Fatores de risco para hanseníase em portadores de HIV e AIDS em áreas de alta endemicidade na Amazônia

Em um país onde a hanseníase é endêmica e onde a infecção pelo HIV continua expandindo-se e interiorizando-se, espera-se encontrar um aumento da prevalência de indivíduos convivendo simultaneamente com hanseníase e HIV/aids. Com o objetivo de identificar fatores de risco para a hanseníase em portadores de HIV/aids e descrever aspectos clínicos e epidemiológicos, realizou-se um estudo de caso controle envolvendo 33 pacientes co-infectados (HIV/hanseníase) e 90 controles (HIV/aids sem hanseníase). Na amostra estudada o sexo masculino foi mais freqüente tanto nos coinfectados quanto nos controles, prevaleceram jovens e adultos jovens em ambos os grupos, Belém foi a área de procedência mais freqüente entre co-infectados e controles, não houve diferença entre renda familiar de co-infectados e controles, os pacientes co-infectados apresentavam-se, em sua maioria, no estágio de aids com grande oscilação de células CD4 periféricas. As formas clínicas mais freqüentem ente encontradas, entre os co-infectados, foram as paucibacilares, sendo a média de células CD4+ no sangue periférico significativamente maior no grupo de co-infectados. Os prováveis fatores de risco para hanseníase relacionados à infecção pelo HIV (situação clínica, situação de imunodeficiência laboratorial e co-morbidades com outras micobacterioses) não foram estatisticamente significantes. Os fatores de risco para hanseníase já descritos na literatura, tais quais contatos intradomiciliares e antecedentes familiares de hanseníase, demonstraram ser significativamente os fatores de risco para a hanseníase em indivíduos com HIV/aids, aumentando em 45 vezes e 21 vezes, respectivamente, a chance de adoecer do mal de Hansen. A recidiva não se configurou como fator de risco para a Hanseníase em pacientes HIV/aids. A maioria dos coinfectados apresentaram sinais e sintomas de hanseníase 6 meses após o inicio da TARV, confirmando estudos anteriores que sugerem ser a hanseníase uma doença associada à reconstituição imunológica no paciente portador de HIV/aids. Estudos subseqüentes fazem-se necessários para complementar este e os anteriores sobre esta tão intrigante e desafiante co-infecção.

Estudo da susceptibilidade à infecção pelo HIV-1 e da progressão da AIDS em associação ao polimorfismo no gene Mbl (Lectina Ligadora de Manose)

As baixas concentrações séricas de Lecitina Ligante de Manose (MBL) estão associadas com a presença das variantes alélicas Mbl-*B, Mbl-*C e Mbl-*D, e resultam em um aumento na susceptibilidade a infecções recorrentes. No presente estudo foi investigada a associação entre o polimorfismo no gene Mbl e a susceptibilidade à infecção pelo HIV-1. Um fragmento de 349 pb do exon 1 do gene Mbl foi amplificado por PCR e, posteriormente, submetido à análise de restrição com as endonucleases BanI e MboII, para a identificação dos alelos. A avaliação de 145 pacientes soropositivos e de 99 controles mostrou a presença dos alelos Mbl-*A, Mbl-*B e Mbl-*D, cujas freqüências foram de 69%, 22% e 9% no grupo de pacientes e de 70,2%, 13,6% e 16,2% entre os controles. A análise das freqüências genotípicas mostrou uma maior prevalência dos genótipos com a variante alélica Mbl-*B entre os pacientes soropositivos quando comparadas à do grupo controle. Ademais, o genótipo B/B foi seis vezes mais freqüente no grupo de pacientes infectados (χ²=4,042; p=0,044). A média da carga viral plasmática foi menor nos pacientes HIV-1 soropositivos, portadores do alelo Mbl-*A, quando comparado aos pacientes soropositivos apresentando a variante alélica Mbl-*B (5.821 cópias/mL x 52.253 cópias/mL; p= 0,05). Ademais os pacientes portadores do alelo Mbl-*A apresentaram uma significativa redução da viremia plasmática (p<0,001), o que não foi observado para os portadores da variante Mbl-*B (p=0,999). Esses resultados sugerem a importância do polimorfismo no gene Mbl na evolução clínica do paciente infectado pelo HIV-1 e que a identificação do perfil genético do gene Mbl, em portadores da infecção pelo HIV-1, pode ser importante na avaliação da evolução e do prognóstico da doença.

Soroepidemiologia da hepatite C em pacientes HIV/AIDS do serviço ambulatorial especializado do Programa DST/AIDS de Imperatriz-Maranhão

A coinfecção do vírus da hepatite C (HCV) em pessoas portadoras do vírus da imunodeficiência humana (HIV) é freqüentemente observada em virtude destes vírus apresentarem similaridade em suas rotas de transmissão, principalmente no que se refere à via parenteral. No Brasil, a prevalência depende da área geográfica considerada, variando de 8,9% a 54%. Nos coinfectados, a progressão da doença pelo HCV é usualmente mais agressiva e apresenta alto nível de viremia, como também, há um risco maior de associação do HCV com a cirrose hepática e/ou hepatocarcinoma. O objetivo do presente estudo foi estimar a prevalência de HCV e fatores de risco associados à coinfecção em pessoas soropositivas para HIV na cidade de Imperatriz Maranhão. Participaram 249 pacientes soropositivos para HIV atendidos no SAE do Programa Municipal de DST/AIDS de Imperatriz do Maranhão. Foi coletado de cada voluntário 10 mL de sangue periférico para realização do teste sorológico, onde foi realizada pesquisa de anticorpos IgG HCV específicos e testes de Biologia Molecular (RT-PCR) para pesquisa do RNA viral e genotipagem. Entre os pacientes observou-se similaridade entre a frequência dos gêneros, 49% masculino e 51% feminino, com média de idade de 40 anos. Foi observado que 98% possuem baixo nível de instrução e 63% possuem renda mensal de até um salário mínimo. A soroprevalência do anti-HCV foi de 2.4% (6/249). Na comparação dos fatores de risco pesquisados entre os pacientes reagentes e não reagentes na pesquisa sorológica de anticorpos HCV específicas demonstraram que a presença de tatuagens e piercing foi o único fator que se mostrou significantes, sendo mais frequente nos reagentes. Esse foi o primeiro estudo que investiga a coinfecção HIV e HCV na cidade de Imperatriz, Maranhão e a identificação de pacientes coinfectados foi de fundamental importância para o serviço que a partir de então irá realizar o acompanhamento destes pacientes.

Anatomopathological characterization of placentas from HIV+ patients associated with p24 expression

INTRODUCTION: The study of placentas from pregnant human immunodeficiency virus (HIV) positive women has become the subject of numerous studies in the literature. Morphological, viral, immune and inflammatory placental aspects have been analyzed in order to grasp the vertical transmission of the virus. OBJECTIVE: To identify the most frequent findings in the placentas by associating them with a viral antigen and correlating them with the infection of newborns. MATERIAL AND METHODS: Thirty-five placentas from HIV- positive pregnant women were pathologically and immunohistochemically analyzed with the use of p24 antibody in the period from 1992 to1997 in accordance with the routine laboratory testing from the Anatomopathological Department - Hospital Universitário Antônio Pedro - Universidade Federal Fluminense (APD/HUAP/UFF). RESULTS: The microscopic alterations detected in all cases, including those with vertical transmission, were arteriopathy in the fetal blood circulation, chorioamnionitis, perivillous fibrin deposition, syncytial knotting, villous edema and villous immaturity. No specific macroscopic or histopathological changes were found in these placentas. The neonatal infection was observed in five cases. Vertical transmission was identified in two out of five placentas that had low weight for the respective stage of pregnancy. Immunohistochemical analysis revealed 14 positive cases, two of which showed vertical transmission. The viral protein was not identified in 10 out of 14 placentas from patients who had been medicated with zidovudine (AZT). CONCLUSION: Our study has contributed to the anatomopathological investigation into placentas from HIV-positive patients, although p24 expression per se did not allow a definite and early diagnosis of the vertical transmission.

Microbiota bucal de pacientes HIV positivos: relação com o uso de drogas antirretrovirais e condições de saúde

Pós-graduação em Odontologia - FOA

Prevalence of anogenital warts in Men with HIV/AIDS and associated factors

Infection with human papilloma virus (HPV) is the most common sexually transmitted disease in the world. Among the 630 million new cases of HPV that occur each year, 30 million develop anogenital warts. Although subclinical infection with HPV is the most common cause, genital warts are also associated with immunosuppression caused by HIV. In view of the high prevalence of HPV/HIV co-infection particularly among men who have sex with men, the objectives of this study were to determine the prevalence of anogenital warts in men with HIV/AIDS and to identify associated factors. A cross-sectional study was conducted on 159 men with HIV/AIDS consecutively selected at a referral service in Botucatu, São Paulo, Brazil, in which the association between sociodemographic, behavioral and clinical variables and the presence of anogenital warts was evaluated. After hierarchical analysis of the data, variables presenting a p value ≤ 0.2 were entered into an unconditional multivariate logistic regression model. Forty-nine (31%) of the HIV-positive patients had anogenital warts. The mean age was 44.6 ± 9.6 years. The main factors associated with the presence of anogenital warts were irregular antiretroviral treatment and genital herpes(HSV). The present study demonstrate that anogenital warts occur in almost one-third of the male population infected with HIV and factors associated with a higher risk of being diagnosed with anogenital warts were irregular cART use and co-infection with HSV, other variables could not be associated.

Avaliação de polimorfismos genéticos na progressão da infecção de pacientes monoinfectados e coinfectados com os Vírus da Imunodeficiência Humana (HIV) e Vírus da Hepatite C (VHC)

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Avaliação da Translocação Microbiana em Gestantes Infectadas pelo HIV

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Insuficiência de vitamina D em pacientes infectados pelo HIV tratados com terapia antirretroviral contendo tenofovir

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Insuficiência de vitamina D em pacientes infectados pelo HIV tratados com terapia antirretroviral contendo tenofovir

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Low-Cost Ultra-Wide Genotyping Using Roche/454 Pyrosequencing for Surveillance of HIV Drug Resistance

Background: Great efforts have been made to increase accessibility of HIV antiretroviral therapy (ART) in low and middle-income countries. The threat of wide-scale emergence of drug resistance could severely hamper ART scale-up efforts. Population-based surveillance of transmitted HIV drug resistance ensures the use of appropriate first-line regimens to maximize efficacy of ART programs where drug options are limited. However, traditional HIV genotyping is extremely expensive, providing a cost barrier to wide-scale and frequent HIV drug resistance surveillance. Methods/Results: We have developed a low-cost laboratory-scale next-generation sequencing-based genotyping method to monitor drug resistance. We designed primers specifically to amplify protease and reverse transcriptase from Brazilian HIV subtypes and developed a multiplexing scheme using multiplex identifier tags to minimize cost while providing more robust data than traditional genotyping techniques. Using this approach, we characterized drug resistance from plasma in 81 HIV infected individuals collected in Sao Paulo, Brazil. We describe the complexities of analyzing next-generation sequencing data and present a simplified open-source workflow to analyze drug resistance data. From this data, we identified drug resistance mutations in 20% of treatment naive individuals in our cohort, which is similar to frequencies identified using traditional genotyping in Brazilian patient samples. Conclusion: The developed ultra-wide sequencing approach described here allows multiplexing of at least 48 patient samples per sequencing run, 4 times more than the current genotyping method. This method is also 4-fold more sensitive (5% minimal detection frequency vs. 20%) at a cost 3-5 x less than the traditional Sanger-based genotyping method. Lastly, by using a benchtop next-generation sequencer (Roche/454 GS Junior), this approach can be more easily implemented in low-resource settings. This data provides proof-of-concept that next-generation HIV drug resistance genotyping is a feasible and low-cost alternative to current genotyping methods and may be particularly beneficial for in-country surveillance of transmitted drug resistance.

Frequency of subtype B and F1 dual infection in HIV-1 positive, Brazilian men who have sex with men

Background: Because various HIV vaccination studies are in progress, it is important to understand how often inter- and intra-subtype co/superinfection occurs in different HIV-infected high-risk groups. This knowledge would aid in the development of future prevention programs. In this cross-sectional study, we report the frequency of subtype B and F1 co-infection in a clinical group of 41 recently HIV-1 infected men who have sex with men (MSM) in Sao Paulo, Brazil. Methodology: Proviral HIV-1 DNA was isolated from subject's peripheral blood polymorphonuclear leukocytes that were obtained at the time of enrollment. Each subject was known to be infected with a subtype B virus as determined in a previous study. A small fragment of the integrase gene (nucleotide 4255-4478 of HXB2) was amplified by nested polymerase chain reaction (PCR) using subclade F1 specific primers. The PCR results were further confirmed by phylogenetic analysis. Viral load (VL) data were extrapolated from the medical records of each patient. Results: For the 41 samples from MSM who were recently infected with subtype B virus, it was possible to detect subclade F1 proviral DNA in five patients, which represents a co-infection rate of 12.2%. In subjects with dual infection, the median VL was 5.3 x 10(4) copies/ML, whereas in MSM that were infected with only subtype B virus the median VL was 3.8 x 10(4) copies/ML (p > 0.8). Conclusions: This study indicated that subtype B and F1 co-infection occurs frequently within the HIV-positive MSM population as suggested by large number of BF1 recombinant viruses reported in Brazil. This finding will help us track the epidemic and provide support for the development of immunization strategies against the HIV.

Age-Related Expansion of Tim-3 Expressing T Cells in Vertically HIV-1 Infected Children

As perinatally HIV-1-infected children grow into adolescents and young adults, they are increasingly burdened with the long-term consequences of chronic HIV-1 infection, with long-term morbidity due to inadequate immunity. In progressive HIV-1 infection in horizontally infected adults, inflammation, T cell activation, and perturbed T cell differentiation lead to an "immune exhaustion'', with decline in T cell effector functions. T effector cells develop an increased expression of CD57 and loss of CD28, with an increase in co-inhibitory receptors such as PD-1 and Tim-3. Very little is known about HIV-1 induced T cell dysfunction in vertical infection. In two perinatally antiretroviral drug treated HIV-1-infected groups with median ages of 11.2 yr and 18.5 yr, matched for viral load, we found no difference in the proportion of senescent CD28(-)CD57(+)CD8(+) T cells between the groups. However, the frequency of Tim-3(+)CD8(+) and Tim-3(+)CD4(+) exhausted T cells, but not PD-1(+) T cells, was significantly increased in the adolescents with longer duration of infection compared to the children with shorter duration of HIV-1 infection. PD-1(+)CD8(+) T cells were directly associated with T cell immune activation in children. The frequency of Tim-3(+)CD8(+) T cells positively correlated with HIV-1 plasma viral load in the adolescents but not in the children. These data suggest that Tim-3 upregulation was driven by both HIV-1 viral replication and increased age, whereas PD-1 expression is associated with immune activation. These findings also suggest that the Tim-3 immune exhaustion phenotype rather than PD-1 or senescent cells plays an important role in age-related T cell dysfunction in perinatal HIV-1 infection. Targeting Tim-3 may serve as a novel therapeutic approach to improve immune control of virus replication and mitigate age related T cell exhaustion.

Quality of sleep and quality of life in adolescents infected with human immunodeficiency virus

Objectives: To assess sleep characteristics of adolescents infected by HIV, and to ascertain whether psychosocial aspects are associated to the quality of sleep. Methods: A cross-sectional study assessing 102 HIV-infected adolescents of both genders, aged between 10 and 20 years-old and 120 Controls. Data collection was performed by applying the Sleep Disturbance Scale for Children, the Epworth Sleepiness Scale, and the Pediatric Quality of Life Inventory. Results: A sleep disturbance prevalence of 77.4% was found in patients, and a 75% prevalence in controls, and there was correlation between quality of sleep and of life. HIV-infected adolescents scored higher for sleep breathing disorders and had higher prevalence of excessive daytime sleepiness. Conclusions: HIV-infected adolescents had similar quality of sleep compared to healthy adolescents. This may be explained by the steady improvements in daily living as a result of successful anti-retroviral therapy, and by the vulnerability that affects Brazilian adolescents living in major urban centers.

Late entry into HIV care: lessons from Brazil, 2003 to 2006

Background: To ascertain the population rates and proportion of late entry into HIV care, as well as to determine whether such late entry correlates with individual and contextual factors. Methods: Data for the 2003-2006 period in Brazil were obtained from public health records. A case of late entry into HIV care was defined as one in which HIV infection was diagnosed at death, one in which HIV infection was diagnosed after the condition of the patient had already been aggravated by AIDS-related diseases, or one in which the CD4(+) T-cell count was <= 200 cells/mm(3) at the time of diagnosis. We also considered extended and stricter sets of criteria (in which the final criterion was <= 350 cells/mm(3) and <= 100 cells/mm(3), respectively). The estimated risk ratio was used in assessing the effects of correlates, and the population rates (per 100,000 population) were calculated on an annual basis. Results: Records of 115,369 HIV-infected adults were retrieved, and 43.6% (50,358) met the standard criteria for late entry into care. Diagnosis at death accounted for 29% (14,457) of these cases. Late entry into HIV care (standard criterion) was associated with certain individual factors (sex, age, and transmission category) and contextual factors (region with less economic development/increasing incidence of AIDS, lower local HIV testing rate, and smaller municipal population). Use of the extended criteria increased the proportion of late entry by 34% but did not substantially alter the correlations analyzed. The overall population rate of late entry was 9.9/100,000 population, specific rates being highest for individuals in the 30-59 year age bracket, for men, and for individuals living in regions with greater economic development/higher HIV testing rates, collectively accounting for more than half of the cases observed. Conclusions: Although the high proportion of late entry might contribute to spreading the AIDS epidemic in less developed regions, most cases occurred in large cities, with broader availability of HIV testing, and in economically developed regions.