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2.
Rev Port Cardiol ; 38(7): 463-470, 2019 07.
Artigo em Inglês, Português | MEDLINE | ID: mdl-31522936

RESUMO

INTRODUCTION: Cardiovascular (CV) risk is known to be increased in HIV-infected individuals. Our aim was to assess CV risk in HIV-infected adults. METHODS: CV risk was estimated for each patient using three different risk algorithms: SCORE, the Framingham risk score (FRS), and DAD. Patients were classified as at low, moderate or high CV risk. Clinical and anthropometric data were collected. RESULTS: We included 571 HIV-infected individuals, mostly male (67.1%; n=383). Patients were divided into two groups according to antiretroviral therapy (ART): naïve (7.5%; n=43) or under ART (92.5%; n=528). The mean time since HIV diagnosis was 6.7±6.5 years in the naive group and 13.3±6.1 years in the ART group. Metabolic syndrome (MS) was identified in 33.9% (n=179) and 16.3% (n=7) of participants in the ART and naïve groups, respectively. MS was associated with ART (OR=2.7; p=0.018). Triglycerides ≥150 mg/dl (OR=13.643, p<0.001) was one of the major factors contributing to MS. Overall, high CV risk was found in 4.4% (n=23) of patients when the SCORE tool was used, in 20.5% (n=117) using the FRS, and in 10.3% (n=59) using the DAD score. The observed agreement between the FRS and SCORE was 55.4% (k=0.183, p<0.001), between the FRS and DAD 70.5% (k=0.465, p<0.001), and between SCORE and DAD 72.3% (k=0.347, p<0.001). CONCLUSION: On the basis of the three algorithms, we detected a high rate of high CV risk, particularly in patients under ART. The FRS was the algorithm that classified most patients in the high CV risk category (20.5%). In addition, a high prevalence of MS was identified in this patient group.


Assuntos
Algoritmos , Doenças Cardiovasculares/epidemiologia , Infecções por HIV/complicações , HIV , Medição de Risco/métodos , Adolescente , Adulto , Idoso , Doenças Cardiovasculares/etiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Portugal/epidemiologia , Prevalência , Estudos Retrospectivos , Fatores de Risco , Adulto Jovem
4.
Clin Nutr ESPEN ; 18: 31-36, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29132735

RESUMO

BACKGROUND & AIMS: The Mediterranean diet (MedDiet) has been associated to a lower prevalence of metabolic syndrome (MS) and a lower cardiovascular risk (CVR). Our aim was to assess HIV infected individual's adherence to the MedDiet and its relationship with nutritional status and CVR. METHODS: Clinical and anthropometric data were collected and a nutritional assessment was performed. Adherence to the MedDiet was assessed using the questionnaire MedDietScore, ranging from 0 to 55, where higher scores indicated a higher adherence. CVR was estimated for each patient using the Framingham Risk Score (FRSs-CVD). RESULTS: We included 571 individuals, mostly males (67.1%; n = 383). MedDiet adherence score was 27.5 ± 5.5 points. The proportion of overweight/obese individuals was 40.3% (n = 230) and MS 33.9% (n = 179); CVD estimation showed that 53.2% (n = 304), 30.1% (n = 172) and 16.6% (n = 95) of patients had a low, moderate and very high CVR, respectively. The group with BMI below 25 kg/m2 presented lower adherence to MedDiet and patients within moderate CVR category and with MS presented a higher adherence to MedDiet. CONCLUSIONS: Overall we found a moderate adherence to the Mediterranean diet. A higher adherence was associated to individuals with a BMI ≥ 25 kg/m2, those with MS and to patients with moderate to high cardiovascular risk, suggesting the adoption of this food pattern in the presence of comorbidities.


Assuntos
Doenças Cardiovasculares/dietoterapia , Dieta Mediterrânea , Infecções por HIV , Cooperação do Paciente , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Fatores de Risco , Adulto Jovem
5.
J Antimicrob Chemother ; 72(10): 2869-2878, 2017 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-29091198

RESUMO

Background: CD4 cell recovery following first-line combination ART (cART) is poorer in HIV-2+ than in HIV-1+ patients. Only large comparisons may allow adjustments for demographic and pretreatment plasma viral load (pVL). Methods: ART-naive HIV+ adults from two European multicohort collaborations, COHERE (HIV-1 alone) and ACHIeV2e (HIV-2 alone), were included, if they started first-line cART (without NNRTIs or fusion inhibitors) between 1997 and 2011. Patients without at least one CD4 cell count before start of cART, without a pretreatment pVL and with missing a priori-defined covariables were excluded. Evolution of CD4 cell count was studied using adjusted linear mixed models. Results: We included 185 HIV-2+ and 30321 HIV-1+ patients with median age of 46 years (IQR 36-52) and 37 years (IQR 31-44), respectively. Median observed pretreatment CD4 cell counts/mm3 were 203 (95% CI 100-290) in HIV-2+ patients and 223 (95% CI 100-353) in HIV-1+ patients. Mean observed CD4 cell count changes from start of cART to 12 months were +105 (95% CI 77-134) in HIV-2+ patients and +202 (95% CI 199-205) in HIV-1+ patients, an observed difference of 97 cells/mm3 in 1 year. In adjusted analysis, the mean CD4 cell increase was overall 25 CD4 cells/mm3/year lower (95% CI 5-44; P = 0.0127) in HIV-2+ patients compared with HIV-1+ patients. Conclusions: A poorer CD4 cell increase during first-line cART was observed in HIV-2+ patients, even after adjusting for pretreatment pVL and other potential confounders. Our results underline the need to identify more potent therapeutic regimens or strategies against HIV-2.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Contagem de Linfócito CD4 , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-2/efeitos dos fármacos , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/virologia , Estudos de Coortes , Europa (Continente) , Feminino , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Humanos , Internacionalidade , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , Carga Viral
6.
AIDS ; 31(17): 2431-2433, 2017 11 13.
Artigo em Inglês | MEDLINE | ID: mdl-29028655

RESUMO

: Potent HIV-neutralizing antibodies are critical for vaccination and viral reservoir control. High levels of neutralizing antibodies characterize HIV-2 infection, a naturally occurring model of attenuated HIV disease with low-to-undectable viremia. We found that HIV-2-specific antibody potency increased in direct association with the loss of both switched and unswitched memory B cells in untreated HIV-2 infection. Thus, HIV antibody affinity maturation is linked to memory B-cell exhaustion even in reduced viremia settings.


Assuntos
Anticorpos Neutralizantes/sangue , Linfócitos B/imunologia , Anticorpos Anti-HIV/sangue , Infecções por HIV/imunologia , HIV-2/imunologia , Memória Imunológica , Adulto , Infecções por HIV/virologia , Humanos
7.
PLoS One ; 10(7): e0131994, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26161559

RESUMO

BACKGROUND: Single-dose nevirapine (sd-NVP) has been the main option for prevention of mother-to-child transmission (PMTCT) of HIV-1 in low-resource settings. However, sd-NVP can induce the selection of HIV-1 resistant mutations in mothers and infants. In Mozambique, there are limited data regarding the profile of NVP resistance associated mutations (RAM) in the context of PMTCT. OBJECTIVES: To assess the prevalence and the factors associated with NVP RAM among children born to HIV-1 infected mothers enrolled in the PMTCT programme adopted in Mozambique. METHODS: One hundred and fifty seven children aged 6 to 48 weeks were sequentially included (July 2011 to March 2012) at four centres in Maputo. Genotyping of RAM was performed in samples with HIV-1 RNA≥ 100 copies/µL (Viroseq). Sequencing was performed with ABI 3100 (Applied Biosystems). Logistic regression modelling was undertaken to identify the factors associated with NVP RAM. RESULTS: Seventy-nine children had their samples genotyped. Their median age was 7.0 (3-12) months and 92.4% received prophylaxis with sd-NVP at birth plus daily NVP. 35.4% of mothers received antiretrovirals (ARVs) for PMTCT. ARV RAM were detected in 43 (54.4%) of the children. 45.6% of these children had at least one NVP RAM. The most common mutations associated with NVP resistance were K103N (n = 16) and Y181C (n = 15). NVP RAM was significantly associated with mother exposure to PMTCT (crude odds ratio [OR] 30.3, 95% CI 4.93-186.34) and with mother's CD4 count < 350 cells/mm3 (crude OR 3.08, 95% CI 1.02-9.32). In the multivariable analysis the mother's exposure to PMTCT was the only variable significantly associated with NVP RAM (adjusted OR 48.65, 95% CI 9.33-253.66). CONCLUSIONS: We found a high prevalence of NVP RAM among children who were exposed to the drug regimen for PMTCT in Mozambique. The mothers' exposure to PMTCT significantly increased the risk of NVP RAM.


Assuntos
Fármacos Anti-HIV/farmacologia , Infecções por HIV/prevenção & controle , HIV-1/genética , Transmissão Vertical de Doença Infecciosa/prevenção & controle , Nevirapina/farmacologia , Fármacos Anti-HIV/uso terapêutico , Estudos Transversais , Análise Mutacional de DNA , Farmacorresistência Viral/genética , Feminino , Genes Virais , Infecções por HIV/transmissão , HIV-1/efeitos dos fármacos , Humanos , Lactente , Controle de Infecções , Masculino , Moçambique , Nevirapina/uso terapêutico
8.
J Infect Dev Ctries ; 9(1): 114-7, 2015 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-25596581

RESUMO

Neurocysticercosis (NCC) is the most common cause of acquired epilepsy in resource-poor countries. We report the case of a 24-year-old woman born and residing in Guinea-Bissau, who was transferred to Portugal two months after the onset of a possible meningitis (fever, headache, seizures, and coma) that did not respond to antibiotic treatment. The diagnosis of NCC was confirmed by MR imaging, which showed multiple lesions compatible with cysticercus, and by polymerase chain reaction (PCR) of the cerebrospinal fluid. After 28 days on albendazole and dexamethasone without improvement, she was started on praziquantel, which she completed in six weeks with progressive recovery.


Assuntos
Neurocisticercose/diagnóstico , Neurocisticercose/patologia , Anti-Helmínticos/uso terapêutico , Líquido Cefalorraquidiano/parasitologia , Feminino , Guiné-Bissau , Cabeça/diagnóstico por imagem , Humanos , Imagem por Ressonância Magnética , Neurocisticercose/tratamento farmacológico , Reação em Cadeia da Polimerase , Portugal , Praziquantel/uso terapêutico , Radiografia , Resultado do Tratamento , Adulto Jovem
9.
J Int AIDS Soc ; 17(4 Suppl 3): 19727, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25397473

RESUMO

INTRODUCTION: Metabolic syndrome (MS) is common in HIV-infected individuals and it is associated with higher cardiovascular risk (CVR). Mediterranean diet has been associated with a better metabolic control and lower CVR. MATERIALS AND METHODS: From December 2013 to May 2014, individuals between 18 and 65 years of age, who attended the outpatient HIV Clinic at the University Hospital Santa Maria, Lisbon, were selected. Adherence to Mediterranean diet was evaluated with MedDietScore, a scale from 0 to 55 that punctuates 11 food items according to the frequency of intake. Higher scores represent higher adherence. CVR was assessed using D.A.D tool (classified as low, moderate or high risk). We excluded individuals with opportunistic disease, hospitalized in the past three months or with renal disease diagnosis. All participants gave written informed consent. RESULTS: In the 571 HIV patients included, 67.1% (n=383) were male, 91.6% (n=523) Caucasian, with a mean age of 46.5±8.9 years. Patients were divided in two groups: naïve (7.5%; n=43) or on antiretroviral treatment (ART) (92.5%; n=528). Mean length of HIV diagnosis was 6.7±6.5 years (naïve) and 13.3±6.1 years (ART); TCD4+ counts were above 500 cel/mm3 in 55.8% (n=24) and 67.6% (n=357) of the patients, respectively. MS was present in 33.9% (n=179) of patients in ART group and 16.3% (n=7) in naïve group. Presence of MS was associated with ART group (OR=2.7; p=0.018). MS was also associated with older age in this group (p=0.000). Overall, mean MedDietScore was 27.3±5.5. Higher score was associated with older age (r=0.319; p=0.000). Naïve patients presented a trend to higher adherence to Mediterranean diet (65.1% vs 51.7% in naïve group; p=0.090). No relation between MS and Mediterranean diet was found. Higher CVR was associated with the presence of MS in the ART group (p=0.001). In this group, individuals with moderate CVR presented higher rates of adherence to Mediterranean diet (p=0.036) when compared to low and high CVR score. CONCLUSIONS: In this cross-sectional study, naïve individuals presented a trend to higher adherence to Mediterranean diet. On the ART group, higher adherence to Mediterranean diet was found in individuals with moderate CVR score. We think that this might suggest that this group of patients adopt this diet only in the presence of metabolic alterations or perceived CVR. Prospective studies in HIV patients are required to determine the impact of adherence to Mediterranean diet on the reduction of CVR.

10.
J Int AIDS Soc ; 17(4 Suppl 3): 19826, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25397570

RESUMO

INTRODUCTION: Recent data indicates that low vitamin D (25(OH)D) levels can lead to a worst prognosis in HIV-infected individuals, even in those on successful antiretroviral therapy (ART) [1]. Portugal is the European country that has the largest average sun exposure time but prevalence of hypovitaminosis D is mostly unknown. Our aim was to determine the prevalence of hypovitaminosis D in HIV patients in Lisbon and the possible association with ART. METHODS: From 2012 to January 2014, plasma samples from 518 HIV-infected patients were collected to 25(OH)D levels determination. Data on demographic features (age, ethnicity, country of origin) and clinical/laboratory parameters were collected from clinical files (HIV subtype, CD4+ cell count, CD4+ nadir, viral load (VL), HBV/HCV co-infection and ART). 25(OH)D status was defined as: deficiency <20 ng/mL, insufficiency 20-30 ng/mL, optimal >30 ng/mL. RESULTS: Median age was 46 years old (±11); 62.0% (321/518) were male; 81.3% (421/518) were Caucasian and 78.6% (407/518) were Portuguese. Most patients (96.1%; 498/518), were HIV-1 infected, 22.9% (114/498) and 4.0% (20/498) of them were HCV and/or HBV co-infected, respectively. Mean CD4+ cell count was 648 cells/µL (±333) and nadir was 219 cells/µL (±179). On treated patients VL was <40 HIV RNA/mL in 86.7% (417/481). The median levels of 25(OH)D was 20.0 ng/mL (range 4.1-99.7) and we found differences between values observed during Winter (median 16.7 ng/mL) and Summer (median 24.9 ng/mL) (p<0.0001). Low 25(OH)D levels were not correlated to ethnicity (p=0.066). 25(OH)D level was <30 ng/mL in 80.1% (415/518) of the patients, from which 30.9% (160/518) and 49.2% (255/518) had insufficiency and deficiency levels, respectively. Most (92.9%; 481/518) were on ART: regimens containing PI (47.5%), NNRTI (40.3%; 41.3% on NVP and 58.7% on EFV), II (1.2%), PI+NNRTI (3.9%). Comparing the 25(OH)D level along the different ART regimens (PI vs NVP; PI vs EFV; PI vs no ART) there were differences between PI and EFV (p=0.044). CONCLUSIONS: In this study, 80.1% of the HIV-infected patients had hypovitaminosis D and ART regimens with EFV were more often associated with low 25(OH)D levels. Understanding the impact of the different antiretroviral drugs on 25(OH)D status could help to decide in clinical practice whether 25(OH)D supplementation or drug switch are the best options for each patient.

11.
J Infect Dev Ctries ; 7(3): 269-72, 2013 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-23493006

RESUMO

INTRODUCTION: Three major public health problems, tuberculosis, malaria and HIV/AIDS, are widespread in Angola, often as co-infections in the same individual. In 2009, it was assumed that 44,151 new cases of TB occurred in Angola. Interestingly, interventions such as treatment/prevention of malaria appear to reduce mortality in HIV-infected and possibly TB co-infected patients. However, despite the seriousness of the situation, current data on TB and co-infection rates are scarce. This study aimed to characterize all TB cases seen at the Hospital Sanatório de Luanda, and to determine the co-infection rate with HIV and/or malaria. METHODOLOGY: This retrospective study collected demographic, diagnostic and clinical data from all patients admitted during 2007. RESULTS: A total of 4,666 patients were admitted, of whom 1,906 (40.8%) were diagnosed with TB. Overall, 1,111 patients (58.3%) were male and most patients (n=1302, 68.3%) were adults (≥ 14 years). The rate of HIV co-infection was 37.4% (n=712). Malaria was diagnosed during admission and hospital stay in 714 patients (37.5%), with Plasmodium falciparum the predominant species. Overall mortality was 15.2% (n=290). CONCLUSIONS: Because Luanda does not have the infrastructure to perform culture-based diagnosis of TB, confirmation of TB is problematic. The HIV-co-infection rate is high, with 37.4% of patients requiring integrated approaches to address this problem. With more than 1/3 of the TB patients co-infected with malaria, even during the hospital stay, the prevention of malaria in TB patients appears to be an effective way to reduce overall mortality.


Assuntos
Coinfecção/epidemiologia , Infecções por HIV/complicações , Infecções por HIV/epidemiologia , Malária Falciparum/complicações , Malária Falciparum/epidemiologia , Tuberculose/complicações , Tuberculose/epidemiologia , Adolescente , Adulto , Idoso , Angola/epidemiologia , Criança , Pré-Escolar , Feminino , Hospitais , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Adulto Jovem
12.
J Infect Dis ; 207(11): 1730-42, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23460749

RESUMO

Monocytes and myeloid dendritic cells (mDCs) are important orchestrators of innate and human immunodeficiency virus (HIV)-specific immune responses and of the generalized inflammation that characterizes AIDS progression. To our knowledge, we are the first to investigate monocyte and mDC imbalances in HIV type 2 (HIV-2)-positive patients, who typically feature reduced viremia and slow disease progression despite the recognized ability of HIV-2 to establish viral reservoirs and overcome host restriction factors in myeloid cells. We found a heightened state of monocyte and mDC activation throughout HIV-2 infection (characterized by CD14(bright)CD16(+) expansion, as well as increased levels of soluble CD14, HLA-DR, and CD86), together with progressive mDC depletion. Importantly, HIV-2-positive patients also featured overexpression of the inhibitory molecule PD-L1 on monocytes and mDCs, which may act by limiting the production of proinflammatory molecules. These data, from patients with a naturally occurring form of attenuated HIV disease, challenge current paradigms regarding the role of monocytes in HIV/AIDS and open new perspectives regarding potential strategies to modulate inflammatory states.


Assuntos
Células Dendríticas/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , HIV-2/imunologia , HIV-2/patogenicidade , Monócitos/imunologia , Adulto , Idoso , Antígenos CD/análise , Antígeno B7-H1/análise , Células Dendríticas/química , Feminino , Antígenos HLA-DR/análise , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Monócitos/química , Adulto Jovem
13.
J Antimicrob Chemother ; 68(4): 911-4, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23228933

RESUMO

OBJECTIVES: Despite a decreasing mortality and morbidity in treated HIV-1 patients, highly active antiretroviral treatment (HAART) can still fail due to the development of drug resistance. Especially, multidrug-resistant viruses pose a threat to efficient therapy. We studied the changing prevalence of multidrug resistance (MDR) over time in a cohort of HIV-1-infected patients in Portugal. PATIENTS AND METHODS: We used data of 8065 HIV-1-infected patients followed from July 2001 up to April 2012 in 22 hospitals located in Portugal. MDR at a specific date of sampling was defined as no more than one fully active drug (excluding integrase and entry inhibitors) at that time authorized by the Portuguese National Authority of Medicines and Health Products (INFARMED), as interpreted with the Rega algorithm version 8.0.2. A generalized linear mixed model was used to study the time trend of the prevalence of MDR. RESULTS: We observed a statistically significant decrease in the prevalence of MDR over the last decade, from 6.9% (95% CI: 5.7-8.4) in 2001-03, 6.0% (95% CI: 4.9-7.2) in 2003-05, 3.7% (95% CI: 2.8-4.8) in 2005-07 and 1.6% (95% CI: 1.1-2.2) in 2007-09 down to 0.6% (95% CI: 0.3-0.9) in 2009-12 [OR=0.80 (95% CI: 0.75-0.86); P<0.001]. In July 2011 the last new case of MDR was seen. CONCLUSIONS: The prevalence of multidrug-resistant HIV-1 is decreasing over time in Portugal, reflecting the increasing efficiency of HAART and the availability of new drugs. Therefore, in designing a new drug, safety and practical aspects, e.g. less toxicity and ease of use, may need more attention than focusing mainly on efficacy against resistant strains.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Mutação de Sentido Incorreto , Portugal/epidemiologia , Prevalência , Proteínas Virais/genética
14.
J Antimicrob Chemother ; 68(1): 190-2, 2013 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-22977160

RESUMO

OBJECTIVES: To investigate mutations selected in viruses from HIV-2-infected patients failing a highly active antiretroviral treatment (HAART) regimen including atazanavir/ritonavir. METHODS: Twenty-eight HIV-2-infected patients previously exposed to atazanavir/ritonavir and failing therapy were studied. The protease (PR) gene was amplified and sequenced, and mutations emerging under atazanavir/ritonavir selective pressure were reported. RESULTS: The I50L mutation emerged in 4 out of 28 HIV-2-infected patients failing a HAART regimen including atazanavir/ritonavir. Besides I50L, four PR mutations previously associated with protease inhibitor resistance (I54L, I64V, V71I and I82F) and six PR mutations of unknown impact (V10I, E37D, S43T, K45R, I75V and F85L) in HIV-2 were also identified in this small group of patients. CONCLUSIONS: Several mutations were associated with virological failure of a regimen including atazanavir/ritonavir in HIV-2-infected patients, including I50L for the first time. It should be included in HIV-2 algorithms for interpretation of genotypic resistance data, and taken into account when making therapeutic decisions for HIV-2-infected patients.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/genética , HIV-2/genética , Mutação/genética , Oligopeptídeos/uso terapêutico , Piridinas/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Sulfato de Atazanavir , Humanos , Ritonavir/uso terapêutico , Falha de Tratamento
15.
AIDS ; 26(9): 1065-71, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-22441249

RESUMO

OBJECTIVE: Hyper-immune activation is a main determinant of HIV disease progression, potentially counter-acted by T-cell inhibitory pathways. Here we investigated, for the first time, inhibitory molecules in HIV-2 infection, a naturally occurring attenuated form of HIV disease, associated with reduced viremia and very slow rates of CD4 T-cell decline. DESIGN: Programmed death (PD)-1/PD-L1, an important pathway in limiting immunopathology, and its possible relationship with T-cell immunoglobulin and mucin-domain containing molecule-3 (TIM-3), a recently identified inhibitory molecule, were studied in untreated HIV-2 and HIV-1 cohorts, matched for degree of CD4 T-cell depletion, and noninfected individuals. METHODS: Flow cytometric analysis of T-cell expression of PD-1, PD-L1 and TIM-3, combined with markers of cell differentiation, activation, cycling and survival. Statistical analysis was performed using ANOVA, Mann-Whitney/Wilcoxon tests, Spearman's correlations, multiple linear regressions and canonical correlation analysis. RESULTS: T-cell expression of PD-1 and PD-L1 was tightly associated and directly correlated with CD4 T-cell depletion and immune activation in HIV-2 infection. No such correlation was found for PD-L1 expression in HIV-1-positive patients. Central memory and intermediate memory cells, rather than terminally differentiated T-cells, expressed the highest levels of both PD-1 and PD-L1 molecules. Conversely, TIM-3 expression was independent of T-cell differentiation and dissociated from cell cycling, suggesting distinct induction mechanisms. Importantly, in contrast with HIV-1, no significant increases in TIM-3 expression were found in the HIV-2 cohort. CONCLUSIONS: Our data suggest that PD-1/PD-L1 molecules, rather than markers of T-cell exhaustion, may act as modulators of T-cell immune activation, contributing to the slower course of HIV-2 infection. These data have implications for the design of antiretroviral therapy-complementary immune-based strategies.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/imunologia , HIV-2/imunologia , Biomarcadores Tumorais/metabolismo , Estudos de Casos e Controles , Infecções por HIV/metabolismo , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Proteínas de Membrana/metabolismo , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/metabolismo , Regulação para Cima
16.
AIDS Res Hum Retroviruses ; 28(5): 510-22, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21902592

RESUMO

Our aim was to characterize for the first time the genetic diversity of HIV in Cape Verde Islands as well as the drug resistance profiles in treated and untreated patients. Blood specimens were collected from 41 HIV-1 and 14 HIV-2 patients living in Santiago Island. Half of the patients were on antiretroviral treatment (ART). Pol and env gene sequences were obtained using in-house methods. Phylogenetic analysis was used for viral subtyping and the Stanford Algorithm was used for resistance genotyping. For HIV-1, the amplification of pol and env was possible in 27 patients (66%). HIV-1 patients were infected with subtypes G (13, 48%), B (2, 7%), F1 (2, 7%), and CRF02_AG (2, 7%), and complex recombinant forms including a new C/G variant (n=8, 30%). Drug resistance mutations were detected in the PR and RT of three (10%) treated patients. M41L and K103N transmitted drug resistance mutations were found in 2 of 17 (12%) untreated patients. All 14 HIV-2 isolates belonged to group A. The origin of 12 strains was impossible to determine whereas two strains were closely related to the historic ROD strain. In conclusion, in Cape Verde there is a long-standing HIV-2 epidemic rooted in ROD-like strains and a more recent epidemic of unknown origin. The HIV-1 epidemic is caused by multiple subtypes and complex recombinant forms. Drug resistance HIV-1 strains are present at moderate levels in both treated and untreated patients. Close surveillance in these two populations is crucial to prevent further transmission of drug-resistant strains.


Assuntos
Farmacorresistência Viral/genética , Soropositividade para HIV/genética , HIV-1/genética , HIV-2/genética , Adolescente , Adulto , Fármacos Anti-HIV/uso terapêutico , Cabo Verde/epidemiologia , Criança , Feminino , Variação Genética , Genótipo , Soropositividade para HIV/tratamento farmacológico , Soropositividade para HIV/epidemiologia , HIV-1/isolamento & purificação , HIV-2/isolamento & purificação , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Filogenia , Adulto Jovem , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética , Produtos do Gene pol do Vírus da Imunodeficiência Humana/genética
17.
Germs ; 2(2): 43-59, 2012 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-24432263

RESUMO

INTRODUCTION: Q fever is a worldwide zoonosis caused by Coxiella burnetii. The main characteristic of acute Q fever is its clinical polymorphism, usually presenting as a febrile illness with varying degrees of hepatitis and/or pneumonia. Q fever is endemic in Portugal, and it is an obligatory notifiable disease since 1999. However, its epidemiological and clinical characteristics are still incompletely described. METHODS: We performed a retrospective study of 32 cases admitted in the Infectious Diseases Department, Santa Maria's University Hospital, from January 2001 to December 2010, in whom acute Q fever was diagnosed by the presence of antibodies to phase II Coxiella burnetii antigens associated with a compatible clinical syndrome. RESULTS: Out of the 32 cases recorded, 29 (91%) were male, with a male:female ratio of 9.7:1. Individuals at productive age were mainly affected (88%, n=28, with ages between 25 and 64 years). Clinically, the most common manifestation of acute Q fever was hepatic involvement (84%, n=27), which occurred isolated in 53% (n=17) of the cases. Hepatitis was more severe, presenting with higher values of liver function tests, in patients presenting both pulmonary and hepatic involvement. Additionally, we report one case of myocarditis and another one with neurological involvement. Empiric but appropriate antibiotic therapy was given in 66% (n=21) of the cases. There was a complete recovery in 94% (n=30) of the patients, and one death. We confirmed the sub-notification of this disease in Portugal, with only 47% (n=15) of the cases notified. CONCLUSION: In Portugal further studies are needed to confirm our results. From the 32 cases studied, acute Q fever presented more frequently as a febrile disease with hepatic involvement affecting mainly young male individuals. Furthermore, acute Q fever is clearly underdiagnosed and underreported in Portugal, which suggests that an increased awareness of the disease is needed, together with a broader use of serological testing.

18.
Clin Infect Dis ; 52(10): 1257-66, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21507923

RESUMO

BACKGROUND: Triple nucleoside reverse-transcriptase inhibitors (NRTIs) are recommended by the World Health Organization as first-line regimen in treatment-naïve HIV-2-infected patients. However, ritonavir-boosted protease inhibitor (PI/r)-containing regimens are frequently prescribed. In the absence of previous randomized trials, we retrospectively compared these regimens in observational cohorts. METHODS: HIV-2-infected patients from 7 European cohorts who started triple NRTI or PI/r since January 1998 were included. Piecewise linear models were used to estimate CD4 cell count and plasma HIV-2 RNA level slopes, differentiating an early phase (until end of month 3) and a second phase (months 4-12). On-treatment analyses censored data at major treatment modification and systematically at month 12. RESULTS: Forty-four patients started triple NRTI therapy and 126 started PI/r therapy. Overall, the median CD4 cell count was 191 cells/mm(3) and the median plasma HIV-2 RNA level was ≥2.7 log(10) copies/ml in 61% of the patients at combination antiretroviral therapy (cART) initiation; the median duration of the first cART was 20 months, not differing between groups. PI/r regimens were associated with better CD4 cell count and HIV-2 RNA level outcomes, compared with NRTI regimens. Estimated CD4 cell count slopes were +6 and +12 cells/mm(3)/month during the early phase (P = .22), and -60 cells/mm(3)/year versus +76 cells/mm(3)/year during the second phase (P = .002), for triple NRTI and PI/r, respectively. Estimated mean HIV-2 RNA levels at month 12 in patients with detectable viremia at cART initiation were 4.0 and 2.2 log(10) copies/ml, respectively (P = .005). CONCLUSIONS: In this observational study, PI/r-containing regimens showed superior efficacy over triple NRTI regimens as first-line therapy in HIV-2-infected patients.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/administração & dosagem , HIV-2/isolamento & purificação , Inibidores da Transcriptase Reversa/administração & dosagem , Ritonavir/administração & dosagem , Adulto , Contagem de Linfócito CD4 , Europa (Continente) , Infecções por HIV/virologia , Humanos , RNA Viral/sangue , Estudos Retrospectivos , Resultado do Tratamento , Carga Viral
19.
J Virol ; 85(5): 2429-38, 2011 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-21159859

RESUMO

Viremia is significantly lower in HIV-2 than in HIV-1 infection, irrespective of disease stage. Nevertheless, the comparable proviral DNA burdens observed for these two infections indicate similar numbers of infected cells. Here we investigated this apparent paradox by assessing cell-associated viral replication. We found that untreated HIV-1-positive (HIV-1(+)) and HIV-2(+) individuals, matched for CD4 T cell depletion, exhibited similar gag mRNA levels, indicating that significant viral transcription is occurring in untreated HIV-2(+) patients, despite the reduced viremia (undetectable to 2.6 × 10(4) RNA copies/ml). However, tat mRNA transcripts were observed at significantly lower levels in HIV-2(+) patients, suggesting that the rate of de novo infection is decreased in these patients. Our data also reveal a direct relationship of gag and tat transcripts with CD4 and CD8 T cell activation, respectively. Antiretroviral therapy (ART)-treated HIV-2(+) patients showed persistent viral replication, irrespective of plasma viremia, possibly contributing to the emergence of drug resistance mutations, persistent hyperimmune activation, and poor CD4 T cell recovery that we observed with these individuals. In conclusion, we provide here evidence of significant ongoing viral replication in HIV-2(+) patients, further emphasizing the dichotomy between amount of plasma virus and cell-associated viral burden and stressing the need for antiretroviral trials and the definition of therapeutic guidelines for HIV-2 infection.


Assuntos
Linfócitos T CD4-Positivos/virologia , Linfócitos T CD8-Positivos/virologia , Infecções por HIV/virologia , HIV-2/fisiologia , Carga Viral , Viremia/virologia , Replicação Viral , Adulto , Idoso , Fármacos Anti-HIV/uso terapêutico , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Estudos de Coortes , Feminino , Infecções por HIV/tratamento farmacológico , Infecções por HIV/imunologia , HIV-2/genética , Humanos , Masculino , Pessoa de Meia-Idade , Viremia/tratamento farmacológico , Viremia/imunologia , Adulto Jovem
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