RESUMEN
INTRODUCTION: Although antiretroviral therapy (ART) leads to reduced tuberculosis (TB) incidence in people with HIV (PWH), ART recipients remain at higher risk of TB compared to HIV-seronegative people. With accelerated ART rollout in sub-Saharan Africa, increasing proportions of TB cases among PWH in people receiving long-term ART have been reported. OBJECTIVE: To determine TB notifications among PWH by ART status in a mainly urban uptake area in Ethiopia during an 8-year period in connection to the introduction of the 'test-and-treat' strategy for HIV. METHODS: PWH were identified from registers at health facilities providing ART in Adama and surrounding areas, Ethiopia 2015-2022. Annual TB notifications were compared over time. PWH within TB were categorized by ART status at the time of TB diagnosis (pre-ART TB: TB diagnosed before or ≤6 months after starting ART; ART-associated TB: TB diagnosed >6 months after starting ART). RESULTS: Among a total of 8,926 PWH, 993 had been diagnosed with TB (11.1%); mean age 40.0 years [SD 11.8], 53.5% were men). Throughout the study period, most TB cases had been notified before ART initiation (617/993; 62.1%). ART-associated TB cases constituted a mean of 37.4% (range 23.8%-44.2%) of all TB cases among PWH annually. Median time from ART initiation to TB diagnosis among ART-associated TB was 6.0 years. CONCLUSION: TB notifications among PWH in this area did not decrease 2015-2022, implying persistently high risk of TB among PWH in this setting. Most TB cases occurred in ART-naïve persons, illustrating late HIV diagnosis in this population.
Main findings: Annual numbers of TB notifications among PWH in Central Ethiopia were persistently high 20152022 and most cases of TB were diagnosed before or within 6 months after ART initiation, implying late diagnosis of HIV in these individuals.Added knowledge: Epidemiology of HIV-associated TB by ART status has not been studied in Ethiopia since the implementation of the 'test-and-treat' strategy and this study shows that, despite ART rollout, most TB cases among PWH still occur before (or in connection to) ART initiation.Global health impact for policy and action: This study provides new and useful information to the readers of Global Health Action and the Ministry of Health in Ethiopia and other countries affected by TB and HIV for current and future management of HIV-associated TB.
Asunto(s)
Infecciones por VIH , Tuberculosis , Humanos , Etiopía/epidemiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Masculino , Femenino , Tuberculosis/epidemiología , Tuberculosis/tratamiento farmacológico , Adulto , Incidencia , Persona de Mediana Edad , Antirretrovirales/uso terapéutico , Fármacos Anti-VIH/uso terapéutico , Adulto JovenRESUMEN
Background: The aim of this study was to investigate the development of fatigue and mental illness between 3 and 12 months after critical COVID-19 and explore risk factors for long-lasting symptoms. Study Design and Methods: A prospective, multicenter COVID-19 study in southern Sweden, including adult patients (≥18 years) with rtPCR-confirmed COVID-19 requiring intensive care. Survivors were invited to a follow-up at 3 and 12 months, where patient-reported symptoms were assessed using the Modified Fatigue Impact Scale (MFIS), the Hospital Anxiety and Depression Scale (HADS) and the Posttraumatic Stress Disorder Checklist version 5 (PCL-5). The development between 3 and 12 months was described by changes in relation to statistical significance and suggested values for a minimally important difference (MID). Potential risk factors for long-lasting symptoms were analyzed by multivariable logistic regression. Results: At the 3-month follow-up, 262 survivors (87%) participated, 215 (72%) returned at 12 months. Fatigue was reported by 50% versus 40%, with a significant improvement at 12 months (MFIS; median 38 vs. 33, P < .001, MID ≥4). There were no significant differences in symptoms of mental illness between 3 and 12 months, with anxiety present in 33% versus 28%, depression in 30% versus 22%, and posttraumatic stress disorder in 17% versus 13%. A worse functional outcome and less sleep compared to before COVID-19 were risk factors for fatigue and mental illness at 12 months. Conclusions: Fatigue improved between 3 and 12 months but was still common. Symptoms of mental illness remained unchanged with anxiety being the most reported. A worse functional outcome and less sleep compared to before COVID-19 were identified as risk factors for reporting long-lasting symptoms.
RESUMEN
OBJECTIVES: Women living with HIV are underrepresented in clinical trials assessing outcomes of antiretroviral treatment (ART), justifying the need for observational studies. We investigated differences in viral non-suppression between women and men in the Swedish InfCareHIV cohort and analysed results in relation to biological and socio-demographic variables and patient-reported outcome measures (PROMs). METHODS: The study included people living with HIV (PLWH) aged ≥18 years, who initiated ART at least 6 months prior to inclusion. Data from the InfCareHIV registry 2011-2018 were collected. Associations between variables and HIV RNA ≥50 copies/mL were investigated in uni- and multivariable analyses using generalized estimating equations, providing relative risks (RRs) as effect size. RESULTS: The study included 38% (n = 2981) women. Women were more likely to have HIV RNA ≥50 copies/mL than were men [RR = 1.20, 95% confidence interval (CI): 1.10-1.31]. After adjusting for origin and route of transmission, sex at birth was no longer associated with viral non-suppression. PROMs were available in 52.4% of PLWH, and items associated with viral non-suppression were impaired adherence in women (RR = 2.38, 95% CI: 1.79-3.17) and men (RR 1.84, 95% CI: 1.40-2.42), and experience of side effects in women (RR = 1.49, 95% CI: 1.10-2.02). CONCLUSIONS: This observational study found a 20% higher relative risk of viral non-suppression in women than in men and the difference was associated with socio-demographic factors. The associations between PROMs and viral non-suppression varied between women and men. PROMs are important health outcomes that may identify PLWH in need of support to achieve viral non-suppression.
Asunto(s)
Infecciones por VIH , Carga Viral , Humanos , Masculino , Femenino , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Suecia/epidemiología , Adulto , Persona de Mediana Edad , Factores Sexuales , Estudios de Cohortes , Medición de Resultados Informados por el Paciente , Fármacos Anti-VIH/uso terapéutico , ARN Viral , Adulto Joven , AdolescenteRESUMEN
BACKGROUND: Targeted viral load (VL) testing has been proposed for antiretroviral treatment (ART) monitoring in resource-limited settings. In this study, we have investigated the performance of the host biomarker galectin-9 (Gal-9), alone and in combination with interferon-γ-inducible protein 10 (IP-10), in identifying individuals at increased likelihood of viremia during ART. SETTING: Cohort of HIV-positive adults receiving ART at Ethiopian health centers. METHODS: We included participants with detectable viremia (VL ≥150 copies/mL) 12 months after starting ART and sex-matched nonviremic controls. Performance to identify individuals with VL ≥1000 copies/mL was determined for Gal-9 and the Gal-9/IP-10 combination, respectively, using receiver operating characteristic (ROC) analysis. RESULTS: Among 191 participants (50.3% women), 46 (24.1%) had VL ≥1000 copies/mL, 23 (12.0%) had 150-999 copies/mL, and 122 (63.9%) had <150 copies/mL. Gal-9 and VL were positively correlated (r s = 0.451, P < 0.001). Sensitivity and specificity for Gal-9 to identify individuals with VL ≥1000 copies/mL were 91.3% (95% CI: 79.2-97.6) and 54.5% (95% CI: 46.0-62.8), respectively. The area under the ROC curve for Gal-9 was 0.810 (95% CI: 0.745-0.875), which was similar to that of the combination of Gal-9 and IP-10 [0.849 (95% CI: 0.792-0.905)]. Assuming 10% prevalence of VL ≥1000 copies/mL, using Gal-9 for targeted VL testing instead of universal VL testing would reduce the number of VL tests from 10 to 5 to identify 1 viremic individual, with misclassification of 1 in 10 viremic individuals. CONCLUSIONS: Gal-9 is a potential screening marker for targeted VL monitoring in ART recipients. Further studies are needed to determine optimal threshold levels.
Asunto(s)
Fármacos Anti-VIH , Infecciones por VIH , Humanos , Adulto , Femenino , Masculino , Infecciones por VIH/tratamiento farmacológico , Quimiocina CXCL10 , Configuración de Recursos Limitados , Viremia/tratamiento farmacológico , Antirretrovirales/uso terapéutico , Carga Viral , Fármacos Anti-VIH/uso terapéuticoRESUMEN
BACKGROUND: Traditional models to predict intensive care outcomes do not perform well in COVID-19. We undertook a comprehensive study of factors affecting mortality and functional outcome after severe COVID-19. METHODS: In this prospective multicentre cohort study, we enrolled laboratory-confirmed, critically ill COVID-19 patients at six ICUs in the Skåne Region, Sweden, between May 11, 2020, and May 10, 2021. Demographics and clinical data were collected. ICU burden was defined as the total number of ICU-treated COVID-19 patients in the region on admission. Surviving patients had a follow-up at 90 days for assessment of functional outcome using the Glasgow Outcome Scale-Extended (GOSE), an ordinal scale (1-8) with GOSE ≥5 representing a favourable outcome. The primary outcome was 90-day mortality; the secondary outcome was functional outcome at 90 days. RESULTS: Among 498 included patients, 74% were male with a median age of 66 years and a median body mass index (BMI) of 30 kg/m2 . Invasive mechanical ventilation was employed in 72%. Mortality in the ICU, in-hospital and at 90 days was 30%, 38% and 39%, respectively. Mortality increased markedly at age 60 and older. Increasing ICU burden was independently associated with a two-fold increase in mortality. Higher BMI was not associated with increased mortality. Besides age and ICU burden, smoking status, cortisone use, Pa CO2 >7 kPa, and inflammatory markers on admission were independent factors of 90-day mortality. Lower GOSE at 90 days was associated with a longer stay in the ICU. CONCLUSION: In critically ill COVID-19 patients, the 90-day mortality was 39% and increased considerably at age 60 or older. The ICU burden was associated with mortality, whereas a high BMI was not. A longer stay in the ICU was associated with unfavourable functional outcomes at 90 days.
Asunto(s)
COVID-19 , Humanos , Masculino , Anciano , Persona de Mediana Edad , Femenino , COVID-19/terapia , SARS-CoV-2 , Estudios de Cohortes , Estudios Prospectivos , Enfermedad Crítica , Unidades de Cuidados IntensivosRESUMEN
Interferon-γ-inducible protein 10 (IP-10) has been suggested as a marker for targeted viral load (VL) monitoring during antiretroviral treatment (ART). We aimed to determine the kinetics of IP-10 during the initial year of ART, with particular regard to the impact of tuberculosis (TB) co-infection on IP-10 secretion. Longitudinal plasma IP-10 levels were quantified in 112 treatment-naive HIV-positive adults at Ethiopian health centers, through enzyme-linked immunosorbent assay (ELISA) using samples obtained before and during the initial 12 months of ART. All participants underwent bacteriological TB investigation before starting ART. In virological responders (VRs; defined as VL < 150 copies/ml with no subsequent VL ≥ 1,000 copies/ml), IP-10 kinetics were analyzed using linear regression models. Among 91/112 (81.3%) participants classified as VRs, 17 (18.7%) had concomitant TB. Median baseline IP-10 was 650 pg/ml (interquartile range [IQR], 428-1,002) in VRs. IP-10 decline was more rapid during the first month of ART (median 306 pg/ml/month) compared with later time intervals (median 7-48 pg/ml/month, P < 0.001 in each comparison). Although VRs with TB had higher IP-10 levels at baseline (median 1106 pg/ml [IQR, 627-1,704]), compared with individuals without TB (median 628 pg/ml [IQR, 391-885]; P = 0.003), the rate of IP-10 decline during ART was similar, regardless of TB-status. During the initial year of ART, IP-10 kinetics followed a biphasic pattern in VRs, with a more rapid decline in the first month of ART compared with later time intervals. Baseline IP-10 was higher in individuals with TB versus individuals without TB, but the kinetics during ART were similar. IMPORTANCE To reach the goal of elimination of HIV as public health threat, access to antiretroviral treatment (ART) has to be further scaled up. To ensure viral suppression in individuals receiving ART, novel and robust systems for treatment monitoring are required. Targeting viral load monitoring to identify individuals at increased likelihood of treatment failure, using screening tools, could be an effective use of limited resources for viral load testing. Interferon-γ-inducible protein 10 (IP-10), a host inflammation mediator, has shown potential for this purpose. Here, we have investigated IP-10 kinetics in Ethiopian adults with HIV during the initial year after ART initiation. IP-10 levels decreased in parallel with viral load during ART, and prevalent tuberculosis at ART initiation did not influence IP-10 kinetics. This study shows satisfactory performance for IP-10 as a surrogate marker for viral load in persons starting ART, with no influence of concomitant tuberculosis.
Asunto(s)
Antirretrovirales/uso terapéutico , Quimiocina CXCL10/análisis , Quimiocina CXCL10/farmacocinética , Infecciones por VIH/tratamiento farmacológico , VIH-1/inmunología , Tuberculosis Pulmonar/inmunología , Adulto , Quimiocina CXCL10/metabolismo , Coinfección/microbiología , Etiopía , Femenino , VIH-1/efectos de los fármacos , Humanos , Interferón gamma/inmunología , Masculino , Carga ViralRESUMEN
BACKGROUND: The increasing prevalence of antiretroviral drug resistance in Sub-Saharan Africa threatens the success of HIV programs. We have characterized patterns of drug resistance mutations (DRMs) during the initial year of antiretroviral treatment (ART) in HIV-positive adults receiving care at Ethiopian health centers and investigated the impact of tuberculosis on DRM acquisition. METHODS: Participants were identified from a cohort of ART-naïve individuals aged ≥18 years, all of whom had been investigated for active tuberculosis at inclusion. Individuals with viral load (VL) data at 6 and/or 12 months after ART initiation were selected for this study. Genotypic testing was performed on samples with VLs ≥500 copies/mL obtained on these occasions and on pre-ART samples from those with detectable DRMs during ART. Logistic regression analysis was used to investigate the association between DRM acquisition and tuberculosis. RESULTS: Among 621 included individuals (110 [17.5%] with concomitant tuberculosis), 101/621 (16.3%) had a VL ≥500 copies/mL at 6 and/or 12 months. DRMs were detected in 64/98 cases with successful genotyping (65.3%). DRMs were detected in 7/56 (12.5%) pre-ART samples from these individuals. High pre-ART VL and low mid-upper arm circumference were associated with increased risk of DRM acquisition, whereas no such association was found for concomitant tuberculosis. CONCLUSIONS: Among adults receiving health center-based ART in Ethiopia, most patients without virological suppression during the first year of ART had detectable DRM. Acquisition of DRM during this period was the dominant cause of antiretroviral drug resistance in this setting. Tuberculosis did not increase the risk of DRM acquisition.
Asunto(s)
Infecciones por Coronavirus/enzimología , Peptidil-Dipeptidasa A/sangre , Neumonía Viral/enzimología , Adolescente , Factores de Edad , Enzima Convertidora de Angiotensina 2 , COVID-19 , Niño , Femenino , Humanos , Masculino , Pandemias , Peptidil-Dipeptidasa A/química , Factores Sexuales , Solubilidad , Adulto JovenRESUMEN
BACKGROUND: The use of surrogate markers for targeting viral load (VL) testing could be an alternative to universal VL testing during antiretroviral treatment (ART) and would allow for more effective resource allocation. We investigated the correlation between levels of HIV RNA and interferon-γ-inducible protein 10 (IP-10) in Ethiopian adults at 12 months after ART initiation. In addition, we specifically investigated differences in IP-10 levels between patients with and without virological suppression. SETTING: Cohort of HIV-positive adults receiving ART at Ethiopian health centers. METHODS: Using a nested case-control design, individuals without virological suppression (HIV RNA ≥ 150 copies/mL) at 12 months after ART initiation were gender-matched with virologically suppressed controls (1:2 ratio). IP-10 levels were correlated with HIV RNA, and the distribution of IP-10 was compared for 3 VL strata: <150 copies/mL (VL < 150), 150-999 copies/mL (VL150-999), and ≥1000 copies/mL (VL ≥ 1000). RESULTS: At 12 months after ART initiation, the following VL distribution was found among 192 individuals (50% women): VL < 150, 122/192 (63.5%); VL150-999, 23/192 (12.0%); and VL ≥ 1000 47/192 (24.5%). IP-10 and HIV RNA levels were positively correlated (r = 0.481; P < 0.0001). Median IP-10 levels for the VL strata were VL < 150: 159 pg/mL [interquartile range (IQR) 121-246], VL150-999: 174 pg/mL (IQR 131-276), and VL ≥ 1000: 343 pg/mL (IQR 190-529), respectively. These differences were statistically significant for VL ≥ 1000 versus VL < 150 (adjusted P < 0.001) and VL150-999 (adjusted P = 0.004), respectively. CONCLUSIONS: IP-10 and HIV RNA levels during ART showed significant correlations, with significantly higher IP-10 concentration in ART recipients with VL ≥ 1000 copies/mL compared to those with suppressed or undetectable VL.
Asunto(s)
Antirretrovirales/uso terapéutico , Quimiocina CXCL10/metabolismo , Infecciones por VIH/tratamiento farmacológico , Interferón gamma/metabolismo , Carga Viral/efectos de los fármacos , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Quimiocina CXCL10/sangre , Etiopía , Femenino , VIH-1/genética , Humanos , Masculino , ARN Viral/sangreRESUMEN
OBJECTIVES: Restricted capacity for viral load (VL) testing is a major obstacle for antiretroviral therapy (ART) programmes in high-burden regions. Algorithms for targeted VL testing could help allocate laboratory resources rationally. We validated the performance of the Viral Load Testing Criteria (VLTC), an algorithm with satisfactory performance in derivation (sensitivity 91%, specificity 43%). METHODS: HIV-positive adults who had been receiving first-line ART for ≥12 months at three Ethiopian public ART clinics were included. Healthcare providers collected data on variables of the VLTC: current CD4 count, mid-upper arm circumference (MUAC) and self-reported treatment interruption. VL testing was performed in parallel. Performance of the algorithm for identification of patients with VL ≥ 1000 copies/ml was evaluated. RESULTS: Of 562 patients (female 62%, median ART duration 92 months), 33 (6%) had VL ≥ 1000 copies/ml. Sensitivity for the VLTC was 85% (95% CI, 68-95), specificity 60% (95% CI, 55-64), positive predictive value 12% (95% CI, 10-14) and negative predictive value 98% (95% CI, 97-99). Use of the algorithm would reduce the number of VL tests required by 57%. Misclassification occurred in 5/33 (15%) of subjects with VL ≥ 1000 copies/ml. CONCLUSION: In validation, the VLTC performed similarly well as derivation. Use of the VLTC may be considered for targeted VL testing for ART monitoring in high-burden regions.
OBJECTIFS: La capacité restreinte de mesure de la charge virale (CV) constitue un obstacle majeur pour les programmes de traitement antirétroviral (ART) dans les régions à prévalence élevée. Des algorithmes pour des tests ciblés de la CV pourraient aider à allouer les ressources de laboratoire de manière rationnelle. Nous avons validé la performance des critères de mesure de la charge virale (VLTC), un algorithme dont la performance de dérivation est satisfaisante (sensibilité de 91%, spécificité de 43%). MÉTHODES: Des adultes VIH positifs qui recevaient un ART de première ligne depuis au moins 12 mois dans trois cliniques ART publiques éthiopiennes ont été inclus. Les prestataires de soins de santé ont collecté des données sur les variables des VLTC: nombre actuel de CD4, périmètre brachial et interruption de traitement auto-déclarée. La mesure de la CV a été réalisée en parallèle. La performance de l'algorithme pour l'identification des patients avec une CV≥1000 copies/mL a été évaluée. RÉSULTATS: Sur 562 patients (femmes 62%, durée médiane de l'ART 92 mois), 33 (6%) avaient une CV ≥1000 copies/mL. La sensibilité des VLTC était de 85% (IC95%: 68-95), sa spécificité de 60% (IC95%: 55-64), sa valeur prédictive positive de 12% (IC95%: 10-14) et sa valeur prédictive négative de 98% (IC95%: 97-99). L'utilisation de l'algorithme réduirait le nombre de tests de CV requis de 57%. Une mauvaise classification est survenue chez 5/33 (15%) des sujets avec CV ≥1000 copies/ml. CONCLUSION: En validation, les VLTC ont obtenu une performance aussi bonne comme dérivation. L'utilisation des VLTC peut être envisagée pour des mesures ciblées de la CV dans le suivi des ART dans les régions à forte charge de morbidité.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Carga Viral , Adulto , Algoritmos , Etiopía , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y EspecificidadRESUMEN
BACKGROUND: In order to increase treatment coverage, antiretroviral treatment (ART) is provided through primary health care in low-income high-burden countries, where tuberculosis (TB) co-infection is common. We investigated the long-term outcome of health center-based ART, with regard to concomitant TB. METHODS: ART-naïve adults were included in a prospective cohort at Ethiopian health centers and followed for up to 4 years after starting ART. All participants were investigated for active TB at inclusion. The primary study outcomes were the impact of concomitant TB on all-cause mortality, loss to follow-up (LTFU), and lack of virological suppression (VS). Kaplan-Meier survival estimates and Cox proportional hazards models with multivariate adjustments were used. RESULTS: In total, 141/729 (19%) subjects had concomitant TB, 85% with bacteriological confirmation (median CD4 count TB, 169 cells/mm3; IQR, 99-265; non-TB, 194 cells/mm3; IQR, 122-275). During follow-up (median, 2.5 years), 60 (8%) died and 58 (8%) were LTFU. After ≥6 months of ART, 131/630 (21%) had lack of VS. Concomitant TB did not influence the rates of death, LTFU, or VS. Male gender and malnutrition were associated with higher risk of adverse outcomes. Regardless of TB co-infection status, even after 3 years of ART, two-thirds of participants had CD4 counts below 500 cells/mm3. CONCLUSIONS: Concomitant TB did not impact treatment outcomes in adults investigated for active TB before starting ART at Ethiopian health centers. However, one-third of patients had unsatisfactory long-term treatment outcomes and immunologic recovery was slow, illustrating the need for new interventions to optimize ART programs.
RESUMEN
BACKGROUND: Early identification of virological failure (VF) limits occurrence and spread of drug-resistant viruses in patients receiving antiretroviral treatment (ART). Viral load (VL) monitoring is therefore recommended, but capacities to comply with this are insufficient in many low-income countries. Clinical algorithms might identify persons at higher likelihood of VF to allocate VL resources. OBJECTIVES: We aimed to construct a VF algorithm (the Viral Load Testing Criteria; VLTC) and compare its performance to the 2013 WHO treatment failure criteria. METHODS: Subjects with VL results available 1 year after ART start (n = 494) were identified from a cohort of ART-naïve adults (n = 812), prospectively recruited and followed 2011-2015 at Ethiopian health centres. VF was defined as VL≥1000 copies/mL. Variables recorded at the time of sampling, with potential association with VF, were used to construct the algorithm based on multivariate logistic regression. RESULTS: Fifty-seven individuals (12%) had VF, which was independently associated with CD4 count <350 cells/mm3, previous ART interruption, and short mid-upper arm circumference (<24cm and <23cm, for men and women, respectively). These variables were included in the VLTC. In derivation, the VLTC identified 52/57 with VF; sensitivity 91%, specificity 43%, positive predictive value (PPV) 17%, negative predictive value (NPV) 97%. In comparison, the WHO criteria identified 38/57 with VF (sensitivity 67%, specificity 74%, PPV 25%, NPV 94%). CONCLUSIONS: The VLTC identified subjects at greater likelihood of VF, with higher sensitivity and NPV than the WHO criteria. If external validation confirms this performance, these criteria could be used to allocate limited VL resources. Due to its limited specificity, it cannot be used to determine treatment failure in the absence of a confirmatory viral load.
Asunto(s)
Algoritmos , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , Carga Viral/efectos de los fármacos , Adulto , Recuento de Linfocito CD4 , Etiopía/epidemiología , Femenino , Seropositividad para VIH/tratamiento farmacológico , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Insuficiencia del TratamientoRESUMEN
INTRODUCTION: Despite increasing access to antiretroviral treatment (ART) in low-income countries, HIV-related mortality is high, especially in the first months following ART initiation. We aimed to evaluate the impact of TB coinfection on early mortality and to assess gender-specific predictors of mortality in a cohort of Ethiopian adults subjected to intensified casefinding for active TB before starting ART. MATERIAL AND METHODS: Prospectively recruited ART-eligible adults (n = 812, 58.6% female) at five Ethiopian health centers were followed for 6 months. At inclusion sputum culture, Xpert MTB/RIF, and smear microscopy were performed (158/812 [19.5%] had TB). Primary outcome was all-cause mortality. We used multivariate Cox models to identify predictors of mortality. RESULTS: In total, 37/812 (4.6%) participants died, 12 (32.4%) of whom had TB. Karnofsky performance score (KPS) and mid-upper arm circumference (MUAC) were associated with mortality in the whole population. However, the associations were different in men and women. In men, only MUAC remained associated with mortality (adjusted hazard ratio [aHR] 0.71 [95% CI 0.57-0.88]). In women, KPS <80% was associated with mortality (aHR 10.95 [95% CI 2.33-51.49]), as well as presence of cough (aHR 3.98 [95% CI 1.10-14.36]). Cough was also associated with mortality for TB cases (aHR 8.30 [95% CI 1.06-65.14]), but not for non-TB cases. CONCLUSIONS: In HIV-positive Ethiopian adults managed at health centers, mortality was associated with reduced performance score and malnutrition, with different distribution with regard to gender and TB coinfection. These robust variables could be used at clinic registration to identify persons at increased risk of early mortality.
Asunto(s)
Antirretrovirales/uso terapéutico , Coinfección/epidemiología , Infecciones por VIH/mortalidad , Tuberculosis/epidemiología , Adulto , Instituciones de Atención Ambulatoria , Coinfección/mortalidad , Etiopía/epidemiología , Femenino , Infecciones por VIH/tratamiento farmacológico , Humanos , Masculino , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Factores de Riesgo , Caracteres Sexuales , Análisis de SupervivenciaRESUMEN
BACKGROUND: Access to second-line antiretroviral therapy (ART) for HIV-positive patients remains limited in sub-Saharan Africa. Furthermore, outcomes of second-line ART may be compromised by mortality and loss to follow-up (LTFU). OBJECTIVE: To determine retention in care among patients receiving second-line ART in a public hospital in Ethiopia, and to investigate factors associated with LTFU among adults and adolescents. DESIGN: HIV-positive persons with documented change of first-line ART to a second-line regimen were retrospectively identified from hospital registers, and data were collected at the time of treatment change and subsequent clinic visits. Baseline variables for adults and adolescents were analyzed using multivariate Cox proportional hazards models comparing subjects remaining in care and those LTFU (defined as a missed appointment of ≥90 days). RESULTS: A total of 383 persons had started second-line ART (330 adults/adolescents; 53 children) and were followed for a median of 22.2 months (the total follow-up time was 906 person years). At the end of study follow-up, 80.5% of patients remained in care (adults and adolescents 79.8%; children 85.7%). In multivariate analysis, LTFU among adults and adolescents was associated with a baseline CD4 cell count <100 cells/mm(3) and a first-line regimen failure that was not confirmed by HIV RNA testing. CONCLUSIONS: Although retention in care during second-line ART in this cohort was satisfactory, and similar to that reported from first-line ART programs in Ethiopia, our findings suggest the benefit of earlier recognition of patients with first-line ART failure and confirmation of suspected treatment failure by viral load testing.
Asunto(s)
Antirretrovirales/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Cumplimiento de la Medicación , Adolescente , Adulto , Anciano , Recuento de Linfocito CD4 , Etiopía , Femenino , Infecciones por VIH/mortalidad , Hospitales Públicos , Humanos , Perdida de Seguimiento , Masculino , Persona de Mediana Edad , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Insuficiencia del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Since treatment for latent cryptococcal infection (CI) before starting antiretroviral therapy (ART) reduces mortality in HIV-infected subjects, screening for cryptococcal antigen (CrAg) in blood is recommended for individuals with CD4 cell counts < 100 cells/µL in regions with high CI prevalence. We assessed CrAg screening using the lateral flow assay in HIV-infected adults eligible for ART in central Ethiopia. RESULTS: HIV-positive patients (age ≥ 18 years, CD4 cell count < 350 cells/µL and/or WHO stage IV, no current or previous ART) were recruited at Adama Regional Hospital, Ethiopia (February 2013 until March 2014). CrAg was determined in plasma by lateral flow assay. Among 129 included participants (median age 35 years, 64 % female) the median CD4 cell count was 210 cells/µL (interquartile range 110-309); 29 (23 %) had CD4 cell count < 100 cells/µL. Two (1.6 %) participants were CrAg-positive (CD4 cell counts 171 vs. 250 cells/µL), one of whom had clinically manifest cryptococcal meningitis at the time of testing. CONCLUSIONS: In contrast to two recent reports from Ethiopia, we found few cases of CI among ART-naïve adults. Our study, which is the first using lateral flow assay for CrAg screening in this country, illustrates the need of larger surveys of CI prevalence among ART-naïve patients before defining recommendations on CI screening.
Asunto(s)
Antígenos Fúngicos/sangre , Criptococosis/sangre , Cryptococcus/inmunología , Infecciones por VIH/sangre , Infecciones Oportunistas Relacionadas con el SIDA/sangre , Adulto , Etiopía , Femenino , Humanos , MasculinoRESUMEN
INTRODUCTION: Antiretroviral therapy (ART) initiation during treatment for tuberculosis (TB) improves survival in HIV/TB co-infected patients. Data on ART outcome for HIV/TB co-infected patients managed in primary health care in low-income regions is limited. We compared virological suppression rates, mortality and retention in care in HIV-positive adults receiving care in five Ethiopian health centres with regard to TB co-infection. MATERIALS AND METHODS: HIV-positive ART-naïve adults eligible for ART initiation were prospectively recruited from October 2011 until March 2013. At inclusion, all patients submitted sputum for microbiological TB testing (smear microscopy, liquid culture and PCR). Virological suppression rates after six months of ART (VS; viral load <40 and <400 copies/mL) with regard to TB status was the primary outcome. The impact of HIV/TB co-infection on VS rates was determined by multivariate regression analysis. Mortality and retention in care were analyzed by proportional hazard models. RESULTS: Among 812 participants (TB 158; non-TB 654), 678 started ART during the follow-up period (TB 135; non-TB 543). Median CD4 cell counts at ART initiation were 161 cells/µL (interquartile range [IQR], 98-243) and 184 (IQR, 118-256) for TB and non-TB patients, respectively (p=0.05). No difference in retention in care between TB and non-TB patients was observed during follow-up; 25 (3.7%) patients died and 17 (2.5%) were lost to follow-up (p=0.30 and p=0.83, respectively). Overall rates of VS at six months were 72.1% (<40 copies/mL) and 88.7% (<400 copies/mL), with similar results for subjects with and without TB co-infection (<40 copies/mL: 65/92 (70.7%) vs. 304/420 (72.4%), p=0.74; <400 copies/mL: 77/92 (83.7%) vs. 377/420 (89.8%), p=0.10, respectively). CD4 cell count increase during treatment was 87 (IQR, 26-178) and 103 cells/µL (IQR, 38-173) for TB and non-TB patients, respectively, with no significant difference between the two groups (p=0.49). CONCLUSIONS: High rates of VS were achieved in adults receiving ART at Ethiopian health centres managed by non-physician clinicians, with no significant difference with regard to TB co-infection. These findings demonstrate the feasibility of combined ART and anti-TB treatment at primary health care level in low-income countries. This study is registered with clinicaltrial.gov, NCT01433796.
RESUMEN
OBJECTIVE: To assess the diagnostic performance of urine lipoarabinomannan (LAM) detection for TB screening in HIV-positive adults in Ethiopia. METHODS: Testing for LAM was performed using the Determine TB-LAM lateral flow assay on urine samples from participants in a prospective cohort with baseline bacteriological categorisation for active TB in sputum. Characteristics of TB patients with regard to LAM status were determined. Participants were followed for 6 months to evaluate survival, retention in care and incident TB. RESULTS: Positive LAM results were found in 78/757 participants. Among 128 subjects with definite (confirmed by culture and/or Xpert MTB/RIF) TB, 33 were LAM-positive (25.8%); the respective figure for clinically diagnosed cases was 2/20 (10%). Five of the remaining 43 LAM-positive individuals had died during the 6-month follow-up period, whereas 38 remained in care without clinical signs of TB. The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were 25.8%, 92.9%, 42.3% and 86.0%, respectively. Among TB patients, LAM positivity was associated with higher WHO clinical stage, lower body mass index (BMI), CD4 cell and haemoglobin levels, and with increased mortality. A combination algorithm of urine LAM testing and sputum smear microscopy detected 49 (38.2%) of definite TB cases; among those with CD4 count ≤100 cells/mm3 , this proportion was 66.7%. CONCLUSIONS: The performance of urine LAM testing for TB detection was poor in this population. However, this was improved among subjects with CD4 count ≤100 cells/mm3 . In combination with sputum microscopy urine, LAM could be considered for targeted TB screening in this subgroup.
RESUMEN
BACKGROUND: Detection of active tuberculosis (TB) before antiretroviral therapy (ART) initiation is important, but optimal diagnostic methods for use in resource-limited settings are lacking. We assessed the prevalence of TB, evaluated the diagnostic yield of Xpert MTB/RIF in comparison with smear microscopy and culture, and the impact of Xpert results on clinical management in HIV-positive adults eligible for ART at health centers in a region of Ethiopia. METHODS: Participants were prospectively recruited and followed up at 5 health centers. Trained nurses collected data on socio-demographic characteristics, medical history and symptoms, and performed physical examination. Two paired morning sputum samples were obtained, and lymph node aspirates in case of lymphadenopathy. Diagnostic yield of Xpert MTB/RIF in sputum was compared with smear microscopy and liquid culture. RESULTS: TB was diagnosed in 145/812 participants (17.9%), with bacteriological confirmation in 137 (16.9%). Among bacteriologically confirmed cases, 31 were smear-positive (22.6%), 96 were Xpert-positive (70.1%), and 123 were culture-positive (89.8%). Xpert MTB/RIF increased the TB detection rate by 64 cases (47.4%) compared with smear microscopy. The overall sensitivity of Xpert MTB/RIF was 66.4%, and was not significantly lower when testing one compared with two samples. While Xpert MTB/RIF was 46.7% sensitive among patients with CD4 cell counts >200 cells/mm(3), this increased to 82.9% in those with CD4 cell counts ≤100 cells/mm(3). Compared with Xpert-positive TB patients, Xpert-negative cases had less advanced HIV and TB disease characteristics. CONCLUSIONS: Previously undiagnosed TB is common among HIV-positive individuals managed in Ethiopian health centers. Xpert MTB/RIF increased TB case detection, especially in patients with advanced immunosuppression. An algorithm based on the use of a single morning sputum sample for individuals with negative sputum smear microscopy could be considered for intensified case finding in patients eligible for ART. However, technical and cost-effectiveness issues relevant for low-income countries warrant further study.
Asunto(s)
Infecciones por VIH/complicaciones , Tamizaje Masivo/métodos , Tuberculosis/diagnóstico , Tuberculosis/epidemiología , Adulto , Antibióticos Antituberculosos/farmacología , Técnicas Bacteriológicas/métodos , Farmacorresistencia Bacteriana , Etiopía/epidemiología , Femenino , Humanos , Masculino , Microscopía/métodos , Técnicas de Diagnóstico Molecular/métodos , Mycobacterium tuberculosis/efectos de los fármacos , Mycobacterium tuberculosis/genética , Técnicas de Amplificación de Ácido Nucleico/métodos , Prevalencia , Estudios Prospectivos , Reproducibilidad de los Resultados , Rifampin/farmacología , Sensibilidad y Especificidad , Esputo/microbiología , Tuberculosis/complicacionesRESUMEN
BACKGROUND: Antiretroviral therapy (ART) initiation during treatment for tuberculosis (TB) improves survival in human immunodeficiency virus (HIV)/TB-coinfected patients. We compared virological suppression (VS) rates, mortality, and retention in care in HIV-positive adults receiving care in 5 Ethiopian health centers with regard to TB coinfection. METHODS: Human immunodeficiency virus-positive ART-naive adults eligible for ART initiation were prospectively recruited. At inclusion, all patients underwent microbiological investigations for TB (sputum smear, liquid culture, and polymerase chain reaction). Virological suppression rates after 6 months of ART (VS; viral load <40 and <400 copies/mL) with regard to TB status was the primary outcome. The impact of HIV/TB coinfection on VS rates was determined by multivariate regression analysis. Mortality and retention in care were analyzed by proportional hazard models. RESULTS: Among 812 participants (TB, 158; non-TB, 654), 678 started ART during the follow-up period (TB, 135; non-TB, 543). No difference in retention in care between TB and non-TB patients was observed during follow-up; 25 (3.7%) patients died, and 17 (2.5%) were lost to follow-up (P = .30 and P = .83, respectively). Overall rates of VS at 6 months were 72.1% (<40 copies/mL) and 88.7% (<400 copies/mL), with similar results for subjects with and without TB coinfection (<40 copies/mL: 65 of 92 [70.7%] vs 304 of 420 [72.4%], P = .74; <400 copies/mL: 77 of 92 [83.7%] vs 377 of 420 [89.8%], P = .10, respectively). CONCLUSIONS: High rates of VS can be achieved in adults receiving ART at health centers, with no significant difference with regard to TB coinfection. These findings demonstrate the feasibility of combined ART and anti-TB treatment in primary healthcare in low-income countries. CLINICAL TRIALS REGISTRATION: NCT01433796.
RESUMEN
BACKGROUND: Injecting drug use (IDU) may lead to exposure to a range of carcinogenic agents. We investigated the risk and distribution of cancers among individuals with a history of IDU in Sweden. MATERIAL AND METHODS: The cancer incidence in a cohort of longitudinally followed participants in a needle exchange program (NEP), recruited between 1987 and 2007, was compared to that in the Swedish general population, matching for age group and gender. Baseline demographic and drug use data were collected and longitudinal testing of serological markers for HIV, hepatitis B and C virus was performed during NEP participation. Standardized incidence ratios (SIR) for types of cancer found in the study cohort were calculated, using data from the Swedish National Cancer Registry for reference. RESULTS: The mean follow-up time for the 3255 participants was 11.8 years, constituting 38 419 person years at risk. The mean age at end of follow-up was 42.7 years, and 75% of participants were men. Seventy-eight cases of cancer were observed (SIR 1.1 [95% CI = 0.9-1.4]). The SIR was significantly increased for five cancer types among men; primary liver, laryngeal, lung, oropharyngeal and non-melanoma skin cancer (respective SIR 12.8 [95% CI = 4.2-30.0], 9.2 [95% CI = 1.9-26.8], 3.2 [95% CI = 1.5-6.1], 7.3 [95% CI = 1.5-21.2], and 3.5 [95% CI = 1.1-8.2]), and for cancers of endocrine organs among women (5.3 [95% CI = 1.7-12.4]). CONCLUSION: Although the standardized overall cancer incidence in this relatively young IDU cohort was similar to that in the general population, the risk of specific types of cancer was significantly increased, suggesting that IDU confers elevated risks for certain malignancies. These findings prompt further studies to investigate causative factors and suggest the need for surveillance among persons with a history of IDU.