RESUMO
BACKGROUND: Improved point-of-care diagnostic tests for tuberculosis (TB) in severe immune suppressed people living with HIV (PLWH) are needed to decrease morbidity and mortality outcomes. The aim of the study is to evaluate the performance of the lipoarabinomannan antigen test (LAM-test) with and without α-mannosidase pre-treated urine in a cohort of PLWH in primary care clinics in Guatemala. We further determined TB incidence, and mortality rates and its risk factors in PLWH with TB symptoms. METHODS: Prospective longitudinal study of PLWH with TB symptoms. Urine samples were collected at 2 HIV sites to test the sensitivity of the LAM-test in urine with and without α-mannosidase pre-treatment. A composite reference standard of either a positive Mycobacterium tuberculosis complex culture and/or GeneXpert® MTB/RIF (Xpert, Cepheid, Sunnyvale, CA, USA) results was used in the LAM-test diagnostic accuracy studies. Cox proportional hazards regression was used to study mortality predictors. RESULTS: The overall sensitivity of the LAM-test was of 56.1% with 95% CI of (43.3-68.3). There were no differences in the LAM-test sensitivity neither by hospital nor by CD4 T cell values. LAM-test sensitivity in PLWH with < 200 CD4 T cells/µl was of 62.2% (95% CI 46.5-76.2). There were no significant differences in sensitivity when comparing LAM-test results obtained from untreated vs. α-mannosidase treated urine [55.2% (95% CI 42.6-67.4) vs. 56.9% (95% CI 44-69.2), respectively]. TB incidence in our cohort was of 21.4/100 person years (PYs) (95% CI 16.6-27.6), and mortality rate was of 11.1/100 PYs (95% CI 8.2-15.0). Importantly, PLWH with a positive LAM-test result had an adjusted hazard ratio (aHR) of death of 1.98 (1.0-3.8) with a significant p value of 0.044 when compared to PLWH with a negative LAM-test result. CONCLUSIONS: In this study, α-mannosidase treatment of urine did not significantly increase the LAM-test performance, however; this needs to be further evaluated in a large-scale study due to our study limitations. Importantly, high rates of TB incidence and mortality were found, and a positive LAM-test result predicted mortality in PLWH with TB clinical symptoms.
Assuntos
Infecções por HIV , Tuberculose , Testes Diagnósticos de Rotina , Guatemala/epidemiologia , Infecções por HIV/diagnóstico , Infecções por HIV/tratamento farmacológico , Infecções por HIV/epidemiologia , Humanos , Lipopolissacarídeos , Estudos Longitudinais , Sistemas Automatizados de Assistência Junto ao Leito , Estudos Prospectivos , Sensibilidade e Especificidade , Tuberculose/diagnóstico , Tuberculose/epidemiologiaRESUMO
Early HIV diagnosis remains a challenge in many regions with delayed diagnosis resulting in increased morbidity and mortality. We conducted a retrospective cohort study of people living with HIV receiving outpatient care at a large tertiary referral center in Guatemala to describe the proportion of late presenters (LP) and missed opportunities for HIV diagnosis. Of 3686 patients, 2990 (81.1%) were LP who were more likely to be male (60.2% vs. 48.0%, p < 0.0001), heterosexual (88.0% vs. 78.0%, p < 0.0001) and rural dwellers (43.7% vs. 33.8%. p < 0.0001). The proportions of patients who presented late or with AIDS at diagnosis decreased over time. Only 665 patients (18.2%) sought care in the 2 years prior to HIV diagnosis. This study, the first of its kind in Central America to focus on late presenters and missed opportunities for HIV diagnosis, demonstrates extremely high rates of LP in Guatemala. Although in recent years rates of LP have improved somewhat, the need for screening outside of traditional healthcare settings is apparent.
Assuntos
Diagnóstico Tardio , Infecções por HIV/diagnóstico , Heterossexualidade/estatística & dados numéricos , Homossexualidade/estatística & dados numéricos , Atenção Primária à Saúde/organização & administração , Adulto , Fatores Etários , Assistência Ambulatorial , Contagem de Linfócito CD4 , Diagnóstico Tardio/estatística & dados numéricos , Diagnóstico Precoce , Feminino , Guatemala/epidemiologia , Infecções por HIV/epidemiologia , Infecções por HIV/etnologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores Sexuais , Fatores de TempoRESUMO
Different explanations exist on how HIV-1 subtype B spread in Central America, but the role of Guatemala, the Central American country with the highest number of people living with the virus, in this scenario is unknown. We investigated the evolutionary history and spatiotemporal dynamics of HIV-1 subtype B in Guatemala. A total of 1,047 HIV-1 subtype B pol sequences, from newly diagnosed ART-naïve, HIV-infected Guatemalan subjects enrolled between 2011 and 2013 were combined with published subtype B sequences from other Central American countries (n = 2,101) and with reference sequences representative of the BPANDEMIC and BCAR lineages from the United States (n = 465), France (n = 344) and the Caribbean (n = 238). Estimates of evolutionary, demographic, and phylogeographic parameters were obtained from sequence data using maximum likelihood and Bayesian coalescent-based methods. The majority of Guatemalan sequences (98.9%) belonged to the BPANDEMIC clade, and 75.2% of these sequences branched within 10 monophyletic clades: four also included sequences from other Central American countries (BCAM-I to BCAM-IV) and six were mostly (>99%) composed by Guatemalan sequences (BGU clades). Most clades mainly comprised sequences from heterosexual individuals. Bayesian coalescent-based analyses suggested that BGU clades originated during the 1990s and 2000s, whereas BCAM clades originated between the late 1970s and mid 1980s. The major hub of dissemination of all BGU, and of BCAM-II, and BCAM-IV clades was traced to the Department of Guatemala, while the root location of BCAM-I and BCAM-III was traced to Honduras. Most Guatemalan clades experienced initial phases of exponential growth (0.23 and 3.6 year-1), followed by recent growth declines. Our observations suggest that the Guatemalan HIV-1 subtype B epidemic is driven by dissemination of multiple BPANDEMIC founder viral strains, some restricted to Guatemala and others widely disseminated in the Central American region, with Guatemala City identified as a major hub of viral dissemination. Our results also suggest the existence of different sub-epidemics within Guatemala for which different targeted prevention efforts might be needed.
Assuntos
Epidemias , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/classificação , HIV-1/genética , Adulto , Teorema de Bayes , América Central/epidemiologia , Evolução Molecular , Feminino , Guatemala/epidemiologia , Infecções por HIV/transmissão , Humanos , Funções Verossimilhança , Masculino , Pessoa de Meia-Idade , Epidemiologia Molecular , Filogenia , Filogeografia , Análise Espaço-Temporal , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genéticaRESUMO
Associations between HLA class I alleles and HIV progression in populations exhibiting Amerindian and Caucasian genetic admixture remain understudied. Using univariable and multivariable analyses we evaluated HLA associations with five HIV clinical parameters in 3,213 HIV clade B-infected, ART-naïve individuals from Mexico and Central America (MEX/CAM cohort). A Canadian cohort (HOMER, n = 1622) was used for comparison. As expected, HLA allele frequencies in MEX/CAM and HOMER differed markedly. In MEX/CAM, 13 HLA-A, 24 HLA-B, and 14 HLA-C alleles were significantly associated with at least one clinical parameter. These included previously described protective (e.g. B*27:05, B*57:01/02/03 and B*58:01) and risk (e.g. B*35:02) alleles, as well as novel ones (e.g. A*03:01, B*15:39 and B*39:02 identified as protective, and A*68:03/05, B*15:30, B*35:12/14, B*39:01/06, B*39:05~C*07:02, and B*40:01~C*03:04 identified as risk). Interestingly, both protective (e.g. B*39:02) and risk (e.g. B*39:01/05/06) subtypes were identified within the common and genetically diverse HLA-B*39 allele group, characteristic to Amerindian populations. While HLA-HIV associations identified in MEX and CAM separately were similar overall (Spearman's rho = 0.33, p = 0.03), region-specific associations were also noted. The identification of both canonical and novel HLA/HIV associations provides a first step towards improved understanding of HIV immune control among unique and understudied Mestizo populations.
Assuntos
Infecções por HIV/genética , HIV-1/isolamento & purificação , Antígenos HLA/genética , Adulto , Canadá/epidemiologia , América Central/epidemiologia , Estudos de Coortes , Feminino , Frequência do Gene , Genética Populacional , Genótipo , Infecções por HIV/epidemiologia , Humanos , Desequilíbrio de Ligação , Masculino , México/epidemiologia , Polimorfismo Genético , Adulto JovemRESUMO
BACKGROUND: Substantial heterogeneity in the epidemiology and management of Staphylococcus aureus bacteraemia (SAB) occurs in Latin America. We conducted a prospective cohort study in 24 hospitals from nine Latin American countries. OBJECTIVES: To assess the clinical impact of SAB in Latin America. PATIENTS AND METHODS: We evaluated differences in the 30 day attributable mortality among patients with SAB due to MRSA compared with MSSA involving 84 days of follow-up. Adjusted relative risks were calculated using a generalized linear model. RESULTS: A total of 1030 patients were included. MRSA accounted for 44.7% of cases with a heterogeneous geographical distribution. MRSA infection was associated with higher 30 day attributable mortality [25% (78 of 312) versus 13.2% (48 of 363), adjusted RR: 1.94, 95% CI: 1.38-2.73, P < 0.001] compared with MSSA in the multivariable analysis based on investigators' assessment, but not in a per-protocol analysis [13% (35 of 270) versus 8.1% (28 of 347), adjusted RR: 1.10, 95% CI: 0.75-1.60, P = 0.616] or in a sensitivity analysis using 30 day all-cause mortality [36% (132 of 367) versus 27.8% (123 of 442), adjusted RR: 1.09, 95% CI: 0.96-1.23, P = 0.179]. MRSA infection was not associated with increased length of hospital stay. Only 49% of MSSA bloodstream infections (BSI) received treatment with ß-lactams, but appropriate definitive treatment was not associated with lower mortality (adjusted RR: 0.93, 95% CI: 0.70-1.23, P = 0.602). CONCLUSIONS: MRSA-BSIs in Latin America are not associated with higher 30 day mortality or longer length of stay compared with MSSA. Management of MSSA-BSIs was not optimal, but appropriate definitive therapy did not appear to influence mortality.
Assuntos
Bacteriemia/epidemiologia , Infecção Hospitalar/epidemiologia , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções Estafilocócicas/epidemiologia , Antibacterianos/uso terapêutico , Bacteriemia/tratamento farmacológico , Bacteriemia/microbiologia , Hemocultura , Estudos de Coortes , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/microbiologia , Feminino , Humanos , América Latina/epidemiologia , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pessoa de Meia-Idade , Estudos Prospectivos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/mortalidade , Vancomicina/uso terapêuticoRESUMO
Resumen Introducción. Las metas globales para controlar la epidemia de HIV contemplan que la carga viral sea indetectable en 90 % de las personas en tratamiento. El costo de la medición de la carga viral en lotes de muestras puede reducirse y, así, aumentar la cobertura cuando los recursos son limitados; sin embargo, su eficacia disminuye al aumentar la prevalencia del fracaso del tratamiento antirretroviral. Objetivo. Evaluar estrategias para disminuir la proporción de pacientes con fracaso del tratamiento antirretroviral en los lotes de muestras y, de esta manera, aumentar el ahorro en las pruebas de carga viral. Materiales y métodos. Las estrategias evaluadas fueron: a) la organización de los lotes de muestras según el esquema de tratamiento antirretroviral, y b) la exclusión de aquellos pacientes con antecedente reciente de fracaso del tratamiento antirretroviral, aquellos con menos de 12 meses de tratamiento antirretroviral y aquellos sin tratamiento antirretroviral previo. Los resultados de los lotes se compararon con los resultados individuales. Resultados. El valor diagnóstico negativo fue similar para los pacientes con esquema de primera línea (100,0 %; IC95% 99,5-100,0) o de segunda línea de tratamiento (99,4 %; IC95% 96,9-99,9). La incidencia del fracaso del tratamiento antirretroviral fue menor en los pacientes con tratamiento de primera línea (p<0,01), lo cual permitió un mayor ahorro en las pruebas de laboratorio en este grupo (74,0 %; IC95% 71,0-76,7) que en los pacientes con tratamiento de segunda línea (50,9 %; IC95% 44,4-57,3) (p<0,01). Conclusión. La selección de las muestras que se incluyeron en los lotes para determinar la carga viral del HIV según el tipo de esquema de tratamiento, permitió maximizar el porcentaje de ahorro en pruebas de laboratorio.
Abstract Introduction: HIV viral load testing is a key factor to evaluate the accomplishment of the UNAIDS target of 90% of viral suppression among people receiving antiretroviral therapy. Pooled samples are a potentially accurate and economic approach in resource-constrained settings, but efficiency can be negatively affected by high prevalence rates of virological failure. Objective: Strategies were assessed to increase the relative efficiency of pooled HIV viral load testing in resource-constrained settings. Materials and methods: We evaluated two strategies: a) plasma samples were not included in pools if patients had <12 months on antiretroviral therapy, patients had previous viral load >1,000 copies/ml, or were antiretroviral therapy naïve patients, and b) plasma pools were organized separately for first and second-line antiretroviral therapy regimens. Individual viral load tests were used to compare pooled results. Results: Negative predictive values were similar for patients on first (100.0%; 95% CI 99.5 to 100.0) and second-line antiretroviral therapy regimens (99.4%; 95% CI 96.9 to 99.9). However, the incidence of virological failure among individuals on first-line antiretroviral therapy was lower than second-line antiretroviral therapypatients (p <0.01), resulting in greater savings in laboratory tests in patients on first-line antiretroviral therapy (74.0%; 95% CI 71.0 to 76.7) compared with the group of patients on second-line antiretroviral therapy (50.9%; 95% CI 44.4 to 57.3) (p<0.01). Conclusion: Selecting the samples to be included in the pools and selecting the pools according to ART regimens are criteria that could lead to decreased spending on laboratory tests for HIV viral load determination in resource-constrained settings.
Assuntos
Feminino , Humanos , Masculino , Manejo de Espécimes/métodos , Viremia/sangue , Infecções por HIV/sangue , HIV-1/isolamento & purificação , Carga Viral/economia , Controle de Custos/métodos , Recursos em Saúde/economia , Manejo de Espécimes/economia , Viremia/economia , Viremia/tratamento farmacológico , RNA Viral/sangue , Infecções por HIV/economia , Infecções por HIV/tratamento farmacológico , Valor Preditivo dos Testes , Falha de Tratamento , Seleção de Pacientes , Carga Viral/métodos , Terapia Antirretroviral de Alta Atividade , Farmacorresistência Viral , Antirretrovirais/classificação , Antirretrovirais/uso terapêutico , Países em Desenvolvimento , GuatemalaRESUMO
BACKGROUND: Migration and travel are major drivers of the spread of infectious diseases. Geographic proximity and a common language facilitate travel and migration in Mesoamerica, which in turn could affect the spread of HIV in the region. METHODS: 6092 HIV-1 subtype B partial pol sequences sampled from unique antiretroviral treatment-naïve individuals from Mexico (40.7%), Guatemala (24.4%), Honduras (19%), Panama (8.2%), Nicaragua (5.5%), Belize (1.4%), and El Salvador (0.7%) between 2011 and 2016 were included. Phylogenetic and genetic network analyses were performed to infer putative relationships between HIV sequences. The demographic and geographic associations with clustering were analyzed and viral migration patterns were inferred using the Slatkin-Maddison approach on 100 iterations of random subsets of equal number of sequences per location. RESULTS: A total of 1685/6088 (27.7%) of sequences linked with at least one other sequence, forming 603 putative transmission clusters (range: 2-89 individuals). Clustering individuals were significantly more likely to be younger (median age 29 vs 33years, p<0.01) and men-who-have-sex-with-men (40.4% vs 30.3%, p<0.01). Of the 603 clusters, 30 (5%) included sequences from multiple countries with commonly observed linkages between Mexican and Honduran sequences. Eight of the 603 clusters included >10 individuals, including two comprised exclusively of Guatemalans (52 and 89 individuals). Phylogenetic and migration analyses suggested that the Central and Southern regions of Mexico along with Belize were major sources of HIV throughout the region (p<0.01) with genetic flow southward from Mexico to the other nations of Mesoamerica. We also found evidence of significant viral migration within Mexico. CONCLUSION: International clusters were infrequent, suggesting moderate migration between HIV epidemics of the different Mesoamerican countries. Nevertheless, we observed important sources of transnational HIV spread in the region, including Southern and Central Mexico and Belize.
Assuntos
Infecções por HIV , HIV-1/genética , Adulto , América Central/epidemiologia , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/transmissão , Infecções por HIV/virologia , Humanos , Masculino , México/epidemiologia , Epidemiologia Molecular , Adulto JovemRESUMO
BACKGROUND: Anecdotal evidence suggests that a high proportion of patients diagnosed with HIV in Guatemala present with AIDS. There remain limited data on the epidemiology of AIDS-defining illnesses (ADIs) in Central America. METHODS: We conducted a retrospective cohort study of all patients living with HIV at the largest HIV clinic in Guatemala. Charts were analyzed for clinical and demographic data. Presence of an ADI was assessed by US Centers for Disease Control definitions; patients who presented with an ADI were compared with those without ADI using descriptive statistics. RESULTS: Of 3686 patients living with HIV, 931 (25.3%) had an ADI at HIV diagnosis, 748 (80.3%) of whom had CD4 counts lower than 200 cells/mm3. Those with ADIs were more likely to be male (67.5% vs 54.6%; P < .0001) and heterosexual (89.4% vs 85.0%; P = .005). The most common ADIs were Mycobacterium tuberculosis (55.0%), Pneumocystis jirovecii pneumonia (13.7%), esophageal candidiasis (13.4%), and histoplasmosis (11.4%). Histoplasmosis and HIV wasting syndrome were both more common among rural patients. CONCLUSIONS: In this large Guatemalan cohort of patients currently living with HIV, a significant portion presented with an ADI. These data inform the most common ADIs diagnosed among survivors, show that histoplasmosis is more commonly diagnosed in rural patients, and suggest that HIV wasting syndrome may reflect missed histoplasmosis diagnoses.
RESUMO
INTRODUCTION: HIV viral load testing is a key factor to evaluate the accomplishment of the UNAIDS target of 90% of viral suppression among people receiving antiretroviral therapy. Pooled samples are a potentially accurate and economic approach in resource-constrained settings, but efficiency can be negatively affected by high prevalence rates of virological failure. OBJECTIVE: Strategies were assessed to increase the relative efficiency of pooled HIV viral load testing in resource-constrained settings. MATERIALS AND METHODS: We evaluated two strategies: a) plasma samples were not included in pools if patients had <12 months on antiretroviral therapy, patients had previous viral load >1,000 copies/ml, or were antiretroviral therapy naïve patients, and b) plasma pools were organized separately for first and second-line antiretroviral therapy regimens. Individual viral load tests were used to compare pooled results. RESULTS: Negative predictive values were similar for patients on first (100.0%; 95% CI 99.5 to 100.0) and second-line antiretroviral therapy regimens (99.4%; 95% CI 96.9 to 99.9). However, the incidence of virological failure among individuals on first-line antiretroviral therapy was lower than second-line antiretroviral therapy patients (p <0.01), resulting in greater savings in laboratory tests in patients on first-line antiretroviral therapy (74.0%; 95% CI 71.0 to 76.7) compared with the group of patients on second-line antiretroviral therapy (50.9%; 95% CI 44.4 to 57.3) (p<0.01). CONCLUSION: Selecting the samples to be included in the pools and selecting the pools according to ART regimens are criteria that could lead to decreased spending on laboratory tests for HIV viral load determination in resource-constrained settings.