Changes in hepatitis A virus seroepidemiology in HIV-infected Brazilian patients.

Shifting of hepatitis A virus (HAV) epidemiology from a high towards an intermediate endemicity pattern and use of antiretroviral therapy increased the risk of HIV/HAV coinfection in developing countries. The aim of this study was to investigate the presence of HAV markers in a cohort of HIV-infected patients from 1988 to 2004. The presence of serum anti-HAV antibodies and HAV-RNA by real-time polymerase chain reaction was investigated in 581 patients. Total anti-HAV antibodies was found in 464/581 (79.8%) patients, however, a changing epidemiologic pattern of hepatitis A among HIV-infected patients from 1988 to 2004 was observed. Among patients susceptible to HAV (n = 117), 5 (4.2%) were coinfected with HAV, all of them had IgM anti-HAV antibodies and were serum HAV-RNA-positive. The high prevalence of anti-HAV antibodies in HIV-infected patients suggests that screening tests for anti-HAV antibodies should be performed before implementation of hepatitis A vaccination, especially in those patients from endemic countries.

Genotypic and phenotypic evidence of different drug-resistance mutation patterns between B and non-B subtype isolates of human immunodeficiency virus type 1 found in Brazilian patients failing HAART.

We have investigated the phenotypic and genotypic susceptibility of 14 HIV-1 strains isolated from individuals failing HAART therapy to protease inhibitors (PI). Proviral and plasma viral pol gene fragment were amplified, sequenced and subtyped. Nine samples clustered with protease subtype B reference strains and the remaining samples were classified as non-B subtype corresponding to subtype F (n = 4) and subtype A (n = 1). Although all patients were treated with similar P1 drug regimen, the non-B subtype isolates did not present the L90M and 184V mutations and used mainly G48V and V82A/F to achieve drug resistance. A strong cross-resistance phenotype among all four PI was associated with the mutation L90M in the subtype-B isolates, and with G48V and V82A/F in the non-B counterparts. This observation revealed that the non-B viruses tested had specific genotypic characteristics contrasting with the subtype-B isolates.

Mycobacterial spindle cell pseudotumor of the appendix vermiformis in a patient with aids.

Mycobacterial pseudotumor (MP) is a rare pathologic presentation of both Mycobacterium tuberculosis and non-tuberculous mycobacterial disease, hitherto reported to occur only in immunosuppressed patients with or without human immunodeficiency virus infection. This lesion shares close pathologic resemblance to certain mesenchymal neoplasms, particularly Kaposi's sarcoma (KS), from which it must be properly differentiated due to distinct prognosis and therapy. We report a case of MP obliterating the lumen of the appendix vermiformis in a 34-year-old patient who died of complications of AIDS at our hospital in Rio de Janeiro. A total of 24 cases of MP (including our patient) have been described in the literature. MP has been found especially in lymph nodes, but extranodal lesions have been described in the skin, spleen, lung, bone marrow, brain and, in our patient, the appendix vermiformis. We offer a review of the other 23 published case reports of MP in both HIV-infected and uninfected patients and discuss the pathologic features that differentiate MP from KS.

Myelopathy in a previously asymptomatic HIV-1-infected patient.

A wide variety of disorders of diverse pathogenic mechanisms can trigger spinal cord dysfunction in HIV-1-infected patients. The most common such condition is HIV-1-associated myelopathy (HM) which characteristically complicates advanced HIV-1 disease in patients with low CD4 cell counts and previous AIDS-defining diagnoses. We describe an unusual presentation of HM in a previously asymptomatic patient with a relatively preserved CD4 cell count (458 cells/mm3) who was even unaware of his serological status. The patient presented with a clinically severe, slowly progressive myelopathy and could not walk unassisted. Significant neurological improvement could be obtained as rapidly as within 4 weeks after the institution of an antiretroviral combination of only two nucleoside analog HIV-1 reverse transcriptase inhibitors (zidovudine and didanosine). An HIV-1 protease inhibitor was also prescribed at that point but could only be added to intensify the regimen 3 months later, when significant neurological improvement had already been recorded. We also review the disorders reported to derange spinal cord function in previously asymptomatic HIV-1-infected patients.

Macrocytosis in patients on stavudine.

We retrospectively reviewed the effects on the erythrocyte mean corpuscular volume (MCV) of the use of stavudine-including antiretroviral regimens in both zidovudine-naive and zidovudine-experienced HIV-infected patients. Macrocytosis was commonly observed among patients on stavudine-based regimens although the MCV usually stabilized at a lower level than that observed with zidovudine.

Drug-resistant reverse transcriptase genotyping and phenotyping of B and non-B subtypes (F and A) of human immunodeficiency virus type I found in Brazilian patients failing HAART.

Development of drug resistance is the inevitable consequence of incomplete suppression of virus plasma levels in HIV-1-infected patients treated with highly active antiretroviral therapy. Resistance mutations previously characterized have been found in B subtype viruses of developed countries. Moreover, mutation profiles for non-B and more divergent B subtype viruses found in developing countries shall be analyzed together with their ex vivo phenotyping in order to establish an exact correlation between the genotyping data and the clinical management counseling for those uncommon virus subtypes. In the present study, we evaluated the mutation profile for individuals infected with B subtype and non-B subtype viruses. Viral DNA fragments corresponding to the RT gene were amplified, sequenced, and subtyped. Phenotyping analysis for reverse transcriptase nucleoside (NRTI) and nonnucleoside inhibitor susceptibility was performed using the recombinant virus assay technology. Brazilian non-B subtypes (subtype F, n = 4, and subtype A, n = 1) isolates showed essentially the same B subtype mutation profile, presenting an NRTI drug resistance with similar MIC50% and MIC90% values for all drugs analyzed regardless of their subtypes. A strong cross-resistance phenotype among AZT, 3TC, and abacavir could be seen in all isolates analyzed. A novel result was that some RT sequences not only revealed the presence of G333D/E mutations but also correlated to the presence of mutation T386I that could abrogate the M184V-surpassing effect of L210W or L210W plus G333D/E. These findings suggest that Brazilian non-B subtype HIV-1 strains use an identical RT drug resistance mutation pattern when compared to B isolates and will contribute to the validation of the genotypic and phenotypic tests in these predominant worldwide-spread viral variants.

Genomic variations of hepatitis B virus strains in patients chronically coinfected with hepatitis B and human immunodeficiency viruses.

Serum samples from 56 human immunodeficiency virus type 1 (HIV-1)-infected adult men were analysed for the presence of hepatitis B virus (HBV) serological markers. Two or more samples from each patient, collected over an interval of 1-6 years, were tested. The antibody against HBV core antigen (anti-HBc) prevalence was 79%. Three (5%) patients No. 5, 7, and 9 were chronic carriers of HBV surface antigen (HBsAg). HBV DNAs from serial samples of these three patients and from two HIV-seronegative control patients were characterised after amplification of different genome regions by polymerase chain reaction (PCR). Size and restriction analyses of the PCR products showed that samples from patients No. 7 (with chronic active hepatitis) and 9 (asymptomatic) contained heterogeneous HBV DNA populations. In patient No. 7, HBV DNA contained a precore gene stop codon mutation at nucleotide (nt) 1896. In addition, a deletion in the core gene was found in a sample collected two years after the onset of acquired immunodeficiency syndrome (AIDS). PCR products from serial samples of patient No. 9 indicated a mixture of HBV DNA molecules that were cloned. Sequencing of the pre-S region of the clones and phylogenetic analysis showed that patient No. 9 was superinfected with three HBV populations of distinct origin, all belonging to genotype A. HBV DNA of patient No. 5 (with AIDS) did not present any variability during a 6-year follow-up. Although two of three HIV/HBV coinfected patients harboured heterogeneous HBV DNA populations during the follow-up, no common event with respect to HBV DNA evolution was observed among the coinfected patients.

[Effects of age, sex and coronary heart disease on the autonomic modulation of the heart]. / Influência da idade, sexo e doença coronária sobre a modulação autonômica do coração.

PURPOSE: To establish the influence of age, sex and the presence of coronary heart disease on heart rate variability. METHODS: The heart rate variability was studied in the time and frequency domain in 77 normal (group I) and 30 coronary heart disease patients (group II). The ECG was recorded during 300 seconds with the patients breathing at their spontaneous rate and at a rate between 10 and 15/ minutes (0.16 to 0.25 Hz). RESULTS: Both time and frequency domain variables were lower in group II than in group I. Energy content in spectral bands decreased with increasing age. No change was observed in relation to the patient's gender. During controlled breathing we found that in both groups the energy concentrated in the range of 0.17 to 0.25 Hz but it only increased in group I. CONCLUSION: Heart rate variability is an important tool for studying the influence of the autonomic system on heart rate modulation. These influences decrease with age and with the presence of coronary heart disease. The controlled breathing maneuver enabled us to precisely separate normal from coronary heart disease patients.

[HIV/AIDS infection. The Brazilian view. AIDS in Brazil]. / Infecção HIV/AIDS. Visão brasileira. AIDS in Brazil.

The Ministry of Health coordinates and orients in Brazil all the activities concerning the acquired immunodeficiency syndrome which is officially designated as AIDS. The first AIDS' case registered in Brazil was, by retrospective diagnosis, in 1981 but it was in 1982 that the first two diagnosis in live patients were made. The incidence is very high in this country that is among the ones where the higher number of cases are being registered. The great majority of the Brazilian cases occurs in the cities and in direct proportion to the population index. The groups of risk are the same universally known and a comparative increase of heterosexual transmission is noted, chiefly due to the use of injectable drugs and bisexuality of the male partners. Another problem that is being increased is pediatric AIDS, with raising importance of perinatal transmission as well as the use of injectable drugs and precocious prostitution in adolescence. The transfusional and haemophilic AIDS have proportionally decreased due to the control of blood products. The control and the orientation activity of the Ministry of Health is directed to varied points such as: compulsory cases notification, cooperation between public and private sectors, preventive and sexual orientation, freely delivered medication and laboratory tests including sigilous tests, lay and technical personnel preparation, diversified informative and educational campaigns. Trial tests with anti-HIV vaccines have begun to be performed. Multiple Reference Centers were officially established by the administration. Among them is to be quoted the Hospital Universitário Gaffrée Guinle of Rio de Janeiro where the authors work. It is credited for its intensive activity and pioneerism. In this Institution special attention was due against discrimination of HIV-infected patients, to diagnosis, to anonymous and sigilous tests, to medical and psychological assistance, to myocardium involvement, to the virologic study of the Brazilian HIV samples, to research on HIV immunogenicity and pathogenicity, to post-mortem diagnosis control through necropsies.

Eficácia do diltiazem em hipertensos moderados. Avaliaçäo utilizando parâmetros obtidos pela monitoraçäo ambulatorial da pressäo arterial em 24h (M.A.P.A.) / Efficacy of diltiazem in moderate arterial hypertension. Evaluation through 24-hour ambulatory blood pressure monitoring (ABPM)

Os parâmetros obtidos pela MAPA foram analisados em 15 pacientes portadores de hipertensäo arterial primária, de forma moderada, sem prévio tratamento, e comparados com aqueles obtidos após 4 semanas em uso de diltiazem, 180 mg (formulaçäo Retard) diários, ingeridos às 8h da manhä. Observou-se reduçäo significativa dos níveis tensionais (sistólicos e diastólicos ) e da carga pressórica, importante atuaçào no descenso noturno (restaurando o ritmo circadiano noturno) e significativa açäo na ascensäo tinal, propiciando rampa de ascensäo mais suave e significativa reduçäo do duplo produto, principalmente no horário das 6h às 7h. Näo foi observada modificaçäo significativa quanto ao índice de reatividade vascular, e houve aumento da variabilidade sisto-diastólica após uso da medicaçäo.

A simplified surveillance case definition of AIDS derived from empirical clinical data. The Clinical AIDS Study Group, and the Working Group on AIDS case definition.

A clinical AIDS case definition is needed for surveillance in countries where the CDC case definition is not practical. To derive such a definition, we compared 110 HIV-seropositive and 135 randomly selected HIV-seronegative adult medical-ward inpatients in Brazil. Multivariate analysis of clinical signs and symptoms and simple diagnoses resulted in a discriminant function with sensitivity of 89% and specificity of 96% in predicting for AIDS. These data were the empirical basis for a clinical definition of AIDS in adults drafted in a Caracas, Venezuela, workshop sponsored by the Pan American Health Organization. The revised "Caracas" definition presented here requires a positive HIV serology, the absence of cancer or other cause of immunosuppression, plus > or = 10 cumulative points, as follows: Kaposi's sarcoma (10 points); extrapulmonary/noncavitary pulmonary tuberculosis (10); oral candidiasis or hairy leukoplakia (5); cavitary pulmonary/unspecified tuberculosis (5); herpes zoster < 60 years of age (5); CNS dysfunction (5); diarrhea > or = 1 month (2); fever > or = 1 month (2); cachexia or > 10% weight loss (2); asthenia > or = 1 month (2); persistent dermatitis (2); anemia, lymphopenia, or thrombocytopenia (2); persistent cough or any pneumonia except TB (2); and lymphadenopathy > or = 1 cm at > or = 2 noninguinal sites for > or = 1 month (2). This definition has a sensitivity of 95% and a specificity of 100% (91% without HIV serology) when applied to the Brazilian patients in this study. The Caracas definition has been adopted by Brazil, Honduras, and Surinam, and is in validation elsewhere. The use of a reasonably sensitive and specific case definition commensurate with available diagnostic resources should facilitate AIDS surveillance in developing countries.

Identification of mixed HIV-1/HIV-2 infections in Brazil by polymerase chain reaction.

Analysis of sera from hospitalized Brazilian patients by whole-virus lysate-based enzyme immunoassay and Western blot indicated that 0.4% were reactive to HIV-2 alone while 4% were reactive to both HIV-1 and HIV-2. When these sera were tested for HIV antibody by type-specific peptide enzyme immunoassays, dual seropositivity was confirmed in only 0.4% of patients. To define genetically the HIV strains within the population, we analyzed peripheral blood mononuclear cells from selected seropositive patients for the presence of HIV-1 and HIV-2 proviral DNA using the polymerase chain reaction (PCR). Independent primers/probes sets were used for the amplification and detection of viral sequences from the long terminal repeat (LTR), gag, and protease (prt) gene regions. Our findings confirmed the serologic evidence of HIV-2 in Brazil and determined the extent of mixed HIV-1 and HIV-2 infections. Detailed evaluation of the amplified viral protease sequences by endonuclease restriction analysis and DNA sequencing independently confirmed mixed HIV-1 and HIV-2 infections in the two patients seropositive for HIV-1 and HIV-2. The data further indicated that these isolates are distinct from the HIV laboratory standards. We interpret the combination of culture and PCR findings to demonstrate the presence of both HIV-1 and HIV-2 in Brazil.

Immunological abnormalities of acquired immunodeficiency syndrome and related disorders in patients from Rio de Janeiro, Brazil.

The immunological profile of acquired immunodeficiency syndrome (AIDS) and chronic lymphadenopathy syndrome (CLAS) in 15 and 11 Brazilian patients, respectively, was studied. The AIDS patients showed reduced percentage of total T (CD3) and T-helper-inducer (CD4) lymphocytes, relative increase in numbers of T-suppressor-cytotoxic (CD8) cells and a marked inversion of T-helper-inducer/suppressor-cytotoxic (CD4/CD8) ratio. Lymphoproliferative responses to PHA, ConA, PPD and PWM were diminished. Hypergammaglobulinemia and high levels of circulating immune complexes were also found. The CLAS patients also showed important immunological alterations, but not so intense as those with AIDS. These data seems to be similar to those observed in other parts of the world.