Unaí Tupinambás

Prevalence of primary drug resistance-associated mutations among HIV type 1 vertically Infected children in Belo Horizonte, Brazil.

In the past few years there has been increasing concern about the transmission of drug-resistant HIV. This study aimed to describe the frequency of primary mutations associated with HIV-1 drug resistance and the prevalence of genetic HIV subtypes in a population of vertically infected children before the initiation of HAART. At the time of genotypic testing, the median age was 6.0 years (IQR 25-75%: 3.8-9.2) and the median age at admission was 3.84 years (IQR 25-75%: 1.23-6.11). Antepartum maternal ARV exposure for PMTCT occurred for three (7.3%) mothers. According to the WHO criteria, primary ARV resistance mutations were detected in four out of 41 (9.8%) children. Subtype B was the most prevalent (63.4%). The relatively high prevalence of primary HIV-1 DRMs in this cohort of perinatally infected children in Brazil supports the local recommendation to perform resistance testing in all newly diagnosed children, regardless of age at diagnosis and antenatal ARV exposure.

Heterosexual transmission of human immunodeficiency virus type 1 subtype C in southern Brazil.

BACKGROUND Human immunodeficiency virus type 1 (HIV-1) subtype B predominates in Brazil, but in the southern region subtype C is the most frequent, followed by subtypes B, F1 and recombinant forms. In southern Brazil, these subtypes co-circulate in subjects with homogeneous demographic and clinical features, enabling a better understanding of the role of HIV-1 subtypes on the characteristics of infection. OBJECTIVES To evaluate the prevalence of different HIV-1 subtypes in subjects with recent diagnosis for HIV infection in the extreme south of Brazil, and to study their association with demographic, behavioral, clinical and laboratorial characteristics. STUDY DESIGN We have determined the genetic sequence of viral protease and reverse transcriptase (polymerase, connection and RNase H domains) isolated from studied subjects. Viral subtype was inferred by comparison with reference HIV sequences, and recombination was determined with Simplot analysis. The association of HIV-1 subtypes with studied characteristics was evaluated by chi-square, Fishers exact, Students t and Kruskal-Wallis tests. RESULTS Two hundred and forty-five HIV isolates were molecularly characterized, and the association with variables was studied for 233 (95.1%) patients. Of those, 46.8% followed AIDS defining criteria. HIV-1C was responsible for 56.3% of infections, and was associated with heterosexual transmission (p=0.001) and with higher CD4(+) T-cell counts (p=0.02). CONCLUSIONS The molecular epidemiology of HIV-1 in the southernmost Brazil is currently steady with predominance of HIV-1C. This is the first study showing a robust association of the infection by this subtype and heterosexual transmission in the state of Rio Grande do Sul, Brazil.

Primary HIV-1 drug resistance in the C-terminal domains of viral reverse transcriptase among drug-naïve patients from Southern Brazil

BACKGROUND Major and accessory drug resistance mutations have been recently characterized in the C-terminal RT subdomains of HIV-1, connection and RNase H. However, their presence in treatment-naïve patients infected with HIV-1 non-B subtypes remains largely unknown. OBJECTIVES To characterize the patterns of primary resistance at the C-terminal RT subdomains of HIV-1 infecting subjects in the southern region of Brazil, where HIV-1 subtypes B and C co-circulate. STUDY DESIGN Plasma viral RNA was extracted from patients recently diagnosed for HIV infection (2005-2008). The protease and reverse transcriptase regions were PCR-amplified and sequenced. Infecting HIV subtypes were assigned by phylogenetic inference and drug resistance mutations were determined following the IAS consensus and recent reports on C-terminal RT mutations. RESULTS The major mutation to NNRTI T369I/V was found in 1.8% of patients, while A376S was present in another 8.3%. In the RNase H domain, the compensatory mutation D488E was more frequently observed in subtype C than in subtype B (p=0.038), while the inverse was observed for mutation Q547K (p<0.001). The calculated codon genetic barrier showed that 22% of subtype B isolates, but no subtype C, carried T360, requiring two transitions to change into the resistance mutation 360V. CONCLUSIONS Major resistance-conferring mutations to NNRTI were detected in 10% of RT connection domain viral sequences from treatment-naïve subjects. We showed for the first time that the presence of specific polymorphisms can constrain the acquisition of definite resistance mutations in the connection and RNase H subdomains of HIV-1 RT.

Diretivas antecipadas de vontade: um modelo brasileiro

O presente artigo e fruto de tese cujo objetivo geral foi propor um modelo de diretivas antecipadas de vontade para o Brasil. Para tanto, realizou-se uma revisao de literatura sobre as diretivas antecipadas nas Americas e na Europa, especialmente nos Estados Unidos da America e na Espanha, e entrevistas semiestruturadas com medicos oncologistas, intensivistas e geriatras de Belo Horizonte-MG. Percebeu-se que o modelo brasileiro deve se distanciar dos padroes de formularios utilizados em muitos estados norte-americanos e provincias espanholas, visando deixar espaco para a subjetividade de cada paciente. Conclui-se, assim, que o modelo proposto tem o condao de auxiliar o cidadao que deseja fazer sua diretiva antecipada, bem como os medicos que desejam apresentar essa possibilidade para seus pacientes, mas deve ser sempre utilizado como guia e nao como um modelo fechado as peculiaridades de cada situacao concreta.Este articulo es el resultado de la tesis doctoral, cuyo objetivo general fue proponer un modelo de directivas anticipadas de voluntad para Brasil. Por lo tanto, se realizo una revision bibliografica sobre las directivas anticipadas en las Americas y en Europa, especialmente en Estados Unidos y Espana, y las entrevistas semiestructuradas con los medicos oncologos, intensivistas y geriatras de Belo Horizonte-MG. Se ha percibido que un modelo brasileno debe alejarse de los modelos de formularios utilizados en muchos estados norteamericanos y provincias de Espana, con el fin de dejar espacio para la subjetividad de cada paciente. Se concluye, por tanto, que el modelo propuesto tiene la capacidad de ayudar a los ciudadanos que desean hacer su directiva anticipada, asi como los medicos que desean ofrecer esta opcion a sus pacientes, pero siempre debe ser utilizado como una guia y no como un modelo cerrado a las peculiaridades de cada situacion concreta.

Durability of the first combined antiretroviral regimen in patients with AIDS at a reference center in Belo Horizonte, Brazil, from 1996 to 2005

Finding a better first antiretroviral regimen is one of the strategies used to improve span and quality of life of HIV/AIDS patients. 891 patients were followed during 24 months or until interruption/abandonment of treatment, changing regimen or death. At the end of 6 months, 69% of the patients were still being treated with the first regimen, 54% at 12 months, 48% at 18 months and 39% at 24 months. AZT-3TC-EFV was the most prescribed regimen and with the lesser discontinuation. NNRTI regimens showed high effectiveness and durability compared to PI regimens. Irregular medication dispensation was the only risk factor for failure/interruption of treatment in multivariate analyses. Intolerance/adverse effects were mainly responsible for first regimen discontinuation, followed by abandonment/non-adherence and virologic failure. Results showed significant difference between causes of interruption of first HAART with higher percentage of intolerance/adverse effects with PI regimens and higher immunologic failure with NNRTI regimens. Even with the availability of more potent and tolerable drugs, lack of adherence to HAART and high level of adverse effects are still the most important barriers to prolonged success of treatment. This study adds relevant information about durability and effectiveness of HAART in the first decade of its use in Brazil.

Virologic and immunologic effectiveness at 48 weeks of darunavir-ritonavir-based regimens in treatment-experienced persons living with HIV-1 infection in clinical practice: a multicenter Brazilian cohort.

Introduction: Published data addressing the effectiveness of darunavir–ritonavir (DRV/r)-based therapy for multiexperienced patients in developing countries are scarce. This study evaluated the 48-week virologic and immunologic effectiveness of salvage therapy based on DRV/r for the treatment of multidrug-experienced HIV-1-infected adults in Brazil. Materials and Methods: A multicenter retrospective cohort study was carried out with multidrug-experienced adults who were on a failing antiretroviral therapy and started a DRV/r-based salvage therapy between 2008 and 2010. The primary effectiveness end point was the proportion of patients with virologic success (plasma HIV-1 RNA <50 copies/mL at week 48). Results: At 48 weeks, 73% of the patients had HIV-RNA <50 copies/mL and a mean increase of 108 CD4 cells/mm3. Higher baseline viral load, lower baseline CD4 count, younger age, and 3 or more DRV/r-associated resistance mutations were significantly predictive of virologic failure. Concomitant use of raltegravir was strongly associated with virologic success. Conclusion: The use of DRV/r-based regimens for salvage therapy is an effective strategy in the clinical care setting of a developing country.

Virologic and immunologic effectiveness of darunavir-based salvage therapy in HIV-1-infected adults in a Brazilian clinical practice setting: results of a multicenter and retrospective cohort study.

BACKGROUND Darunavir has been proven efficacious for antiretroviral-experienced HIV-1-infected patients in randomized trials. However, effectiveness of darunavir-based salvage therapy is understudied in routine care in Brazil. METHODS Retrospective cohort study of HIV-1-infected patients from three public referral centers in Belo Horizonte, who received a darunavir-based therapy between 2008 and 2010, after virologic failure. Primary endpoint was the proportion of patients with viral load<50 copies/mL at week 48. Change in CD4 cell count was also evaluated. Outcome measures were analyzed on an intent-to-treat basis applied to observational studies. Sensitivity analysis was conducted to evaluate the impact of missing data at week 48. Predictors of virologic failure were examined using rare-event, finite sample, bias-corrected logistic regression. RESULTS Among 108 patients, the median age was 44.2 years, and 72.2% were male. They had long-standing HIV-1 infection (median 11.6 years) and advanced disease (76.9% had an AIDS-defining event). All patients had previously received protease inhibitors and nucleoside reverse transcriptase inhibitors, 75% nonnucleoside reverse transcriptase inhibitors, and 4.6% enfuvirtide. The median length of protease inhibitor use was 8.9 years, and 90.8% of patients had prior exposure to unboosted protease inhibitor. Genotypic resistance profile showed a median of three primary protease inhibitor mutations and 10.2% had three or more darunavir resistance-associated mutations. Virologic success at week 48 was achieved by 78.7% (95% CI=69.7-86%) of patients and mean CD4 cell count increase from baseline was 131.5 cells/μL (95% CI=103.4-159.6). In multiple logistic regression analysis, higher baseline viral load (RR=1.04 per 10,000 copies/mL increase; 95% CI=1.01-1.09) and higher number of darunavir resistance-associated mutations (RR=1.23 per each; 95% CI=0.95-1.48) were independently associated with virologic failure. CONCLUSION Virologic suppression is a realistic endpoint for most treatment-experienced patients who begin a darunavir-based therapy outside the controlled conditions of a randomized trial, at routine care settings.

HIV-1 genotypes related to failure of nelfinavir as the first protease inhibitor treatment

Combined antiretroviral therapy results in sustained viral suppression and a decrease in mortality and morbidity due to HIV infection. Intrinsic strength, durability and absence of cross-resistance are key factors in the selection of antiretrovirals. Failure with nelfinavir has been associated with two protease gene mutations, D30N and L90M. The D30N mutation does not result in cross-resistance with other protease inhibitors, and it decreases viral fitness. In order to check for this mutation after failure with nelfinavir, the 246 HIV-1 genotyping test was performed on virus samples from 55 patients with failure of nelfinavir as the first protease inhibitor. Most (84%) of the viral strains were of subtype B. Nucleosides associated with mutations (NAM) were observed in 80% of the tests; no INS69, complex 151, K65R and L74V mutations, which give multi-resistance to nucleoside analogue reverse transcriptase inhibitors to tenofovir and DDI, respectively, were observed. In the tests for protease gene mutations, the D30N mutation was found in 57%, L90M in 18% and the wild-type virus in 25%. These data are similar to published reports, showing that alternative therapies used after failure with nelfinavir may be more successful, as the D30N mutation does not cause cross-resistance to other protease inhibitors.

Outbreak of laboratory-acquired Brucella abortus in Brazil: a case report

Human brucellosis is an occupational disease affecting workers in slaughterhouses, butcher shops and the milk and dairy product industry as well as individuals who work in clinical or research laboratories. We report the first outbreak of a Brucella abortus infection in a Brazilian laboratory and compare the data obtained with reports available in the literature. Exposure was a result of damage to a biological safety cabinet and failure of the unidirectional airflow ventilation system. An epidemiological investigation identified 3 seroconverted individuals, 1 of whom had clinical manifestations and laboratory results compatible with infection at the time of exposure (n=11; attack rate=9.1%).

Transmitted human immunodeficiency virus-1 drug resistance in a cohort of men who have sex with men in Belo Horizonte, Brazil--1996-2012.

The presence of transmitted human immunodeficiency virus (HIV)-1 drug-resistance (TDR) at the time of antiretroviral therapy initiation is associated with failure to achieve viral load (VL) suppression. Here, we report TDR surveillance in a specific population of men who have sex with men (MSM) in Belo Horizonte, Brazil. In this study, the rate of TDR was evaluated in 64 HIV-infected individuals from a cohort of MSM between 1996-June 2012. Fifty-four percent had a documented recent HIV infection, with a seroconversion time of less than 12 months. The median CD4+T lymphocyte count and VL were 531 cells/mm3 and 17,746 copies/mL, respectively. Considering the surveillance drug resistance mutation criteria, nine (14.1%) patients presented TDR, of which three (4.7%), five (7.8%) and four (6.2%) had protease inhibitors, resistant against nucleos(t)ide transcriptase inhibitors and against non-nucleoside reverse-transcriptase inhibitors mutations, respectively. Two of the patients had multi-drug-resistant HIV-1. The most prevalent viral subtype was B (44, 68.8%), followed by subtype F (11, 17.2%). This study shows that TDR may vary according to the population studied and it may be higher in clusters of MSM.