Impacto da Haart na prevalência de otite média crônica em crianças brasileiras infectadas pelo HIV

O advento de novas drogas anti-retrovirais como os inibidores de protease provocou mudanças sensíveis na morbidade e mortalidade de pacientes infectados pelo HIV. OBJETIVOS: Avaliar o impacto das novas drogas anti-retrovirais (Highly Active Anti-retroviral Therapy - HAART) na prevalência de otite média crônica em população pediátrica infectada pelo HIV. MÉTODOS: Analisamos os prontuários de 471 crianças com idade entre zero e 12 anos e 11 meses portadoras de HIV atendidas no ambulatório de AIDS de Clínica Otorrinolaringológica do HCFMUSP. As crianças foram divididas em dois grupos, de acordo com a faixa etária: 0 a 5 anos e 11 meses e 6 a 12 anos e 11 meses, e classificadas como portadoras de otite média crônica, baseadas em achados de anamnese, otoscopia, audiometria e imitanciometria. As prevalências de otite média crônica apresentadas e as contagens de linfócitos T CD4+ foram comparadas entre as crianças em uso ou não de HAART. RESULTADOS: Das 459 crianças atendidas, 65 (14,2%) apresentavam otite média crônica. Observamos, nas crianças de 0 a 5 anos e 11 meses que o uso de HAART esteve associado a significante menor prevalência de otite média crônica (p = 0,02), e maior contagem de linfócitos T CD4+ (p < 0,001). CONCLUSÃO: O uso de HAART esteve associado à menor prevalência da forma crônica de otite média entre crianças menores de 6 anos infectadas pelo HIV, provavelmente como conseqüência do aumento promovido na contagem de linfócitos T CD4+.

Analysis of HIV- type 1 protease and reverse transcriptase in Brazilian children failing highly active antiretroviral therapy (HAART)

The aim of this study was to evaluate the genotypic resistance profiles of HIV-1 in children failing highly active antiretroviral therapy (HAART). Forty-one children (median age = 67 months) receiving HAART were submitted to genotypic testing when virological failure was detected. cDNA was extracted from PBMCs and amplified by nested PCR for the reverse transcriptase and protease regions of the pol gene. Drug resistance genotypes were determined from DNA sequencing. According to the genotypic analysis, 12/36 (33.3%) and 6/36 (16.6%) children showed resistance and possible resistance, respectively, to ZDV; 5/36 (14%) and 4/36 (11.1%), respectively, showed resistance and possible resistance to ddI; 4/36 (11.1%) showed resistance to 3TC and D4T; and 3/36 (8.3%) showed resistance to Abacavir. A high percentage (54%) of children exhibited mutations conferring resistance to NNRTI class drugs. Respective rates of resistance and possible resistance to PIs were: RTV (12.2%, 7.3%); APV (2.4%, 12.1%); SQV(0%, 12.1%); IDV (14.6%, 4.9%), NFV (22%, 4.9%), LPV/RTV (2.4%, 12.1%). Overall, 37/41 (90%) children exhibited virus with mutations related to drug resistance, while 9% exhibited resistance to all three antiretroviral drug classes.

Withdrawal of maintenance therapy for cytomegalovirus retinitis in AIDS patients exhibiting immunological response to HAART

BACKGROUND: Before the introduction of highly active antiretroviral therapy (HAART), CMV retinitis was a common complication in patients with advanced HIV disease and the therapy was well established; it consisted of an induction phase to control the infection with ganciclovir, followed by a lifelong maintenance phase to avoid or delay relapses. METHODS: To determine the safety of CMV maintenance therapy withdrawal in patients with immune recovery after HAART, 35 patients with treated CMV retinitis, on maintenance therapy, with CD4+ cell count greater than 100 cells/mm³ for at least three months, but almost all patients presented these values for more than six months and viral load < 30000 copies/mL, were prospectively evaluated for the recurrence of CMV disease. Maintenance therapy was withdrawal at inclusion, and patients were monitored for at least 48 weeks by clinical and ophthalmologic evaluations, and by determination of CMV viremia markers (antigenemia-pp65), CD4+/CD8+ counts and plasma HIV RNA levels. Lymphoproliferative assays were performed on 26/35 patients. RESULTS: From 35 patients included, only one had confirmed reactivation of CMV retinitis, at day 120 of follow-up. No patient returned positive antigenemia tests. No correlation between lymphoproliferative assays and CD4+ counts was observed. CONCLUSION: CMV retinitis maintenance therapy discontinuation is safe for those patients with quantitative immune recovery after HAART.

THE INFLUENCE OF HIV-1 SUBTYPES C, CRF31_BC AND B ON DISEASE PROGRESSION AND INITIAL VIROLOGIC RESPONSE TO HAART IN A SOUTHERN BRAZILIAN COHORT

Background: Although most HIV-1 infections in Brazil are due to subtype B, Southern Brazil has a high prevalence of subtype C and recombinant forms, such as CRF31_BC. This study assessed the impact of viral diversity on clinical progression in a cohort of newly diagnosed HIV-positive patients. Methods: From July/2004 to December/2005, 135 HIV-infected patients were recruited. The partial pol region was subtyped by phylogeny. A generalized estimating equation (GEE) model was used to examine the relationship between viral subtype, CD4+ T cell count and viral load levels before antiretroviral therapy. Hazard ratio (Cox regression) was used to evaluate factors associated with viral suppression (viral load < 50 copies/mL at six months). Results: Main HIV-1 subtypes included B (29.4%), C (28.2%), and CRF31_BC (23.5%). Subtypes B and C showed a similar trend in CD4+ T cell decline. Comparison of non-B (C and CRF31_BC) and B subtypes revealed no significant difference in the proportion of patients with viral suppression at six months (week 24). Higher CD4+ T cell count and lower viral load were independently associated with viral suppression. Conclusion: No significant differences were found between subtypes; however, lower viral load and higher CD4+ T cell count before therapy were associated with better response.

CHAGASIC MENINGOENCEPHALITIS IN AN HIV INFECTED PATIENT WITH MODERATE IMMUNOSUPPRESSION: PROLONGED SURVIVAL AND CHALLENGES IN THE HAART ERA

The reactivation of Chagas disease in HIV infected patients presents high mortality and morbidity. We present the case of a female patient with confirmed Chagasic meningoencephalitis as AIDS-defining illness. Interestingly, her TCD4+ lymphocyte cell count was 318 cells/mm3. After two months of induction therapy, one year of maintenance with benznidazol, and early introduction of highly active antiretroviral therapy (HAART), the patient had good clinical, parasitological and radiological evolution. We used a qualitative polymerase chain reaction for the monitoring of T. cruzi parasitemia during and after the treatment. We emphasize the potential value of molecular techniques along with clinical and radiological parameters in the follow-up of patients with Chagas disease and HIV infection. Early introduction of HAART, prolonged induction and maintenance of antiparasitic therapy, and its discontinuation are feasible, in the current management of reactivation of Chagas disease.

Oral cavity lymphoma as secondary AIDS-defining neoplasm in a patient on HAART with immune reconstitution

Lymphomas of the oral cavity are a rare complication of advanced HIV/AIDS disease. The clinical appearance of these neoplasms includes masses or ulcerative lesions that involve the oral soft tissue and the jaw as the predominant manifestation. We report the case of a patient with AIDS who developed diffuse large B-cell non-Hodgkin’s lymphoma of the oral cavity during highly active antiretroviral therapy, with undetectable plasma viral load and immune reconstitution.

HAART: a risk factor for development of porphyria cutanea tarda?

Porphyria cutanea tarda (PCT) is caused by inherited or acquired partial deficiency of the uroporphyrinogen-decarboxylase (Uro-D) enzyme activity. It is the most common form of porphyria. The main triggering factors to the development of porphyria cutanea tarda are alcohol, hepatitis C virus and human immunodeficiency virus. There are several reports of PCT associated with drugs, among them, antiretroviral therapy. We describe three HIV-positive patients, which showed photosensitivity as well as the emergence of tense blisters on sun-exposed areas during the use of highly active antiretroviral therapy (HAART) and discuss the possibility of PCT after the use of these drugs by those patients.

Estudo do autorrelato de adesão e uso problemático de álcool em uma população de indivíduos com AIDS em uso de HAART

OBJETIVO: O objetivo deste estudo foi analisar a força de associação entre as variáveis autorrelato de adesão à medicação e uso problemático de álcool em uma população de indivíduos com AIDS que fazem uso de HAART. MÉTODO: Foram entrevistados 103 pacientes com AIDS, em uso de HAART há pelo menos seis meses, que frequentavam o ambulatório do Instituto de Doenças Tropicais Natan Portela (IDTNP), localizado na cidade de Teresina, PI. A variável independente estudada foi o uso problemático de álcool, além de variáveis sociodemográficas. O questionário utilizado para avaliar o uso problemático de álcool foi o AUDIT (Alcohol Use Disorders Identification Test). A variável dependente avaliada neste estudo foi o autorrelato de adesão ao tratamento para o HIV. Para sua mensuração, optou-se por utilizar o QSAM (Questionário Simplificado de Adesão à Medicação), por tratar-se de um questionário bastante simples e de fácil aplicação. RESULTADOS: A frequência de AUDIT > 08 foi de 33%; já o autorrelato de adesão, avaliado pelo QSAM, foi positivo em 45% da amostra. Testada a associação entre a frequência de QSAM positivo e o AUDIT positivo, encontrou-se forte associação entre essas variáveis (p = 0,004). CONCLUSÃO: Conclui-se deste estudo que o autorrelato de falha na adesão ao HAART aferido por meio do QSAM é um fator de risco para a presença de uso problemático de álcool.

HIV-1 tropism and CD4 T lymphocyte recovery in a prospective cohort of patients initiating HAART in Ribeirão Preto, Brazil

While human immunodeficiency virus (HIV)-1 chemokine co-receptors 5 tropism and the GWGR motif in the envelope third variable region (V3 loop) have been associated with a slower disease progression, their influence on antiretroviral response remains unclear. The impact of baseline V3 characteristics on treatment response was evaluated in a randomised, double blind, prospective cohort study with patients initiating highly active antiretroviral therapy with lopinavir or efavirenz plus azithothymidine/3TC (1:1) over 48 weeks. Similar virological and immunological responses were observed for both treatment regimens. The 43 individuals had a mean baseline CD4 T cell count of 119 cells/mm³ [standard deviation (SD) = 99] and a mean viral load of 5.09 log10 copies/mL (SD = 0.49). The GWGR motif was not associated with a CD4 T cell response, but predicted R5 tropism by the geno2pheno[clinical20%] algorithm correlated with higher CD4 T cell levels at all monitoring points (p < 0.05). Moreover, higher false-positive rates (FPR) values from this analysis revealed a strong correlation with CD4 T cell recovery (p < 0.0001). Transmitted drug resistance mutations, documented in 3/41 (7.3%) cases, were unrelated to the assigned antiretroviral regimen and had no impact on patient outcomes. In conclusion, naÏve HIV-1 R5 infected patients exhibited higher CD4 T cell counts at baseline; this difference was sustained throughout therapy. The geno2pheno[clinical] option FPR positively correlated with CD4 T cell gain and may be useful in predicting CD4 T cell recovery.

Imbalance of naive and memory T lymphocytes with sustained high cellular activation during the first year of life from uninfected children born to HIV-1-infected mothers on HAART

The immune consequences of in utero HIV exposure to uninfected children whose mothers were submitted to highly active antiretroviral therapy (HAART) during gestation are not well defined. We evaluated 45 HIV-exposed uninfected (ENI) neonates and 45 healthy unexposed control (CT) neonates. All HIV-infected mothers received HAART during pregnancy, and the viral load at delivery was <50 copies/mL for 56.8%. Twenty-three ENI neonates were further evaluated after 12 months and compared to 23 unexposed healthy age-matched infants. Immunophenotyping was performed by flow cytometry in cord and peripheral blood. Cord blood lymphocyte numbers did not differ between groups. However, ENI neonates had a lower percentage of naive T cells than CT neonates (CD4+, 76.6 vs 83.1%, P < 0.001; CD8+, 70.9 vs 79.6%, P = 0.003) and higher percentages of central memory T cells than CT neonates (CD4+, 13.9 vs 8.7%, P < 0.001; CD8+, 8.6 vs 4.8%, P = 0.001). CD38 mean fluorescence intensity of T cells was higher in ENI neonates (CD4+, 62.2 vs 52.1, P = 0.007; CD8+, 47.7 vs 35.3, P < 0.001). At 12 months, ENI infants still had higher mean fluorescence intensity of CD38 on T cells (CD4+, 34.2 vs 23.3, P < 0.001; CD8+, 26.8 vs 19.4, P = 0.035). Despite effective maternal virologic control at delivery, HIV-exposed uninfected children were born with lower levels of naive T cells. Immune activation was present at birth and remained until at least 12 months of age, suggesting that in utero exposure to HIV causes subtle immune abnormalities.

Rinossinusites em crianças infectadas pelo HIV sob terapia anti-retroviral

A associação dos inibidores de protease (IP) à terapia anti-retroviral provocou mudanças importantes na morbidade e mortalidade de pacientes infectados pelo HIV. OBJETIVOS: Avaliar o impacto desta associação na prevalência de rinossinusite (RS) e na contagem sérica de linfócitos CD4 em crianças infectadas pelo HIV. CASUÍSTICA E MÉTODOS: A forma de estudo foi cross-sectional com 471 crianças infectadas pelo HIV. Em 1996, inibidores de protease foram liberados para terapia anti-retroviral. Desta forma, dois grupos de crianças foram formados: as que não fizeram uso de IP e as que fizeram uso desta droga após 1996. A prevalência de RS e a contagem sérica de linfócitos CD4 foram comparadas entre estes grupos. RESULTADOS: 14,4% das crianças infectadas pelo HIV apresentaram RS. A RS crônica foi mais prevalente que a RS aguda em ambos os grupos. Crianças menores de 6 anos tratadas com a associação de IP apresentaram maior prevalência de RS aguda. A associação de IP esteve associada à maior contagem de linfócitos CD4 séricos com menor prevalência de RS crônica. CONCLUSÕES: A terapia com IP esteve associada ao aumento na contagem de linfócitos CD4. Crianças abaixo dos 6 anos em uso de IP apresentaram menor tendência à cronificação da doença.

Perfil de mortalidade de pacientes com tuberculose relacionada à comorbidade tuberculose-Aids

OBJETIVO: Analisar o perfil dos óbitos entre pacientes com tuberculose, e descrever a co-infecção tuberculose-Aids e a causa básica de morte nas coortes anuais. MÉTODOS: Foi realizado estudo descritivo dos indivíduos residentes na cidade de Campinas, SP, que foram a óbito durante o tratamento para tuberculose e também dos pacientes notificados após o óbito, mesmo sem ter iniciado o tratamento. As informações foram obtidas do Banco de Dados em Tuberculose /Universidade Estadual de Campinas (Unicamp) e do Banco de Óbitos da Secretaria Municipal de Saúde/Unicamp. Para análise estatística utilizou-se o software Epi Info versão 6. Os óbitos foram agrupados em dois períodos (1993-1996 e 1997-2000) e as proporções, comparadas. RESULTADOS: Foram notificados 4.680 pacientes, totalizando 737 óbitos, com coeficiente de letalidade de 18,1%, de 1993 a 1996, e 13,5%, de 1997 a 2000. Em 78 óbitos (10,6%) a notificação foi no post mortem e não chegou a ser instituído tratamento específico. Verificou-se predomínio do sexo masculino (71,3%) nos dois períodos estudados. A comorbidade tuberculose-Aids esteve presente em 55% dos óbitos. O perfil etário diferiu segundo a presença ou não da Aids: em ambos os períodos, a mediana da idade nos óbitos com Aids esteve na faixa de 30 a 39 e entre 50 e 59 naqueles sem Aids. Os pacientes que nunca haviam sido tratados de tuberculose representaram 81,3% CONCLUSÕES: Destaca-se entre os achados a marcante redução do número de óbitos, a partir de 1997, que pode estar relacionada com a utilização da terapia anti-retroviral (HAART) para Aids.

Metabolic changes associated with antiretroviral therapy in HIV-positive patients

OBJECTIVE: To evaluate metabolic changes associated with highly active antiretroviral therapy (HAART) in HIV-positive patients, and to identify risk factors associated. METHODS: Retrospective study that included 110 HIV-positive patients who where on HAART in the city of Porto Alegre (Southern Brazil) between January 2003 and March 2004. Data on demographic variables, cigarette smoking, diabetes mellitus, cholesterol and triglyceride levels, stage of HIV infection, antiretroviral therapy and HCV coinfection were collected. General linear models procedure for repeated measures was used to test the interaction between HAART and HCV coinfection or protease inhibitor treatment. RESULTS: Total cholesterol, triglycerides, and glucose levels significantly increased after receiving HAART (p<0.001 for all variables), but no interaction with protease inhibitors was seen for total cholesterol, glucose and triglyceride levels (interaction treatment*protease inhibitors p=0.741, p=0.784, and p=0.081, respectively). An association between total cholesterol levels and HCV coinfection was found both at baseline and follow-up (effect of HCV coinfection, p=0.011). Glucose levels were increased by HAART (treatment effect, p=0.036), but the effect was associated to HCV coinfection (treatment*HCV effect, p=0.018). Gender, smoking habit, intravenous drug use and age were not significantly associated with cholesterol, triglyceride and glucose changes. CONCLUSIONS: HCV-infected patients at baseline were significantly less likely to develop hypercholesterolemia. The results provide further evidence of the role of HAART for the development of metabolic disturbances.

Characteristics of HIV patients who missed their scheduled appointments

ABSTRACT OBJECTIVE: To analyze whether sociodemographic characteristics, consultations and care in special services are associated with scheduled infectious diseases appointments missed by people living with HIV. METHODS: This cross-sectional and analytical study included 3,075 people living with HIV who had at least one scheduled appointment with an infectologist at a specialized health unit in 2007. A secondary data base from the Hospital Management & Information System was used. The outcome variable was missing a scheduled medical appointment. The independent variables were sex, age, appointments in specialized and available disciplines, hospitalizations at the Central Institute of the Clinical Hospital at the Faculdade de Medicina of the Universidade de São Paulo, antiretroviral treatment and change of infectologist. Crude and multiple association analysis were performed among the variables, with a statistical significance of p ≤ 0.05. RESULTS: More than a third (38.9%) of the patients missed at least one of their scheduled infectious diseases appointments; 70.0% of the patients were male. The rate of missed appointments was 13.9%, albeit with no observed association between sex and absences. Age was inversely associated to missed appointment. Not undertaking anti-retroviral treatment, having unscheduled infectious diseases consultations or social services care and being hospitalized at the Central Institute were directly associated to missed appointments. CONCLUSIONS: The Hospital Management & Information System proved to be a useful tool for developing indicators related to the quality of health care of people living with HIV. Other informational systems, which are often developed for administrative purposes, can also be useful for local and regional management and for evaluating the quality of care provided for patients living with HIV.