Classification of clinical risk in people with AIDS followed up in specialized care / Clasificación de riesgo clínico en personas con SIDA acompañadas de la atención especializada / Classificação de risco clínico em pessoas com aids acompanhadas na atenção especializada

ABSTRACT Aim: To develop a clinical risk stratification score for people living with AIDS and to analyze its association with clinical and sociodemographic aspects. Method: Cross-sectional study involving 150 adults with AIDS, in outpatient follow-up. A structured instrument was applied and, sequentially, inferential statistical techniques on the developed score. Results: 45.3% of the participants were classified as in high clinical risk. TL-CD4+ <500cel/mm3 count, detectable viral load, presence of opportunistic diseases, chronic diseases and clinical manifestations were associated with high clinical risk. There was a significant difference in the mean risk between the categories of variables employment status (p = 0.003) and economic class (p = 0.035). There was a higher risk for brown people (OR = 5.55), unemployed status (OR = 16,51) and belonging to classes C (OR = 20.07) and D (OR = 53,32), and a lower risk for individuals with higher schooling (OR = 0.02). Conclusion: The proposed score quantifies clinical situations and points out sociodemographic aspects that predispose to instability and aggravation of AIDS, supporting the qualification of care.

RESUMEN Objetivo: Elaborar una puntuación para estratificación de riesgo clínico de personas viviendo con sida y analizar su asociación con aspectos clínicos y sociodemográficos. Método: Estudio transversal que involucra a 150 adultos con sida, en seguimiento de ambulatorio. Se aplicó instrumento estructurado y, secuencialmente, técnicas estadísticas que interfieren en la puntuación elaborada. Resultados: El 45,3% de los participantes fueron clasificados en el riesgo clínico alto. La cuenta de LT−CD4+<500cel/mm3, la carga viral detectable, la presencia de enfermedades oportunistas, las enfermedades crónicas y manifestaciones clínicas se asociaron al riesgo clínico elevado. Se verificó una diferencia significativa en el riesgo medio entre las categorías de variables de empleo (p=0,003) y la clase económica (p=0,035). Se constató un mayor riesgo para las personas pardas (OR=5,55), alejadas del empleo (OR=16,51) y pertenecientes a las clases C (OR=20,07) y D (OR=53,32), y menor riesgo entre los individuos con mayor escolaridad (OR=0,02). Conclusión: La puntuación propuesta cuantifica situaciones clínicas y apunta aspectos sociodemográficos que predisponen a la inestabilidad y agudización del sida, subsidiando la calificación del cuidado.

RESUMO Objetivo: Elaborar um escore para estratificação de risco clínico de pessoas vivendo co.m Aids e analisar sua associação com aspectos clínicos e sociodemográficos. Método: Estudo transversal envolvendo 150 adultos com aids, em acompanhamento ambulatorial. Aplicou-se instrumento estruturado e, sequencialmente, técnicas estatísticas inferenciais sobre o escore elaborado. Resultados: 45,3% dos participantes foram classificados no risco clínico alto. A contagem de LT-CD4+<500cel/mm3, carga viral detectável, presença de doenças oportunistas, doenças crônicas e manifestações clínicas associaram-se ao risco clínico elevado. Verificou-se diferença significativa no risco médio entre as categorias das variáveis situação empregatícia (p = 0,003) e classe econômica (p = 0,035). Constatou-se maior risco para pessoas pardas (OR = 5,55), afastadas do emprego (OR = 16,51) e pertencentes às classes C (OR = 20,07) e D (OR = 53,32), e menor risco entre os indivíduos com maior escolaridade (OR = 0,02). Conclusão: O escore proposto quantifica situações clínicas e aponta aspectos sociodemográficos que predispõem a instabilidade e agudização da aids, subsidiando a qualificação do cuidado.

Safety of monitoring antiretroviral therapy response in HIV-1 infection using CD4+ T cell count at long-term intervals / Segurança do monitoramento da resposta à terapia antirretroviral em pacientes com infecção pelo HIV-1 através da contagem de linfócitos T CD4+ a intervalos mais longos / Seguridad en la monitorización de la respuesta a la terapia antirretroviral ante el VIH-1, usando el recuento celular CD4+ T en intervalos a largo plazo

Abstract: The latest Brazilian guideline recommended the reduction of routine CD4+ T cell counts for the monitoring of patients with human immunodeficiency virus type 1 (HIV-1) under combination antiretroviral therapy (cART). The aim of this study was to evaluate the safety of monitoring response to cART in HIV-1 infection using routine viral load at shorter intervals and CD4+ T cell count at longer intervals. CD4+ T cell counts and HIV-1 viral load were evaluated in 1,906 HIV-1-infected patients under cART during a three-year follow-up. Patients were stratified as sustained, non-sustained and non-responders. The proportion of patients who showed a CD4+ T > 350cells/µL at study entry among those with sustained, non-sustained and non-responders to cART and who remained with values above this threshold during follow-up was 94.1%, 81.8% and 71.9%, respectively. HIV-1-infected patients who are sustained virologic responders and have initial CD4+ T cell counts > 350cells/µL showed a higher chance of maintaining the counts of these cells above this threshold during follow-up than those presenting CD4+ T ≤ 350cells/µL (OR = 39.9; 95%CI: 26.5-60.2; p < 0.001). This study showed that HIV-1-infected patients who had sustained virologic response and initial CD4+ T > 350cells/µL were more likely to maintain CD4+ T cell counts above this threshold during the next three-year follow-up. This result underscores that the evaluation of CD4+ T cell counts in longer intervals does not impair the safety of monitoring cART response when routine viral load assessment is performed in HIV-1-infected patients with sustained virologic response.

Resumo: O último consenso brasileiro recomenda reduzir a rotina de contagem de linfócitos T CD4+ para monitorar os pacientes com HIV-1 sob terapia antirretroviral combinada (TARV). O estudo teve como objetivo avaliar a segurança do monitoramento à TARV na infecção pelo HIV-1, realizando a carga viral a intervalos mais curtos e a contagem de linfócitos T CD4+ a intervalos mais longos. Foram avaliadas a contagem de linfócitos T CD4+ e a carga viral do HIV-1 em 1.906 pacientes com HIV-1 em uso de TARV durante um seguimento de três anos. Os pacientes foram estratificados em: resposta sustentada, não sustentada e não respondedores. As proporções de pacientes com linfócitos T CD4+ > 350células/µL na linha de base do estudo entre de resposta sustentada, não sustentada e não respondedores à TARV e que permaneceram com valores acima desse limiar ao longo do seguimento foram 94,1%, 81,8% e 71,9%, respectivamente. Os pacientes com resposta virológica sustentada e que tinham contagem de T CD4+ > 350células/µL mostraram maior probabilidade de manter a contagem acima desse limiar durante o seguimento, quando comparados àqueles com T CD4+ ≤ 350células/µL (OR = 39,9; 95%CI: 26,5-60,2; p < 0,001). O estudo mostrou que pacientes HIV-1+ com resposta virológica sustentada e contagem de linfócitos T CD4+ > 350células/µL tinham maior probabilidade de manter a contagem de células T CD4+ acima desse limiar durante o seguimento de três anos subsequentes. O resultado corrobora que a contagem de linfócitos T CD4+ com intervalos mais longos não compromete a segurança do monitoramento da resposta à TARV quando a avaliação da carga viral é feita de rotina em pacientes HIV-1+ com resposta virológica sustentada.

Resumen: Las últimas directrices brasileñas recomendaron la reducción de la rutina en el recuento celular CD4+ T para pacientes con el virus de inmunodeficiencia humano tipo 1 (VIH-1), con terapia de combinación antirretroviral (cART por sus siglas en inglês). El objetivo de este estudio fue evaluar la seguridad de la monitorización de la respuesta a la cART en una infección por VIH-1, usando rutinas de carga viral en intervalos más cortos y recuento celular CD4+ T en intervalos más largos. Se evaluaron el recuento celular CD4+ T y la carga viral VIH-1 en 1.906 pacientes infectados con VIH-1 y con cART durante un seguimiento que duró tres años. Los pacientes fueron estratificados como constantes, inconstantes y sin respuesta. La proporción de pacientes que mostraron CD4+ T > 350células/µL en el estudio entran dentro del grupo de los constantes, inconstantes y sin respuesta al cART, y quienes permanecieron con valores por encima de este umbral durante los seguimientos fueron 94,1%, 81,8% y 71,9%, respectivamente. Los pacientes infectados por VIH-1 que cuentan con la respuesta virológica constante y tienen un recuento inicial CD4+ T > 350células/µL mostraron una oportunidad más alta de mantener el recuento de estas células por encima del umbral durante los seguimientos, respecto a quienes presentaban CD4+ T células ≤ 350células/µL (OR = 39,9; IC95%: 26,5-60,2; p < 0,001). Este estudio expuso que los pacientes infectados por VIH-1, que habían tenido una respuesta virológica constante e inicial CD4+ T > 350células/µL, eran más propensos a mantener el recuento de células CD4+ T por encima de este umbral durante los tres años posteriores de seguimiento. Este resultado destaca que la evaluación del cómputo de células CD4+ T en intervalos más largos no obstaculiza la seguridad al realizar una monitorización en la respuesta a cART, cuando la evaluación de la carga viral rutinaria se realiza en pacientes infectados por VIH-1 con una respuesta virológica constante.

Hospitalization of people 50 years old or older living with HIV/AIDS / Hospitalización de personas de 50 o más años viviendo con VIH/SIDA / Hospitalização de pessoas com 50 anos ou mais vivendo com HIV/Aids

ABSTRACT Objective: Identify the rate and predictive factors of the hospitalization of people living with HIV/AIDS (PLHA), aged 50 years or older. Method: A quantitative, cross-sectional study was conducted at two inpatient units specialized in infectious diseases in a teaching hospital. Data were gathered through individual interviews between August 2011 and February 2015. All ethical precepts were followed. Results: Of the 532 admitted patients, 95 were PLHA 50 years old or older; 30.5% were admitted 3 to 4 times after being diagnosed with HIV/AIDS. Conclusion: Rate of hospitalization was 17.8%, and being 50 to 60 years old was a protective factor against hospitalization.

RESUMEN Objetivo: Identificar la tasa y los factores predictivos para hospitalización de personas viviendo con VIH/SIDA (PVHS), de edad igual o superior a 50 años. Método: Estudio cuantitativo, transversal, realizado en dos unidades de internación especializadas en cuidado de enfermedades infecciosas de un hospital universitario. Datos recolectados mediante entrevista individual, de agosto de 2011 a febrero de 2015. Fueron contemplados todos los preceptos éticos. Resultados: De las 532 internaciones, 95 correspondían a PVVS con edad igual o superior a 50 años; 56,8% recibieron el diagnóstico de VIH/SIDA antes de llegar a sus 50 años; 30,5% fueron hospitalizadas de 3 a 4 veces después del diagnóstico de infección por VIH/SIDA. Conclusión: La tasa de hospitalización fue del 17,8%, y la faja etaria de 50 a 60 años constituyó factor de protección para la hospitalización.

RESUMO Objetivo: Identificar a taxa e os fatores preditores para a hospitalização de pessoas vivendo com HIV/Aids (PVHA), com idade igual ou superior a 50 anos. Método: Estudo quantitativo, transversal, realizado em duas unidades de internação especializadas em cuidados às doenças infecciosas, de um hospital universitário. A coleta de dados foi realizada por meio de entrevista individual, no período de agosto de 2011 a fevereiro de 2015. Todos os preceitos éticos foram contemplados. Resultados: Das 532 internações, 95 eram de PVHA com idade igual ou superior a 50 anos; 56,8% receberam o diagnóstico de HIV/Aids antes de terem completado 50 anos de idade; 30,5% foram hospitalizadas de 3 a 4 vezes após o diagnóstico da infecção pelo HIV/Aids. Conclusão: A taxa de hospitalização foi de 17,8%, e a faixa etária de 50 a 60 anos foi fator de proteção para a hospitalização.

Comportamiento de las enfermedades oftalmológicas en pacientes con VIH-SIDA / Behavior of eye diseases in HIV-Aids patients

Objetivo: caracterizar las enfermedades oftalmológicas en pacientes con VIH-SIDA diagnosticadas en el Servicio de Uveítis e Inflamaciones Oculares del Instituto Cubano de Oftalmología Ramón Pando Ferrer. Métodos: se realizó un estudio descriptivo longitudinal retrospectivo en 39 ojos (24 pacientes) quienes cumplieron los criterios de inclusión y exclusión de la investigación. Las variables estudiadas fueron: edad, sexo, enfermedades oftalmológicas asociadas, lateralidad, agudeza visual y conteo de linfocitos TCD4+ al inicio y al final de la enfermedad oftalmológica, las complicaciones asociadas y la pérdida de la agudeza visual. Resultados: predominó el sexo masculino (83,3 por ciento) y el grupo etario entre 31 y 45 años, que representó el 45,8 por ciento de la muestra. Existió un gran deterioro visual desde el inicio de la enfermedad, sin mejorias significativas una vez estabilizada esta (p= 0,503). Las enfermedades oftalmológicas más frecuentes en orden de frecuencia fueron la sífilis ocular (32,1 por ciento), la retinitis por citomegalovirus (28,6 por ciento) y la toxoplasmosis (17,8 por ciento). El desprendimiento de retina (27,2 por ciento), las membranas epirretinales (22,7 por ciento) y las cataratas (18,2 por ciento) fueron las complicaciones más frecuentes. Conclusiones: la sífilis ocular es la enfermedad más frecuente en pacientes con VIH-SIDA y no guarda relación con el conteo CD4+. La retinitis por citomegalovirus se asocia a conteos de CD4+ bajos y provoca mayor cantidad de complicaciones. Más de la mitad de los ojos con enfermedades oftalmológicas en los pacientes con VIH- SIDA evolucionan a la ceguera(AU)

Objective: to characterize the eye diseases observed in HIV-AIDS patients diagnosed at the Uveitis and Eye Inflammation Service at "Ramon Pando Ferrer" Cuban Institute of Ophthalmology. Methods: retrospective, longitudinal and descriptive study of 39 eyes (24 patients, who met the inclusion and exclusion criteria of the research. The study variables were age, sex, associated eye diseases, laterality, visual acuity and TCD4+ lymphocyte count at the beginning and the end of the eye disease, the related complications and the loss of visual acuity. Results: males (83.3 percent) and the 31-45 y age group (45.8 percent) of the sample predominated. There was great visual deterioration since the onset of disease, without any significant improvement once the patient is stabilized (p= 0.503). The most common eye diseases were ocular syphilis (32.1 percent), cytomegalovirus retinitis (28.6 percent) and toxoplasmoxis (17.8 percent). Retinal detachment (27.2 percent), epiretinal membranes (22.7 percent) and cataract (18.2 percent) were the most frequent complications. Conclusions: Ocular syphilis is the most common disease in HIV-AIDS patients and is unrelated to CD4+ count. Cytomegalovirus retinitis is associated to low CD4+ counts and unleash higher number of complications. Over half of the eyes with diseases in HIV-AIDS patients evolved into blindness(AU)

Low-cost assays for monitoring HIV infected individuals in resource-limited settings.

Use of a combination of CD4 counts and HIV viral load testing in the management of antiretroviral therapy (ART) provides higher prognostic estimation of the risk of disease progression than does the use of either test alone. The standard methods to monitor HIV infection are flow cytometry based for CD4+ T cell count and molecular assays to quantify plasma viral load of HIV. Commercial assays have been routinely used in developed countries to monitor ART. However, these assays require expensive equipment and reagents, well trained operators, and established laboratory infrastructure. These requirements restrict their use in resource-limited settings where people are most afflicted with the HIV-1 epidemic. With the advent of low-cost and/or low-tech alternatives, the possibility of implementing CD4 count and viral load testing in the management of ART in resource-limited settings is increasing. However, an appropriate validation should have been done before putting them to use for patient testing.

Mortality in HIV infected individuals in Pune, India.

Background & objectives: With the presence of HIV epidemic for more than two decades in India, rise in the number of HIV related deaths is expected. Data on mortality in HIV infected individuals from prospective studies are scanty in India. We report here data on mortality in a systematically followed cohort of HIV infected individuals at Pune, Maharashtra, India Methods: A total of 457 HIV infected individuals were enrolled in a prospective study in Pune between September 2002 and November 2004. They were evaluated clinically and monitored for CD4 counts at every quarterly visit. Mortality data were collected from the records of hospital facilities provided by the study. If the death occurred outside such hospitals; relatives of the participants were requested to inform about the death. Results: Median CD4 count in study participants was 218 cells/µl (95% CI: 107-373) at baseline. The median duration of follow up was 15 months (IQR: 12, 22). Mortality was higher in antiretroviral therapy (ART) naive patients compared to those who received treatment (16.59 vs. 7.25 per 100 person years). Participants above 35 yr of age, CD4 count less than or equal to 100 cells/µl at baseline, tuberculosis at any study time point and ART status were independently associated with high mortality [(RR=1.97; 95% CI: (1.23, 3.14), P=0.005, (RR=33.20, 95%CI (7.59, 145.29), P<0.001, (RR=2.38, 95% CI (1.38, 4.09), P= 0.002 and RR=5.60, 95% CI (3.18, 9.86), P<0.001, respectively]. Interpretation & conclusions: High mortality at advanced immunosuppression highlights the importance of early detection of HIV infection. Emphasis needs to be given at timely diagnosis and management of tuberculosis and ART initiation. It is important to create awareness about availability of free antiretroviral drugs in the government ART roll out programme.

Evaluation of a manual CD4+ count kit for determination of absolute CD4+ T-lymphocyte counts.

OBJECTIVE: The aim of the present study was to evaluate a manual CD4+ count kit assay (CD4+: cytospheres) for CD4+ T-lymphocyte count compared with flow cytometric method in HIV infected patients. MATERIAL AND METHOD: One hundred thirty three HIV infected patients were recruited from the out patient department of Khon Kaen Hospital. Blood samples were done by a manual CD4+ count kit assay (CD4+: cytospheres) and flow cytometry for CD4+ T-lymphocyte count. The data were analyzed for diagnostic test and correlation coefficient. RESULTS: The data of cytospheres assay and flow cytomeric method showed good correlation (r = 0.88) for the total group. At the absolute CD4+ T-lymphocyte 200 cells/cu.mm, the cytospheres assay demonstrated sensitivity 83.10% (76.73-89.47%), specificity 93.55% (89.37-97.72%), PPV 93.65% (89.51-97.79%), NPV 82.86% (76.45-89.26%). In the case of CD4+ T-lymphocyte count were lower than 200 cells/cu.mm, the cytospheres assay displayed progressive decrease in sensitivity successive increase in specificity. CONCLUSION: The cytospheres technique is an alternative noncytofluorometric assay for CD4+ T-lymphocyte count. This test may be useful for screening in HIV infected adult patients in community hospitals where flow cytometry technique is not available. But the assay is limited in determination only absolute CD4+ T-lymphocyte count with higher than 30 cells/cu.mm. This technique is not benefit in pediatric HIV/AIDS patient due to percentage CD4+ value did not obtained. The quality control should be concern technical skill and proficiency testing for laboratory setting.

Evidence for lower CD4+ T cell and higher viral load in asymptomatic HIV-1 infected individuals of India: implications for therapy initiation.

PURPOSE: We have earlier documented that the south Indian population had lower CD4 counts. The aim of this study was to investigate a previous suggestion on a new CD4+ T cell cut off and association with HIV-1 RNA levels for decision on anti retroviral therapy in India (south). METHODS: We evaluated a new methodology i.e., artus real-time PCR and CD4+ T cell count by Guava EasyCD4 system. From 146 HIV infected individuals seen at a tertiary care centre, blood was collected for CD4+ T cell and HIV-1 RNA estimation. RESULTS: The receiver operating characteristic curve cut off value for the CD4 counts to distinguish between CDC clinical categories A and B was 243 cells/microL, and to distinguish B and C was 153 cells/microL. The RNA level that differentiated CDC A and B was 327473 RNA copies/mL, while for CDC B and C was 688543 copies/mL. There was a significant negative correlation (r = -0.55, P + T cell counts in HIV infected individuals. CONCLUSIONS: A majority with CD4 counts of 201-350 cells/microL in our population had higher viral load than the treatment threshold suggested by the International AIDS society and the above two methodologies are useful in monitoring HIV infections.

Microbiological infections in HIV positive Bahraini patients with low CD4+ T-lymphocyte count.

The correlation of CD4+ T-lymphocyte count and the distribution of pathogenic or opportunistic microbial infection most commonly found in HIV positive individuals differ from one area to the other. The present study reports such findings in 67 HIV positive Bahraini patients in the period May 1997 to Nov. 1998. CD4+ T-lymphocyte count was measured using flow cytometry. Bacterial and fungal cultures were performed. Serological diagnosis was performed when indicated. Viral study was done serologically. The distribution of CD4+ T-lymphocyte count in the studied group was: 21 patients (31.3%) less than 100 cells/microl, 5 patients (7.5%) 100-200 cells/microl, 25 patients (37.3%) 201-500 cells/microl and 16 patients (23.9%) with count more than 500 cells/microl. Among patients with low CD4 count (less than 100 cells/microl) (n=21), microbial infections varied from fungal infections 66%, bacterial infections 57% and viral infections 4.8%. Bacterial infections included Salmonellosis (14.3%), Staphylococcus epidermidis (14.3%), Pseudomonas aeruginosa (9.5%), H. influenzae (9.5%), Legionellosis (4.8%) and E. coli (4.8%). Fungal infection included Candida albicans (52.4%), Pneumocystis carinii (9.5%), Cryptococcus neoformans (4.8%). Viral infection included H. simplex to (4.8%). Fungal infections were the highest common infection in thus study. The most common microbial infection was Candida albicans. P. carinii and Cryptococcus neoformans were less common than found in other studies world wide.

Production of monoclonal antibody to CD4 antigen and development of reagent for CD4+ lymphocyte enumeration.

A hybridoma secreting monoclonal antibody (mAb) specific to CD4 protein was generated. This monoclonal antibody, named MT4, was proved to be specific to CD4 protein as it reacted with CD4-DNA transfected COS cells, CD4+ cell lines and CD4+ lymphocytes. Furthermore, MT4 mAb inhibited the binding of standard CD4 monoclonal antibodies to CD4 proteins on CD4+ cells. To develop a home made reagent for CD4+ lymphocyte determination by flow cytometry, fluorescein isothiocyanate (FITC) was conjugated to MT4 mAb. To evaluate the developed reagent, 30 HIV infected and 30 healthy individuals were determined for CD4+ lymphocytes by using both a commercial Simultest reagent kit and home made FITC labeled MT4 mAb simultaneously. The study has shown that both percentages and absolute CD4+ lymphocyte counts obtained from both reagents were equivalent. The correlation coefficient for regression analysis was 0.995 and 0.996 for percentages and absolute CD4+ lymphocyte counts, respectively. The results suggest that home made FITC labeled MT4 reagent is an acceptable alternative reagent for monitoring CD4+ lymphocytes in blood samples by flow cytometry.

Flow cytometric three-color determination of CD4 T-lymphocytes on blood specimens from AIDS patients who have a large number of contaminating non-lymphocytes.

A three-color flow cytometric determination of CD4 T-lymphocytes on whole blood specimens from AIDS patients which contain a high proportion of non-lymphocyte elements is described. Peripheral blood cells were stained by a three-color method using monoclonal antibodies conjugated respectively with fluorescein isothiocyanate (FITC)-CD3, phycoerythrin (PE)-CD4 and peridinin chlorophyll protein (PerCP)-CD45. CD45 stains all leukocytes with the highest fluorescence expression of CD45 antigen in lymphocytes. By combining light scatter with CD45 in the fluorescence 3 (FL3) channel, a light scattering window can be drawn to include almost all bright CD45 lymphocytes. This live gate of lymphocytes was then acquired and analysed simultaneously using other irrelevant two-color (FITC/PE) antibodies of CD3 and CD4 in the FITC and PE channels, respectively. This method is easy and straightforward, and gives successful analysis of CD4 T-lymphocytes in AIDS blood specimens contaminated with an unusually large number of non-lymphocytic cells.