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AIMS: We measured the association between a history of incarceration and HIV positivity among people who inject drugs (PWID) across Europe. DESIGN, SETTING AND PARTICIPANTS: This was a cross-sectional, multi-site, multi-year propensity-score matched analysis conducted in Europe. Participants comprised community-recruited PWID who reported a recent injection (within the last 12 months). MEASUREMENTS: Data on incarceration history, demographics, substance use, sexual behavior and harm reduction service use originated from cross-sectional studies among PWID in Europe. Our primary outcome was HIV status. Generalized linear mixed models and propensity-score matching were used to compare HIV status between ever- and never-incarcerated PWID. FINDINGS: Among 43 807 PWID from 82 studies surveyed (in 22 sites and 13 countries), 58.7% reported having ever been in prison and 7.16% (n = 3099) tested HIV-positive. Incarceration was associated with 30% higher odds of HIV infection [adjusted odds ratio (aOR) = 1.32, 95% confidence interval (CI) = 1.09-1.59]; the association between a history of incarceration and HIV infection was strongest among PWID, with the lowest estimated propensity-score for having a history of incarceration (aOR = 1.78, 95% CI = 1.47-2.16). Additionally, mainly injecting cocaine and/or opioids (aOR = 2.16, 95% CI = 1.33-3.53), increased duration of injecting drugs (per 8 years aOR = 1.31, 95% CI = 1.16-1.48), ever sharing needles/syringes (aOR = 1.91, 95% CI = 1.59-2.28) and increased income inequality among the general population (measured by the Gini index, aOR = 1.34, 95% CI = 1.18-1.51) were associated with a higher odds of HIV infection. Older age (per 8 years aOR = 0.84, 95% CI = 0.76-0.94), male sex (aOR = 0.77, 95% CI = 0.65-0.91) and reporting pharmacies as the main source of clean syringes (aOR = 0.72, 95% CI = 0.59-0.88) were associated with lower odds of HIV positivity. CONCLUSIONS: A history of incarceration appears to be independently associated with HIV infection among people who inject drugs (PWID) in Europe, with a stronger effect among PWID with lower probability of incarceration.
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Consumidores de Drogas , Infecciones por VIH , Seropositividad para VIH , Abuso de Sustancias por Vía Intravenosa , Humanos , Masculino , Infecciones por VIH/epidemiología , Estudios Transversales , Abuso de Sustancias por Vía Intravenosa/epidemiología , Puntaje de Propensión , Europa (Continente)/epidemiologíaRESUMEN
SARS-CoV-2 infection and/or vaccination elicit a broad range of neutralizing antibody responses against the different variants of concern (VOC). We established a new variant-adapted surrogate virus neutralization test (sVNT) and assessed the neutralization activity against the ancestral B.1 (WT) and VOC Delta, Omicron BA.1, BA.2, and BA.5. Analytical performances were compared against the respective VOC to the reference virus neutralization test (VNT) and two CE-IVD labeled kits using three different cohorts collected during the COVID-19 waves. Correlation analyses showed moderate to strong correlation for Omicron sub-variants (Spearman's r = 0.7081 for BA.1, r = 0.7205 for BA.2, and r = 0.6042 for BA.5), and for WT (r = 0.8458) and Delta-sVNT (r = 0.8158), respectively. Comparison of the WT-sVNT performance with two CE-IVD kits, the "Icosagen SARS-CoV-2 Neutralizing Antibody ELISA kit" and the "Genscript cPass, kit" revealed an overall good correlation ranging from 0.8673 to -0.8773 and a midway profile between both commercial kits with 87.76% sensitivity and 90.48% clinical specificity. The BA.2-sVNT performance was similar to the BA.2 Genscript test. Finally, a correlation analysis revealed a strong association (r = 0.8583) between BA.5-sVNT and VNT sVNT using a double-vaccinated cohort (n = 100) and an Omicron-breakthrough infection cohort (n = 91). In conclusion, the sVNT allows for the efficient prediction of immune protection against the various VOCs.
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Anticuerpos Neutralizantes , COVID-19 , Humanos , Pruebas de Neutralización , SARS-CoV-2 , Infección Irruptiva , Anticuerpos AntiviralesRESUMEN
The prevalence of active hepatitis B among asymptomatic persons remains unclear in Africa. Of 1206 newly diagnosed persons in Senegal, 12.3% had significant fibrosis and 31.3% had hepatitis B virus (HBV) DNA levels >2000â IU/mL. Overall, 128 (12.9%) were eligible for antiviral therapy. Generalized HBV screening allowed the identification of a large population requiring HBV care.
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We describe four SARS-CoV-2 re-infections with a B.1.351 variant in 2021, in healthcare workers (HCWs) previously infected in 2020, before detection of this variant in Europe. Cases live in France, near the border with Luxembourg, where variants B.1.351 and B.1.1.7 circulated. All work in the same hospital unit where a cluster of COVID 19 with B1.351 variant occurred, affecting patients and HCWs. Before the cluster onset, HCWs used surgical masks, as per recommendations. After cluster onset, HCWs used FFP2 masks.
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COVID-19 , SARS-CoV-2 , Europa (Continente) , Francia , Personal de Salud , Humanos , Luxemburgo , ReinfecciónRESUMEN
During 2011-16, HIV outbreaks occurred among people who inject drugs (PWID) in Canada (southeastern Saskatchewan), Greece (Athens), Ireland (Dublin), Israel (Tel Aviv), Luxembourg, Romania (Bucharest), Scotland (Glasgow), and USA (Scott County, Indiana). Factors common to many of these outbreaks included community economic problems, homelessness, and changes in drug injection patterns. The outbreaks differed in size (from under 100 to over 1000 newly reported HIV cases among PWID) and in the extent to which combined prevention had been implemented before, during, and after the outbreaks. Countries need to ensure high coverage of HIV prevention services and coverage higher than the current UNAIDS recommendation might be needed in areas in which short acting drugs are injected. In addition, monitoring of PWID with special attention for changing drug use patterns, risk behaviours, and susceptible subgroups (eg, PWID experiencing homelessness) needs to be in place to prevent or rapidly detect and contain new HIV outbreaks.
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Brotes de Enfermedades , Infecciones por VIH/epidemiología , Abuso de Sustancias por Vía Intravenosa/epidemiología , Europa (Continente)/epidemiología , Femenino , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Personas con Mala Vivienda/estadística & datos numéricos , Humanos , Israel/epidemiología , Masculino , América del Norte/epidemiología , Factores SocioeconómicosRESUMEN
INTRODUCTION: The chemokine receptor CCR5 is the main co-receptor for R5-tropic HIV-1 variants. We have previously described a novel 24-base pair deletion in the coding region of CCR5 among individuals from Rwanda. Here, we investigated the prevalence of hCCR5Δ24 in different cohorts and its impact on CCR5 expression and HIV-1 infection in vitro. METHODS: We screened hCCR5Δ24 in a total of 3232 individuals which were either HIV-1 uninfected, high-risk HIV-1 seronegative and seropositive partners from serodiscordant couples, Long-Term Survivors, or HIV-1 infected volunteers from Africa (Rwanda, Kenya, Guinea-Conakry) and Luxembourg, using a real-time PCR assay. The role of the 24-base pair deletion on CCR5 expression and HIV infection was assessed in cell lines and PBMC using mRNA quantification, confocal analysis, flow and imaging cytometry. RESULTS AND DISCUSSION: Among the 1661 patients from Rwanda, 12 individuals were heterozygous for hCCR5Δ24 but none were homozygous. Although heterozygosity for this allele may not confer complete resistance to HIV-1 infection, the prevalence of the mutation was 2.41% (95%CI: 0.43; 8.37) in 83 Long-Term Survivors (LTS) and 0.99% (95%CI: 0.45; 2.14) in 613 HIV-1 exposed seronegative members as compared with 0.35% (95% Cl: 0.06; 1.25) in 579 HIV-1 seropositive members. The prevalence of hCCR5Δ24 was 0.55% (95%CI: 0.15; 1.69) in 547 infants from Kenya but the mutation was not detected in 224 infants from Guinea-Conakry nor in 800 Caucasian individuals from Luxembourg. Expression of hCCR5Δ24 in cell lines and PBMC showed that the hCCR5Δ24 protein is stably expressed but is not transported to the plasma membrane due to a conformational change. Instead, the mutant receptor was retained intracellularly, colocalized with an endoplasmic reticulum marker and did not mediate HIV-1 infection. Co-transfection of hCCR5Δ24 and wtCCR5 did not indicate a transdominant negative effect of CCR5Δ24 on wtCCR5. CONCLUSIONS: Our findings indicate that hCCR5Δ24 is not expressed at the cell surface. This could explain the higher prevalence of the heterozygous hCCR5Δ24 in LTS and HIV-1 exposed seronegative members from serodiscordant couples. Our data suggest an East-African localization of this deletion, which needs to be confirmed in larger cohorts from African and non-African countries.
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Infecciones por VIH/genética , Receptores CCR5/genética , Receptores CCR5/inmunología , Alelos , Membrana Celular/genética , Membrana Celular/metabolismo , Estudios de Cohortes , Resistencia a la Enfermedad , Femenino , Guinea , Infecciones por VIH/inmunología , Infecciones por VIH/metabolismo , VIH-1/fisiología , Heterocigoto , Humanos , Lactante , Kenia , Leucocitos Mononucleares/inmunología , Leucocitos Mononucleares/virología , Masculino , Mutación , Receptores CCR5/metabolismo , Rwanda , Eliminación de SecuenciaRESUMEN
BACKGROUND: An outbreak of HIV infections among people who inject drugs (PWID) started in 2014 in Luxembourg. OBJECTIVES: We conducted phylogenetic and epidemiological analyses among the PWID infected with HIV in Luxembourg or attending the supervised drug consumption facility (SDCF) to understand the main causes of the outbreak. METHODS: Between January 2013 and December 2017, analysis of medical files were performed from all PWID infected with HIV at the National Service of Infectious Diseases (NSID) providing clinical care nationwide. PWID were interviewed at NSID and SDCF using a standardized questionnaire focused on drug consumption and risk behaviours. The national drug monitoring system RELIS was consulted to determine the frequency of cocaine/heroin use. Transmission clusters were analysed by phylogenetic analyses using approximate maximum-likelihood. Univariate and multivariate logistic regression analyses were performed on epidemiological data collected at NSID and SDCF to determine risk factors associated with cocaine use. RESULTS: From January 2013 to December 2017, 68 new diagnosis of HIV infection reported injecting drug use as the main risk of transmission at NSID. The proportion of female cases enrolled between 2013-2017 was higher than the proportion among cases enrolled prior to 2013. (33% vs 21%, p < 0.05). Fifty six viral sequences were obtained from the 68 PWID newly diagnosed for HIV. Two main transmission clusters were revealed: one HIV-1 subtype B cluster and one CRF14_BG cluster including 37 and 9 patients diagnosed since 2013, respectively. Interviews from 32/68 (47%) newly diagnosed PWID revealed that 12/32 (37.5%) were homeless and 27/32 (84.4%) injected cocaine. Increased cocaine injection was indeed reported by the RELIS participants from 53 to 63% in drug users with services contacts between 2012 and 2015, and from 5 to 22% in SDCF users between 2012 and 2016. Compared with PWID who injected only heroin (n = 63), PWID injecting cocaine and heroin (n = 107) were younger (mean of 38 vs 44 years, p≤0.001), reported more frequent piercing (≤0.001), shared and injected drugs more often (p≤0.01), and were more frequently HIV positive (p<0.05) at SDCF using univariate logistic regression analysis. Finally, in the multivariate analysis, use of heroin and cocaine was independently associated with younger age, piercing, sharing of drugs, and regular consumption (p<0.05). CONCLUSIONS: Injecting cocaine is a new trend of drug use in Luxembourg associated with HIV infection in this recent outbreak among PWID.
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Cocaína/administración & dosificación , Brotes de Enfermedades , Infecciones por VIH/epidemiología , Abuso de Sustancias por Vía Intravenosa/epidemiología , Adulto , Cocaína/efectos adversos , Consumidores de Drogas , Femenino , VIH/clasificación , VIH/genética , Infecciones por VIH/transmisión , Humanos , Inyecciones , Modelos Logísticos , Luxemburgo , Masculino , Persona de Mediana Edad , Filogenia , Estudios Retrospectivos , Abuso de Sustancias por Vía Intravenosa/complicacionesRESUMEN
INTRODUCTION: The World Health Organization (WHO) 2010 guidelines recommended to treat all HIV-infected children less than two years of age. We described the inclusion process and its correlates of HIV-infected children initiated on early antiretroviral therapy (EART) at less than two years of age in Abidjan, Côte d'Ivoire, and Ouagadougou, Burkina Faso. METHODS: All children with HIV-1 infection confirmed with a DNA PCR test of a blood sample, aged less than two years, living at a distance less than two hours from the centres and whose parents (or mother if she was the only legal guardian or the legal caregiver if parents were not alive) agreed to participate in the MONOD ANRS 12206 project were included in a cohort to receive EART based on lopinavir/r. We used logistic regression to identify correlates of inclusion. RESULTS: Among the 217 children screened and referred to the MONOD centres, 161 (74%) were included and initiated on EART. The main reasons of non-inclusion were fear of father's refusal (48%), mortality (24%), false-positive HIV infection test (16%) and other ineligibility reasons (12%). Having previously disclosed the child's and mother's HIV status to the father (adjusted odds ratio (aOR): 3.20; 95% confidence interval (95% CI): 1.55 to 6.69) and being older than 12 months (aOR: 2.05; 95% CI: 1.02 to 4.12) were correlates of EART initiation. At EART initiation, the median age was 13.5 months, 70% had reached WHO Stage 3/4 and 57% had a severe immune deficiency. CONCLUSIONS: Fear of stigmatization by the father and early competing mortality were the major reasons for missed opportunities of EART initiation. There is an urgent need to involve fathers in the care of their HIV-exposed children and to promote early infant diagnosis to improve their future access to EART and survival.
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Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Factores de Edad , Estudios de Cohortes , Femenino , Infecciones por VIH/mortalidad , Humanos , Lactante , Recién Nacido , Modelos Logísticos , Masculino , Factores de TiempoAsunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-2/aislamiento & purificación , Quinolonas/uso terapéutico , Carga Viral , Recuento de Linfocito CD4 , Infecciones por VIH/inmunología , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
Cytochrome P450 CYP2B6 is a highly polymorphic enzyme that metabolizes numerous drugs, pesticides, and environmental toxins. Sequence analysis of a Rwandese population identified eight functionally uncharacterized nonsynonymous variants c.329G>T (p.G110V), c.341T>C (p.I114T), c.444G>T (p.E148D), c.548T>G (p.V183G), c.637T>C (p.F213L), c.758G>A (p.R253H), c.835G>C (p.A279P), and c.1459C>A (p.R487S), and five novel alleles termed CYP2B6*33 to CYP2B6*37 were assigned. Recombinant expression in COS-1 cells and functional characterization using the antidepressant bupropion and the antiretroviral efavirenz (EFV) as substrates demonstrated complete or almost complete loss-of-function for variants p.G110V, p.I114T, p.V183G, and p.F213L, whereas p.E148D, p.R253H, p.A279P, and p.R487S variants were functional. The data were used to assess the predictive power of eight online available functional prediction programs for amino-acid changes. Although none of the programs correctly predicted the functionality of all variants, substrate docking simulation analyses indicated similar conformational changes by all four deleterious mutations within the enzyme's active site, thus explaining lack of enzymatic function for both substrates. Because low-activity alleles of CYP2B6 are associated with impaired EFV metabolism and adverse drug response, these results are of potential utility for personalized treatment strategies in HIV/AIDS therapy.
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Hidrocarburo de Aril Hidroxilasas/genética , Genética de Población , Oxidorreductasas N-Desmetilantes/genética , Hidrocarburo de Aril Hidroxilasas/química , Western Blotting , Citocromo P-450 CYP2B6 , Haplotipos , Humanos , Simulación de Dinámica Molecular , Mutación , Oxidorreductasas N-Desmetilantes/química , Polimorfismo de Nucleótido Simple , RwandaRESUMEN
Until now, we have all been desperately trying to run behind the HIV/AIDS epidemic and catch up with it, but despite all our efforts, the epidemic remains well ahead of us. In 2010, the antiretroviral treatment (ART) gap was about 60%, AIDS-related deaths were almost two million a year, and on top of these figures, for every one person started on ART, there were two new HIV infections. What is needed to change this situation is to think ahead of the epidemic in terms of the programmatic tasks we will be faced with and try to act boldly in trying to implement those tasks. From a programmatic perspective, we: a) highlight what needs to fundamentally change in our thinking and overall approach to the epidemic; and b) outline a number of key task areas for implementation and related operational research.
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Infecciones por VIH/epidemiología , Investigación Operativa , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Síndrome de Inmunodeficiencia Adquirida/economía , Síndrome de Inmunodeficiencia Adquirida/epidemiología , Síndrome de Inmunodeficiencia Adquirida/prevención & control , África del Sur del Sahara/epidemiología , Fármacos Anti-VIH/economía , Fármacos Anti-VIH/uso terapéutico , Control de Enfermedades Transmisibles , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/economía , Infecciones por VIH/prevención & control , Humanos , Programas Nacionales de SaludRESUMEN
Entry of Human Immunodeficiency Virus type 1 (HIV-1) into target cells is mediated by the CD4 receptor and a coreceptor, CCR5 or CXCR4. Maraviroc interferes with HIV entry by binding the CCR5 coreceptor. Virological failure to maraviroc-containing regimens can occur through the emergence of resistance, or through tropism evolution and broadened coreceptor usage. In the latter case, the physiological relevance of minority strains is a major concern. Here we report a retrospective analysis of coreceptor-usage and evolution based on 454-ultra-deep-sequencing of plasma and Peripheral Blood Mononuclear Cell (PBMC)-derived envelope V3-loops, accounting for coreceptor usage, from a patient who failed a maraviroc-containing regimen through the emergence of X4 strains. The X4 maraviroc-escape variant resulted from recombination between a long time archived proviral sequence from 2003 (5'-portion, including the V3-loop) and the dominant R5 strains circulating in plasma at the time of maraviroc-treatment initiation (3'-portion). Phylogenetic analyses and BEAST modeling highlighted that an early diverse viral quasispecies underwent a severe bottleneck following reinitiation of HAART and repeated IL-2 cycles between 1999 and 2001, leading to the transient outgrowth and archiving of one highly homogeneous X4 population from plasma, and to the expansion in plasma of one PBMC-derived R5 strain. Under maraviroc selective pressure, the early, no longer detectable X4 strains archived in PBMC were partially rescued to provide X4-determinants to the main circulating strain.
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Ciclohexanos/uso terapéutico , Inhibidores de Fusión de VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , Triazoles/uso terapéutico , Terapia Antirretroviral Altamente Activa , Secuencia de Bases , Antagonistas de los Receptores CCR5 , Recuento de Linfocito CD4 , Ciclohexanos/farmacología , Genotipo , Inhibidores de Fusión de VIH/farmacología , VIH-1/clasificación , VIH-1/genética , Humanos , Leucocitos Mononucleares/virología , Maraviroc , Pruebas de Sensibilidad Microbiana , Datos de Secuencia Molecular , Filogenia , Receptores CCR5/genética , Receptores CXCR4/genética , Receptores CXCR4/metabolismo , Alineación de Secuencia , Insuficiencia del Tratamiento , Triazoles/farmacología , Carga Viral , Tropismo ViralRESUMEN
Kaposi's sarcoma (KS) is a rare cutaneous tumor caused by human herpes virus-8 (HHV-8) infection that preferentially develops in case of severe immunosuppression, such as in HIV/AIDS disease. Haptoglobin (Hp), a polymorphic multifunctional plasma protein, exerts several immunomodulatory effects and is characterized by a genetic polymorphism leading to three major phenotypes (Hp 1-1, Hp 2-1 and Hp 2-2). This study investigated the influence of Hp genetic polymorphism on the development of KS in HIV-positive patients. 661 HIV patients were enrolled in the study with a median age of 35 years and a median follow-up time of 57 months. Hp phenotyping was performed using hemoglobin-supplemented starch gel electrophoresis. In case of low Hp concentration high pressure gel permeation chromatography (HPGPC) was used. The Hp 1-1 phenotype was associated with a significant higher risk of KS compared to the combined group of Hp 2-1 and Hp 2-2 patients (p < 0.0005) which remained significant after adjustment for possible confounding variables (age, gender and AIDS status) (p < 0.001). In contrast, the Hp 2-1 phenotype carried the lowest risk. These findings point to the involvement of Hp phenotypes in the pathogenesis of KS, which may be due to a difference in skin immunosurveillance between the Hp phenotypes.
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Infecciones por VIH/genética , VIH/inmunología , Haptoglobinas/genética , Infecciones por Herpesviridae/genética , Herpesvirus Humano 8/inmunología , Sarcoma de Kaposi/genética , Adulto , Análisis Mutacional de ADN , Femenino , Estudios de Seguimiento , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , VIH/patogenicidad , Infecciones por VIH/complicaciones , Infecciones por VIH/inmunología , Infecciones por VIH/metabolismo , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/inmunología , Infecciones por Herpesviridae/metabolismo , Herpesvirus Humano 8/patogenicidad , Humanos , Terapia de Inmunosupresión , Masculino , Polimorfismo Genético , Factores de Riesgo , Sarcoma de Kaposi/etiología , Sarcoma de Kaposi/inmunología , Sarcoma de Kaposi/metabolismoRESUMEN
OBJECTIVE: The aim of our study was to assess the diagnostic performance of various serological markers and scores for predicting significant fibrosis retrospectively in a population of patients referring to our hospital for liver biopsy and chronic hepatitis C. MATERIALS AND METHODS: Stored serum obtained from 186 patients were tested for a number of biological markers putatively associated with liver fibrosis. Fibrotest and Forns scores were compared with liver fibrosis pathology scored according to the METAVIR system by multiple logistic regression. RESULTS: The prevalence of significant fibrosis was 44%. Aspartate amino transferase (AST) and gamma-glutamyltransferase (GGT) were most correlated with METAVIR staging, followed by platelet counts and alpha2-macroglobulin. The negative predictive value was 77% and 83% and the positive predictive value was 100% and 84% for the Forns score and the Fibrotest, respectively. In multivariate analysis AST, GGT and alpha2-macroglobulin had independent predictive power. CONCLUSIONS: The accuracy of serological markers in predicting significant fibrosis is limited, because approximately two thirds of patients lie into an indeterminate "grey zone". Serological markers might be useful for patients reluctant to undergo liver biopsy but current predictive scoring systems are too inaccurate to replace biopsies in a routine manner.
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Aspartato Aminotransferasas/sangre , Cirrosis Hepática/sangre , alfa-Macroglobulinas/análisis , gamma-Glutamiltransferasa/sangre , Adolescente , Adulto , Anciano , Biomarcadores , Biopsia , Femenino , Hepatitis C/complicaciones , Humanos , Hígado/patología , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Modelos Logísticos , Luxemburgo , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
Saliva may provide interesting advantages as matrix for compliance measurements, pharmacokinetic studies and therapeutic drug monitoring in resource limited countries. We investigated the feasibility of using saliva for compliance monitoring of zidovudine (ZDV), lamivudine (3TC) and nevirapine (NVP) in 29 HIV-1 infected patients from Rwanda. ZDV, 3TC and NVP drug levels were quantified by an LC/MS-MS method in plasma and stimulated saliva samples and compared using Bland-Altman analysis. Seven patients demonstrated undetectable saliva ZDV levels while five out of these seven also showed no 3TC salivary concentrations. For the other samples, we observed a good agreement between salivary and plasma concentrations of each antiretroviral drug. A significant relation between the difference in saliva and plasma ZDV concentrations and the average ZDV concentration in the two matrices was deduced as follow: y = -380.15 + 1.79 x. The log saliva and plasma concentration difference of both 3TC and NVP was consistent across the range of average log concentration. Overall, we showed large agreement limits suggesting a wide inter patient variability that may result to non-reliable plasma level predictions from saliva drug measurements. Therefore, our results indicate that saliva may serve as a valuable tool only for NVP compliance testing because of its high salivary concentration.
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Fármacos Anti-VIH/análisis , Fármacos Anti-VIH/uso terapéutico , Monitoreo de Drogas/métodos , Infecciones por VIH/tratamiento farmacológico , Saliva/química , Adulto , Estudios Transversales , Estudios de Factibilidad , Femenino , Infecciones por VIH/sangre , VIH-1 , Humanos , Lamivudine/análisis , Lamivudine/uso terapéutico , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Nevirapina/análisis , Nevirapina/uso terapéutico , Rwanda , Zidovudina/análisis , Zidovudina/uso terapéuticoRESUMEN
Despite the enormous progress made in scaling up antiretroviral therapy (ART) in sub-Saharan Africa, many challenges remain, not least of which are the identification and management of patients who have failed first-line therapy. Less than 3% of patients are receiving second-line treatment at present, whereas 15-25% of patients have detectable viral loads 12 months or more into treatment, of whom a substantial proportion might have virological failure. We discuss the reasons why virological ART failure is likely to be under-diagnosed in the routine health system, and address the current difficulties with standard recommended second-line ART regimens. The development of new diagnostic tools for ART failure, in particular a point-of-care HIV viral-load test, combined with simple and inexpensive second-line therapy, such as boosted protease-inhibitor monotherapy, could revolutionise the management of ART failure in resource-limited settings.
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Fármacos Anti-VIH/administración & dosificación , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/economía , Infecciones por VIH/terapia , África del Sur del Sahara/epidemiología , Fármacos Anti-VIH/economía , Infecciones por VIH/epidemiología , Costos de la Atención en Salud , Humanos , ARN Viral , Insuficiencia del Tratamiento , Carga ViralRESUMEN
OBJECTIVE: To assess the 9-month HIV-free survival of children with two strategies to prevent HIV mother-to-child transmission. DESIGN: Nonrandomized interventional cohort study. SETTING: Four public health centres in Rwanda. PARTICIPANTS: Between May 2005 and January 2007, all consenting HIV-infected pregnant women were included. INTERVENTION: Women could choose the mode of feeding for their infant: breastfeeding with maternal HAART for 6 months or formula feeding. All received HAART from 28 weeks of gestation. Nine-month cumulative probabilities of HIV transmission and HIV-free survival were determined using the Kaplan-Meier method and compared using the log-rank test. Determinants were analysed using a Cox model analysis. RESULTS: Of the 532 first-liveborn infants, 227 (43%) were breastfeeding and 305 (57%) were formula feeding. Overall, seven (1.3%) children were HIV-infected of whom six were infected in utero. Only one child in the breastfeeding group became infected between months 3 and 7, corresponding to a 9-month cumulative risk of postnatal infection of 0.5% [95% confidence interval (CI) 0.1-3.4%; P = 0.24] with breastfeeding. Nine-month cumulative mortality was 3.3% (95% CI 1.6-6.9%) in the breastfeeding arm group and 5.7% (95% CI 3.6-9.2%) for the formula feeding group (P = 0.20). HIV-free survival by 9 months was 95% (95% CI 91-97%) in the breastfeeding group and 94% (95% CI 91-96%) for the formula feeding group (P = 0.66), with no significant difference in the adjusted analysis (adjusted hazard ratio for breastfeeding: 1.2 (95% CI 0.5-2.9%). CONCLUSION: : Maternal HAART while breastfeeding could be a promising alternative strategy in resource-limited countries.
Asunto(s)
Terapia Antirretroviral Altamente Activa/métodos , Lactancia Materna , Infecciones por VIH/transmisión , VIH-1 , Fórmulas Infantiles/administración & dosificación , Transmisión Vertical de Enfermedad Infecciosa/prevención & control , Adulto , Estudios de Cohortes , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Lactante , Recién Nacido , Profilaxis Posexposición/métodos , Embarazo , Complicaciones Infecciosas del Embarazo/tratamiento farmacológico , Complicaciones Infecciosas del Embarazo/epidemiología , Rwanda/epidemiología , Análisis de SupervivenciaRESUMEN
INTRODUCTION: All infants born to HIV-positive mothers have maternal HIV antibodies, sometimes persistent for 18 months. When Polymerase Chain Reaction (PCR) is not available, August 2006 World Health Organization (WHO) recommendations suggest that clinical criteria may be used for starting antiretroviral treatment (ART) in HIV seropositive children <18 months. Predictors are at least two out of sepsis, severe pneumonia and thrush, or any stage 4 defining clinical finding according to the WHO staging system. METHODS AND RESULTS: From January 2005 to October 2006, we conducted a prospective study on 236 hospitalized children <18 months old with a positive HIV serological test at the national reference hospital in Kigali. The following data were collected: PCR, clinical signs and CD4 cell count. Current proposed clinical criteria were present in 148 of 236 children (62.7%) and in 95 of 124 infected children, resulting in 76.6% sensitivity and 52.7% specificity. For 87 children (59.0%), clinical diagnosis was made based on severe unexplained malnutrition (stage 4 clinical WHO classification), of whom only 44 (50.5%) were PCR positive. Low CD4 count had a sensitivity of 55.6% and a specificity of 78.5%. CONCLUSION: As PCR is not yet widely available, clinical diagnosis is often necessary, but these criteria have poor specificity and therefore have limited use for HIV diagnosis. Unexplained malnutrition is not clearly enough defined in WHO recommendations. Extra pulmonary tuberculosis (TB), almost impossible to prove in young children, may often be the cause of malnutrition, especially in HIV-affected families more often exposed to TB. Food supplementation and TB treatment should be initiated before starting ART in children who are staged based only on severe malnutrition.
Asunto(s)
Infecciones por VIH/diagnóstico , Seropositividad para VIH , Recuento de Linfocito CD4 , Femenino , Anticuerpos Anti-VIH/inmunología , Infecciones por VIH/inmunología , Humanos , Lactante , Masculino , Rwanda , Organización Mundial de la SaludRESUMEN
In Western Africa, hepatitis B virus (HBV) genotype E predominates throughout a vast crescent spanning from Senegal to Namibia and at least to the Central African Republic to the East. Although from most of the eastern parts of sub-Saharan Africa only limited sets of strains have been characterized, these belong predominantly to genotype A. To study how far the genotype E crescent extends to the East, a larger number of HBV strains from Rwanda were analyzed. Phylogenetic analysis of 45 S fragment sequences revealed strains of genotypes A (n = 30), D (n = 10), C (n = 4), and B (n = 1). Twelve genotype A sequences formed a new cluster clearly separated from the reference strains of the known sub-genotypes. Thus, with four genotypes and at least six sub-genotypes and a new cluster of genotype A strains, HBV shows an exceptional genetic variability in this small country, unprecedented in sub-Saharan Africa. Despite this exceptional genetic variability, not a single genotype E virus was found indicating that this country does not belong to the genotype E crescent, but is east of an emerging African genotype E/A1 divide.
Asunto(s)
Variación Genética , Virus de la Hepatitis B/clasificación , Virus de la Hepatitis B/genética , Hepatitis B/epidemiología , Hepatitis B/virología , Análisis por Conglomerados , ADN Viral/química , ADN Viral/genética , Femenino , Genotipo , Virus de la Hepatitis B/aislamiento & purificación , Humanos , Datos de Secuencia Molecular , Filogenia , Mujeres Embarazadas , Rwanda/epidemiología , Análisis de Secuencia de ADNRESUMEN
We conducted a prospective study to investigate access to treatment in hepatitis C in 268 prisoners. Hepatitis C positivity had been known for 182 prisoners previously and 19 reported previous attempts to treat (10%). In comparison, during our study, 86/268 prisoners (32%) started therapy (P < 0.0001). They represented 41% of 211 prisoners with a positive viral load. In the genotype 2 or 3 group, 46 prisoners (50%) started therapy versus 40 prisoners (33%) with other genotypes (P = 0.01). This difference was due to prisoners waiting for liver biopsy. On an intention to treat basis, 45 prisoners (52%) achieved sustained virological response 6 months after the end of therapy. We conclude that a stay in prison is an effective opportunity to treat a group of hepatitis C patients which otherwise have very limited access to therapy.