DBCollHIV: a database system for collaborative HIV analysis in Brazil

We developed a database system for collaborative HIV analysis (DBCollHIV) in Brazil. The main purpose of our DBCollHIV project was to develop an HIV-integrated database system with analytical bioinformatics tools that would support the needs of Brazilian research groups for data storage and sequence analysis. Whenever authorized by the principal investigator, this system also allows the integration of data from different studies and/or the release of the data to the general public. The development of a database that combines sequences associated with clinical/epidemiological data is difficult without the active support of interdisciplinary investigators. A functional database that securely stores data and helps the investigator to manipulate their sequences before publication would be an attractive tool for investigators depositing their data and collaborating with other groups. DBCollHIV allows investigators to manipulate their own datasets, as well as integrating molecular and clinical HIV data, in an innovative fashion.

Human immunodeficiency virus type 1 (HIV-1) genotyping in Rio de Janeiro, Brazil: assessing subtype and drug-resistance associated mutations in HIV-1 infected individuals failing highly active antiretroviral therapy.

In order to assess the human immunodeficiency virus type 1 (HIV-1) drug resistance mutation profiles and evaluate the distribution of the genetic subtypes in the state of Rio de Janeiro, Brazil, blood samples from 547 HIV-1 infected patients failing antiretroviral (ARV) therapy, were collected during the years 2002 and 2003 to perform the viral resistance genotyping at the Renageno Laboratory from Rio de Janeiro (Oswaldo Cruz Foundation). Viral resistance genotyping was performed using ViroSeq Genotyping System (Celera Diagnostic-Abbott, US). The HIV-1 subtyping based on polymerase (pol) gene sequences (protease and reverse transcriptase-RT regions) was as follows: subtype B (91.2%), subtype F (4.9%), and B/F viral recombinant forms (3.3%). The subtype C was identified in two patients (0.4%) and the recombinant CRF_02/AG virus was found infecting one patient (0.2%). The HIV-1 genotyping profile associated to the reverse transcriptase inhibitors has shown a high frequency of the M184V mutation followed by the timidine-associated mutations. The K103N mutation was the most prevalent to the non-nucleoside RT inhibitor and the resistance associated to protease inhibitor showed the minor mutations L63P, L10F/R, and A71V as the more prevalent. A large proportion of subtype B was observed in HIV-1 treated patients from Rio de Janeiro. In addition, we have identified the circulation of drug-resistant HIV-1 subtype C and are presenting the first report of the occurrence of an African recombinant CRF_02/AG virus in Rio de Janeiro, Brazil. A clear association between HIV-1 subtypes and protease resistance mutations was observed in this study. The maintenance of resistance genotyping programs for HIV-1 failing patients is important to the management of ARV therapies and to attempt and monitor the HIV-1 subtype prevalence in Brazil.

[Risk behavior among Brazilian Military conscripts, 1998: an study of HIV infections following socioeconomic differences]. / Comportamento de risco dos conscritos do Exército Brasileiro, 1998: uma apreciação da infecção pelo HIV segundo diferenciais sócio-econômicos.

A study of HIV-related risk behavior was carried out in 1998 among Brazilian military conscripts aged 17-20 years. A sample of 30,318 subjects was selected in three strata, pertaining to counties from: 1) the North and Central-West (N/CW); 2) South (S); and the states of Rio de Janeiro and São Paulo. HIV prevalence rates were estimated in all strata. The objective of this paper was to analyze the results according to differences in socioeconomic status (SES). The statistical analysis used an index of sexual risk behavior and logistic regression models. The N/CW stratum showed the worst indicators for SES, sexual risk behavior, and sexually transmitted infections (STIs), as well as the highest HIV seroprevalence rate. The best indicators for all variables were found in the RJ/SP stratum. The South showed intermediate results. Level of schooling also played a relevant role. In all three strata the conscripts with an incomplete high school education displayed the worst sexual risk behavior index, shown to be a relevant predictor of STI-related problems, including HIV infection.

HIV-1 diversity in Brazil: genetic, biologic, and immunologic characterization of HIV-1 strains in three potential HIV vaccine evaluation sites. Brazilian Network for HIV Isolation and Characterization.

The Brazilian Network for HIV Isolation and Characterization was established for the surveillance of HIV variability in Brazil. Here, we report characterization of HIV strains and virus-specific immune responses from 35 clinical samples collected from three potential HIV vaccine sites. Three genetic subtypes of HIV-1 were identified by heteroduplex mobility assay (HMA) B (in 82.9% of the samples), F (14.3%), and C (2.9%). Phylogenetic analysis based on the C2V3/env DNA sequence from all 25 specimens examined was 100% concordant with HMA results. Four variants of subtype B with different tetrapeptides at the tip of the V3 loop were found: the GPGR motif (North American), GWGR motif (Brazilian B"), and two minor variants, GFGR and GPGS, as previously detected. No significant association was found between HIV-1 subtypes and the mode of transmission or biologic properties of HIV-1 isolates (derived from 88.6% of the specimens). Only 5 of 16 isolates studied were neutralized by the autologous sera. Consistent with previous results, no relation between viral subtype and peptide enzyme-linked immunosorbent assay (ELISA) seroreactivity or neutralization was evident. This study also demonstrated the effectiveness of the collaborative approach followed by Brazilian scientists when addressing a complex subject such as HIV variability.

HIV specific humoral immune response in Rio de Janeiro, Brazil. The HEC/Fiocruz AIDS Clinical Research Group.

Efforts to characterize HIV-1 polymorphism and anti-HIV immune response are being made in areas where anti-HIV/AIDS vaccines are to be employed. Anti-HIV-1 humoral immune response is being studied in infected individuals residents in Rio de Janeiro, in distinct cohorts involving recent seroconvertors, pregnant women or intravenous drug users (IDU). Comparative analyses of specificity of antibody response towards epitopes important for anti-HIV-1 immune response indicate quantitative differences between cohorts, with an exceptionally strong response in IDUs and weakest response in pregnant women. However, a comparative analysis between pregnant women cohorts from Rio de Janeiro and Rio Grande do Sul indicated an even lower response (with exception of the anti-V3-C clade peptide recognition) for the southern cohort. Studies analysing the immune function of the humoral response indicate a quite elevated occurrence of antibodies capable for neutralizing heterologous primary HIV-1 isolates from Rio de Janeiro. Attempts to correlate seroreactivity with HIV-1 neutralization with respect to HIV-1 polymorphism were not very successful: while the Brazilian B clade B " variant could be recognized by binding assays, no significant distinction of HIV-1 clades/variants was observed in viral neutralization assays.

HIV specific humoral immune response in Rio de Janeiro, Brazil

Efforts to characterize HIV-1 polymorphism and anti-HIV immune response are being made in areas where anti-HIV/AIDS vaccines are to be employed. Anti-HIV-1 humoral immune response is being studied in infected individuals resident in Rio de Janeiro, in distinct cohorts involving recent seroconvertors, pregnant women or intravenous drug users (IDU). Comparative analysis of specificity of antibody response towards epitopes important for anti-HIV-1 immune response indicate quantitative differences between cohorts, with an exceptionally strong response in IDUs and weakest response in pregnant women. However, a comparative analysis between pregnant women cohorts from Rio de Janeiro and Rio Grande do Sul indicated an even lower response (with exception of the anti-V3-C clade peptide recognition) for the southern cohort. Studied analysing the immune function of the humoral response indicate a quite elevated occurrence of antibodies capable of neutralizing heterologous primary HIV-1 isolates from Rio de Janeiro. Attempts to correlate seroreactivity with HIV-1 neutralization with respect to HIV-1 polymorphism were not very successfull: while the Brazilian B clade B" variant could be recognized by binding assays, no significant distinction of HIV-1 clades/variants was observed in viral neutralization assays.

[Acquired immunodeficiency syndrome in Brazil and the State of Ceará]. / Le syndrome d'immunodéficience acquise au Brésil et dans l'Etat du Ceará.

Since February 1998, a total of 129,000 cases of acquired immune deficiency syndrome have been reported in Brazil. The cumulative frequency of the disease is 82 per 100,000 which makes Brazil one of the countries moderately affected. There are considerable differences between regions in the frequency of cases, from 25 per 100,000 in the north and north east to 152 per 100,000 in the south east. Sexual intercourse is still the predominant means of transmission. Transmission in the early years of the epidemic was mostly between homosexuals and bisexuals, but transmission via heterosexual intercourse is increasing. The contribution made by intravenous drug use differs between the regions, and is particularly large in the mid-south region. A pilot project in the city of Fortaleza has shown that it is possible to successfully integrate the diagnosis of STD and AIDS in health care units at an intermediate level. This appears to be an appropriate strategy for the integration of STD treatment into primary health care in Ceará State. The non-uniform pattern of development of this epidemic must be taken into account in epidemiological analyses of AIDS in Brazil.

Validation of national algorithms for the diagnosis of sexually transmitted diseases in Brazil: results from a multicentre study.

OBJECTIVE: To validate STD flow charts for the management of genital discharge and genital ulcer currently recommended by the National STD Control Programme in Brazil. METHODS: A study was conducted in five Brazilian STD clinics from January to June 1995. After an interview, a clinical examination was performed by a physician, who recorded a presumptive diagnosis, based on his/her clinical experience. This diagnosis was compared with a gold standard laboratory diagnosis in order to calculate sensitivity, specificity, and positive predictive value of the clinical diagnosis. The validity of the simulated national flow charts was assessed using the same method. RESULTS: A total of 607 men and 348 women participated in the study. Gonorrhoea was the aetiology most frequently detected in men with urethral discharge. The sensitivity of the clinical diagnosis was far lower than the sensitivity fo the national flow chart, using the syndromic approach, for both gonococcal and chlamydial urethritis. Adding a simple laboratory test (Gram stain) to the national flow chart increased the specificity and positive predictive value for gonorrhoea. Among the women with vaginal discharge, a cervical infection was detected in 17%, a vaginal infection in 74%, and mixed infection in 9%. The sensitivity of the diagnosis for cervical infection increased from 16% (clinical aetiological approach) to 54% (when adding a syndromic approach) and to 68% when adding a risk assessment, as in the national flow charts. The cure or improved rate of genital ulcers was 96% after 1 week. CONCLUSIONS: The results of the study will help to convince policy makers and those involved in training healthcare workers in Brazil of the public health advantages of the syndromic approach, as an essential part of STD/HIV control activities.

Acquired immune deficiency syndrome in brazil and the state of cear

Since February 1998, a total of 129,000 cases of acquired immune deficiency syndrome have been reported in Brazil. The cumulative frequency of the disease is 82 per 100,000, which makes Brazil one of the countries moderatly affected. There are considerable differences between regions in the frequency of cases, from 25 per 100,000 in the north and north east to 152 per 100,000 in the south east. Sexual intercourse is still the predominant means of transmission. Transmission in the early years of the epidemic was mostly between homosexuals and bisexuals, but transmission via heterosexual intercourse is increasing. The contribution made by intravenous drug use differs between the regions, and is particularly large in the mid-south region. A pilot project in the city of Fortaleza has shown that it is possible to successfully integrate the diagnosis of STD and AIDS in health care units at an intermediate level. This appears to be an appropriate strategy for the integration of STD treatment into primary health care in Ceara State. The non-uniform pattern of development of this epidemic must be taken into account in epidemiological analyses of AIDS in Brazil.

AIDS and condoms in Brasilia: a telephone survey.

A telephone survey was conducted to measure AIDS knowledge, media usage and condom attitudes and behaviors among 500 adults aged 18 to 49 in Brasilia, as well as to evaluate the feasibility of the telephone survey method in a developing country. The response rate was 91.6%. Respondents had good knowledge about correct modes of HIV transmission and prevention but also believed HIV was transmitted through blood donation, public toilets, swimming pools, and mosquito bites. TV and newspapers were the most important sources of information on health matters and AIDS, though health workers were considered the most credible sources of such information. Only 19% of sexual encounters in the 4 weeks prior to the survey included condoms. Single and younger respondents and those with more positive attitudes used condoms more frequently. More work is needed to identify appropriate messages to motivate people to use condoms. Telephone surveys regarding AIDS and sexual attitudes and behaviors are feasible in Brasilia, a planned community with universal telephone coverage.

PIP: This study examines the knowledge, attitudes, and behavior of AIDS and condom use in Brazil. Data were obtained during March-April 1994 from 500 completed telephone interviews among a sample of adults 18-49 years old living in the Plano Piloto sector of Brasilia, Brazil. The survey was conducted about 2 months after a national television and radio campaign on AIDS prevention, use of condoms, and avoidance of sharing syringes or needles. The questionnaire was based on questions from the Global Program on AIDS protocol. 99% of the sample reported that AIDS was one of the most important health problems facing Brazil today. The other health problems mentioned were cancer, famine, and cholera. 27% did not consider themselves at risk of AIDS. 2% considered themselves at great risk. The rest believed they had a small to moderate risk. 93% were aware that people with AIDS might appear healthy looking. 95% indicated sexual contact as a mode of transmission. 34% reported condom use as a means of avoiding AIDS transmission. 19% reported sexual abstinence as a preventive measure. 15% reported that people should inform others of their AIDS status as a way to avoid transmitting AIDS. 41% knew someone with AIDS. Less educated respondents held more inaccurate beliefs about the general means of transmission, but there were no educational differences about safe activities involving specific contact with persons infected with AIDS. Most misinformation pertained to public toilets, blood donations, use of swimming pools, and mosquito bites. 89% believed in a high risk at dental clinics used by AIDS patients. 72% were regular television users. Television and newspapers were the most important sources of information on AIDS and health. Only 19% used condoms in sexual activity occurring in the prior 4 weeks. Psychosocial factors were more important than demographic factors in predicting condom use.

Determinants of survival in adult Brazilian AIDS patients, 1982-1989. The Brazilian State AIDS Program Co-Ordinators.

OBJECTIVE: Little has been published about the length and determinants of survival for persons with AIDS in developing countries. This study examined the survival experience of Brazilian AIDS patients from 1982 to 1989. DESIGN: A retrospective cohort study involving record review of reported AIDS cases. METHODS: We obtained information about 2135 adult AIDS patients in Brazil. Local health officials supplied data regarding demographic and clinical characteristics and length of survival. Statistical techniques of survival analysis were applied. RESULTS: Median survival was 5.1 months, much shorter than in developed countries, and there was no improvement in survival for cases diagnosed more recently. Younger patients and those in the intravenous drug use exposure category lived longer than other AIDS patients. Those presenting with Kaposi's sarcoma, esophageal candidiasis, and tuberculosis fared relatively well, while those presenting with multiple diagnoses or toxoplasmosis did more poorly. CONCLUSIONS: These results tend to confirm the predictors of AIDS survival previously reported from developed countries and to document the poor survival of AIDS patients in the developing world.

AIDS in Brazil, 1982-1988.

AIDS was first identified in Brazil in 1982, and by mid-1988 a total of 3,952 cases had been detected. The highest concentrations of cases have occurred in the Southeast region of the country (81.8%), which includes the States of Rio de Janeiro and São Paulo, and in the 25-to-40 year-old age group (58.2%). Sexual transmission is responsible for 72.8% of the cases; 18.8% of the cases were transmitted by contact with contaminated blood or blood products; perinatal transmission is responsible for 1.0% of the total recorded cases. On the basis of serologic surveys of certain population groups and projections of the prevalence of infection based on the number of actual cases at the end of 1987, the number of asymptomatic infected individuals would be between 200,000 and 400,000.