Poor long-term outcomes despite improved hospital survival for patients with cryptococcal meningitis in rural, Northern Uganda.

BACKGROUND: Cryptococcal meningitis (CM) remains a major cause of death among people living with HIV in rural sub-Saharan Africa. We previously reported that a CM diagnosis and treatment program (CM-DTP) improved hospital survival for CM patients in rural, northern Uganda. This study aimed to evaluate the impact on long-term survival. METHODS: We conducted a retrospective study at Lira Regional Referral Hospital in Uganda evaluating long-term survival (≥1 year) of CM patients diagnosed after CM-DTP initiation (February 2017-September 2021). We compared with a baseline historical group of CM patients before CM-DTP implementation (January 2015-February 2017). Using Cox proportional hazards models, we assessed time-to-death in these groups, adjusting for confounders. RESULTS: We identified 318 CM patients, 105 in the Historical Group, and 213 in the CM-DTP Group. The Historical Group had a higher 30-day mortality of 78.5% compared to 42.2% in the CM-DTP Group. The overall survival rate for the CM-DTP group at three years was 25.6%. Attendance at follow-up visits (HR:0.13, 95% CI: [0.03-0.53], p <0.001), ART adherence (HR:0.27, 95% CI: [0.10-0.71], p = 0.008), and fluconazole adherence: (HR:0.03, 95% CI: [0.01-0.13], p <0.001), weight >50kg (HR:0.54, 95% CI: [0.35-0.84], p = 0.006), and performance of therapeutic lumbar punctures (HR:0.42, 95% CI: [0.24-0.71], p = 0.001), were associated with lower risk of death. Altered mentation was associated with increased death risk (HR: 1.63, 95% CI: 1.10-2.42, p = 0.016). CONCLUSION: Long-term survival of CM patients improved after the initiation of the CM-DTP. Despite this improved survival, long-term outcomes remained sub-optimal, suggesting that further work is needed to enhance long-term survival.

Survival and mortality profile among people living with HIV in a cohort in the Northeastern region of Brazil.

Conditions related to the acquired immune deficiency syndrome (AIDS) are still a significant cause of morbidity and mortality among people living with HIV (PLHIV). Longer survival in this population were reported to increase the risk of developing noncommunicable chronic diseases (NCDs). This study aimed to estimate the survival and causes of death according to age group and sex among PLHIV monitored at two referral centers in the Northeastern Brazil. This is a prospective, retrospective cohort with death records from 2007 to 2018, based on a database that registers causes of death using the International Classification of Disease (ICD-10), which were subsequently coded following the Coding Causes of Death in HIV (CoDe). A total of 2,359 PLHIV participated in the study, with 63.2% being men, with a follow-up period of 13.9 years. Annual mortality rate was 1.46 deaths per 100 PLHIV (95% CI: 1.33 - 1.60) with a frequency of 20.9%. Risk of death for men increased by 49% when compared to women, and the risk of death in PLHIV increased by 51% among those aged 50 years and over at the time of diagnosis. It was observed that 73.5% accounted for AIDS-related deaths, 6.9% for non-AIDS defining cancer, 6.3% for external causes, and 3.2% for cardiovascular diseases. Among the youngest, 97.2% presented an AIDS-related cause of death. Highest frequency of deaths from neoplasms was among women and from external causes among men. There is a need for health services to implement strategies ensuring greater adherence to treatment, especially among men and young people. Moreover, screening for chronic diseases and cancer is essential, including the establishment of easily accessible multidisciplinary care centers that can identify and address habits such as illicit drug use and alcoholism, which are associated with violent deaths.

[Meningeal cryptococcosis in patients living with HIV. Experience in intensive care]. / Criptococosis meníngea en pacientes viviendo con HIV. Experiencia en cuidados intensivos.

INTRODUCTION: Meningeal cryptococcosis (MC) is a frequent cause of meningoencephalitis in people living with HIV (PLHIV), leading to substantial morbidity (20-55%). Clinical characteristics, lethality and adverse prognostic factors in PLHIV with MC admitted to intensive care units (ICUs) are described. METHODS: A retrospective observational study. Period from 11/21/2006 to 05/24/2023. It involved 154 adult PLHIV diagnosed with MC and admitted to ICUs. Percentages and absolute values were compared by Chi-Square or Fisher's test and medians by Mann-Whitney test. The association with mortality was assessed by logistic regression. SPSS 23.0 software was used. A p-value <0.05 was considered significant. RESULTS: Patients who died and those who survived were comparable in age and sex (p>0.05). Univariate analysis showed that impaired functional and nutritional status, lack of previous highly active antiretroviral therapy, CD4 <100 cells, APACHE II ≥ 13 and a PLHIV prognostic score ≥ 8 points, requiring mechanical ventilation (MV), respiratory failure, renal failure, neurological dysfunction or sepsis could be associated (p<0.05) with mortality. Logistic regression established that impaired functional and nutritional status, a PLHIV prognostic score ≥ 8, need for MV and presence of sepsis would be independent variables associated with mortality. CONCLUSION: The results indicate that altered functional and nutritional status, a PLHIV prognostic score ≥ 8 points, requiring MV and suffering sepsis on admission to the ICU are more frequent in deceased patients, and they could therefore serve as independent variables to predict a higher risk of mortality.

Introducción: La criptococosis meníngea (CM) es una causa frecuente de meningoencefalitis en personas que viven con HIV (PVHIV) y produce una importante morbimortalidad (20-55%). Se describen las características clínicas, la letalidad y las variables de mal pronóstico en PVHIV con CM, en unidades de cuidados intensivos (UCI). Métodos: Estudio observacional y retrospectivo. Período 21/11/2006 a 24/05/2023. Población evaluada: 154 PVHIV adultos, admitidos en UCI con diagnóstico de CM. Los porcentajes y valores absolutos, fueron comparados mediante Chi-Cuadrado o test de Fisher y las medianas mediante test de Mann-Whitney. La asociación con mortalidad se evaluó por regresión logística. Se utilizó el programa SPSS 23.0. Un valor p<0.05 fue considerado significativo. Resultados: Los pacientes que fallecieron y los que sobrevivieron fueron comparables en edad y sexo (p>0.05). El análisis univariado, observó que un estado funcional y nutricional alterado, falta de tratamiento antirretroviral previo (TARV), CD4 <100 células/µl, APACHE II ≥ 13 y un score pronóstico de PVHIV ≥ 8 puntos, requerir ventilación mecánica (VM), sufrir insuficiencia respiratoria, renal, disfunción neurológica o sepsis, podrían estar asociados (p<0.05) con mortalidad. La regresión logística estableció que un estado funcional y nutricional alterado, un score pronóstico PVHIV ≥ 8, necesitar VM y sufrir sepsis serían variables independientes asociadas a mortalidad. Conclusión: Los resultados indican que el estado funcional y nutricional alterado, un score pronóstico PVHIV ≥ 8 puntos, requerir VM y sufrir sepsis al ingreso a UCI podrían servir como variables independientes para predecir un mayor riesgo de mortalidad.

Evaluating Clinic-Based Interventions to Reduce Racial Differences in Mortality Among People With Human Immunodeficiency Virus in the United States.

BACKGROUND: Mortality remains elevated among Black versus White adults receiving human immunodeficiency virus (HIV) care in the United States. We evaluated the effects of hypothetical clinic-based interventions on this mortality gap. METHODS: We computed 3-year mortality under observed treatment patterns among >40 000 Black and >30 000 White adults entering HIV care in the United States from 1996 to 2019. We then used inverse probability weights to impose hypothetical interventions, including immediate treatment and guideline-based follow-up. We considered 2 scenarios: "universal" delivery of interventions to all patients and "focused" delivery of interventions to Black patients while White patients continued to follow observed treatment patterns. RESULTS: Under observed treatment patterns, 3-year mortality was 8% among White patients and 9% among Black patients, for a difference of 1 percentage point (95% confidence interval [CI], .5-1.4). The difference was reduced to 0.5% under universal immediate treatment (95% CI, -.4% to 1.3%) and to 0.2% under universal immediate treatment combined with guideline-based follow-up (95% CI, -1.0% to 1.4%). Under the focused delivery of both interventions to Black patients, the Black-White difference in 3-year mortality was -1.4% (95% CI, -2.3% to -.4%). CONCLUSIONS: Clinical interventions, particularly those focused on enhancing the care of Black patients, could have significantly reduced the mortality gap between Black and White patients entering HIV care from 1996 to 2019.

Caracterización de los pacientes con VIH/sida en Guanabacoa, La Habana / Characterization of HIV or AIDS Patients from Guanabacoa, Havana

Introducción: La infección por VIH es actualmente una pandemia que afecta millones de personas, que provoca complicaciones y la muerte a muchos pacientes. Objetivo: Caracterizar clínica y epidemiológicamente a los pacientes con VIH/sida, pertenecientes al municipio de Guanabacoa, La Habana. Métodos: Se realizó un estudio descriptivo, retrospectivo en el municipio de Guanabacoa, La Habana, en el periodo comprendido entre enero 1986 y diciembre 2019. El universo de estudio quedó conformado por 647 pacientes con diagnóstico de VIH/sida. Las principales variables a medir fueron: edad, sexo, orientación sexual, color de la piel, estado civil y nivel escolar. Resultados: Predominó el sexo masculino sobre el femenino (538 v/s 109), el grupo de edad de 20 -29 años, la homosexualidad (404 pacientes, para un 62,44 por ciento) y el color de piel blanca (51,93 por ciento) y valor p < 0,0001, los solteros (526 pacientes) y los pacientes con nivel escolar de secundaria básica (292 pacientes). Conclusiones: Predominó el sexo masculino, la homosexualidad, el color de piel blanca, los solteros y el nivel escolar de secundaria básica(AU)

Introduction: Human immunodeficiency virus (HIV) infection is currently a pandemic affecting millions of people, causing complications and death to many patients. Objective: To characterize, clinically and epidemiologically, patients with HIV or AIDS in Guanabacoa Municipality, Havana. Methods: A descriptive and retrospective study was carried out in Guanabacoa Municipality, Havana, between January 1986 and December 2019. The study universe consisted of 647 patients diagnosed with HIV or AIDS. The main variables to be measured were age, sex, sexual orientation, skin color, marital status, and school level. Results: There was a predominance of the male sex over the female (538 versus 109), together with the age group 20-29 years, homosexuality (404 patients, 62.44 percent), and the white skin color (51.93 percent); P-value was under 0.0001. There was also a predominance of single patients (526) and patients with junior high school level (292). Conclusions: The male sex, homosexuality, white skin color, single as marriage status, and junior high school level predominated(AU)

Descripción de situación epidemiológica del virus inmunodeficiencia humana en Chile durante los años 2016 a 2021 / Description of the epidemiological situation of human immunodeficiency virus in Chile during the years 2016 to 2021

Introducción: El virus de inmunodeficiencia humana (VIH) causa una infección que destruye los linfocitos del huésped. Su fase avanzada conlleva al Síndrome de Inmunodeficiencia Adquirida (SIDA) que trae consigo una alta morbimortalidad a nivel mundial, convirtiéndose en una pandemia de gran preocupación para las organizaciones mundiales de salud. Materiales y Métodos: Estudio de carácter observacional, descriptivo, ecológico y longitudinal retrospectivo. Se analizaron los datos del Departamento de Estadísticas de Información de Salud, número de casos confirmados, defunciones ocurridas en la población chilena, por región, entre los años 2016 y 2021 con causa básica de muerte Enfermedad por VIH [SIDA] y la cantidad total de exámenes realizados. Resultados: Se observa un aumento tanto en el número de exámenes realizados como de los casos diagnosticados hasta el año 2019. Respecto a la mortalidad se describe una tendencia decreciente desde el año 2016, con un alza puntual en 2019 tanto a nivel nacional como regional, por rango etario y sexo. A nivel regional se identifican mayores cifras en las macrozonas norte y centro. Discusión: En todas las regiones se evidenció una disminución durante los años 2020 y 2021, posiblemente asociada a un camuflaje en su categorización. La población chilena presenta una mayor tasa de mortalidad en el rango de 40 a 44 años, a diferencia del contexto mundial donde se observa un rango de 55 a 59 años. En causas específicas de mortalidad, se destaca el segundo lugar asociado a tumores malignos siendo importante destacar la necesidad de evidencia enfocada en el diagnóstico temprano de estas patologías.

Introduction: Human immunodeficiency virus (HIV) causes an infection that destroys host lymphocytes. Its advanced stage leads to Acquired Immunodeficiency Syndrome (AIDS) that brings with it a high morbimortality worldwide, becoming a pandemic of great concern for world health organizations. Materials and Methods: Observational, descriptive, ecological and retrospective longitudinal study. Data from the Department of Health Information Statistics, number of confirmed cases, deaths occurred in the Chilean population, by region, between the years 2016 and 2021 with basic cause of death HIV disease [AIDS] and the total number of tests performed were analyzed. Results: An increase is observed both in the number of examinations performed and cases diagnosed until 2019. Regarding mortality, a decreasing trend is described since 2016, with a punctual increase in 2019 both at national and regional level, by age range and sex. At the regional level, higher figures are identified in the northern and central macro-zones. Discussion: A decrease was evident in all regions during 2020 and 2021, possibly associated with a camouflage in their categorization. The Chilean population presents a higher mortality rate in the range of 40 to 44 years, unlike the world context where a range of 55 to 59 years is observed. In specific causes of mortality, the second place associated with malignant tumors stands out, being important to highlight the need for evidence focused on the early diagnosis of these pathologies.

Fatores associados ao óbito por HIV/Aids / Factores asociados al fallecimiento por VIH/Sida / Factors associated with death due to HIV/AIDS

Resumo Objetivo Analisar os fatores associados ao óbito em pessoas com HIV/Aids. Método Estudo epidemiológico e analítico, realizado a partir das notificações de HIV/Aids do estado de Mato Grosso do Sul, no período de 2009 à 2018. Os dados foram analisados por meio de estatística descritiva, análise de sobrevida via método de Kaplan-Meier e regressão de Cox. Resultados Foram analisadas 8.712 notificações, com taxa de sobrevida de 86% ao longo dos 10 anos. Os fatores associados ao óbito foram:sexo masculino (=1,22; p=0,006), cor da pele parda (=1,30; p=0,012), oito anos ou menos de estudo (=1,57; p=0,000), e possível transmissão sexual mediante relação com mulheres (=2,72; p=0,000) ou com ambos - homens e mulheres (=2,24; p=0,002) e utilização de drogas injetáveis (=2,57; p=0,016). Conclusão Características sociais, culturais e comportamentais podem contribuir para redução da sobrevida das pessoas com HIV/Aids. Esses fatores sinalizam especificidades a serem consideradas no planejamento assistencial e monitoramento dos casos, em especial no que concerne à necessidade de busca ativa, monitoramento contínuo, além de intervenções que envolvam mudanças de comportamento.

Resumen Objetivo Analizar los factores asociados al fallecimiento de personas con VIH/Sida. Método Estudio epidemiológico y analítico, realizado a partir de las notificaciones de VIH/Sida en el estado de Mato Grosso do Sul, en el período de 2009 a 2018. El análisis de los datos se realizó por medio de estadística descriptiva, análisis de sobrevida por el método de Kaplan-Meier y de regresión de Cox. Resultados Se analizaron 8.712 notificaciones, con un índice de sobrevida del 86 % a lo largo de los 10 años. Los factores asociados al fallecimiento fueron: sexo masculino (=1,22; p=0,006), color de piel parda (=1,30; p=0,012), ocho años o menos de estudio (=1,57; p=0,000), y posible transmisión sexual mediante relación con mujeres (=2,72; p=0,000) o con ambos, hombres y mujeres (=2,24; p=0,002), y uso de drogas inyectables (=2,57; p=0,016). Conclusión Características sociales, culturales y de comportamiento pueden contribuir para la reducción de la sobrevida de las personas con VIH/Sida. Esos factores señalan especificidades que se deben considerar en la planificación asistencial y en el monitoreo de los casos, en especial en lo que atañe a la necesidad de la búsqueda activa, el monitoreo continuo e intervenciones que incluyan cambios de comportamiento.

Abstract Objective To analyze the factors associated with death in people with HIV/AIDS. Method This is an epidemiological and analytical study, carried out from the HIV/AIDS notifications of the state of Mato Grosso do Sul, from 2009 to 2018. Data were analyzed using descriptive statistics, Kaplan-Meier survival analysis and Cox regression. Results A total of 8,712 notifications were analyzed, with a survival rate of 86% over the 10 years. Factors associated with death were: males (=1.22; p=0.006), brown skin color (=1.30; p=0.012), eight years or less of study (=1.57; p=0.000), and possible sexual transmission through intercourse with women (=2.72; p=0.000) or with both men and women (=2.24; p=0.002) and use of injectable drugs (=2.57; p=0.016). Conclusion Social, cultural and behavioral characteristics may contribute to reduce the survival of people with HIV/AIDS. These factors indicate specificities to be considered in care planning and monitoring of cases, especially with regard to the need for an active search, continuous monitoring, in addition to interventions that involve changes in behavior.

Análise da tendência da mortalidade por doenças definidoras e não definidoras de HIV/aids segundo características sociodemográficas, por Unidade da Federação e Brasil, 2000-2018 / Análisis de las tendencias de mortalidad por enfermedades definitorias y no definitorias de VIH/SIDA, según características sociodemográficas por Unidad de la Federación y Brasil, 2000-2018 / Analysis of trend in mortality due to HIV/AIDS-defining and non-HIV/AIDS defining illnesses according to sociodemographic characteristics, by Federative Unit and Brazil, 2000-2018

Objetivo: Analisar a tendência temporal da taxa mortalidade por doenças definidoras e não definidoras de HIV/aids no Brasil entre 2000 e 2018. Métodos: Estudo ecológico de série temporal, com dados do Sistema de Informações sobre Mortalidade, no Brasil e Unidades da Federação. Utilizou-se a regressão de Prais-Winsten para a análise de tendências, de acordo com taxa de mortalidade geral, sexo, faixa etária, estado civil e raça/cor da pele. Resultados: Foram registrados 237.435 óbitos no período. No país, as doenças definidoras apresentaram taxas mais elevadas (7,4 a 4,4 óbitos/100 mil habitantes no período) que as observadas entre as não definidoras (0,4 a 0,8 óbito/100 mil hab. no período). A mortalidade geral por doenças definidoras foi decrescente (-6,3%; IC95% -8,8;-3,8); e por doenças não definidoras, crescente (11,0%; IC95% 6,5;15,7). Conclusão: Houve mudança no perfil de mortalidade por HIV/aids no decorrer dos anos observados, verificando-se decréscimo de óbitos por doenças definidoras de HIV/aids.

Objetivo: Analizar la tendencia temporal de la tasa de mortalidad por enfermedades definitorias y no definitorias de VIH/SIDA en Brasil entre 2000 y 2018. Métodos: Estudio de serie temporal ecológica con datos del Sistema de Información de Mortalidad de Brasil y Unidades de la Federación. Se utilizó la regresión de Prais-Winsten para analizar las tendencias según tasa de mortalidad general, sexo, grupo de edad, estado civil y raza/color. Resultados: Se registraron 237.435 muertes en el período. En el país, las enfermedades definitorias presentaron tasas superiores (7,4 a 4,4 óbitos/100 mil habitantes en el período) que las observadas entre las enfermedades no definitorias (0,4 a 0,8 óbito/100 mil habitantes en el período). La mortalidad general por enfermedades definitorias estaba disminuyendo (-6,3%; IC95% -8,8;-3,8) y para las enfermedades no definitorias estaba aumentando (11,0%; IC95% 6,5;-15,7). Conclusión: Hubo un cambio en el perfil de mortalidad por VIH/SIDA a lo largo de los años, con una disminución en las muertes por enfermedades definitorias de VIH/SIDA.

Objective: To analyze the temporal trend of mortality rate due to HIV/AIDS defining and non-HIV/AIDS defining illnesses in Brazil between 2000 and 2018. Methods: This was an ecological time series study, using data from the Mortality Information System, in Brazil and the Federative Units. Trend analysis was performed by means of Prais-Winsten regression model, according to overall mortality rate, sex, age group, marital status and race/skin color. Results: A total of 237,435 deaths were recorded in the period. In the country, defining illnesses showed higher rates (7.4 to 4.4 deaths/100,000 inhabitants in the period) than those observed among non-defining diseases (0.4 to 0.8 death/100,000 inhabitants in the period). It could be seen a decrease in overall mortality due to defining diseases (-6.3%; 95%CI -8.8;-3.8); while it increased due to non-defining diseases (11.0%; 95%CI 6.5;15.7). Conclusion: There was a change in HIV/AIDS mortality profile over the years, with a decrease in deaths due to HIV/AIDS-defining diseases.

Delirium in HIV-infected patients admitted to acute medical wards post universal access to antiretrovirals in South Africa.

BACKGROUND: Delirium is associated with increased mortality and length of hospital stay. Limited data are available from HIV-infected acute hospital admissions in developing countries. We conducted a prospective study of delirium among acute medical admissions in South Africa (SA), a developing country with universal antiretroviral therapy (ART) access and high burdens of tuberculosis (TB) and non-communicable disease. OBJECTIVES: To identify the prevalence of, risk factors for and outcomes of delirium in HIV-infected individuals in acute general medical admissions. METHODS: Three cohorts of adult acute medical admissions to Groote Schuur and Victoria Wynberg hospitals, Cape Town, SA, were evaluated for prevalent delirium within 24 hours of admission. Reference delirium testing was performed by either consultant physicians or neuropsychologists, using the Confusion Assessment Method. RESULTS: The study included 1 182 acute medical admissions, with 318 (26.9%) HIV-infected. The median (interquartile range) age and CD4 count were 35 (30 - 43) years and 132 (61 - 256) cells/µL, respectively, with 140/318 (44.0%) using ART on admission. The prevalence of delirium was 17.6% (95% confidence interval (CI) 13.7 - 22.1) among HIV-infected patients, and delirium was associated with increased inpatient mortality. In multivariable logistic regression analysis, factors associated with delirium were age ≥55 years (adjusted odds ratio (aOR) 6.95 (95% CI 2.03 - 23.67); p=0.002), and urea ≥15 mmol/L (aOR 4.83 (95% CI 1.7 - 13.44); p=0.003), while ART use reduced risk (p=0.014). A low CD4 count, an unsuppressed viral load and active TB were not predictors of delirium; nor were other previously reported risk factors such as non-opportunistic acute infections or polypharmacy. CONCLUSIONS: Delirium is common and is associated with increased mortality in HIV-infected acute medical admissions in endemic settings, despite increased ART use. Older HIV-infected patients with renal dysfunction are at increased risk for inpatient delirium, while those using ART on admission have a reduced risk.

Cause of hospitalization and death in the antiretroviral era in Sub-Saharan Africa published 2008-2018: A systematic review.

BACKGROUND: Worldwide despite the availability of antiretroviral therapy, human immunodeficiency virus/acquired immunodeficiency syndrome still causes morbidity and mortality among patients. In Sub-Saharan Africa, human immunodeficiency virus/acquired immunodeficiency syndrome remains a major public health concern. The aim of this study was to identify the causes of morbidity and mortality in the modern antiretroviral therapy era in Sub-Saharan Africa. METHODS: We conducted a systematic review according to the Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. We searched relevant studies from 3 databases which are Google Scholar, PubMed, and CINAHL. Two review authors independently screened titles, abstracts, and full-text articles in duplicate, extracted data, and assessed bias. Discrepancies were resolved by discussion or arbitration of a third review author. R software version 3.6.2 was used to analyze the data. Maximum values were used in order to show which disease was mostly spread out by looking at the highest prevalence reported. This systematic review protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO). RESULTS: A total of 409 articles were obtained from the database search, finally 12 articles met the inclusion criteria and were eligible for data extraction. Among them, 3 were conducted in Nigeria, 2 were conducted in Uganda, 3 were conducted in South Africa, 1 in Gabon, 1 in Ethiopia, 1 in Ghana, and 1 in Burkina Faso. In most of the included studies, tuberculosis was the leading cause of hospitalization which accounted for between 18% and 40.7% and it was also the leading cause of death and accounted for between 16% and 44.3%, except in 1 which reported anemia as the leading cause of hospitalization and in 2 which reported wasting syndrome and meningitis respectively as the leading causes of death. Opportunistic malignancies accounted between for 1.8% to 5% of hospitalization and 1.2% to 9.8% of deaths. CONCLUSIONS: Tuberculosis is the commonest cause of hospitalization and death in Sub-Saharan Africa, but it is always followed by other infectious disease and other non-AIDS related causes.

Effect of a patient-centered hypertension delivery strategy on all-cause mortality: Secondary analysis of SEARCH, a community-randomized trial in rural Kenya and Uganda.

BACKGROUND: Hypertension treatment reduces morbidity and mortality yet has not been broadly implemented in many low-resource settings, including sub-Saharan Africa (SSA). We hypothesized that a patient-centered integrated chronic disease model that included hypertension treatment and leveraged the HIV care system would reduce mortality among adults with uncontrolled hypertension in rural Kenya and Uganda. METHODS AND FINDINGS: This is a secondary analysis of the SEARCH trial (NCT:01864603), in which 32 communities underwent baseline population-based multidisease testing, including hypertension screening, and were randomized to standard country-guided treatment or to a patient-centered integrated chronic care model including treatment for hypertension, diabetes, and HIV. Patient-centered care included on-site introduction to clinic staff at screening, nursing triage to expedite visits, reduced visit frequency, flexible clinic hours, and a welcoming clinic environment. The analytic population included nonpregnant adults (≥18 years) with baseline uncontrolled hypertension (blood pressure ≥140/90 mm Hg). The primary outcome was 3-year all-cause mortality with comprehensive population-level assessment. Secondary outcomes included hypertension control assessed at a population level at year 3 (defined per country guidelines as at least 1 blood pressure measure <140/90 mm Hg on 3 repeated measures). Between-arm comparisons used cluster-level targeted maximum likelihood estimation. Among 86,078 adults screened at study baseline (June 2013 to July 2014), 10,928 (13%) had uncontrolled hypertension. Median age was 53 years (25th to 75th percentile 40 to 66); 6,058 (55%) were female; 677 (6%) were HIV infected; and 477 (4%) had diabetes mellitus. Overall, 174 participants (3.2%) in the intervention group and 225 participants (4.1%) in the control group died during 3 years of follow-up (adjusted relative risk (aRR) 0.79, 95% confidence interval (CI) 0.64 to 0.97, p = 0.028). Among those with baseline grade 3 hypertension (≥180/110 mm Hg), 22 (4.9%) in the intervention group and 42 (7.9%) in the control group died during 3 years of follow-up (aRR 0.62, 95% CI 0.39 to 0.97, p = 0.038). Estimated population-level hypertension control at year 3 was 53% in intervention and 44% in control communities (aRR 1.22, 95% CI 1.12 to 1.33, p < 0.001). Study limitations include inability to identify specific causes of death and control conditions that exceeded current standard hypertension care. CONCLUSIONS: In this cluster randomized comparison where both arms received population-level hypertension screening, implementation of a patient-centered hypertension care model was associated with a 21% reduction in all-cause mortality and a 22% improvement in hypertension control compared to standard care among adults with baseline uncontrolled hypertension. Patient-centered chronic care programs for HIV can be leveraged to reduce the overall burden of cardiovascular mortality in SSA. TRIAL REGISTRATION: ClinicalTrials.gov NCT01864603.

HIV viral exposure and mortality in a multicenter ambulatory HIV adult cohort, United States, 1995-2016.

ABSTRACT: The aim of this study was to identify viral exposure (VE) measures and their relationship to mortality risk among persons with HIV.Prospective multicenter observational study to compare VE formulae.Eligible participants initiated first combination antiretroviral therapy (cART) between March 1, 1995 and June 30, 2015. We included 1645 participants followed for ≥6 months after starting first cART, with cART prescribed ≥75% of time, who underwent ≥2 plasma viral load (VL) and ≥1 CD4+ T-lymphocyte cell (CD4) measurement during observation. We evaluated all-cause mortality from 6 months after cART initiation until June 30, 2016. VE was quantified using 2 time-updated variables: viremia copy-years and percent of person-years (%PY) spent >200 or 50 copies/mL. Cox models were fit to estimate associations between VE and mortality.Participants contributed 10,453 person years [py], with median 14 VLs per patient. Median %PY >200 or >50 were 10% (interquartile range: 1%-47%) and 26% (interquartile range: 6%-72%), respectively. There were 115 deaths, for an overall mortality rate of 1.19 per 100 person years. In univariate models, each measure of VE was significantly associated with mortality risk, as were older age, public insurance, injection drug use HIV risk history, and lower pre-cART CD4. Based on model fit, most recent viral load and %PY >200 copies/mL provided the best combination of VE factors to predict mortality, although all VE combinations evaluated performed well.The combination of most recent VL and %PY >200 copies/mL best predicted mortality, although all evaluated VE measures performed well.

Progressive multifocal leukoencephalopathy and Creutzfeldt-Jakob disease: population-wide incidences, comorbidities, costs of care, and outcomes.

Neurological disorders associated with chronic infections are often progressive as well as challenging to diagnose and manage. Among 4.4 million persons from 2004 to 2019 receiving universal health, progressive multifocal leukoencephalopathy (PML, n = 58) and Creutzfeldt-Jakob disease (CJD, n = 93) cases were identified, revealing stable yearly incidence rates with divergent comorbidities: HIV/AIDS affected 37.8% of PML cases while cerebrovascular disease affected 26.9% of CJD cases. Most CJD cases died within 1 year (73%) although PML cases lived beyond 5 years (34.1%) despite higher initial costs of care. PML and CJD represent important neurological disorders with evolving risk variables and impact on health care.

Survival of HIV/AIDS patients treated under ART follow-up at the University hospital, northwest Ethiopia.

INTRODUCTION: The survival of HIV/AIDS patients on antiretroviral therapy (ART) is determined by a number of factors, including economic, demographic, behavioral, and institutional factors. Understanding the survival time and its trend is crucial to developing policies that will result in changes. The aim of this study was to compare the survival estimates of different subgroups and look into the predictors of HIV/AIDS patient survival. METHODS: A retrospective cohort study of HIV/AIDS patients receiving ART at the University of Gondar teaching hospital was carried out. To compare the survival of various groups, a Kaplan-Meier survival analysis was performed. The Cox proportional hazards model was used to identify factors influencing HIV/AIDS patient survival rates. RESULTS: In the current study, 5.91% of the 354 HIV/AIDS patients under ART follow-up were uncensored or died. Age (HR = 1.051) and lack of formal education (HR = 5.032) were associated with lower survival rate, whereas family size of one to two (HR = 0.167), three to four (HR = 0.120), no alcoholic consumption (HR = 0.294), no smoking and chat use (HR = 0.101), baseline weight (HR = 0.920), current weight (HR = 0.928), baseline CD4 cell count (HR = 0.990), baseline hemoglobin (HR = 0.800), and no TB diseases were associated with longer survival rate. CONCLUSIONS: Fewer deaths were reported in a study area due to high patient adherence, compared to previous similar studies. Age, educational status, family size, alcohol consumption, tobacco and chat usage, baseline and current weight, baseline CD4 cell count, baseline hemoglobin, and tuberculosis (TB) diseases were all significant predictors of survival of HIV/AIDS patients.

Trends in knowledge of HIV status and efficiency of HIV testing services in sub-Saharan Africa, 2000-20: a modelling study using survey and HIV testing programme data.

BACKGROUND: Monitoring knowledge of HIV status among people living with HIV is essential for an effective national HIV response. This study estimates progress and gaps in reaching the UNAIDS 2020 target of 90% knowledge of status, and the efficiency of HIV testing services in sub-Saharan Africa, where two thirds of all people living with HIV reside. METHODS: For this modelling study, we used data from 183 population-based surveys (including more than 2·7 million participants) and national HIV testing programme reports (315 country-years) from 40 countries in sub-Saharan Africa as inputs into a mathematical model to examine trends in knowledge of status among people living with HIV, median time from HIV infection to diagnosis, HIV testing positivity, and proportion of new diagnoses among all positive tests, adjusting for retesting. We included data from 2000 to 2019, and projected results to 2020. FINDINGS: Across sub-Saharan Africa, knowledge of status steadily increased from 5·7% (95% credible interval [CrI] 4·6-7·0) in 2000 to 84% (82-86) in 2020. 12 countries and one region, southern Africa, reached the 90% target. In 2020, knowledge of status was lower among men (79%, 95% CrI 76-81) than women (87%, 85-89) across sub-Saharan Africa. People living with HIV aged 15-24 years were the least likely to know their status (65%, 62-69), but the largest gap in terms of absolute numbers was among men aged 35-49 years, with 701 000 (95% CrI 611 000-788 000) remaining undiagnosed. As knowledge of status increased from 2000 to 2020, the median time to diagnosis decreased from 9·6 years (9·1-10) to 2·6 years (1·8-3·5), HIV testing positivity declined from 9·0% (7·7-10) to 2·8% (2·1-3·9), and the proportion of first-time diagnoses among all positive tests dropped from 89% (77-96) to 42% (30-55). INTERPRETATION: On the path towards the next UNAIDS target of 95% diagnostic coverage by 2025, and in a context of declining positivity and yield of first-time diagnoses, disparities in knowledge of status must be addressed. Increasing knowledge of status and treatment coverage among older men could be crucial to reducing HIV incidence among women in sub-Saharan Africa, and by extension, reducing mother-to-child transmission. FUNDING: Steinberg Fund for Interdisciplinary Global Health Research (McGill University); Canadian Institutes of Health Research; Bill & Melinda Gates Foundation; Fonds the recherche du Québec-Santé; UNAIDS; UK Medical Research Council; MRC Centre for Global Infectious Disease Analysis; UK Foreign, Commonwealth & Development Office.

Use of pembrolizumab with or without pomalidomide in HIV-associated non-Hodgkin's lymphoma.

BACKGROUND: Non-Hodgkin's lymphoma (NHL) is currently the most common malignancy among people living with HIV (PLWH) in the USA. NHL in PLWH is more frequently associated with oncogenic viruses than NHL in immunocompetent individuals and is generally associated with increased PD-1 expression and T cell exhaustion. An effective immune-based second-line approach that is less immunosuppressive than chemotherapy may decrease infection risk, improve immune control of oncogenic viruses, and ultimately allow for better lymphoma control. METHODS: We conducted a retrospective study of patients with HIV-associated lymphomas treated with pembrolizumab±pomalidomide in the HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer Institute. RESULTS: We identified 10 patients with stage IV relapsed and/or primary refractory HIV-associated NHL who were treated with pembrolizumab, an immune checkpoint inihibitor, with or without pomalidomide. Five patients had primary effusion lymphoma (PEL): one had germinal center B cell-like (GCB) diffuse large B cell lymphoma (DLBCL); two had non-GCB DLBCL; one had aggressive B cell lymphoma, not otherwise specified; and one had plasmablastic lymphoma. Six patients received pembrolizumab alone at 200 mg intravenously every 3 weeks, three received pembrolizumab 200 mg intravenously every 4 weeks plus pomalidomide 4 mg orally every day for days 1-21 of a 28-day cycle; and one sequentially received pembrolizumab alone and then pomalidomide alone. The response rate was 50% with particular benefit in gammaherpesvirus-associated tumors. The progression-free survival was 4.1 months (95% CI: 1.3 to 12.4) and overall survival was 14.7 months (95% CI: 2.96 to not reached). Three patients with PEL had leptomeningeal disease: one had a complete response and the other two had long-term disease control. There were four immune-related adverse events (irAEs), all CTCAEv5 grade 2-3; three of the four patients were able to continue receiving pembrolizumab. No irAEs occurred in patients receiving the combination of pembrolizumab and pomalidomide. CONCLUSIONS: Treatment of HIV-associated NHL with pembrolizumab with or without pomalidomide elicited responses in several subtypes of HIV-associated NHL. This approach is worth further study in PLWH and NHL.

Sensitivity and Specificity of the National Death Index for Multiple Causes of Death in People With HIV.

OBJECTIVES: Inaccuracies in cause-of-death information in death certificates can reduce the validity of national death statistics and result in poor targeting of resources to reduce morbidity and mortality in people with HIV. Our objective was to measure the sensitivity, specificity, and agreement between multiple causes of deaths from death certificates obtained from the National Death Index (NDI) and causes determined by expert physician review. METHODS: Physician specialists determined the cause of death using information collected from the medical records of 50 randomly selected HIV-infected people who died in San Francisco from July 1, 2016, through May 31, 2017. Using expert review as the gold standard, we measured sensitivity, specificity, and agreement. RESULTS: The NDI had a sensitivity of 53.9% and a specificity of 66.7% for HIV deaths. The NDI had a moderate sensitivity for non-AIDS-related infectious diseases and non-AIDS-related cancers (70.6% and 75.0%, respectively) and high specificity for these causes (100.0% and 94.7%, respectively). The NDI had low sensitivity and high specificity for substance abuse (27.3% and 100.0%, respectively), heart disease (58.3% and 86.8%, respectively), hepatitis B/C (33.3% and 97.7%, respectively), and mental illness (50.0% and 97.8%, respectively). The measure of agreement between expert review and the NDI was lowest for HIV (κ = 0.20); moderate for heart disease (κ = 0.45) and hepatitis B/C (κ = 0.40); high for non-AIDS-related infectious diseases (κ = 0.76) and non-AIDS-related cancers (κ = 0.72); and low for all other causes of death (κ < 0.35). CONCLUSIONS: Our findings support education and training of health care providers to improve the accuracy of cause-of-death information on death certificates.

Neurocognitive status and risk of mortality among people living with human immunodeficiency virus: an 18-year retrospective cohort study.

HIV-related neurocognitive impairment (NCI) may increase the risk of death. However, a survival disadvantage for patients with NCI has not been well studied in the post-combination antiretroviral therapy (cART) era. Specifically, limited research has been conducted considering the reversible nature and variable progression of the impairment and this area demands further evaluation. We performed multivariable Cox proportional hazards modeling to assess the association between baseline NCI (global T scores) and mortality. A joint modeling approach was then used to model the trajectory of global neurocognitive functioning over time and the association between neurocognitive trajectory and mortality. Among the National NeuroAIDS Tissue Consortium's (NNTC) HIV-infected participants, we found a strong negative association between NCI and mortality in the older age groups (e.g., at age = 55, HR = 0.79; 95% CI 0.64-0.99). Three neurocognitive sub-domains (abstraction and executive functioning, speed of information processing, and motor) had the strongest negative association with mortality. Joint modelling indicated a 33% lower hazard for every 10-unit increase in global T scores (HR = 0.67; 95% CI 0.56-0.80). The study identified older HIV-infected individuals with NCI as a group needing special attention for the longevity of life. The study has considerable prognostic utility by not only predicting mortality hazard, but also future cognitive status.

Consistent use of lipid lowering therapy in HIV infection is associated with low mortality.

BACKGROUND: In people living with HIV (PLWH), statins may be disproportionately effective but remain underutilized. A large prospective trial in patients with low to moderate cardiovascular (ASCVD) risk will reveal whether they should be considered in all PLWH. But its effect size may not apply to real-world PLWH with higher ASCVD and mortality risk. Also, the clinical role of non-statin lipid-lowering therapy (LLT) and LLT adherence in this population is unknown. METHODS: Comparative multi-level marginal structural model for all-cause mortality examining four time-updated exposure levels to LLT, antihypertensives, and aspirin in a virtual cohort of older PLWH. Incident coronary, cerebrovascular, and overall ASCVD events, serious infections, and new cancer diagnoses served as explanatory outcomes. RESULTS: In 23,276 HIV-infected US-veterans who were followed for a median of 5.2 years after virologic suppression overall mortality was 33/1000 patient years: > 3 times higher than in the US population. Use of antihypertensives or aspirin was associated with increased mortality. Past LLT use (> 1 year ago) had no effect on mortality. LLT exposure in the past year was associated with a reduced hazard ratio (HR) of death: 0.59, 95% confidence interval (CI) 0.51-0.69, p < 0.0001 for statin containing LLT and 0.71 (CI: 0.54-0.93), p = 0.03 for statin-free LLT. For consistent LLT use (> 11/12 past months) the HR of death was 0.48 (CI: 0.35-0.66) for statin-only LLT, 0.34 (CI: 0.23-0.52) for combination LLT, and 0.27 (CI: 0.15-0.48) for statin-free LLT (p < 0.0001 for all). The ASCVD risk in these patients was reduced in similar fashion. Use of statin containing LLT was also associated with reduced infection and cancer risk. Multiple contrasting subgroup analyses yielded comparable results. Confounding is unlikely to be a major contributor to our findings. CONCLUSIONS: In PLWH, ongoing LLT use may lead to substantially lower mortality, but consistent long-term adherence may be required to reduce ASCVD risk. Consistent non-statin LLT may be highly effective and should be studied prospectively.

Secular Trends in Breast Cancer Risk Among Women With HIV Initiating ART in North America.

BACKGROUND: Studies suggest lower risk of breast cancer in women with HIV versus without HIV. These estimates may be biased by lower life expectancy and younger age distribution of women with HIV. Our analysis evaluated this bias and characterized secular trends in breast cancer among women with HIV initiating antiretroviral therapy. We hypothesized breast cancer risk would increase over time as mortality decreased. SETTING: Women with HIV prescribed antiretroviral therapy in the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) from 1997 through 2016. METHODS: We estimated breast cancer hazard (cause-specific hazard ratios) and cumulative incidence accounting for competing risks (subdistribution hazard ratios) to assess changes in breast cancer risk over time. This was assessed overall (1997-2016) and within/across calendar periods. Analyses were adjusted for race/ethnicity and inverse probability weighted for cohort. Cumulative incidence was graphically assessed by calendar period and race/ethnicity. RESULTS: We observed 11,587 women during 1997-2016, contributing 63 incident breast cancer diagnoses and 1,353 deaths [73,445 person-years (median follow-up = 4.5 years)]. Breast cancer cumulative incidence was 3.2% for 1997-2016. We observed no secular trends in breast cancer hazard or cumulative incidence. There were annual declines in the hazard and cumulative incidence of death (cause-specific hazard ratios and subdistribution hazard ratios: 0.89, 95% confidence interval: 0.87 to 0.91) which remained within and across calendar periods. CONCLUSIONS: These findings contradict the hypothesis of increasing breast cancer risk with declining mortality over time among women with HIV, suggesting limited impact of changing mortality on breast cancer risk. Additional inquiry is merited as survival improves among women with HIV.