TRATAMENTO ANTIRRETROVIRAL DO PACIENTE HIV/AIDS: VARIÁVEIS QUE INFLUENCIAM A ADESÃO

A AIDS (do inglês Acquired Immunodeficiency Syndrom) é uma epidemia generalizada com cerca de 38 milhões de pessoas no mundo infectadas pelo vírus. No Brasil, até junho de 2019, tem-se registrado 966,058 pessoas vivendo com HIV/aids. O Estado do Rio Grande do Sul destaca-se no ranking das 100 cidades com mais de 100 mil habitantes com 12 cidades com os maiores índices de detecção de HIV (Vírus da Imunodeficiência Humana), sendo Porto Alegre, a 11ª entre as demais cidades do ranking. O início da terapia antirretroviral (TARV), preconizada pela Organização Mundial de Saúde (OMS) se dava a partir das manifestações clínicas do paciente, sendo a contagem de linfócitos TCD4+ e a carga viral os indicadores efetivos para a conduta medicamentosa. A partir de 2015, a OMS passou a recomendar o início de tratamento imediato para todas as pessoas diagnosticadas com o vírus HIV e a adoção do esquema terapêutico 3 em 1 (Tenofovir, Lamivudina e Efavirenz). Diversos estudos contribuem para demonstrar que o início precoce da TARV e adesão adequada estão associados a menores taxas de mortalidade, morbidade e diminuição da transmissão viral, auxiliando a controlar a disseminação da epidemia mundial. Entretanto, ainda que esta medida tenha contribuído para a adesão ao tratamento por conta da redução dos efeitos adversos, bem como a facilidade de administração em dose fixa combinada, inúmeros problemas têm sido relacionados à adesão ao tratamento pelos portadores de HIV/aids. Na esfera pública, dentre os principais podem ser citados a ineficiência observada nos serviços prestados pelo sistema de saúde (dificuldade quanto ao monitoramento dos pacientes a partir do sistema de notificações e realização de exames periódicos, disponibilidade e dispensação dos medicamentos, entre outros). Do mesmo modo, tanto os efeitos colaterais e as dificuldades inerentes ao uso da TARV quanto variáveis sócio econômicas e principalmente, comportamentais, têm sido apontados como relevantes para os resultados observados quanto à disseminação do vírus nas populações. Diante da complexidade de elementos que constituem a adesão a tratamentos desta natureza, faz-se necessário reconhecer e estabelecer as variáveis que contribuem para a efetividade ou ineficiência dos tratamentos preconizados para esta doença. Nesse sentido, o presente trabalho estabeleceu variáveis que possam influenciar a adesão ao tratamento, sob três aspectos principais: a efetividade do sistema de saúde, a 6 recuperação imunológica em decorrência da medicação e o contexto comportamental dos indivíduos As análises foram conduzidas a partir de coleta de dados de 678 pacientes de dois Serviços de Atendimento Especializado (SAE de Novo Hamburgo e SAE de Viamão), definidos como pontos de coleta por conta das notificações dos altos índices de infecção pelo vírus nestas regiões. O período de coleta de dados definido considerou a atendimento à normativa da OMS quanto ao uso da TARV de forma compulsória a partir do diagnóstico de infecção, independentemente dos resultados clínicos, compreendendo os anos de 2015 à 2017.Os dados relativos à carga viral e linfócitos TCD4+ , bem como a dispensação de medicamentos, comorbidades e demais dados epidemiológicos foram obtidos a partir de prontuários físicos, eletrônicos e dos Sistemas de Monitoramento do Ministério da Saúde (MS) (SISCEL Sistema de Monitoramento Clínico e SINAN Sistema Nacional de Agravos e Notificações). A fim de observar a influência do atendimento dispensado pelos profissionais de saúde responsáveis no SAE de Novo Hamburgo, bem como as percepções destes relativas à gestão do controle da epidemia, foram aplicados o questionário CEAT-HIV para PVHA (Pessoas Vivendo com HIV/aids) para 181 pacientes usuários do SAE, um questionário para 10 funcionários dos SAE e o questionário QualiAids (para gestores). Os dados avaliados indicam que o comportamento do indivíduo, adesão medicamentosa insuficiente e o serviço de saúde influenciam a adesão ao tratamento. Os resultados obtidos pelo presente estudo visam contribuir para a elaboração de indicadores que permitam o entendimento sobre quais variáveis atribuem maior valor ao processo de adesão ao tratamento, a fim de subsidiar estudos para o aprimoramento de políticas que atendam às necessidades individuais e coletivas frente à epidemia do HIV/aids, com especial foco na adesão ao tratamento na região sul do Brasil.

AIDS (Acquired Immunodeficiency Syndrom) is a widespread epidemic of the nearly 38 million people worldwide have been infected with virus. In Brazil, until June 2019, 966,058 people living with HIV / AIDS. The state of Rio Grande do Sul stands out in the ranking of 100 cities with more than 100 thousand inhabitants with 12 cities with the highest rates of detection of HIV (Human Immunodeficiency Virus), with Porto Alegre being the 11th among the other cities in the ranking. The initiation of antiretroviral therapy (ART), recommended by the World Health Organization (WHO), was based on the clinical manifestations of the patient, with the TCD4 + lymphocyte count and viral load being the effective indicators for medication management. From 2015, the WHO began to recommend the beginning of immediate treatment for all people diagnosed with the HIV virus and the adoption of the 3-in-1 therapeutic scheme (Tenofovir, Lamivudine and Efavirenz). Several studies contribute to demonstrate that the early onset of ART and adequate adherence are associated with lower rates of mortality, morbidity and decreased viral transmission, helping to control the spread of the worldwide epidemic. However, even though this measure has contributed to adherence to treatment due to the reduction of adverse effects, as well as the ease of oral administration, numerous problems have been related to adherence to treatment by people with HIV / AIDS. In the public sphere, among the main ones can be cited the inefficiency observed in the services provided by the health system (difficulty in monitoring patients from the notification system and conducting periodic examinations, availability and dispensing of medications, among others). Likewise, both the side effects and the difficulties inherent to the use of HAART and socioeconomic and, mainly, behavioral variables, have been pointed out as relevant to the results observed regarding the spread of the virus in populations. In view of the complexity of elements that constitute adherence to treatments of this nature, it is necessary to recognize and establish the variables that contribute to the effectiveness or inefficiency of the treatments recommended for this epidemic. In this sense, the present study established variables that can influence adherence to treatment, under three main aspects: the effectiveness of the health system, the immune recovery due to medication and the behavioral context of individuals 8 The analyzes were conducted based on data collection from 678 patients from two Specialized Care Services (SAE de Novo Hamburgo and SAE de Viamão), defined as collection points due to notifications of the high rates of infection by the virus in these regions. The defined data collection period considered complying with WHO regulations regarding the use of ART on a compulsory basis from the diagnosis of infection, regardless of clinical results, comprising the years 2015 to 2017. Data on viral load and lymphocytes TCD4 +, as well as the dispensing of medications, comorbidities and other epidemiological data were obtained from physical and electronic medical records and the Monitoring Systems of the Ministry of Health (MS) (SISCEL - Clinical Monitoring System and SINAN - National System of Diseases and Notifications). In order to observe the influence of the care provided by the responsible health professionals in the SAE of Novo Hamburgo, as well as their perceptions regarding the management of the control of the epidemic, the CEAT-HIV questionnaire for PLWHA (People Living with HIV / AIDS) was applied for 181 patients using SAE, a questionnaire for 10 SAE employees and the QualiAids questionnaire (for managers). The evaluated data indicate that the individual's behavior, insufficient medication adherence and the health service influence treatment adherence. The data obtained by the present study aim to contribute to the development of indicators that allow an understanding of which variables attribute greater value to the treatment adherence process, in order to support studies for the improvement of policies that meet individual and collective needs in the face of the epidemic. HIV / AIDS, with a special focus on adherence to treatment in southern Brazil.

Hepatitis B virus surface antigen seroconversion in HIV-infected individual after pegylated interferon-alpha treatment: a case report

Hepatitis B virus (HBV) infects from 6 to 14% of HIV-infected individuals. Concurrent HIV/HBV infection occurs due to the overlapping routes of transmission, particularly sexual and parenteral. HIV-infected patients that have acute hepatitis B have six times greater risk of developing chronic hepatitis B, with higher viral replication, rapid progression to end-stage liver disease and shorter survival. The coinfection is also associated with poor response to hepatitis B treatment with interferon-alpha and increased liver toxicity to the antiretroviral therapy. Herein, we describe the case of a 35-year-old man who engages in sex with men and presented with newly diagnosed HIV-1, serological markers for acute hepatitis B and progression to chronic hepatitis B infection (HBsAg+ > 6 months, high alanine aminotransferase levels and moderate hepatitis as indicated by liver biopsy). Lacking indication of antiretroviral treatment (CD4 768 cells/mm 3 ), he was treated with pegylated-interferon alpha2b (1.5 mg/kg/week) by subcutaneous injection for 48 weeks. Twelve weeks after treatment, the patient presented HBeAg seroconversion to anti-HBe. At the end of 48 weeks, he presented HBsAg seroconversion to anti-HBs. One year after treatment, the patient maintained sustained virological response (undetectable HBV-DNA). The initiation of antiretroviral therapy with nucleosides and nucleotides is recommended earlier for coinfected individuals. However, this report emphasizes that pegylated interferon remains an important therapeutic strategy to be considered for selected patients, in whom the initiation of HAART may be delayed.

Hepatitis B virus surface antigen seroconversion in HIV-infected individual after pegylated interferon-alpha treatment: a case report

Hepatitis B virus (HBV) infects from 6 to 14% of HIV-infected individuals. Concurrent HIV/HBV infection occurs due to the overlapping routes of transmission, particularly sexual and parenteral. HIV-infected patients that have acute hepatitis B have six times greater risk of developing chronic hepatitis B, with higher viral replication, rapid progression to end-stage liver disease and shorter survival. The coinfection is also associated with poor response to hepatitis B treatment with interferon-alpha and increased liver toxicity to the antiretroviral therapy. Herein, we describe the case of a 35-year-old man who engages in sex with men and presented with newly diagnosed HIV-1, serological markers for acute hepatitis B and progression to chronic hepatitis B infection (HBsAg+ > 6 months, high alanine aminotransferase levels and moderate hepatitis as indicated by liver biopsy). Lacking indication of antiretroviral treatment (CD4 768 cells/mm 3 ), he was treated with pegylated-interferon alpha2b (1.5 mg/kg/week) by subcutaneous injection for 48 weeks. Twelve weeks after treatment, the patient presented HBeAg seroconversion to anti-HBe. At the end of 48 weeks, he presented HBsAg seroconversion to anti-HBs. One year after treatment, the patient maintained sustained virological response (undetectable HBV-DNA). The initiation of antiretroviral therapy with nucleosides and nucleotides is recommended earlier for coinfected individuals. However, this report emphasizes that pegylated interferon remains an important therapeutic strategy to be considered for selected patients, in whom the initiation of HAART may be delayed.

Hepatitis B virus surface antigen seroconversion in HIV-infected individual after pegylated interferon-alpha treatment: a case report

Hepatitis B virus (HBV) infects from 6 to 14% of HIV-infected individuals. Concurrent HIV/HBV infection occurs due to the overlapping routes of transmission, particularly sexual and parenteral. HIV-infected patients that have acute hepatitis B have six times greater risk of developing chronic hepatitis B, with higher viral replication, rapid progression to end-stage liver disease and shorter survival. The coinfection is also associated with poor response to hepatitis B treatment with interferon-alpha and increased liver toxicity to the antiretroviral therapy. Herein, we describe the case of a 35-year-old man who engages in sex with men and presented with newly diagnosed HIV-1, serological markers for acute hepatitis B and progression to chronic hepatitis B infection (HBsAg+ > 6 months, high alanine aminotransferase levels and moderate hepatitis as indicated by liver biopsy). Lacking indication of antiretroviral treatment (CD4 768 cells/mm 3 ), he was treated with pegylated-interferon alpha2b (1.5 mg/kg/week) by subcutaneous injection for 48 weeks. Twelve weeks after treatment, the patient presented HBeAg seroconversion to anti-HBe. At the end of 48 weeks, he presented HBsAg seroconversion to anti-HBs. One year after treatment, the patient maintained sustained virological response (undetectable HBV-DNA). The initiation of antiretroviral therapy with nucleosides and nucleotides is recommended earlier for coinfected individuals. However, this report emphasizes that pegylated interferon remains an important therapeutic strategy to be considered for selected patients, in whom the initiation of HAART may be delayed.(AU)

Diphtheria Antibodies and T lymphocyte Counts in Patients Infected with HIV-1

We assessed the IgG levels anti-diphtheria (D-Ab) and T cell counts (CD4+ and CD8+) in HIV-1 infected subjects undergoing or not highly active antiretroviral therapy (HAART). Approximately 70% of all HIV-1 patients were unprotected against diphtheria. There were no differences in D-Ab according to CD4 counts. Untreated patients had higher D-Ab (geometric mean of 0.62 IU/ml) than HAART-patients (geometric mean of 0.39 IU/ml). The data indicated the necessity of keeping all HIV-1 patients up-to-date with their vaccination.

Toxoplasmose aguda em pacientes HIV/aids no extremo sul do Brasil

A infecção por Toxoplasma gondii em indivíduos imunossuprimidos pelo HIV pode evoluir para doença oportunista. A neurotoxoplasmose tende a ser a forma mais prevalente, levando a quadros mais ou menos graves, a depender do grau de imunossupressão. Este trabalho objetivou analisar os aspectos clínico-epidemiológicos da toxoplasmose aguda em pacientes HIV/aids atendidos no Serviço de Assistência Especializada da Faculdade de Medicina da Universidade Federal de Pelotas. Os dados foram coletados através da análise de prontuários de todos os pacientes que estiveram em tratamento no período de 1998 a 2016, após a implantação do uso da terapia antirretroviral (HAART). A prevalência de toxoplasmose aguda foi de 3,65%. Destes, os índices foram de 77,6% para neurotoxoplasmose, 13% para toxoplasmose ocular e 9,3% para títulos elevados de IgG. Hemiparesia e diminuição de acuidade visual foram os sinais clínicos mais comuns de neurotoxoplasmose e toxoplasmose ocular, respectivamente. Foram constatados como fatores de risco para o desenvolvimento de infecção aguda por T. gondii, através do modelo de regressão logística: níveis baixos de linfócitos T CD4+ (OR=6,65), baixa relação CD4/CD8 (OR=8,03), uso irregular de antirretrovirais (OR=2,83; IC95%=2,34 -12,73) e o não uso dos mesmos (OR=1,13). Os resultados indicam a frequência de infecção aguda por T.gondii entre esses pacientes, com lesões predominantemente neurológicas, e que sua ocorrência está diretamente relacionada ao não uso ou uso inadequado da terapia específica antirretroviral, que resulta em grave imunossupressão, permitindo a agudização da infecção pelo protozoário, até então latente.

Toxoplasma gondii infection in HIV-immunocompromised individuals may progress to opportunistic diseases. Neurotoxoplasmosis tends to be the most prevalent form leading to more or less severe immunosuppression, depending on the degree of immunosuppression. This study aimed to analyze the clinical and epidemiological aspects of acute toxoplasmosis in HIV/AIDS patients who have been treated at the Specialized Assistance Service in the School of Medicine in Federal University of Pelotas. Data were collected through the medical records analysis of all patients who underwent treatment from 1998 to 2016, after the implementation of antiretroviral therapy (HAART). The prevalence of acute toxoplasmosis was 3.65%. From them, the rates were 77.6% for neurotoxoplasmosis, 13% for ocular toxoplasmosis and 9.3% for increased IgG titers. Hemiparesis and decreased visual acuity were the most common clinical signs of neurotoxoplasmosis and ocular toxoplasmosis, respectively. Low CD4 +T lymphocytes (OR=6.65), low CD4/CD8 ratio (OR=8.03), irregular use of antiretrovirals (OR=2.83, 95% CI=2.34-12.73) and non-use (OR=1.13) have been found as risk factors for the development of acute toxoplasmosis using a logistic regression model. The findings show the frequency of clinical toxoplasmosis among the patients with predominantly neurological lesions, and occurrence of them is directly related to the inadequate use or non-use at all of specific antiretroviral therapy, which leads to severe immunosuppression, allowing exacerbation of infection by the protozoan, latent until then.

Intestinal parasitic infections in HIV/AIDS patients: epidemiological, nutritional and immunological aspects

This study applied a socioeconomic questionnaire designed to evaluate the frequency of intestinal parasites and characterize epidemiological, nutritional, and immunological variables in 105 HIV/AIDS patients - with and without parasitic infections, attending the Day Hospital in Botucatu, UNESP, from 2007 to 2008. Body mass index was calculated and the following tests performed: parasitological stool examinations; eosinophil, IgE, CD4+ T and CD8+ T lymphocyte cell counts; albumin test; viral load measure; and TNF-α, IFN-γ, IL-2, IL-5 and IL-10 cytokine levels. Results were positive for parasitic intestinal infections in 12.4% of individuals. Most patients had good socioeconomic conditions with basic sanitation, urban dwellings, treated water supply and sewage, good nutritional and immunological status and were undergoing HAART. Parasites were found at the following frequencies: Entamoeba - five patients (38.5%), Giardia lamblia - four (30.7%), Blastocystis hominis - three (23.0%), Endolimax nana - two (15.4%), and Ascaris lumbricoides - one (7.7%). There were no significant differences between the two groups for eosinophils, albumin, IgE, CD4+ T and CD8+ T lymphocytes, INF-γ, IL-2, or IL-10. Most patients also showed undetectable viral load levels. Significant differences were found for TNF-α and IL-5. These results show the importance of new studies on immunodeficient individuals to increase understanding of such variables.(AU)

Intestinal parasitic infections in HIV/AIDS patients: epidemiological, nutritional and immunological aspects

This study applied a socioeconomic questionnaire designed to evaluate the frequency of intestinal parasites and characterize epidemiological, nutritional, and immunological variables in 105 HIV/AIDS patients - with and without parasitic infections, attending the Day Hospital in Botucatu, UNESP, from 2007 to 2008. Body mass index was calculated and the following tests performed: parasitological stool examinations; eosinophil, IgE, CD4+ T and CD8+ T lymphocyte cell counts; albumin test; viral load measure; and TNF-α, IFN-γ, IL-2, IL-5 and IL-10 cytokine levels. Results were positive for parasitic intestinal infections in 12.4% of individuals. Most patients had good socioeconomic conditions with basic sanitation, urban dwellings, treated water supply and sewage, good nutritional and immunological status and were undergoing HAART. Parasites were found at the following frequencies: Entamoeba - five patients (38.5%), Giardia lamblia - four (30.7%), Blastocystis hominis - three (23.0%), Endolimax nana - two (15.4%), and Ascaris lumbricoides - one (7.7%). There were no significant differences between the two groups for eosinophils, albumin, IgE, CD4+ T and CD8+ T lymphocytes, INF-γ, IL-2, or IL-10. Most patients also showed undetectable viral load levels. Significant differences were found for TNF-α and IL-5. These results show the importance of new studies on immunodeficient individuals to increase understanding of such variables.(AU)

HAART therapy does not reduce the proteinase and phospholipase secretion by oral Candida albicans isolated from HIV-positive patients

Production of exoenzymes, specifically the proteinase and phospholipase, is considered one of the most important of pathogenicity mechanisms of C. albicans, which is crucial for tissue invasion. This study aimed at evaluating the production of these exoenzymes in 50 oral C. albicans isolates from HIV-positive (HIV+) patients treated with highly active anti-retroviral therapy (HAART), and from 50 control individuals. For testing the production of phospholipase and proteinase, the culture media containing egg yolk and bovine albumin were used, respectively. The results were obtained by measuring the diameter of the colony and divided by the diameter of colony plus the precipitation zone, defined as Pz. Data were statistically analyzed by Students t test (5). Statistically significant difference (p = 0.001) was observed between the mean values of Pz for proteinase in isolates from HIV+ patients (Pz = 0.358±0.295) and from control group (Pz = 0.660±0.370). The same results were observed for phospholipase production (Pz = 0.399±0.227 for HIV+ group; Pz =0.635±0.292 control group). Both enzymes were highly produced by C. albicans isolated from HIV+ patients when compared with those secreted by C. albicans obtained from control group, suggesting that HAART did not reduce the secretion of these enzymes by this pathogenic fungus infecting HIV+ patients.(AU)

Morphometric analysis of dendritic cells from anal mucosa of HIV-positive patients and the relation to intraepithelial lesions and cancer seen at a tertiary health institution in Brazil / Análise morfométrica das células dendríticas da mucosa anal de pacientes HIV-positivos e relação com as lesões intraepiteliais e o câncer numa instituição de saúde terciária no Brasil

PURPOSE: To morphometrically quantify CD1a+ dentritic cells and DC-SIGN+ dendritic cells in HIV-positive patients with anal squamous intraepithelial neoplasia and to evaluate the effects of HIV infection, antiretroviral therapy and HPV infection on epithelial and subepithelial dendritic cells. METHODS: A prospective study was performed to morphometrically analyze the relative volume of the dendritic cells and the relationship between anal intraepithelial neoplasia and cancer in HIV-positive patients from the Tropical Medicine Foundation of Amazonas, Brazil. All patients were submitted to biopsies of anorectal mucosa to perform a classic histopathological and immunohistochemical analysis, employing antibodies against CD1a and DC-SIGN for the morphometric quantification of dendritic cells. RESULTS: HIV-negative patients displayed a CD1a DC density significantly higher than that of HIV-positives patients (3.75 versus 2.54) (p=0.018), and in patients with severe anal intraepithelial neoplasia had correlated between DC CD1a density with levels of CD4 + cells (p: 0.04) as well as the viral load of HIV-1 (p: 0.035). A not significant rise in the median density of CD1a+ DC was observed in the HIV positive/ HAART positive subgroup compared to the HIV positive/ HAART negative subgroup. The CD1a+ DC were also significantly increased in HIV-negative patients with anorectal condyloma (2.33 to 3.53; p=0.05), with an opposite effect in HIV-positive patients. CONCLUSIONS: Our data support an enhancement of the synergistic action caused by HIV-HPV co-infection on the anal epithelium, weakening the DC for its major role in immune surveillance. Notoriously in patients with severe anal intraepithelial neoplasia, the density of CD1a+ epithelial dendritic cells was influenced by the viral load of HIV-1.(AU)

OBJETIVO: Quantificar morfometricamente as células dendríticas DC CD1a+ e DC DC-SIGN+ em pacientes HIV positivos portadores de neoplasia escamosa intraepitelial anal e avaliar os efeitos da infecção pelo HIV, da terapia antirretroviral e da infecção pelo HPV sobre as células dendríticas epiteliais e subepiteliais. MÉTODOS: Um estudo prospectivo foi realizado para analisar morfometricamente o volume relativo das células dendríticas e as relações entre neoplasia intraepitelial anal e o câncer em pacientes HIV positivos da Fundação de Medicina Tropical do Amazonas, Brasil.Todos os pacientes foram submetidos a biópsia da mucosa retal para realizar uma análise clássica histopatológica e imunohistoquímica utilizando anticorpos contra anti-CD1a e anti-DC-SIGN, para a quantificação morfométrica das células dendríticas. RESULTADOS: Os pacientes HIV negativos apresentaram densidade das DC CD1a+ significativamente maior do que a dos pacientes HIV positivos (3,75 versus 2,54) (p:0,018), e os pacientes com severa apresentaram correlação das DC CD1a com os níveis de células TCD4(p:0,04) assim como a carga viral do HIV-1 (p:0,035). Observamos no subgrupo HIV-positivo/HAART positivo elevação não significativa na mediana da densidade das DC CD1a+ em relação ao grupo HIV-positivo/HAART negativo. As DC CD1a+ também se elevaram nos pacientes HIV negativo portadores de condiloma anorretal(2,33 para 3,53; p:0,05), com efeito inverso nos pacientes HIV positivos. CONCLUSÕES: Nossos dados confirmam a potencialização da ação sinérgica representada pela coinfecção HIV-HPV sobre o epitélio anal, fragilizando as DC em sua função primordial de vigilância imune. Notoriamente nos pacientes com neoplasia intraepithelial anal grave, a densidade das DC CD1a+ epiteliais sofreu influência da carga viral do HIV-1.(AU)

Occurrence of pneumocystis pneumonia in hiv-infected patients and the interference of the highly active antiretroviral therapy

From the beginning of the AIDS epidemic, pneumocystis pneumonia (PCP) has been distinguished as one of the most frequent opportunistic diseases with high morbid-mortality. As from 1996, the advent of the highly active antiretroviral therapy (HAART) has changed the characteristics of such epidemic by reducing its related diseases and, as a result, AIDS-related mortality. With the purpose to estimate PCP occurrence and HAART interference, 376 HIV-infected or AIDS patients were studied from January 1992 to December 2002. Among them, 58 (15.5%) PCP cases were found. There was a higher occurrence of PCP in the group of patients in which HAART was not used, with 40 (69.0%) of the episodes. As regards the studied period, a tendency to a linear reduction in annual PCP incidence was observed. The mean of T CD4+ lymphocytes in the patients with PCP (117 cells/mm³) was significantly lower when compared to that of the other individuals (325 cells/mm³). Therefore, this study suggests a temporal reduction in PCP occurrence related to HAART use with higher T CD4+ lymphocyte counts. Nevertheless, this opportunistic infection still shows significant incidence in AIDS patients. (NCT00516581).

Assessment of cytokine values in serum by RT-PCR in HIV-1 infected individuals with and without highly active anti-retroviral therapy (HAART)

A cross-sectional study was performed on HIV-1 infected individuals with or without antiretroviral treatment (ARV) in the AIDS Day Hospital, Botucatu Medical School, UNESP. Between August 2004 and October 2005, 73 HIV-1 infected individuals were divided into three groups: infected individuals with or without AIDS who had never received ARV (G1 = 15); patients on HAART that had had plasma HIV-1 RNA viral load (VL) equal to or greater than 50 copies/mL (G2 = 27); and patients on HAART with undetectable VL for at least the past six months (G3 = 31). There was also an additional group that comprised blood donors without any sign of the disease and with negative HIV serum tests (G4 = 20), which was the control group. Serum cytokine levels (values in pg/mL) were measured by enzyme-linked immunosorbent assay (ELISA) and specific mRNA expression by reverse transcription polymerase chain reaction (RT-PCR). Both techniques were performed on the four groups for TNF-, IL-2, INF-, IL-4 and IL-10. All patients were submitted to VL determination and CD4+ and CD8+T lymphocyte counts. The analysis of the results revealed a significant comparison among groups for both methods and an association between the latter (> 80% r² > 0.80). There was only one exception, in control individuals for IL-2 by ELISA. The cytokine profiles, in both methods, for the three patient groups, were mature Th-0. The behaviors of IL-2 and INF- required emphasis due to consequent expression of dominant Th profile. Both methods showed low IL-2 and high mean values of INF- in the three groups. Several authors have recently drawn attention to the substantial apoptosis of infected and non-infected CD4+T cells, mainly during primary infection, persisting only in those with INF- phenotype producer and not IL-2. HIV infected individuals submitted to HAART are expected to produce IL-2 in an attempt to present Th-1 profile, but in most cases this did not occur.

Assessment of cytokine values in serum by RT-PCR in HIV-1 infected individuals with and without highly active anti-retroviral therapy (HAART)

A cross-sectional study was performed on HIV-1 infected individuals with or without antiretroviral treatment (ARV) in the AIDS Day Hospital, Botucatu Medical School, UNESP. Between August 2004 and October 2005, 73 HIV-1 infected individuals were divided into three groups: infected individuals with or without AIDS who had never received ARV (G1 = 15); patients on HAART that had had plasma HIV-1 RNA viral load (VL) equal to or greater than 50 copies/mL (G2 = 27); and patients on HAART with undetectable VL for at least the past six months (G3 = 31). There was also an additional group that comprised blood donors without any sign of the disease and with negative HIV serum tests (G4 = 20), which was the control group. Serum cytokine levels (values in pg/mL) were measured by enzyme-linked immunosorbent assay (ELISA) and specific mRNA expression by reverse transcription polymerase chain reaction (RT-PCR). Both techniques were performed on the four groups for TNF-á, IL-2, INF-ã, IL-4 and IL-10. All patients were submitted to VL determination and CD4+ and CD8+T lymphocyte counts. The analysis of the results revealed a significant comparison among groups for both methods and an association between the latter (> 80% r² > 0.80). There was only one exception, in control individuals for IL-2 by ELISA. The cytokine profiles, in both methods, for the three patient groups, were mature Th-0. The behaviors of IL-2 and INF-ã required emphasis due to consequent expression of dominant Th profile. Both methods showed low IL-2 and high mean values of INF-ã in the three groups. Several authors have recently drawn attention to the substantial apoptosis of infected and non-infected CD4+T cells, mainly during primary infection, persisting only in those with INF-ã phenotype producer and not IL-2. HIV infected individuals submitted to HAART are expected to produce IL-2 in an attempt to present Th-1 profile, but in most cases this did not occur.(AU)

Cytokine profile and clinical metabolic alterations in HIV-1 infected individuals with and without lipodistrophy

The extensive use of Highly Active Antiretroviral Therapy (HAART) has transformed HIV infection into a chronic condition. Thus, metabolic alterations including lipodystrophy and dyslipidemia have been associated with the use of such medications. The objective of the present study was to analyze clinical metabolic alterations and the profile of TNF-alpha, IFN-Y, IL-2, IL-10, and TNF-alpha type II soluble receptor in serum of HIV-1 individuals with and without lipodystrophy. Eighty-four adults were evaluated, 42 males and 42 females, mean age 37 years, and HAART time of at least 15 months. Two groups were formed, G1: 42 individuals with lipodystrophy, and G2: 42 without lipodistropy. From the HAART used, stavudine was more associated with the lipodystrophy group and zidovudine with the non-lipodystrophy group. CD4 and CD8 values, viral load, glucose, albumin, and lipids were not different between groups, except for triglycerides, which were high in the lipodystrophy group, and HDL, whose concentration was reduced in G1. TNF-alpha, TNF-RII, and IL-10 profiles were high and had positive correlation; IL-2 and IFN-gamma had reduced levels in the lipodystrophy group. High TNF-alpha and its receptor levels seem to be associated with lipodystrophy development in individuals under HAART therapy.

Cryptosporidium SP in HIV-infected individuals attending a Brazilian University Hospital

The aim of the current work was to evaluate the occurrence of Cryptosporidium sp in AIDS patients in a region of São Paulo State, Brazil. Patients were divided into groups according to CD4+ T lymphocyte count and use of potent antiretroviral treatment. Two hundred and ten fecal samples from 105 patients were fixed in 10% formalin and subjected to centrifuge formol-ether sedimentation. Slides were stained with auramine and confirmed by modified Ziehl-Neelsen. Cryptosporidiosis occurrence was 10.5% with no relationship among gender, age or the presence of diarrhea. The number of oocysts in all samples was small, independent of CD4+ T lymphocyte count, HIV plasma viral load, and presence of diarrhea. These results may be due to the reduced prevalence of opportunistic infections in AIDS individuals after the advent of highly active antiretroviral therapy.

HIV-1 anti-retroviral drug effect on the C. albicans hyphal growth rate by a Bio-Cell Tracer system

Declining incidence of oropharyngeal candidosis and opportunistic infections over recent years can be attributed to the use of highly active anti-retroviral therapy (HAART). Infection with C. albicans generally involves adherence and colonization of superficial tissues. During this process, budding yeasts are able to transform to hyphae and penetrate into the deep tissue. Using the biocell tracer system, C. albicans hyphal growth was dynamically observed at the cellular level. Ritonavir was effective in the inhibition of hyphal growth with growth rate of 0.8 mum/min. This study showed the in vitro effect of HIV anti-retroviral drug on the growth rate of the C. albicans hyphae.

O declínio na incidência de candidose orofaríngea e infecções oportunistas associadas a infecção pelo HIV tem sido atribuído a introdução da terapia antiretroviral combinada (HAART). Infecção por C. albicans envolve aderência e colonização da mucosa superficial. Durante este processo leveduras são capazes de transformar-se na forma de hifas e penetrar nos tecidos mais profundos. Usando o sistema "Bio-Cell Tracer", o crescimento de hifas de C. albicans foi observado dinamicamente a nível celular. Ritonavir, inibidor de protease do HIV, foi efetivo na inibição do crescimento de hifas com media de 0.8 mim/min.O presente estudo demonstrou o efeito in vitro de um agente anti-retroviral HIV sobre o crescimento de hifas de C. albicans.

Immune reconstitution in HIV-1 infected patients treated for two years with highly active antiretroviral therapy

The aim of this paper was to evaluate the immune reconstitution of HIV-1 patients subjected to highly active antiretroviral therapy (HAART) for two years or more according to CD45RA and CD45RO cell count; determination of IL-2, IFN-gamma, IL-4, IL-10 and TNF-alpha serum levels; CD4+ T and CD8+ T lymphocyte count; and plasma viral load (VL) determination. For this purpose, a cross sectional study was carried out in the Tropical Diseases Area, Botucatu School of Medicine, São Paulo State University, UNESP, Botucatu, São Paulo, Brazil. Between June 2001 and April 2002, 37 HIV-1 infected patients were evaluated, 13 with treatment indication but untreated (G1), 9 subjected to HAART for 5-7 months (G2), and 15 treated for two years or more (G3); both treated groups used medication regularly and without failure. Forty-nine normal individuals were studied as controls (GC-1 and GC-2). There was a tendency (p 0.10) for the predominance of two nucleoside reverse transcriptase inhibitors (NRTI) associated with one non-nucleoside reverse transcriptase inhibitor (NNRTI) regimen in G2; and two NRTI associated with a protease inhibitor (PI) in G3. Statistical differences between groups were seen for CD45RA (G1 [G3=GC-2]; p 0.05) and CD45RO (G1 GC-2 G3; p 0.01) cells, and CD4+ T lymphocyte count (G1 G3; G2-intermediate; p 0.05), VL determination (G1>[G2=G3]; p 0.001), TNF-alpha serum determination ([G1>G3; G2=intermediate]>GC-1; p 0.001), IL-2 (G1 [G2=G3=GC-1]; p 0.01), IFN-gamma ([G1=GC-1] [GC-2=G3]; p 0.001), IL-4 and IL-10 ([G1=G2=G3]>GC-1; p 0.001), serum cytokine profiles, with a higher proportion of subtype 2 in G1 and mature subtype 0 in G2 and G3 (p 0.005). There was no statistical difference for CD8+ T lymphocyte counts (G1=G2=G3; p 0.50). Consistency was seen between positive correlations of profile 1 definer cytokines (IL-2 and IFN-gamma), CD45RA and CD45RO cells, and CD4+ T lymphocyte counts and between positive correlations of profile 2 definer cytokines (IL-4 and IL-10) with TNF-alpha, and VL. The negative correlations were also consistent as they expressed the inverse of the positives. The variables with the highest number of correlations were IL-2, IFN-gamma, and VL, followed by CD45RA and CD45RO cells, and IL-10. The variables with the lowest number of correlations were CD4+ T and CD8+ T lymphocytes. The results express the partial but important immune reconstitution in HIV-1 infected individuals with the interference of HAART and the importance of cytokines especially IL-2 and IFN-gamma, and CD45RA and CD45RO cells as surrogate markers of this reconstitution.

Lipid profile and body composition of HIV-1 infected patients treated with highly active antiretroviral therapy

Highly active antiretroviral therapy (HAART) has been associated with the development of a clinical group and metabolic disorders such as peripheral lipodystrophy syndrome in AIDS. The aim of this study was to analyze the lipid profile, the clinical aspects, and the body composition of HIV-1 infected individuals treated with or without protease inhibitor (PI) during the highly active antiretroviral therapy. In total, 62 individuals were evaluated in this study; 15 healthy individuals (Control Group: CG), 11 HIV-1 infected individuals treated without antiretroviral therapy (Group 1: G1), 14 HIV-1 infected individuals treated with antiretroviral therapy plus protease inhibitor (Group 2: G2), and 22 HIV-1 infected individuals treated with antiretroviral therapy without protease inhibitor (Group 3: G3), mean age 35 years old. The time interval for G2 and G3 was greater than or equal to nine months. Patients receiving HAART with PI had significantly lower viral loads, hypertriglyceridemia, and low HDL levels (p 0.05). There were no differences between groups in relation to the lean body mass percentage obtained by mid-arm muscle circumference adequacy or by bioelectrical impedance. The lower percentage of body fat observed in all the HIV-1 infected patients by antropometric assessment and the decreased tricipital skinfold adequacy in the group treated with PI in relation to CG may suggest lipodystrophy in the upper limbs, especially on those treated with PI.

Correlation between cytokine serum levels, number of CD4+ T cells/mm³ and viral load in HIV-1 infected individuals with or without antiretroviral therapy

Seventy-nine HIV-1 infected patients were studied in three groups: Group G1 - 11 patients with no antiretroviral therapy; G2 - 40 patients undergoing antiretroviral therapy, 33 with only two nucleoside reverse transcriptase inhibitors (NRTI), and seven with two NRTI and one protease inhibitor (PI), all with viral load (VL) equal or higher than 80 copies of plasma RNA/ml; Group G3 - 28 patients, 23 on highly active antiretroviral therapy (HAART), 18 with two NRTI and one PI, and five with two NRTI and one non-nucleoside reverse transcriptase inhibitor (NNRTI), the remaining five with combination of two NRTI. All G3 patients had undetectable viral load for at least the past six months. The control group (Gc) included 20 normal blood donors without clinical complaints or signs of disease and negative for anti-HIV-1/2 antibodies. Serum cytokine levels pg/ml (TNF-alpha, INF-gamma, IL-2, IL-4, and IL-10) were determined in all patients including controls. CD4+ T and CD8+ T lymphocyte counts were made in the 79 patients by flow cytometry; VL determination was by NASBA technology. Analysis of results showed that the number of CD4+ T and CD8+ T lymphocytes were higher in G2 than G1, while VL was 0.5 log lower. G3 patients had similar lymphocyte values to G2, however they were chosen for G3 because their VL was undetectable, different by 4.0 log to G2. These results show the effect of antiretroviral treatment in G2 and G3 patients with better performance in the latter. Statistical difference was seen between the three groups and controls for serum cytokine behavior: TNF-alpha [H=48.323; p 0.001;(G1=G2=G3)>Gc]; INF-gamma[H=28.992; p 0.001; (G1=G2=G3)>Gc]; IL-4[H=48.323; p 0.001; (G1=G2=G3)>Gc]; IL-10[H=47.256; p 0.001; (G1=G2=G3)>Gc. There was no statistical difference in IL-2 values between all groups (H=6.071; p>0.10; G1=G2=G3=Gc). In absolute values however, G3 showed slightly lower TNF-alpha, IL-4, and IL-10, and higher INF-gamma and IL-2, to G1 and G2. This suggests a better performance in G3 patients, especially in IL-2 behavior. For cytokine profile, the three groups showed mature Th0 subset. In G1 72.73% were mature Th0, and 27.27% Th2; G2, 72.50% mature Th0, and 27.50% Th2; and G3, 89.29% mature Th0, and 10.71% Th2. There was no statistical difference between groups (chi22=3.014; p>0.10; G1=G2=G3). Statistical difference was seen between G2 and G3 for antiretroviral regimes used (chi21=27.932; p 0.001; G3>G2); HAART with PI predominated in G3, suggesting that it was responsible for this better performance. Linear correlation between pairs of variables was made with patient groups only, excluding controls. This was made separately for G1 and G2, 51 patients with detectable VL, and G1, G2, and G3 also including those with undetectable VL. The results showed a strong positive correlation between TNF-alpha and IL-4; TNF-alpha and IL-10; INF-gamma and IL-2; IL-4 and IL-10; IL-2 and CD4+. Weak negative correlation was seen between IL-2 and VL. Considering all correlations together, we found that IL-2 had the most correlations - eleven - strong, weak, positive, and negative; it was the only one that correlated with CD4+ (positively) and LV (negatively). The number of correlations allowed us to evaluate qualitative aspects such as IL-2 correlated positively with INF-gamma and CD4+ and negatively with LV; this somehow expresses the compatible profile with subset Th1, which could signify a tendency towards immune response recovery. Determination of cytokine serum values, especially IL-2, could be useful in follow-up of HIV-1 infected patients under HAART together with CD4+ and VL count.