disseminated through peer-reviewed publications and at international and country-level policy meetings. TRIAL REGISTRATION: ISRCTN 7250 9687; Pre-results.


Asunto(s)
Anfotericina B/administración & dosificación , Costos de los Medicamentos , Gastos en Salud/estadística & datos numéricos , Meningitis Criptocócica/tratamiento farmacológico , África del Sur del Sahara/epidemiología , Anfotericina B/economía , Antifúngicos/administración & dosificación , Antifúngicos/economía , Análisis Costo-Beneficio , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Estudios de Seguimiento , Humanos , Meningitis Criptocócica/economía , Meningitis Criptocócica/epidemiología , Estudios Prospectivos
6.
Open Forum Infect Dis ; 6(1): ofy333, 2019 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-30648127

RESUMEN

Background: There are no host biomarkers of risk for HIV-associated cryptococcal meningitis (CM) except CD4+ T-cell deficiency. At present, serum cryptococcal antigen (CrAg) screening of those with CD4 <100 cells/µL is used to identify persons at risk for HIV-associated CM. We determined if plasma antibody profiles could discriminate CrAg+ from CrAg- patients. Methods: We performed serological analyses of 237 HIV-infected asymptomatic Zimbabwean patients with CD4 <100 cells/µL; 125 CrAg- and CrAg+ but cerebrospinal fluid CrAg- by CrAg lateral flow assay. We measured plasma immunoglobulin M (IgM), immunoglobulin G (IgG) 1, and IgG2 concentrations by Luminex, and titers of Cryptococcus neoformans (Cn) glucuronoxylomannan (GXM) polysaccharide and naturally occurring Laminarin (natural Lam, a ß-(1-3)-glucan linked polysaccharide)-binding IgM and IgG by enzyme-linked immunosorbent assay. Results: GXM-IgG, -IgM, and -IgG2 levels were significantly higher in CrAg+ patients, whereas natural Lam-IgM and Lam-IgG were higher in CrAg- patients before and after adjustment for age, sex, and CD4 T-cell count, despite overlap of values. To address this variability and better discriminate the groups, we used Akaike Information Criteria to select variables that independently predicted CrAg+ status and included them in a receiver operating characteristic curve to predict CrAg status. By inclusion of CD4, GXM-IgG, GXM-IgM, and Lam-IgG, -IgG2, and -IgM, this model had an 80.4% probability (95% confidence interval, 0.75-0.86) of predicting CrAg+ status. Conclusions: Statistical models that include multiple serological variables may improve the identification of patients at risk for CM and inform new directions in research on the complex role that antibodies may play in resistance and susceptibility to CM.

8.
Trials ; 19(1): 649, 2018 Nov 23.
Artículo en Inglés | MEDLINE | ID: mdl-30470259

RESUMEN

BACKGROUND: Cryptococcal meningitis (CM) is a major cause of mortality in HIV programmes in Africa despite increasing access to antiretroviral therapy (ART). Mortality is driven in part by limited availability of amphotericin-based treatment, drug-induced toxicities of amphotericin B deoxycholate and prolonged hospital admissions. A single, high-dose of liposomal amphotericin (L-AmB, Ambisome) on a fluconazole backbone has been reported as non-inferior to 14 days of standard dose L-AmB in reducing fungal burden. This trial examines whether single, high-dose L-AmB given with high-dose fluconazole and flucytosine is non-inferior to a seven-day course of amphotericin B deoxycholate plus flucytosine (the current World Health Organization [WHO] recommended treatment regimen). METHODS: An open-label phase III randomised controlled non-inferiority trial conducted in five countries in sub-Saharan Africa: Botswana, Malawi, South Africa, Uganda and Zimbabwe. The trial will compare CM induction therapy with (1) a single dose (10 mg/kg) of L-AmB given with 14 days of fluconazole (1200 mg/day) and flucytosine (100 mg/kg/day) to (2) seven days amphotericin B deoxycholate (1 mg/kg/day) given alongside seven days of flucytosine (100 mg/kg/day) followed by seven days of fluconazole (1200 mg/day). The primary endpoint is all-cause mortality at ten weeks with a non-inferiority margin of 10% and 90% power. Secondary endpoints are early fungicidal activity, proportion of grade III/IV adverse events, pharmacokinetic parameters and pharmacokinetic/pharmacodynamic associations, health service costs, all-cause mortality within the first two and four weeks, all-cause mortality within the first ten weeks (superiority analysis) and rates of CM relapse, immune reconstitution inflammatory syndrome and disability at ten weeks. A total of 850 patients aged ≥ 18 years with a first episode of HIV-associated CM will be enrolled (425 randomised to each arm). All patients will be followed for 16 weeks. All patients will receive consolidation therapy with fluconazole 800 mg/day to complete ten weeks of treatment, followed by fluconazole maintenance and ART as per local guidance. DISCUSSION: A safe, sustainable and easy to administer regimen of L-AmB that is non-inferior to seven days of daily amphotericin B deoxycholate therapy may reduce the number of adverse events seen in patients treated with amphotericin B deoxycholate and shorten hospital admissions, providing a highly favourable and implementable alternative to the current WHO recommended first-line treatment. TRIAL REGISTRATION: ISRCTN, ISRCTN72509687 . Registered on 13 July 2017.


Asunto(s)
Anfotericina B/administración & dosificación , Antifúngicos/administración & dosificación , Cryptococcus neoformans/efectos de los fármacos , Meningitis Criptocócica/tratamiento farmacológico , África del Sur del Sahara , Anfotericina B/efectos adversos , Anfotericina B/economía , Anfotericina B/farmacocinética , Antifúngicos/efectos adversos , Antifúngicos/economía , Antifúngicos/farmacocinética , Ensayos Clínicos Fase III como Asunto , Análisis Costo-Beneficio , Cryptococcus neoformans/patogenicidad , Esquema de Medicación , Costos de los Medicamentos , Quimioterapia Combinada , Estudios de Equivalencia como Asunto , Fluconazol/administración & dosificación , Flucitosina/administración & dosificación , Humanos , Quimioterapia de Inducción , Meningitis Criptocócica/economía , Meningitis Criptocócica/microbiología , Meningitis Criptocócica/mortalidad , Estudios Multicéntricos como Asunto , Factores de Tiempo , Resultado del Tratamiento
9.
Artículo en Inglés | MEDLINE | ID: mdl-29881632

RESUMEN

Background: Anti-retroviral therapy (ART) regimes for HIV are associated with raised levels of circulating triglycerides (TG) in western populations. However, there are limited data on the impact of ART on cardiometabolic risk in sub-Saharan African (SSA) populations. Methods: Pooled analyses of 14 studies comprising 21 023 individuals, on whom relevant cardiometabolic risk factors (including TG), HIV and ART status were assessed between 2003 and 2014, in SSA. The association between ART and raised TG (>2.3 mmol/L) was analysed using regression models. Findings: Among 10 615 individuals, ART was associated with a two-fold higher probability of raised TG (RR 2.05, 95% CI 1.51-2.77, I2=45.2%). The associations between ART and raised blood pressure, glucose, HbA1c, and other lipids were inconsistent across studies. Interpretation: Evidence from this study confirms the association of ART with raised TG in SSA populations. Given the possible causal effect of raised TG on cardiovascular disease (CVD), the evidence highlights the need for prospective studies to clarify the impact of long term ART on CVD outcomes in SSA.

10.
Glob Health Sci Pract ; 6(1): 82-92, 2018 03 21.
Artículo en Inglés | MEDLINE | ID: mdl-29602867

RESUMEN

BACKGROUND: Sub-Saharan Africa has an inadequate number of health professionals, leading to a reduced capacity to respond to health challenges, including HIV/AIDS. From 2010 to 2015, the Medical Education Partnership Initiative (MEPI)-sponsored by the U.S. Presidents Emergency Plan for AIDS Relief (PEPFAR) and the National Institutes of Health (NIH)-was enthusiastically taken up by the University of Zimbabwe College of Health Sciences (UZCHS) and 12 other sub-Saharan African universities to develop models of training to improve medical education and research capacity. In this article, we describe the outcomes and challenges of MEPI in Zimbabwe. METHODS: UZCHS in partnership with the University of Colorado, Denver; Stanford University; University of Cape Town; University College London; and King's College London designed the Novel Education Clinical Trainees and Researchers (NECTAR) program and 2 linked awards addressing cardiovascular disease and mental health to pursue MEPI objectives. A range of medical education and research capacity-focused programs were implemented, including faculty development, research support, mentored scholars, visiting professors, community-based education, information and technology support, cross-cutting curricula, and collaboration with partner universities and the ministries of health and education. We analyzed quantitative and qualitative data from several data sources, including annual surveys of faculty, students, and other stakeholders; workshop exit surveys; and key informant interviews with NECTAR administrators and leaders and the UZCHS dean. FINDINGS: Improved Internet connectivity and electronic resource availability were early successes of NECTAR. Over the 5-year period, 69% (115 of 166) of faculty members attended at least 1 of 15 faculty development workshops. Forty-one faculty members underwent 1-year advanced faculty development training in medical education and leadership. Thirty-three mentored research scholars were trained under NECTAR, and 52 and 12 in cardiovascular and mental health programs, respectively. Twelve MEPI scholars had joined faculty by 2015. Full-time faculty grew by 36% (122 to 166), annual postgraduate and medical student enrollment increased by 61% (75 to 121) and 71% (123 to 210), respectively. To institutionalize and sustain MEPI innovations, the Research Support Center and the Department of Health Professions Education were established at UZCHS. CONCLUSION: MEPI has synergistically revitalized medical education, research capacity, and leadership at UZCHS. Investments in creating a new research center, health professions education department, and, programs have laid the foundation to help sustain faculty development and research capacity in the country.


Asunto(s)
Educación Médica/organización & administración , Cooperación Internacional , Creación de Capacidad , Humanos , Liderazgo , Evaluación de Programas y Proyectos de Salud , Investigación/organización & administración , Estados Unidos , Zimbabwe
11.
Pediatr Infect Dis J ; 37(8): 794-800, 2018 08.
Artículo en Inglés | MEDLINE | ID: mdl-29356763

RESUMEN

BACKGROUND: Increasing numbers of children are requiring long-term HIV care and antiretroviral treatment (ART) in public ART programs in Africa, but temporal trends and long-term outcomes in care remain poorly understood. METHODS: We analyzed outcomes in a longitudinal cohort of infants (<2 years of age) and children (2-10 years of age) enrolling in a public tertiary ART center in Zimbabwe over an 8-year period (2004-2012). RESULTS: The clinic enrolled 1644 infants and children; the median age at enrollment was 39 months (interquartile range: 14-79), with a median CD4% of 17.0 (interquartile range: 11-24) in infants and 15.0 (9%-23%) in children (P = 0.0007). Among those linked to care, 33.5% dropped out of care within the first 3 months of enrollment. After implementation of revised guidelines in 2009, decentralization of care and increased access to prevention of mother to child transmission services, we observed an increase in infants (48.9%-68.3%; P < 0.0001) and children (48.9%-68.3%; P < 0.0001) remaining in care for more than 3 months. Children enrolled from 2009 were younger, had lower World Health Organization clinical stage, improved baseline CD4 counts than those who enrolled in 2004-2008. Long-term retention in care also improved with decreasing risk of loss from care at 36 months for infants enrolled from 2009 (aHR: 0.57; 95% confidence interval: 0.34-0.95; P = 0.031). ART eligibility at enrollment was a significant predictor of long-term retention in care, while delayed ART initiation after 5 years of age resulted in failure to fully reconstitute CD4 counts to age-appropriate levels despite prolonged ART. CONCLUSIONS: Significant improvements have been made in engaging and retaining children in care in public ART programs in Zimbabwe. Guideline and policy changes that increase access and eligibility will likely to continue to support improvement in pediatric HIV outcomes.


Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Salud Pública/estadística & datos numéricos , Resultado del Tratamiento , Recuento de Linfocito CD4 , Niño , Preescolar , Estudios de Cohortes , Femenino , VIH/efectos de los fármacos , Infecciones por VIH/epidemiología , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Estudios Longitudinales , Masculino , Salud Pública/legislación & jurisprudencia , Estudios Retrospectivos , Carga Viral , Zimbabwe/epidemiología
12.
J Clin Microbiol ; 55(7): 2172-2179, 2017 07.
Artículo en Inglés | MEDLINE | ID: mdl-28468852

RESUMEN

Although Roche COBAS Ampliprep/COBAS TaqMan (CAP/CTM) systems are widely used in sub-Saharan Africa for early infant diagnosis of HIV from dried blood spots (DBS), viral load monitoring with this system is not practical due to nonspecific extraction of both cell-free and cell-associated viral nucleic acids. A simplified DBS extraction technique for cell-free virus elution using phosphate-buffered saline (PBS) may provide an alternative analyte for lower-cost quantitative HIV virus load (VL) testing to monitor antiretroviral therapy (ART). We evaluated the CAP/CTM v2.0 assay in 272 paired plasma and DBS specimens using the cell-free virus elution method and determined the level of agreement, sensitivity, and specificity at thresholds of target not detected (TND), target below the limit of quantification (BLQ) (<20 copies/ml in plasma or <400 copies/ml in DBS), and VL of <1,000 copies/ml, and VL of <5,000 copies/ml. Reported plasma VL ranged from TND, or <20, to 5,781,592 copies/ml, and DBS VL ranged from TND, or <400, to 467,600 copies/ml. At <1000 copies/ml, agreement between DBS and plasma was 96.7% (kappa coefficient, 0.93; P < 0.0001). The mean difference between DBS and plasma VL values was -1.06 log10 copies/ml (95% confidence interval [CI], -1.17, -0.97; P < 0.0001). At a treatment failure threshold of >1,000 copies/ml, the sensitivities, specificities, positive predictive values (PPV), and negative predictive values (NPV) were 92.7%, 100%, 100%, and 94.3%, respectively. PBS elution of DBS offers a sensitive and specific method for monitoring plasma viremia among adults and children on ART at the WHO-recommended threshold of >1,000 copies/ml on the Roche CAP/CTM system.


Asunto(s)
Sangre/virología , Infecciones por VIH/diagnóstico , Manejo de Especímenes/métodos , Carga Viral/métodos , Adolescente , Adulto , África del Sur del Sahara , Anciano , Anciano de 80 o más Años , Tampones (Química) , Niño , Preescolar , Desecación , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Sensibilidad y Especificidad , Adulto Joven
13.
Afr Health Sci ; 16(3): 860-865, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27917222

RESUMEN

BACKGROUND: The Medical Education Partnership Initiative, has helped to mitigate the digital divide in Africa. The aim of the study was to assess the level of access, attitude, and training concerning meaningful use of electronic resources and EBM among medical students at an African medical school. METHODS: The study involved medical students at the University of Zimbabwe College of Health Sciences, Harare. The needs assessment tool consisted of a 21-question, paper-based, voluntary and anonymous survey. RESULTS: A total of 61/67 (91%), responded to the survey. 60% of the medical students were 'third-year medical students'. Among medical students, 85% of responders had access to digital medical resources, but 54% still preferred printed medical textbooks. Although 25% of responders had received training in EBM, but only 7% found it adequate. 98% of the participants did not receive formal training in journal club presentation or analytical reading of medical literature, but 77 % of them showed interest in learning these skills. CONCLUSION: Lack of training in EBM, journal club presentation and analytical reading skills have limited the impact of upgraded technology in enhancing the level of knowledge. This impact can be boosted by developing a curriculum with skills necessary in using EBM.


Asunto(s)
Acceso a la Información , Medicina Basada en la Evidencia , Conocimientos, Actitudes y Práctica en Salud , Informática Médica/educación , Estudiantes de Medicina/psicología , Humanos , Encuestas y Cuestionarios , Zimbabwe
14.
Trials ; 16: 276, 2015 Jun 17.
Artículo en Inglés | MEDLINE | ID: mdl-26081985

RESUMEN

BACKGROUND: Cryptococcal meningitis (CM) is a leading cause of mortality among HIV-infected individuals in Africa. Poor outcomes from conventional antifungal therapies, unavailability of flucytosine, and difficulties administering 14 days of amphotericin B are key drivers of this mortality. Novel treatment regimes are needed. This study examines whether short-course high-dose liposomal amphotericin B (AmBisome), given with high dose fluconazole, is non-inferior (in terms of microbiological and clinical endpoints) to standard-dose 14-day courses of AmBisome plus high dose fluconazole for treatment of HIV-associated CM. METHODOLOGY/DESIGN: This is an adaptive open-label phase II/III randomised non-inferiority trial comparing alternative short course AmBisome regimens. Step 1 (phase II) will compare four treatment arms in 160 adult patients (≥ 18 years old) with a first episode of HIV-associated CM, using early fungicidal activity (EFA) as the primary outcome: 1) AmBisome 10 mg/kg day one (single dose); 2) AmBisome 10 mg/kg day one and AmBisome 5 mg/kg day three (two doses); 3) AmBisome 10 mg/kg day one, and AmBisome 5 mg/kg days three and seven (three doses); and 4) AmBisome 3 mg/kg/d for 14 days (control); all given with fluconazole 1200 mg daily for 14 days. STEP 2 (phase III) will enrol 300 participants and compare two treatment arms using all-cause mortality within 70 days as the primary outcome: 1) the shortest course AmBisome regimen found to be non-inferior in terms of EFA to the 14-day control arm in STEP 1, and 2) AmBisome 3 mg/kg/d for 14 days (control), both given with fluconazole 1200 mg daily for 14 days. STEP 2 analysis will include all patients from STEP 1 and STEP 2 taking the STEP 2 regimens. All patients will be followed for ten weeks, and mortality and safety data recorded. All patients will receive consolidation therapy with fluconazole 400-800 mg daily and ART in accordance with local guidelines. The primary analysis (for both STEP 1 and STEP 2) will be intention-to-treat. TRIAL REGISTRATION: ISRCTN10248064. Date of Registration: 22 January 2014.


Asunto(s)
Infecciones Oportunistas Relacionadas con el SIDA/tratamiento farmacológico , Anfotericina B/administración & dosificación , Antifúngicos/administración & dosificación , Coinfección , Fluconazol/administración & dosificación , Meningitis Criptocócica/tratamiento farmacológico , Infecciones Oportunistas Relacionadas con el SIDA/diagnóstico , Infecciones Oportunistas Relacionadas con el SIDA/microbiología , Infecciones Oportunistas Relacionadas con el SIDA/mortalidad , Anfotericina B/efectos adversos , Antifúngicos/efectos adversos , Botswana , Protocolos Clínicos , Esquema de Medicación , Quimioterapia Combinada , Fluconazol/efectos adversos , Humanos , Meningitis Criptocócica/diagnóstico , Meningitis Criptocócica/microbiología , Meningitis Criptocócica/mortalidad , Proyectos de Investigación , Tanzanía , Factores de Tiempo , Resultado del Tratamiento
15.
Acad Med ; 89(8 Suppl): S88-92, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-25072588

RESUMEN

The University of Zimbabwe College of Health Sciences (UZCHS) is Zimbabwe's premier health professions training institution. However, several concerns were raised during the past decade over the quality of health education at UZCHS. The number of faculty and students declined markedly until 2010, when there was a medical student intake of 147 while the faculty comprised only 122 (39%) of a possible 314 positions. The economic and political crises that the country experienced from 1999 to 2009 compounded the difficulties faced by the institution by limiting the availability of resources. The Medical Education Partnership Initiative funding opportunity has given UZCHS the stimulus to embark on reforms to improve the quality of health education it offers. UZCHS, in partnership with the University of Colorado School of Medicine, the University of Colorado Denver Evaluation Center, and Stanford University, designed the Novel Education Clinical Trainees and Researchers (NECTAR) program to implement a series of health education innovations to meet this challenge. Between 2010 and 2013, innovations that have positively affected the quality of health professions education at UZCHS include the launch of comprehensive faculty development programs and mentored clinical and research programs for postgraduate students. A competency-based curriculum reform process has been initiated, a health professions department has been established, and the Research Support Center has been strengthened, providing critical resources to institutionalize health education and research implementation at the college. A core group of faculty trained in medical education has been assembled, helping to ensure the sustainability of these NECTAR activities.


Asunto(s)
Empleos en Salud/educación , Cooperación Internacional , Universidades , Curriculum/tendencias , Difusión de Innovaciones , Docentes Médicos , Humanos , Reino Unido , Zimbabwe
16.
PLoS One ; 9(1): e87322, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24475271

RESUMEN

INTRODUCTION & OBJECTIVES: Due to the scale up of antiretroviral therapy, increasing numbers of HIV-infected children are living into adolescence. As these children grow and surpass the immediate threat of death, the issue of informing them of their HIV status arises. This study aimed to understand how perinatally-infected adolescents learn about their HIV-status as well as to examine their preferences for the disclosure process. METHODS: In-depth interviews were conducted with 31 (14 male, 17 female) perinatally-infected adolescents aged 16-20 at an HIV clinic in Harare, Zimbabwe, and focused on adolescents' experiences of disclosure. In addition, 15 (1 male, 14 female) healthcare workers participated in two focus groups that were centred on healthcare workers' practices surrounding disclosure in the clinic. Purposive sampling was used to recruit participants. A coding frame was developed and major themes were extracted using grounded theory methods. RESULTS: Healthcare workers encouraged caregivers to initiate disclosure in the home environment. However, many adolescents preferred disclosure to take place in the presence of healthcare workers at the clinic because it gave them access to accurate information as well as an environment that made test results seem more credible. Adolescents learned more specific information about living with an HIV-positive status and the meaning of that status from shared experiences among peers at the clinic. CONCLUSIONS: HIV-status disclosure to adolescents is distinct from disclosure to younger children and requires tailored, age-appropriate guidelines. Disclosure to this age group in a healthcare setting may help overcome some of the barriers associated with caregivers disclosing in the home environment and make the HIV status seem more credible to an adolescent. The study also highlights the value of peer support among adolescents, which could help reduce the burden of psychosocial care on caregivers and healthcare workers.


Asunto(s)
Revelación/estadística & datos numéricos , Infecciones por VIH/psicología , Conocimientos, Actitudes y Práctica en Salud , Personal de Salud/psicología , Pacientes/psicología , Adolescente , Femenino , Humanos , Masculino , Adulto Joven , Zimbabwe
17.
Int J Epidemiol ; 42(6): 1754-71, 2013 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-24415610

RESUMEN

BACKGROUND: Sub-Saharan Africa (SSA) has the highest burden of HIV in the world and a rising prevalence of cardiometabolic disease; however, the interrelationship between HIV, antiretroviral therapy (ART) and cardiometabolic traits is not well described in SSA populations. METHODS: We conducted a systematic review and meta-analysis through MEDLINE and EMBASE (up to January 2012), as well as direct author contact. Eligible studies provided summary or individual-level data on one or more of the following traits in HIV+ and HIV-, or ART+ and ART- subgroups in SSA: body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TGs) and fasting blood glucose (FBG) or glycated hemoglobin (HbA1c). Information was synthesized under a random-effects model and the primary outcomes were the standardized mean differences (SMD) of the specified traits between subgroups of participants. RESULTS: Data were obtained from 49 published and 3 unpublished studies which reported on 29 755 individuals. HIV infection was associated with higher TGs [SMD, 0.26; 95% confidence interval (CI), 0.08 to 0.44] and lower HDL (SMD, -0.59; 95% CI, -0.86 to -0.31), BMI (SMD, -0.32; 95% CI, -0.45 to -0.18), SBP (SMD, -0.40; 95% CI, -0.55 to -0.25) and DBP (SMD, -0.34; 95% CI, -0.51 to -0.17). Among HIV+ individuals, ART use was associated with higher LDL (SMD, 0.43; 95% CI, 0.14 to 0.72) and HDL (SMD, 0.39; 95% CI, 0.11 to 0.66), and lower HbA1c (SMD, -0.34; 95% CI, -0.62 to -0.06). Fully adjusted estimates from analyses of individual participant data were consistent with meta-analysis of summary estimates for most traits. CONCLUSIONS: Broadly consistent with results from populations of European descent, these results suggest differences in cardiometabolic traits between HIV-infected and uninfected individuals in SSA, which might be modified by ART use. In a region with the highest burden of HIV, it will be important to clarify these findings to reliably assess the need for monitoring and managing cardiometabolic risk in HIV-infected populations in SSA.


Asunto(s)
Terapia Antirretroviral Altamente Activa/estadística & datos numéricos , Diabetes Mellitus/epidemiología , Dislipidemias/epidemiología , Infecciones por VIH/epidemiología , Hipertensión/epidemiología , África del Sur del Sahara/epidemiología , Fármacos Anti-VIH/uso terapéutico , Terapia Antirretroviral Altamente Activa/métodos , Índice de Masa Corporal , Infecciones por VIH/tratamiento farmacológico , Humanos
18.
Clin Infect Dis ; 55(1): 145-52, 2012 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-22474177

RESUMEN

BACKGROUND: Long-term survivors of vertically acquired human immunodeficiency virus (HIV) infection are reaching adolescence in large numbers in Africa and are at high risk of delayed diagnosis and chronic complications of untreated HIV infection. Chronic respiratory symptoms are more common than would be anticipated based on the HIV literature. METHODS: Consecutive adolescents with presumed vertically acquired HIV attending 2 HIV care clinics in Harare, Zimbabwe, were recruited and assessed with clinical history and examination, CD4 count, pulmonary function tests, Doppler echocardiography, and chest radiography (CXR). Those with suspected nontuberculous chronic lung disease (CLD) were scanned using high-resolution computed tomography (HRCT). RESULTS: Of 116 participants (43% male; mean age, 14 ± 2.6 years, mean age at HIV diagnosis, 12 years), 69% were receiving antiretroviral therapy. Chronic cough and reduced exercise tolerance were reported by 66% and 21% of participants, respectively; 41% reported multiple respiratory tract infections in the previous year, and 10% were clubbed. More than 40% had hypoxemia at rest (13%) or on exercise (29%), with pulmonary hypertension (mean pulmonary artery pressure >25 mm Hg) in 7%. Forced expiratory volume in 1 second (FEV(1)) was <80% predicted in 45%, and 47% had subtle CXR abnormalities. The predominant HRCT pattern was decreased attenuation as part of a mosaic attenuation pattern (31 of 56 [55%]), consistent with small airway disease and associated with bronchiectasis (Spearman correlation coefficient (r(2) = 0.8) and reduced FEV(1) (r(2) = -0.26). CONCLUSIONS: Long-term survivors of vertically acquired HIV in Africa are at high risk of a previously undescribed small airway disease, with >40% of unselected adolescent clinic attendees meeting criteria for severe hypoxic CLD. This condition is not obvious at rest. Etiology, prognosis, and response to treatment are currently unknown.


Asunto(s)
Diagnóstico Tardío , Infecciones por VIH/diagnóstico , Enfermedades Pulmonares/virología , Adolescente , Niño , Enfermedad Crónica/epidemiología , Femenino , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Humanos , Transmisión Vertical de Enfermedad Infecciosa , Pulmón/diagnóstico por imagen , Pulmón/patología , Enfermedades Pulmonares/diagnóstico por imagen , Enfermedades Pulmonares/epidemiología , Masculino , Radiografía Torácica , Pruebas de Función Respiratoria , Esputo/microbiología
19.
Am J Public Health ; 101(12): 2325-32, 2011 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-22021300

RESUMEN

OBJECTIVES: We investigated attitudes toward provider-initiated HIV testing and counseling (PITC) in the suburbs of Harare, Zimbabwe, where late presentation after mother-to-child HIV transmission (MTCT) is a major cause of adolescent mortality. METHODS: Adolescents (10-18 years) attending 2 primary clinics were offered PITC. Participants completed a questionnaire investigating acceptability of PITC, and in-depth interviews with 41 adolescents and 30 guardians explored understanding of long-term survival after MTCT. RESULTS: Of 506 participants, 16 were known to be HIV-positive; of the remaining 490, only 5 (1%) declined HIV testing. Infected adolescents and their guardians often anticipated a positive result and reported being advised by relatives (but not health workers) to be tested because of chronic illness, especially if parents or siblings had died or were HIV-infected. However, HIV-negative participants were not aware that long-term survival following MTCT could occur. All adolescents felt that HIV diagnosed at their age would be assumed to have been sexually acquired regardless of the true mode of transmission. CONCLUSIONS: Including late diagnosis of MTCT in pretest counseling and health educational messages may facilitate PITC for older children and adolescents, especially for those who have not had their sexual debut.


Asunto(s)
Serodiagnóstico del SIDA , Actitud Frente a la Salud , Consejo , Infecciones por VIH/diagnóstico , Transmisión Vertical de Enfermedad Infecciosa , Aceptación de la Atención de Salud/psicología , Adolescente , Niño , Femenino , Infecciones por VIH/psicología , Infecciones por VIH/transmisión , Seropositividad para VIH/psicología , Humanos , Tutores Legales/psicología , Masculino , Riesgo , Zimbabwe
20.
Trop Med Int Health ; 16(3): 349-55, 2011 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-21176006

RESUMEN

OBJECTIVE: To present an algorithm for primary-care health workers for identifying HIV-infected adolescents in populations at high risk through mother-to-child transmission. METHODS: Five hundred and six adolescent (10-18 years) attendees to two primary care clinics in Harare, Zimbabwe, were recruited. A randomly extracted 'training' data set (n = 251) was used to generate an algorithm using variables identified as associated with HIV through multivariable logistic regression. Performance characteristics of the algorithm were evaluated in the remaining ('test') records (n = 255) at different HIV prevalence rates. RESULTS: HIV prevalence was 17%, and infection was independently associated with client-reported orphanhood, past hospitalization, skin problems, presenting with sexually transmitted infection and poor functional ability. Classifying adolescents as requiring HIV testing if they reported >1 of these five criteria had 74% sensitivity and 80% specificity for HIV, with the algorithm correctly predicting the HIV status of 79% of participants. In low-HIV-prevalence settings (<2%), the algorithm would have a high negative predictive value (≥ 99.5%) and result in an estimated 60% decrease in the number of people needing to test to identify one HIV-infected individual, compared with universal testing. CONCLUSIONS: Our simple algorithm can identify which individuals are likely to be HIV infected with sufficient accuracy to provide a screening tool for use in settings not already implementing universal testing policies among this age-group, for example immigrants to low-HIV-prevalence countries.


Asunto(s)
Infecciones por VIH/diagnóstico , Transmisión Vertical de Enfermedad Infecciosa , Atención Primaria de Salud/métodos , Adolescente , Algoritmos , Niño , Métodos Epidemiológicos , Femenino , Infecciones por VIH/epidemiología , Infecciones por VIH/transmisión , Humanos , Masculino , Zimbabwe/epidemiología
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...