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Cryptococcosis (Cr) and tuberculosis (TB) are infectious diseases potentially fatal to HIV-AIDS patients, and coinfection with Cr/TB in endemic regions may represent a new challenge in the panorama of the HIV-AIDS pandemic. This retrospective study aims to describe the clinic-epidemiological data of cryptococcosis and tuberculosis (Cr/TB) coinfection in HIV-AIDS patients from Southern Brazil. A retrospective study including all cases of coinfection by the Cryptococcus neoformans species complex and Mycobacterium tuberculosis, diagnosed in HIV-AIDS patients at the Specialized Customer Service of University Hospital - Federal University of Rio Grande (SAE-HU-FURG), during the period January 2010 to December 2012 was performed. During the 3 years of study, ten cases of Cr/TB coinfection were detected. The mean age was 39.3 years and 80% were male. Cr meningitis with pulmonary TB occurred in 40% of the cases and pulmonary presentation in both diseases occurred in 30%. The mean TCD4 + rate was 118.6 cel/mm3 (SD = 135.36), with 80% of the patients maintaining TCD4 +

We report a case of fungal and mycobacterial co-infection in an immunosuppressed patient from Southern Brazil. Histoplasmosis was diagnosed in an AIDS patient admitted to the hospital with nonspecific respiratory signs. However, 4 months post hospital discharge, the patient worsened and a co-infection with Mycobacterium avium was detected. Physicians must consider and investigate a broad spectrum of diseases which can occur as co-infections and which share the same clinical symptoms and signs in immunosuppressed patients.

Background Sporotrichosis has been occurring as outbreaks in Brazil, reaching epidemic levels in some regions. Zoonotic transmission is the main route to acquire Sporothrix. Case report We describe a case of disseminated sporotrichosis caused by Sporothrix brasiliensis in an HIV/AIDS patient, with the presentation of immune reconstitution inflammatory syndrome (IRIS). Conclusions This case reinforces that sporotrichosis should always be suspected in patients with IRIS from endemic regions, even in patients without the typical cutaneous lesions of this mycosis.

Introduction. Nosocomial transmission of Mycobacterium tuberculosis is an important health issue and the detection of tuberculosis (TB) cases is the main tool for controlling this disease. Aim. We aimed to assess the possible occurrence of nosocomial transmission of M. tuberculosis in a reference hospital for HIV/AIDS patients and evaluate both the performance of the Xpert MTB/RIF (Xpert) platform and drug resistance profiles. Methodology. We evaluated the performance of the Xpert platform. Samples that tested positive on the BACTEC MGIT 320 (MGIT320) platform were submitted for genotyping and drug susceptibility testing. Results. In this study, pulmonary and extrapulmonary samples from 407 patients were evaluated, and among these, 15.5 % were diagnosed with TB by the MGIT320 platform, with a TB/HIV coinfection rate of 52.4 %. The Xpert platform gave positive results for TB for 11 samples with negative results on the MGIT320 platform. In the genotyping results, 53.3 % of the strains clustered; of these strains, half were in two of the four clusters formed, and the patients had visited the hospital on the same day. Drug resistance was observed in 11.7 % of the strains. Conclusion. Putative nosocomial transmission of M. tuberculosis was detected, showing that genotyping is a powerful approach for understanding the dynamics of M. tuberculosis transmission, especially in a high-burden TB and HIV landscape.

Previous studies have demonstrated that coinfection with HPgV is a protective factor for human immunodeficiency virus (HIV)-infected patients, leading to slower disease progression, and longer survival after established disease. The present study sought to estimate the prevalence of HPgV infection and associated risk factors in patients harboring C or non-C HIV-1 subtypes followed-up at HU-FURG, southern Brazil. Samples from 347 HIV-1-infected subjects were subjected to plasma RNA extraction, cDNA synthesis, HPgV RNA detection, and HIV-1 genotyping. The overall prevalence of HPgV RNA was 34%. Individuals aged 18-30 years had higher chances of infection compared with those 50 years or older (95%CI 1.18-52.36, P = 0.03). The number of sexual partner between one and three was a risk factor for HPgV infection (95%CI 1.54-10.23; P

Recent studies have suggested that human pegivirus 1 (HPgV-1) may have some pathogenic potential. In the southernmost region of Brazil, studies on HPgV-1 are scarce, and circulating genotypes have not yet been identified. The current study aimed to evaluate the prevalence of HPgV-1 among blood donors from the southernmost region of Brazil and identify the genotypes involved with associated factors. A cross-sectional study was conducted with 281 blood donors, who had their plasma subjected to RNA extraction, complementary DNA synthesis, HPgV-1 detection by nested polymerase chain reaction, and subsequent genotyping. The observed prevalence of HPgV-1-RNA was 21.7%. The only variable that was significantly associated with virus infection was the relationship status of the donor. Single or no fixed partner blood donors were twice as likely to have HPgV-1 (95% CI, 1.12 to 4.56; P = 0.02). Genotype 2-subtypes 2b (69%) and 2a (29%)-was the most prevalent. In the absence of risk factors for parenteral transmission, it is likely that sexual transmission was the route of infection in the individuals studied. Further work will be needed to determine whether this virus is inert in the population, or if there are potential deleterious effects in infected individuals.

The aim of this study was to determine the rate and risk factors of HIV-1 mother-to-child transmission (MTCT), the timing of transmission and the transmitted subtype in a population where subtypes B and C co-circulate. One hundred and forty-four babies born to HIV-1-infected mothers were studied. Subtype and timing of transmission were determined by a nested polymerase chain reaction of the gp41 gene. Seven children were infected (4.9%): four were infected intrautero and one intrapartum. The higher frequency of intrautero transmission was statistically significant ( P = 0.001). Use of antiretrovirals (ARVs) in the three stages of gestation was a protective risk factor for MTCT (PR = 0.42; CI: 0.21–0.83; P = 0.013). A higher HIV viral load at delivery was the only independent risk factor for MTCT. Early and universal access to ARVs during pregnancy are the most important measures to decrease vertical HIV-1 transmission even in areas where HIV clade distribution differs.

Made available in DSpace on 2018-11-26T15:29:43Z (GMT). No. of bitstreams: 0 Previous issue date: 2016-06-01 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) The hypothesis of the present study is that the polymorphisms in the APOC3, CEPT, ACE, and ACTN3 genes can affect the outcome of nutritional intervention and the plasma lipid profile of HIV+ patients. To test the hypothesis, genetic material was collected from buccal cells, and serum was collected for biochemical analysis. Sixty-five patients were analyzed. The incorporation of protease inhibitor (PI) was more frequent in women (77% vs 33% in men). Nutritional intervention improved anthropometric parameters independent of the genotype. Patients with the RR genotype for the ACTN3 R577X polymorphism had lower glycemia (RR = 95.4 +/- 6.5 mg/dL, RX = 102.6 +/- 10.6 mg/dL, XX = 110.1 +/- 16.3 mg/dL; P = .03) and a greater reduction in low-density lipoproteins (LDL) after intervention (LDL: RR = -23.7 +/- 15.8 mg/dL, RX = 1.32 +/- 5.13 mg/dL, XX = 30.21 +/- 24.4 mg/dL; P = .01). Patients using PI had a negative response to dietary intervention regarding the levels of high-density lipoprotein (-2.4 +/- 1.70 with PI, 2.56 +/- 1.60 mg/dL without PI; P = .02), very low density lipoprotein (0.84 +/- 2.73 with IP, -5.46 +/- 3.37 mg/dL without PI; P = .03), and triglycerides (1.79 +/- 13.22 with PI, -34.00 +/- 17.67 mg/dL without PI; P = .052). This response was also independent of the genotype (P > 0.05) and suggested the need for oral lipid-lowering drugs in all HIV+ patients using PI. Our results indicate that the ACTN3 R577X polymorphism is a good predictor of both the lipid profile and the prognosis of nutritional intervention in reducing LDL in HIV+ patients. (C) 2016 Elsevier Inc. All rights reserved. Univ Fed Pelotas, Sch Nutr, R Gomes Carneiro 01, Pelotas, Brazil Univ Estadual Paulista, Rua Luis Goes,2211 Mirandopolis, Sao Paulo, Brazil Univ Fed Rio Grande do Sul, Univ Hosp Dr Miguel Riet Correa Jr, Porto Alegre, RS, Brazil Univ Fed Sao Paulo, Dept Biophys, R Botucatu 862, Sao Paulo, Brazil Univ Fed Sao Paulo, Dept Biochem, R Botucatu 862, Sao Paulo, Brazil Univ Estadual Paulista, Rua Luis Goes,2211 Mirandopolis, Sao Paulo, Brazil

OBJETIVO: Considerando a relevância da co-infecção vírus da imunodeficiência humana/tuberculose, este estudo foi desenvolvido para determinar a prevalência e os fatores associados à tuberculose em pacientes residentes em uma zona de alta prevalência das duas infecções. MÉTODOS: Todos os pacientes atendidos no ano de 1999 no Serviço HIV/AIDS do Hospital Universitário da Universidade Federal do Rio Grande foram avaliados retrospectivamente desde o momento do diagnóstico da presença do vírus da imunodeficiência humana, em relação à ocorrência de tuberculose e sua associação com fatores sociodemográficos, comportamentais e imunológicos. RESULTADOS: A amostra incluiu 204 pacientes e a prevalência encontrada de tuberculose foi de 27%. A análise multivariada mostrou que existe uma associação significativa do desenvolvimento de tuberculose com a raça negra (razão de chance: 4,76; intervalo de confiança de 95%: 1,93 -11,72) e uma relação inversa com a contagem de linfócitos TCD4+ no momento do diagnóstico do vírus da imunodeficiência humana (razão de chance: 0,995; intervalo de confiança de 95%: 0,993-0,997). O sexo masculino (razão de chance: 2,49; intervalo de confiança de 95%: 1,15-5,39) e o uso de drogas (razão de chance: 2,1; intervalo de confiança: 95% de 1,02-4,31) podem também ser fatores de risco quando analisados separadamente. CONCLUSÃO: Os fatores responsáveis pelo desenvolvimento da tuberculose entre os pacientes soropositivos para o vírus da imunodeficiência humana incluem os aspectos imunitários e fatores socioeconômicos e demográficos. A alta taxa de tuberculose em pacientes soropositivos torna urgente implementar estratégias que combinem rápida identificação e tratamento dos casos, comunicantes e indivíduos com infecção latente.OBJECTIVE: In view of the relevance of co-infection with tuberculosis and human immunodeficiency virus, this study was designed to determine tuberculosis prevalence and identify factors related to tuberculosis in patients residing in a region in which both infections are highly prevalent. METHODS: All patients treated during 1999 at the HIV/AIDS Clinic of the Universidade Federal do Rio Grande (Rio Grande Federal University) University Hospital were evaluated retrospectively, from the time of human immunodeficiency virus diagnosis, in terms of the incidence of tuberculosis and its relationship to sociodemographic, behavioral and immunological factors. RESULTS: The sample included 204 patients, and tuberculosis prevalence was found to be 27%. The multivariate analysis showed a significant correlation between the development of tuberculosis and being of African descent (odds ratio: 4.76; 95% confidence interval: 1.93-11.72) and an inverse correlation between the development of tuberculosis and the TCD4+ lymphocyte count at the time of human immunodeficiency virus diagnosis (odds ratio: 0.995; 95% confidence interval: 0.993-0.997). When analyzed separately, other variables were found to be potential risk factors: being of the male gender (odds ratio: 2.49; 95% confidence interval: 1.15-5.39); and using illicit drugs (odds ratio: 2.1; 95% confidence interval: 1.02-4.31). CONCLUSION: The factors responsible for the development of tuberculosis among patients who are human immunodeficiency virus seropositive include immunological, socioeconomic and demographic factors. The high rate of tuberculosis prevalence among the seropositive patients underscores the urgent need to implement strategies that combine rapid identification and prompt treatment of individuals with active or latent infection, as well as of those with whom they have been in contact.

Made available in DSpace on 2022-04-28T18:59:18Z (GMT). No. of bitstreams: 0 Previous issue date: 2014-01-01 Introduction: Published data addressing the effectiveness of darunavirritonavir (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

OBJECTIVE TLRs (Toll-like receptors) and RLRs (RIG-I-like receptors) mediate innate immune responses by detecting microorganism invasion. RIG-I activation results in the production of interferon (IFN) type 1 and IFN responsive genes (ISGs). As the ubiquitin ligases RNF125 and TRIM25 are involved in regulating RIG-I function, our aim was to assess whether the levels of these three genes vary between healthy and HIV-infected individuals and whether these levels are related to disease progression. DESIGN Gene expression analyses for RIG-I, RNF125, and TRIM25 were performed for HIV-infected adults and the children's peripheral blood mononuclear cells (PBMCs). METHODS Reverse transcription-quantitative PCRs (RT-qPCRs) were performed in order to quantify the expression levels of RIG-I, RNF125 and TRIM25 from PBMCs purified from control or HIV-infected individuals. RESULTS Controls express higher levels of the three genes when compared to HIV-infected patients. These expressions are clearly distinct between healthy and progressors, and are reproduced in adults and children. In controls, RNF125 is the highest expressed gene, whereas in progressors, RIG-I is either the highest expressed gene or is expressed similarly to RNF125 and TRIM25. CONCLUSION A pattern of expression of RIG-I, RNF125, and TRIM25 genes in HIV patients is evident. The high expression of RNF125 in healthy individuals reflects the importance of keeping RIG-I function off, inhibiting unnecessary IFN production. Consistent with this assumption, RNF125 levels are lower in HIV patients and importantly, the RNF125/RIG-I ratio is lower in patients who progress to AIDS. Our results might help to predict disease progression and unveil the role of poorly characterized host genes during HIV infection.

To evaluate antiretroviral phenotypic susceptibility of wild-type HIV-1 strains circulating in Brazil, samples from antiretroviral-naive individuals infected with subtypes C (n=16), F (n=9), or B/F (n=7), where reverse transcriptase is B and protease is F, were phenotyped using the Antivirogram Assay (Virco, Mechelen, Belgium). Reduced susceptibility to protease inhibitors (PIs) was observed in one C and three F isolates. None of these samples had any known PI resistance mutations. The phenotypic fold change to one PI was above the biological cut-off in three of 96 (3.1%) clade F phenotypic determinations and in one of 96 (1.0%) clade C. Phenotypic resistance to at least one nucleoside reverse transcriptase inhibitor (NRTI) was found for two B/F, four C, and three F isolates. The phenotypic fold change in susceptibility to NRTIs was above the cut-off value in nine of 111 (8.1%) clade C determinations, as compared to three of 63 (4.8%) for clade F and two of 49 (4.1%) for clade B. The phenotypic fold change to non-NRTI (NNRTI) was above the cut-off in seven of 32 (21.9%) of C isolates determinations, whereas none of the F isolates had a decrease of susceptibility. Only two of the 16 C samples had a known NNRTI resistance mutation. The NNRTI fold change was above the cut-off value in three of 14 (21.4%) phenotypic determinations of Brazilian B/F recombinants, representing clade B reverse transcriptase. NNRTI susceptibility should be better investigated in clade C and B/F recombinants.

This study evaluated the impact of 9 single nucleotide polymorphisms (SNPs) in 6 candidate genes (APOB, APOA5, APOE, APOC3, SCAP, andLDLR) over dyslipidemia in HIV-infected patients on stable antiretroviral therapy (ART) with undetectable viral loads. Blood samples were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas, and Rio Grande in Brazil. The SNPs were genotyped by conventional polymerase chain reaction (PCR) and real-time PCR. The prevalence of dyslipidemia was particularly high among the protease inhibitors-treated patients (79%).APOE(rs429358 and rs7412) genotypes andAPOA5−1131T>C (rs662799) were associated with plasma triglycerides (TG) and low-density-lipoprotein cholesterol levels (LDL-C). TheAPOA5−1131T>C (rs662799) andSCAP2386A>G (rs12487736) polymorphisms were significantly associated with high-density-lipoprotein cholesterol levels. The mean values of the total cholesterol and LDL-C levels were associated with both theAPOBSPIns/Del(rs17240441) andAPOB XbaI(rs693) polymorphisms. In conclusion, our data support the importance of genetic factors in the determination of lipid levels in HIV-infected individuals. Due to the relatively high number of carriers of these risk variants, studies to verify treatment implications of genotyping before HAART initiation may be advisable to guide the selection of an appropriate antiretroviral therapy regimen.

Mutations in the connection subdomain (CN) and RNase H domain (RH) of HIV-1 reverse transcriptase (RT) from subtype B-infected patients enhance nucleoside and nonnucleoside RT inhibitor (NRTI and NNRTI) resistance by affecting the balance between polymerization and RNase H activity. To determine whether CN mutations in subtype C influence drug sensitivity, single genome sequencing was performed on Brazilian subtype C-infected patients failing RTI therapy. CN mutations identified were similar to subtype B, including A376S, A400T, Q334D, G335D, N348I, and A371V, and increased AZT resistance in the presence of thymidine analog mutations. CN mutations also enhanced NNRTI resistance in the presence of classical NNRTI mutations: etravirine resistance was enhanced 6- to 11-fold in the presence of L100I/K103N/Y181C. These results indicate that selection of CN mutations in treatment-experienced patients also occurs in subtype-C-infected patients and are likely to provide valuable information in predicting clinical RTI resistance.

Objective: To investigate genetic single nucleotide polymorphisms (SNPs) in estrogen receptor-a (ERa) (ESR1, rs2234693, rs1801132, rs7757956 and rs2813544) and ERb (ESR2, rs3020450, rs7154455 and rs4986938) genes and relate them to the adverse effects lipodystrophy, dyslipidemia and metabolic syndrome as well as to differences in their prevalence between sexes in HIV-infected individuals on HAART. Design: Cross-sectional study. Methods: Blood samples and anthropometric measurements were collected from 614 patients at reference services in the cities of Porto Alegre, Pelotas and Rio Grande in Brazil. The SNPs were genotyped by real-time PCR. Results: The lipodystrophy subtype frequencies in patients of different sexes showed statistically significant differences; the atrophic pattern was more prevalent in men, and the hypertrophic pattern was more prevalent in women. Furthermore, metabolic syndrome prevalence was higher in women than in men. The ESR1 rs2813544 G-allele was associated with higher measurements of several anthropometric variables in women: BMI, total subcutaneous fat and subcutaneous fat of limbs. Additionally, patients who were AA homozygous for ESR2 rs3020450 presented an increased risk for developing lipoatrophy (prevalence ratio 1.37, 95% confidence interval 1.09–1.73, P ¼ 0.007). Conclusion: Significant differences in lipodystrophy and metabolic syndrome prevalence were detected between sexes. Moreover, the ESR1 gene (rs2813544) presented significant sex-specific associations with anthropometric variables, and the ESR2 gene (rs3020450) was associated with an increased risk of developing lipoatrophy. Our results suggest that these genes are in part responsible for the sexual dimorphism in fat tissue redistribution and patterns of lipodystrophy.

BackgroundMajor 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.ObjectivesTo 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 designPlasma 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.ResultsThe 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

O Brasil tem um programa modelo de prevenção, diagnóstico e tratamento da infecção pelo HIV-1 e os monitoramentos regionais da epidemiologia molecular e da resistência transmitida às drogas (RTD) são primordiais. No estudo de mutações do HIV-1 são habitualmente incluídas as regiões da protease (PR) e polimerásica da transcriptase reversa (TR), mas estudos recentes indicam que mutações nos domínios C-terminais da TR podem contribuir para a resistênciaprimária ou compensatória na presença ou ausência de mutações aos análogos timidínicos (TAM). Em relação à heterogeneidade genética do HIV-1, a região Sul apresenta um padrão diferente do Brasil, com predomínio do subtipo C, seguido pelo B, formas recombinantes e subtipo F1. Objetivos: avaliar a prevalência de RTD em pacientes com diagnóstico recente de infecção pelo HIV-1 com diferentes subtipos virais no extremo sul do Brasil e correlacionar estes dadoscom as características demográficas, comportamentais, clínicas e laboratoriais da população estudada. Pacientes e métodos: Foi realizado um estudo transversal com pacientes virgens de TARV diagnosticados entre janeiro-2005 e dezembro- 2008 no Hospital Universitário da Universidade Federal do Rio Grande (RS).Foram sequenciadas as regiões genômicas virais referentes à protease (PR) e regiões polimerásica, Conexão (CN) e RNase H da TR. O subtipo viral foi determinado usando sequências-referência obtidas na base de dados de Los Alamos. Sequências em que o subtipo atribuído variava em função da região genômica foram submetidas à análises de recombinação no programa Simplot. A pesquisa de mutações de RTD foi feita na base de dados de HIV de Stanford eanalisada segundo o algoritmo específico para RTD. Nos domínios CN e RNAse H, as mutações consideradas nesta pesquisa foram: N348I; 360V; T369I/V; A371V. A400T na CN e I506L, Q509L; Q547K na RNaseH. Um banco de dados com as variáveis estudadas foi montado no programa Excel para posterior análise estatística no programa Stata 9.2. Para estudar a associação dos subtipos e das mutações de resistência com as variáveis incluídas foram usados os testes de qui-quadrado, exato de Fisher, t de Student e o teste não-paramétrico de Kruskal-Wallis. Resultados: foram obtidas análises moleculares de 245 isolados e a correlação com os dados clínicos foi estudada em 233 pacientes. Destes, 46,8% preenchiam critérios de Aids. O subtipo C foi responsável por 56,3% das infecções e associado com transmissão heterossexual (p=0,001) e maior contagem de LTCD4+ (p=0,02). A prevalência de RTD no domínio polimerásico da TR e PR foi de 6,56%, com 3,45% aos INTRs e INNTRs; 1,42% para IP e 1,64% MDR. Na região da CN, a prevalência de resistência foi de 36%, com 3,65% paraA371V; 1,82% para T369I/V e 32,92% para A400T. No domínio RNase H a prevalência de resistência foi de 3,57%, com 2,98% para Q547K e 0,60% para I506L. As mutações A360V; N348I e Q509L não foram encontradas. A associação de mutações de resistência nos domínios C-terminais com os subtipos mostrou que o C teve menor RTD na CN (p = 0,001) às custas da substituição A400T, presente em 36% dos isolados, que teve menor prevalência neste subtipo (p =0,001) e na RNase H (p = 0,003). Conclusões: A epidemiologia molecular do HIV-1 no extremo sul do Brasil encontra-se estabilizada com predomínio do subtipo C. Este é o 1º estudo mostrando associação entre o subtipo C e a transmissão heterossexual do HIV-1 no Brasil. A prevalência de RTD na região polimerásica da TR e PR é baixa e não foi associada com os subtipos. Entretanto, nos domínios C-terminais houve associação significativa entre RTD e subtipos virais. Brazil has a program which is a model in the prevention, diagnosis and treatment of HIV-1 infections. Besides, the regional monitoring of molecular epistemology and transmitted drug resistance (TDR) are essential. The studies of HIV-1 mutations usually include protease (PR) and polymerase regions of reverse transcriptase (RT), however, recent studies have shown that mutations in the Cterminal of RT domains may contribute to primary or compensatory resistance in the presence or absence of timidine analog mutation (TAM). Regarding the HIV-1 genetic heterogeneity, the southern region has shown a pattern which is different from the whole countrys: there is predominance of subtype C, followed by B, recombined forms and subtype F1. Objectives: to evaluate the prevalence of TDR in patients who have just been diagnosed with HIV-1 infection with different viral subtypes in the very south of Brazil and to correlate these data to the demographic, behavioral, clinical and laboratorial characteristics of the population under study. Patients and methods: A transversal study with patients who had not undergone HAART (High Activity Antiretroviral Therapy), diagnosed from January 2005 to December 2008 in the university hospital that belongs to the Universidade Federal do Rio Grande, RS, was carried out. Genomic viral regions which refer to the protease (PR) and the polymerase regions, Connection (CN) and the RNase H of the reverse transcriptase (RT) were sequenced. The viral subtype was determined by using reference-sequences obtained from the Los Alamos database. Sequences in which the attributed subtype varied according to the genomic region underwent recombination analyses in the Simplot program. The research on TDR mutations was carried out in the Stanford HIV database and analyzed according to the specific TDR algorithm. In the CN and RNase H domains, the mutations that were considered in this research were: N348I; 360V; T369I/V; A371V and A400T in CN and I506L, Q509L and Q547K in RNase H. A database with the variables under study was assembled in an Excel program for further statistical analysis in Stata10.2. In order to study the association of subtypes and the mutations of resistance with the variables, the Chi square test, the Fischers exact test, the Students t-test and the Kruskal-Wallis non-parametric test were applied. Results: Molecular analyses of 245 isolates were obtained and the correlation with the clinical data was studied in 231 patients; 46.8% of them met the AIDS criteria. Subtype C was responsible for 56.3% of infections and associated with heterosexuality (p=0.001) and the highest LTCD4+ counting (p=0.02). The prevalence of TDR in the polymerase domain of PR and RT was 6.56%, with 3.45% to NRTI and NNRTI; 1.42% to IP and 1.64% MRD. In the CN region, the prevalence of resistance was 36%, with 3.65% to A371V; 1.82% to T369I/V and 32.92% to A400T. In the RNase H domain, the prevalence of resistance was 3.57%, with 2.98% to Q547K and 0.60% to I506L. Mutations A360V, N348I and Q509L were not found. The association of the mutations of resistance in the C-terminal domains with the subtypes showed that C had lower TDR in CN (p=0.001) due to the substitution A400T, present in 36% of the isolates which had lower prevalence in this subtype (p= 0.001) and in RNase H (p= 0.003). Conclusions: The molecular epidemiology of HIV-1 has been stabilized with predominance of subtype C in the very south of Brazil. This is the first study which shows the association of subtype C and the HIV-1 heterosexual transmission in Brazil. The prevalence of TDR in the polymerase region of RT and PR is low and was not associated with the subtypes. However, there was meaningful association among TDR and viral groups in the C-terminal domains.

Polymorphisms in genes that encode chemokines or their receptors can modulate susceptibility to human immunodeficiency virus (HIV) infection and disease progression. The objective of this study was to assess the frequency of polymorphisms CCR5-Δ32, CCR2-64I, CCR5-59029A and SDF1-3’A and their role in the course of HIV infection in a southern Brazilian population. Clinical data were obtained from 249 patients for an average period of 6.4 years and genotypes were determined by standard polymerase chain reaction (PCR) and PCR-restriction fragment length polymorphism. Survival analyses were conducted for three outcomes: CD4+ T-cell counts below 200 cells/ μl, acquired immune deficiency syndrome (AIDS) or death. The frequency of the polymorphisms CCR5-Δ32, CCR2- 64I, CCR5-59029A and SDF1-3’A were 0.024, 0.113, 0.487 and 0.207, respectively. CCR5-Δ32 was associated with a reduction in the risk for CD4+ T-cell depletion and with an increased risk for death after AIDS diagnosis. CCR2-64I was associated with a reduction in the risk for developing AIDS. SDF1-3’A was also associated with decreased risk for AIDS, but its effect was only evident when CCR2-64I was present as well. These results highlight the possibility of using these markers as indicators for the prognosis of disease progression and provide evidence for the importance of analysing the effects of gene polymorphisms in a combined fashion.

The aim of the study was to assess the prevalence of oral lesions in AIDS patients and identify associated factors. A cross-sectional study collected data from interviews, clinical examination, and a review of medical records for adult patients treated at the HIV/AIDS clinic in the University Hospital of the Federal University in Rio Grande, Rio Grande do Sul State, Brazil, focusing on socio- demographic, immune status, and treatment factors. Poisson regression was used in a hierarchical analytical model. From April 2006 to January 2007, 300 patients were observed (51% males; mean age 40 years). Of the total, 39% presented oral lesions, with candidiasis as the most frequent (59.1%), followed by hairy leukoplakia (19.5%). Women showed a lower risk of oral lesions, and there was an inverse association with CD4 count. Increased risk was associated with lower schooling, low income, smoking, alcohol addiction, time since HIV seroconversion, and higher viral load. The data confirm the increased prevalence of opportunistic oral lesions and show their relationship to socioeconomic conditions and modifiable habits and customs. O objetivo deste estudo foi avaliar a prevalência de lesões bucais entre pacientes HIV positivos e identificar fatores associados a tais lesões. Foi realizado estudo transversal que coletou dados mediante entrevista, exame clínico e consulta aos prontuários médicos de pacientes adultos atendidos no Serviço de HIV-AIDS do Hospital Universitário da Universidade Federal do Rio Grande, Rio Grande do Sul, Brasil, sendo considerados fatores sócio-demográficos, imunológicos e terapêuticos. Foi utilizada a regressão de Poisson num modelo hierárquico de análise. Entre abril de 2006 a janeiro de 2007 foram observados 300 pacientes, sendo 51% do sexo masculino e média de idade de 40 anos; 39% apresentaram lesões bucais, sendo a candidíase a mais freqüente (59,1%), seguida de leucoplasia pilosa (19,5%). As mulheres apresentaram um risco menor, com observância de uma associação inversa com o CD4. Houve um risco maior entre aqueles pacientes com menor escolaridade, menor renda, tabagistas, dependentes do álcool, com maior tempo de infecção pelo HIV e carga viral mais elevada. Os dados confirmaram a elevada prevalência das manifestações bucais oportunistas e evidenciaram a sua relação com a situação social, assim como sua relação com determinados hábitos e costumes passíveis de modificação.

Background: To evaluate the impact of HIV-1 CRF31_BC in the southern Brazilian HIV epidemic. Methods: Blood plasma from 284 patients was collected from July 2002 to January 2003 at 2 reference HIV/AIDS centers in southern Brazil. Viral protease and reverse transcriptase (RT) genomic regions were amplified by RT polymerase chain reaction, sequenced, and subtyped. Evolutionary analyses were performed to estimate the CRF31_BC most recent common ancestor and its population growth rate with BEAST version 1.3. Results: CRF31_BC was responsible for 7.4% of infections. The average time of HIV diagnosis and the proportion of patients on antiretroviral treatment were shorter for CRF31_BC and subtype C than for subtype B. CRF31_BC was found as early as in 1990 in the Brazilian epidemic. Evolutionary analysis of CRF31_BC revealed that it appeared immediately after the introduction of subtype C in Brazil and has been growing at a similar rate as subtype C. Conclusions: CRF31_BC plays an important role in the HIV epidemic of southern Brazil, and its prevalence has increased throughout the years. This circulating recombinant form corresponds to approximately 25% of total HIV isolates in this region in 2004. Understanding the cause of this spread is important for public health strategies in Brazil and in Latin America.

BACKGROUND: Subtype C is the most prevalent HIV-1 subtype in the world, mainly in countries with the highest HIV prevalence. However, few studies have evaluated the impact of antiretroviral therapy on this subtype. In southern Brazil, the first developing country to offer free and universal treatment, subtypes B and C co-circulate with equal prevalence, allowing for an extensive evaluation of this issue. METHODS AND FINDINGS: Viral RNA of 160 HIV-1+ patients was extracted, and the protease and reverse transcriptase genes were sequenced, subtyped and analyzed for ARV mutations. Sequences were grouped by subtype, and matched to type (PI, NRTI and NNRTI) and time of ARV exposure. Statistical analyses were performed to compare differences in the frequency of ARV-associated mutations. There were no significant differences in time of treatment between subtypes B and C groups, although they showed distinct proportions of resistant strains at different intervals for two of three ARV classes. For PI, 26% of subtype B strains were resistant, compared to only 8% in subtype C (p = 0.0288, Fisher's exact test). For NRTI, 54% of subtype B strains were resistant versus 23% of subtype C (p = 0.0012). Differences were significant from 4 years of exposure, and remained so until the last time point analyzed. The differences observed between both subtypes were independent of time under rebound viremia in cases of virologic failure and of the number of HAART regimens used by treated patients. CONCLUSIONS: Our results pointed out to a lower rate of accumulation of mutations conferring resistance to ARV in subtype C than in subtype B. These findings are of crucial importance for current initiatives of ARV therapy roll-out in developing countries, where subtype is C prevalent.

Objectives: To describe the molecular and epidemiological profile of HIV-1 in patients followed at the University Hospital of Rio Grande, Brazil. Design and methods: A cross-sectional study was conducted from September to December 2002. Plasma viral RNA of 85 patients was extracted and protease and reverse transcriptase genes were polymerase chain reaction-amplified and sequenced. Sequences were subtyped and examined to antiretroviral resistance mutations. Laboratory data and past history of antiretroviral treatment were also collected. Results: Most viruses were either subtype B (42%) or subtype C (45%). No risk behaviour, sexual orientation or laboratory parameter was associated with any specific subtype, but subtype C tended to be more frequently found in women (P ¼ 0.06). The prevalence of subtype C has increased over the HIV/AIDS epidemic, accounting for almost 60% of cases diagnosed in 2002. Intra-subtype genetic distances were smaller in subtype C than in subtype B, suggesting a more recent introduction of the former in the epidemic. Of patients under treatment, 60% had at least one antiretroviral drug resistance mutation, but no mutation was specifically associated with any HIV-1 subtype. Only one resistance mutation each was found in drug-naive patients with subtypes B and C. Conclusion: Despite the fact that subtype C appeared in southern Brazil more recently than subtype B, it is now the predominant strain in Rio Grande. The epidemic spread of subtype C could be taking place in Brazil, and possibly in south America, a phenomenon similar to that seen in other countries where this subtype is now totally dominant.

In view of the relevance of co-infection with tuberculosis and human immunodeficiency virus, this study was designed to determine tuberculosis prevalence and identify factors related to tuberculosis in patients residing in a region in which both infections are highly prevalent.All patients treated during 1999 at the HIV/AIDS Clinic of the Universidade Federal do Rio Grande (Rio Grande Federal University) University Hospital were evaluated retrospectively, from the time of human immunodeficiency virus diagnosis, in terms of the incidence of tuberculosis and its relationship to sociodemographic, behavioral and immunological factors.The sample included 204 patients, and tuberculosis prevalence was found to be 27%. The multivariate analysis showed a significant correlation between the development of tuberculosis and being of African descent (odds ratio: 4.76; 95% confidence interval: 1.93-11.72) and an inverse correlation between the development of tuberculosis and the TCD4+ lymphocyte count at the time of human immunodeficiency virus diagnosis (odds ratio: 0.995; 95% confidence interval: 0.993-0.997). When analyzed separately, other variables were found to be potential risk factors: being of the male gender (odds ratio: 2.49; 95% confidence interval: 1.15-5.39); and using illicit drugs (odds ratio: 2.1; 95% confidence interval: 1.02-4.31).The factors responsible for the development of tuberculosis among patients who are human immunodeficiency virus seropositive include immunological, socioeconomic and demographic factors. The high rate of tuberculosis prevalence among the seropositive patients underscores the urgent need to implement strategies that combine rapid identification and prompt treatment of individuals with active or latent infection, as well as of those with whom they have been in contact.

We conducted a molecular epidemiological study to investigate HIV-1 strains in Rio Grande, southern Brazil, searching for an association with transmission mode and risk behavior. Patients (185) identified at an AIDS treatment reference Hospital, from 1994 to 1997, were included; from which 107 blood samples were obtained. Nested PCR was realized once for each sample; for amplified samples (69) HIV subtypes were classified using the heteroduplex mobility assay. Subtypes identified were B (75%), C (22%) and F (3%). All infections with C were diagnosed after 1994. Comparing patients with B and C, no differences were detected regarding demographic, clinical and laboratory characteristics; survival analysis did not reveal differences in HIV to AIDS evolution. A higher proportion of injecting drug users, IDU (not significant, p

Background Although extensive HIV drug resistance information is available for the first 400 amino acids of its reverse transcriptase, the impact of antiretroviral treatment in C-terminal domains of Pol (thumb, connection and RNase H) is poorly understood. Methods and Findings We wanted to characterize conserved regions in RT C-terminal domains among HIV-1 group M subtypes and CRF. Additionally, we wished to identify NRTI-related mutations in HIV-1 RT C-terminal domains. We sequenced 118 RNase H domains from clinical viral isolates in Brazil, and analyzed 510 thumb and connection domain and 450 RNase H domain sequences collected from public HIV sequence databases, together with their treatment status and histories. Drug-naive and NRTI-treated datasets were compared for intra- and inter-group conservation, and differences were determined using Fisher's exact tests. One third of RT C-terminal residues were found to be conserved among group M variants. Three mutations were found exclusively in NRTI-treated isolates. Nine mutations in the connection and 6 mutations in the RNase H were associated with NRTI treatment in subtype B. Some of them lay in or close to amino acid residues which contact nucleic acid or near the RNase H active site. Several of the residues pointed out herein have been recently associated to NRTI exposure or increase drug resistance to NRTI. Conclusions This is the first comprehensive genotypic analysis of a large sequence dataset that describes NRTI-related mutations in HIV-1 RT C-terminal domains in vivo. The findings into the conservation of RT C-terminal domains may pave the way to more rational drug design initiatives targeting those regions.

BackgroundHuman 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.ObjectivesTo 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 designWe 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, Fisher's exact, Student's t and Kruskal–Wallis tests.ResultsTwo 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).ConclusionsThe 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.