HIV-1 genetic diversity and transmitted drug resistance to integrase strand transfer inhibitors among recently diagnosed adults in Porto Alegre, South Brazil.

OBJECTIVES: The HIV-1 genetic diversity and the presence of transmitted drug resistance mutations (TDRMs) against integrase strand transfer inhibitors (INSTIs) were assessed sequencing samples of antiretroviral (ARV)-naive HIV-1-infected individuals from South Brazil. METHODS: Viral RNA from 42 ART-naive individuals was submitted to complete HIV-1 integrase gene amplification by RT-PCR and sequencing. RESULTS: Viral strains carrying TDRMs against INSTIs were not detected in the present study. However, the polymorphisms L74M and L74I were each observed in 4.8% of the individuals. These accessory mutations have been reported as putative causes of TDRMs in ART with raltegravir, but only when associated with additional major mutations. When submitted to HIV-1 subtyping, 50% were classified as subtype C, 21% as recombinant BC, 19% as subtype B, 4.8% as subtype F1 and 4.8% as recombinant CF1. CONCLUSIONS: All 42 ARV-naive individuals were apparently susceptible to INSTIs, included in the Brazilian therapeutic guideline since 2009. To the best of our knowledge, this is the first study to evaluate TDRMs against INSTIs in Brazil. The most prevalent HIV-1 subtypes were subtype C, followed by the recombinant BC and subtype B, which is in agreement with previous studies. However, the presence of subtype F1 and recombinant CF1 reported herein was not observed in previous studies.

The influence of HIV-1 subtypes C, CRF31_BC and B on disease progression and initial virologic response to HAART in a Southern Brazilian cohort.

BACKGROUND: Although most HIV-1 infections in Brazil are due to subtype B, Southern Brazil has a high prevalence of subtype C and recombinant forms, such as CRF31_BC. This study assessed the impact of viral diversity on clinical progression in a cohort of newly diagnosed HIV-positive patients. METHODS: From July/2004 to December/2005, 135 HIV-infected patients were recruited. The partial pol region was subtyped by phylogeny. A generalized estimating equation (GEE) model was used to examine the relationship between viral subtype, CD4+ T cell count and viral load levels before antiretroviral therapy. Hazard ratio (Cox regression) was used to evaluate factors associated with viral suppression (viral load < 50 copies/mL at six months). RESULTS: Main HIV-1 subtypes included B (29.4%), C (28.2%), and CRF31_BC (23.5%). Subtypes B and C showed a similar trend in CD4+ T cell decline. Comparison of non-B (C and CRF31_BC) and B subtypes revealed no significant difference in the proportion of patients with viral suppression at six months (week 24). Higher CD4+ T cell count and lower viral load were independently associated with viral suppression. CONCLUSION: No significant differences were found between subtypes; however, lower viral load and higher CD4+ T cell count before therapy were associated with better response.

The influence o hiv-1 subtypes c, crf31_bc andb on disease progression and innitial virologic response to haart in a southern Brazilian cohort / A influência dos subtipos C, CRF31_BC e B do vírus HIV-1 na progressão da infecção e resposta virológica inicial a terapia antirretroviral em uma coorte no sul do Brasil

Background: Although most HIV-1 infections in Brazil are due to subtype B, Southern Brazil has a high prevalence of subtype C and recombinant forms, such as CRF31_BC. This study assessed the impact of viral diversity on clinical progression in a cohort of newly diagnosed HIV-positive patients. Methods: From July/2004 to December/2005, 135 HIV-infected patients were recruited. The partial pol region was subtyped by phylogeny. A generalized estimating equation (GEE) model was used to examine the relationship between viral subtype, CD4+ T cell count and viral load levels before antiretroviral therapy. Hazard ratio (Cox regression) was used to evaluate factors associated with viral suppression (viral load < 50 copies/mL at six months). Results: Main HIV-1 subtypes included B (29.4%), C (28.2%), and CRF31_BC (23.5%). Subtypes B and C showed a similar trend in CD4+ T cell decline. Comparison of non-B (C and CRF31_BC) and B subtypes revealed no significant difference in the proportion of patients with viral suppression at six months (week 24). Higher CD4+ T cell count and lower viral load were independently associated with viral suppression. Conclusion: No significant differences were found between subtypes; however, lower viral load and higher CD4+ T cell count before therapy were associated with better response.

Introdução: Embora a maioria das infecções de HIV-1 no Brasil seja devido ao subtipo B, o Sul do Brasil apresenta uma alta prevalência do subtipo C e formas recombinantes, como CRF31_BC. Este estudo avaliou o impacto da diversidade viral na evolução clínica em uma coorte de pacientes HIV-positivos recém diagnosticados. Métodos: De julho/2004 a dezembro/2005, 135 pacientes anti-HIV reagentes foram recrutados. A região pol parcial foi subtipada por filogenia. Um modelo de equação de estimativa generalizada (GEE) foi utilizado para examinar a relação entre subtipo viral, contagem de células CD4 e níveis de carga viral pré-terapia antirretroviral. Hazard ratio (regressão de Cox) foi utilizada para avaliar os fatores associados à supressão viral (carga viral < 50 cópias/mL em seis meses). Resultados: Os principais subtipos de HIV-1 incluíram B (29,4%), C (28,2%) e CRF31_BC (23,5%). Os subtipos B e C apresentaram uma tendência semelhante no declínio de células CD4. Quando comparados os subtipos não B (C e CRF31_BC) e B, não houve diferença significativa na proporção de pacientes com supressão viral aos seis meses (24 semanas). CD4 mais alto e carga viral mais baixa demonstraram associação independente com supressão viral. Conclusão: Não houve diferença significativa entre os subtipos; entretanto, viremia mais baixa e CD4 mais alto pré-terapia mostraram associação com melhor resposta.

High prevalence and association of HIV-1 non-B subtype with specific sexual transmission risk among antiretroviral naïve patients in Porto Alegre, RS, Brazil.

In South Brazil the circulation of two HIV-1 subtypes with different characteristics represents an important scenario for the study of the impact of HIV-1 diversity on the evolution of the HIV-1 epidemic and AIDS disease. HIV-1 B, the predominant variant in industrialized countries and HIV-1 C, the most prevalent subtype in areas with rapid epidemic growth, are implicated in most infections. We evaluated blood samples from 128 antiretroviral (ARV) naïve patients recruited at entry to the largest HIV outpatient service in Porto Alegre. Based on partial pol region sequencing, HIV-1 C was observed in 29%, HIV-1 B in 22.6% and, the recently identified CRF31_BC, in 23.4% of 128 volunteers. Other variants were HIV-1 F in 10% and other mosaics in 5.5%. In order to evaluate the association of socio-behavioral characteristics and HIV-1 subtypes, interviews and laboratory evaluation were performed at entry. Our data suggest an established epidemic of the three major variants, without any evidence of partitioning in either of the subgroups analyzed. However, anal sex practices were associated with subtype B, which could indicate a greater transmissibility of non-B variants by vaginal intercourse. This study provides baseline information for epidemiologic surveillance of the changes of the molecular characteristics of HIV-1 epidemics in this region.

High prevalence and association of HIV-1 non-B subtype with specific sexual transmission risk among antiretroviral naïve patients in Porto Alegre, RS, Brazil / Alta prevalência e associação do subtipo não-B do vírus HIV-1 com risco específico de transmissão sexual entre pacientes virgens de tratamento antirretroviral em Porto Alegre, Brasil

In South Brazil the circulation of two HIV-1 subtypes with different characteristics represents an important scenario for the study of the impact of HIV-1 diversity on the evolution of the HIV-1 epidemic and AIDS disease. HIV-1 B, the predominant variant in industrialized countries and HIV-1 C, the most prevalent subtype in areas with rapid epidemic growth, are implicated in most infections. We evaluated blood samples from 128 antiretroviral (ARV) naïve patients recruited at entry to the largest HIV outpatient service in Porto Alegre. Based on partial pol region sequencing, HIV-1 C was observed in 29 percent, HIV-1 B in 22.6 percent and, the recently identified CRF31_BC, in 23.4 percent of 128 volunteers. Other variants were HIV-1 F in 10 percent and other mosaics in 5.5 percent. In order to evaluate the association of socio-behavioral characteristics and HIV-1 subtypes, interviews and laboratory evaluation were performed at entry. Our data suggest an established epidemic of the three major variants, without any evidence of partitioning in either of the subgroups analyzed. However, anal sex practices were associated with subtype B, which could indicate a greater transmissibility of non-B variants by vaginal intercourse. This study provides baseline information for epidemiologic surveillance of the changes of the molecular characteristics of HIV-1 epidemics in this region.

No sul do Brasil a circulação de dois subtipos de HIV-1 com características diferentes representa importante cenário para o estudo do impacto da diversidade do HIV-1 na evolução da epidemia e na AIDS. O HIV-1 B, variante predominante nos países industrializados e o HIV-1 C, o subtipo mais prevalente em áreas com maiores taxas de crescimento da epidemia, estão implicados na maioria das infecções. Avaliamos amostras de sangue de 128 pacientes sem exposição a antirretrovirais, recrutados ao ingressarem no maior serviço ambulatorial de HIV/AIDS de Porto Alegre. Com base no sequenciamento parcial da região pol, o HIV-1 C foi observado em 29 por cento, HIV-1 B em 22,6 por cento e uma forma recombinante recentemente descrita, CRF31_BC, foi observada em 23,4 por cento entre 128 voluntários. Outras variantes encontradas foram HIV-1 F em 10 por cento e outros mosaicos em 5,5 por cento. Para avaliar associações entre características sócio-comportamentais e subtipos do HIV-1 foram realizadas entrevistas e exames laboratoriais na entrada do estudo. Nossos dados sugerem uma epidemia estabelecida dessas três variantes principais, sem evidência de compartilhamento em nenhum subgrupo analisado. Entretanto, prática sexual anal se mostrou associada à transmissão de subtipo B, o que pode indicar maior transmissibilidade das variantes não-B por intercurso vaginal. Este estudo permite delinear uma linha de base para o monitoramento epidemiológico das mudanças nas características moleculares da epidemia do HIV-1 nesta região.

Metabolic changes associated with antiretroviral therapy in HIV-positive patients / Alterações metabólicas associadas à terapia anti-retroviral em pacientes HIV-positivos / Alteraciones metabólicas asociadas a la terapia anti-retroviral en pacientes HIV-positivos

OBJECTIVE: To evaluate metabolic changes associated with highly active antiretroviral therapy (HAART) in HIV-positive patients, and to identify risk factors associated. METHODS: Retrospective study that included 110 HIV-positive patients who where on HAART in the city of Porto Alegre (Southern Brazil) between January 2003 and March 2004. Data on demographic variables, cigarette smoking, diabetes mellitus, cholesterol and triglyceride levels, stage of HIV infection, antiretroviral therapy and HCV coinfection were collected...

OBJETIVO: Avaliar as alterações metabólicas associadas à terapia anti-retroviral potente em pacientes HIV-positivos e identificar fatores de risco associados. MÉTODOS: Estudo retrospectivo com 110 pacientes HIV-positivos que estavam sob terapia anti-retroviral potente (HAART) na cidade de Porto Alegre (RS), entre janeiro de 2003 e março de 2004. Os dados coletados incluem variáveis demográficas, tabagismo, diabetes mellitus, níveis de colesterol e triglicerídeos, estágio da infecção viral, terapia anti-retroviral e co-infecção com hepatite C...

OBJETIVO: Evaluar las alteraciones metabólicas asociadas a la terapia anti-retroviral potente en pacientes HIV-positivos e identificar factores de riesgo asociados. MÉTODOS: Estudio retrospectivo con 110 pacientes HIV-positivos que estaban en terapia anti-retroviral potente (HAART) en la ciudad de Porto Alegre (Sur de Brasil), entre enero de 2003 y marzo de 2004. Los datos colectados incluyen variables demográficas, tabaquismo, diabetes mellitas, niveles de colesterol y triglicéridos, fase de la infección viral, terapia anti-retroviral y co-infección con hepatitis C...

Metabolic changes associated with antiretroviral therapy in HIV-positive patients.

OBJECTIVE: To evaluate metabolic changes associated with highly active antiretroviral therapy (HAART) in HIV-positive patients, and to identify risk factors associated. METHODS: Retrospective study that included 110 HIV-positive patients who where on HAART in the city of Porto Alegre (Southern Brazil) between January 2003 and March 2004. Data on demographic variables, cigarette smoking, diabetes mellitus, cholesterol and triglyceride levels, stage of HIV infection, antiretroviral therapy and HCV coinfection were collected. General linear models procedure for repeated measures was used to test the interaction between HAART and HCV coinfection or protease inhibitor treatment. RESULTS: Total cholesterol, triglycerides, and glucose levels significantly increased after receiving HAART (p<0.001 for all variables), but no interaction with protease inhibitors was seen for total cholesterol, glucose and triglyceride levels (interaction treatment*protease inhibitors p=0.741, p=0.784, and p=0.081, respectively). An association between total cholesterol levels and HCV coinfection was found both at baseline and follow-up (effect of HCV coinfection, p=0.011). Glucose levels were increased by HAART (treatment effect, p=0.036), but the effect was associated to HCV coinfection (treatment*HCV effect, p=0.018). Gender, smoking habit, intravenous drug use and age were not significantly associated with cholesterol, triglyceride and glucose changes. CONCLUSIONS: HCV-infected patients at baseline were significantly less likely to develop hypercholesterolemia. The results provide further evidence of the role of HAART for the development of metabolic disturbances.

Comparação entre dois anti-retrovirais, efavirenz e atazanavir, utilizados em pacientes ambulatoriais infectados pelo HIV / Comparicion betwen two antiretroviral regimens including zidovudina, lamivudina and efavirenz or atazanavir in hiv positive patients (naive patients)

A eficácia de associações terapeuticas, aliada a acessibilidade aos medicamentos, proporciona aumento significativo na sobrevida e qualidade de vida dos portadores do HIV e pacientes com AIDS. O objetivo deste estudo foi comparar a eficacia de dois esquemas terapeuticos antiretrovirais, diferindo somente quantos aos farmacos efavirenz(EFV) e atazanavir(ATV), em pacientes ambulatoriais infectados pelo HIV, sem historia prévia de tratamento especifico. Este estudo foi realizado no Serviço de Assistencia Especializada em DST/Aids do Posto de Saude Vila dos Comerciários da cidade de Porto Alegre/RS. Através de uma coorte retrospectiva foram observados dados clinicos, epidemiologicos e laboratoriais obtidos de prontuarios medicos dos pacientes. A amostra final estudada foi constituida por 50 prontuarios de pacientes que completaram os tratamentos (n=28EFV e 22ATV). Foram comparados os periodos pré e transtratamento, atraves da determinação do numero de linfócitos T CD$+ e da carga viral serica. A amostra foi caracterizada por 33 homens(36,6 anos) e 17 mulheres (35,2 anos); Considerando-se os periodos pré e pós-tratamento, houve aumento significativo (p<0,05) de linfocitos TCD4+ e redução da carga viral para ambos os tratamentos (ATV e EFV). Comparados entre si (ATV x EFV) não houve diferença significativa no aumento de linfócitos TCD4+; o tratamento com EFV entretanto, resultou em maior redução de carga viral, na primeira avaliacao realizada. Esquemas anti-retrovirais combinados contendo atazanavir ou efavirenz são eficazes para pacientes sem historia previa de terapia especifica.