HIV-1 subtypes among intravenous drug users from two neighboring cities in São Paulo State, Brazil.

In order to assess the molecular epidemiology of HIV-1 in two neighboring cities located near the epicenter of the HIV-1 epidemics in Brazil (Santos and São Paulo), we investigated 83 HIV-1 strains obtained from samples collected in 1995 from intravenous drug users. The V3 through V5 region of the envelope of gp 120 was analyzed by heteroduplex mobility analysis. Of the 95 samples, 12 (12.6%) were PCR negative (6 samples from each group); low DNA concentration was the reason for non-amplification in half of these cases. Of the 42 typed cases from São Paulo, 34 (81%, 95% confidence limits 74.9 to 87.0%) were B and 8 (19%, 95% confidence limits 12.9 to 25.0%) were F, whereas of the 41 typed cases from Santos, 39 (95%, 95% confidence limits 91.6 to 98.4%) were B and 2 (5%, 95% confidence limits 1.6 to 8.4%) were C. We therefore confirm the relationship between clade F and intravenous drug use in São Paulo, and the presence of clade C in Santos. The fact that different genetic subtypes of HIV-1 are co-circulating indicates a need for continuous surveillance for these subtypes as well as for recombinant viruses in Brazil.

HIV-1 subtypes among intravenous drug users from two neighboring cities in São Paulo State, Brazil

In order to assess the molecular epidemiology of HIV-1 in two neighboring cities located near the epicenter of the HIV-1 epidemics in Brazil (Santos and São Paulo), we investigated 83 HIV-1 strains obtained from samples collected in 1995 from intravenous drug users. The V3 through V5 region of the envelope of gp 120 was analyzed by heteroduplex mobility analysis. Of the 95 samples, 12 (12.6 percent) were PCR negative (6 samples from each group); low DNA concentration was the reason for non-amplification in half of these cases. Of the 42 typed cases from São Paulo, 34 (81 percent, 95 percent confidence limits 74.9 to 87.0 percent) were B and 8 (19 percent, 95 percent confidence limits 12.9 to 25.0 percent) were F, whereas of the 41 typed cases from Santos, 39 (95 percent, 95 percent confidence limits 91.6 to 98.4 percent) were B and 2 (5 percent, 95 percent confidence limits 1.6 to 8.4 percent) were C. We therefore confirm the relationship between clade F and intravenous drug use in São Paulo, and the presence of clade C in Santos. The fact that different genetic subtypes of HIV-1 are co-circulating indicates a need for continuous surveillance for these subtypes as well as for recombinant viruses in Brazil

Randomized, double-blind trial comparing indinavir alone, zidovudine alone and indinavir plus zidovudine in antiretroviral therapy-naive HIV-infected individuals with CD4 cell counts between 50 and 250/mm3.

Treatment with indinavir has been shown to result in marked decreases in viral load and increases in CD4 cell counts in HIV-infected individuals. A randomized double-blind study to evaluate the efficacy of indinavir alone (800 mg q8h), zidovidine alone (200 mg q8h) or the combination was performed to evaluate progression to AIDS. 996 antiretroviral therapy-naive patients with CD4 cell counts of 50-250/mm3 were allocated to treatment. During the trial the protocol was amended to add lamivudine to the zidovudine-containing arms. The primary endpoint was time to development of an AIDS-defining illness or death. The study was terminated after a protocol-defined interim analysis demonstrated highly significant reductions in progression to a clinical event in the indinavir-containing arms, compared to the zidovudine arm (p<0. 0001). Over a median follow-up of 52 weeks (up to 99 weeks), percent reductions in hazards for the indinavir plus zidovudine and indinavir groups compared to the zidovudine group were 70% and 61%, respectively. Significant reductions in HIV RNA and increases in CD4 cell counts were also seen in the indinavir-containing groups compared to the zidovudine group. Improvement in both CD4 cell count and HIV RNA were associated with reduced risk of disease progression. All three regimens were generally well tolerated.

Clinical implications of autoantibodies in HIV infection.

OBJECTIVE: To study the frequency and specificity of autoantibodies in HIV-infected subjects and their association with rheumatic manifestations, immunodeficiency, and prognosis. DESIGN: Prospective study of sequentially selected HIV-infected patients. Indirect immunofluorescence reading was performed by two independent observers blinded for the patient diagnosis. Enzyme-linked immunosorbent assay (ELISA) was performed using coded serum samples. SETTING: The study was performed at the Infectious Disease and Rheumatology Divisions of a tertiary care university hospital. PATIENTS: One hundred sequentially selected HIV-infected patients formed group A. Controls included 80 non-HIV-infected high-risk individuals (group B), 20 herpesvirus-infected patients (group C), and 30 healthy blood donors (group D). MAIN OUTCOME MEASURES: Patients were followed for 2 years and evaluated for the presence of immunodeficiency, rheumatic manifestations, circulating autoantibodies and total CD4+ cell count. Indirect immunofluorescence was used to investigate antinuclear antibodies, antibodies to native DNA, smooth muscle, parietal cell, glomeruli, thyroid, and neutrophil cytoplasm. Agglutination was used to detect antibodies to erythrocytes and rheumatoid factor. ELISA was used to determine antibodies to cardiolipin and denatured DNA. CD4+ lymphocytes were counted by flow cytometry. Immunoglobulin (Ig) G, IgM and IgA serum levels were determined by radial immunodiffusion. RESULTS: HIV-infected patients presented higher overall frequency of autoantibodies than the other groups. No difference was observed between immunodeficient and asymptomatic HIV-infected patients. The most frequent specificities were antibodies to cardiolipin and to denatured DNA. Ig serum levels did not correlate with the occurrence of autoantibodies. The presence of autoantibodies was associated with lower CD4+ cell counts and with higher mortality within 2 years. Rheumatic manifestations were observed in 35 HIV-infected patients and were not associated with the occurrence of autoantibodies or the presence of immunodeficiency. CONCLUSIONS: HIV infection is associated with an increased incidence of autoantibodies. Although not related to the occurrence of rheumatic manifestations, the presence of autoantibodies was significantly associated with lower CD4+ lymphocyte counts and increased mortality, which implies prognostic significance to this phenomenon in the context of HIV infection.

PIP: A study was conducted at the Infectious Disease and Rheumatology Divisions of a tertiary care university hospital in Sao Paulo to assess the frequency and specificity of autoantibodies in HIV-infected subjects and their association with rheumatic manifestations, immunodeficiency, and prognosis. 100 sequentially selected HIV-infected patients formed group A, 80 non-HIV-infected high-risk subjects served as controls in group B, 20 herpesvirus-infected patients formed group C, and 30 healthy blood donors formed group D. The patients were followed for 2 years and evaluated for the presence of immunodeficiency, rheumatic manifestations, circulating autoantibodies, and total CD4+ cell counts. HIV-infected patients presented with a higher overall frequency of autoantibodies than did the other groups. No difference was observed between immunodeficient and asymptomatic HIV-infected patients. The most frequent specificities were antibodies to cardiolipin and to denatured DNA, while Ig serum levels did not correlate with the occurrence of autoantibodies. The presence of autoantibodies was associated with lower CD4+ cell counts and with higher mortality within 2 years. Rheumatic manifestations were observed in 35 HIV-infected patients and were not associated with the occurrence of autoantibodies or the presence of immunodeficiency.

Quantitation of red cell-bound IgG by an enzyme-linked antiglobulin test in human immunodeficiency virus-infected persons.

Anemia, thrombocytopenia, and neutropenia have been observed in patients with acquired immune deficiency syndrome (AIDS) and AIDS-related complex. To investigate whether red cells (RBCs) of patients with human immunodeficiency virus infection were coated with IgG and/or complement (C3), blood samples of 239 patients were tested. The prevalence of a positive direct antiglobulin test on RBCs was 16.7 percent. By use of an enzyme-linked antiglobulin test (ELAT) to measure more accurately the number of IgG molecules per RBC in a group of 67 patients, 30 of the 67 individuals were observed to have increased numbers (mean, 155) compared to normal controls and to patients with hypergammaglobulinemia due to multiple myeloma or chronic liver disease. Hemoglobin level was correlated with the number of IgG molecules per RBC (p = 0.008), but no correlation could be demonstrated between those numbers and serum immunoglobulin (p = 0.10) or circulating immune complexes (p = 0.38). Our results with ELAT suggest that some AIDS patients may have specific binding of IgG on the surface of their RBCs, rather than nonspecific uptake; further clinical correlations are necessary to confirm these findings.

Estudo caso-controle da infecçäo pelo HIV em pacientes em programa de hemodiálises / Control case study of HIV infection in dialysis patients

O Brasil é o quarto país no mundo em número de casos de AIDS, apresentando elevada proporçäo da doença adquirida através de transfusäo de sangue. Uma vez que os pacientes com insuficiência renal crônica em programa de hemodiálise säo freqüentemente submetidos a transfusöes sanguíneas, constituem-se em grupo com risco potencial de exposiçäo ao HIV. Estudou-se a prevalência de infecçäo pelo HIV em 117 pacientes em programa de hemodiálise na Casa de Saúde Santa Marcelina, identificando-se nove (7,7%) pacientes soropositivos pelos métodos ELISA e Western Blot. Nenhum paciente tinha outro fator de risco para infecçäo, além das transfusöes. Cada pacientes soropositivo foi comparado com três controles soronegativos, pareados por sexo. O número médio de transfusöes foi de 29,3 unidades para os casos e 26,7 unidades para os controles. O tempo médio de diálise foi de 28,2 e 27,2 meses para casos e controles, respectivamente. O risco de infecçäo pelo HIV näo foi associado ao número de transfusöes ou ao tempo de diálise. A relaçäo OKT/OKT foi menor ou igual a um em todos os pacientes infectados