RESUMO
Objectives: To analyse lipid changes and tolerability in a cohort of HIV-infected patients who switched their antiretroviral regimens to rilpivirine/emtricitabine/tenofovir (RPV/FTC/TDF) in a real-world setting. Methods: PRO-STR is a 48 week prospective observational post-authorization study in 25 hospitals. Patients with a viral load <1000 copies/mL, receiving at least 12 months of combination ART (cART), with constant posology for at least the prior 3 months, were categorized according to previous treatment [NNRTI or ritonavir-boosted PI (PI/r)]. Analytical tests were performed at the baseline visit, between week 16 and week 32, and at week 48. Results: A total of 303 patients were included (mean age 46.6 years; male 74.0%; previous treatment 74.7% NNRTI and 25.3% PI/r). Both groups exhibited significantly reduced lipid profiles, except for HDL cholesterol, for which a non-significant increase was observed. [NNRTI patients: total cholesterol (baseline: 195.5â±â38.4 mg/dL; week 48: 171.0â±â35.5 mg/dL), total cholesterol/HDL ratio (baseline: 4.2â±â1.2; week 48: 4.0â±â1.2), HDL (baseline: 49.1â±â12.0 mg/dL; week 48: 49.2â±â45.8 mg/dL), LDL (baseline: 119.2â±â30.2 mg/dL; week 48: 114.2â±â110.7 mg/dL), and triglycerides (baseline: 136.6â±â86.8 mg/dL; week 48: 113.4â±â67.8 mg/dL); PI/r patients: total cholesterol (baseline: 203.2â±â48.8 mg/dL; week 48: 173.4â±â36.9 mg/dL), total cholesterol/HDL ratio (baseline: 4.7â±â1.6; week 48: 4.0â±â1.2), HDL (baseline: 46.4â±â12.5 mg/dL; week 48: 52.1â±â54.4 mg/dL), LDL (baseline: 127.0â±â36.3 mg/dL; week 48: 111.4â±â35.8 mg/dL), and triglycerides (baseline: 167.6â±â107.7 mg/dL; week 48: 122.7â±â72.1 mg/dL)]. The most common intolerances were neuropsychiatric in the NNRTI patients and gastrointestinal and metabolic in the PI/r patients, and these intolerances were significantly reduced in both groups at week 48 [NNRTI: neuropsychiatric (baseline: 81.3%; week 48: 0.0%); PI/r: gastrointestinal (baseline: 48.7%; week 48: 0.0%) and metabolic (baseline: 42.1%; week 48: 0.0%)]. Conclusions: RPV/FTC/TDF improved the lipid profiles and reduced the intolerances after switching from NNRTI or PI-based regimens, in a cohort of HIV-infected patients.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Substituição de Medicamentos , Dislipidemias/patologia , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Lipídeos/sangue , Adulto , Emtricitabina/administração & dosagem , Feminino , Humanos , Masculino , Estudos Prospectivos , Rilpivirina/administração & dosagem , Tenofovir/administração & dosagem , Carga ViralRESUMO
OBJECTIVES: To present clinical experience with a regimen including abacavir/lamivudineâ+âdarunavir/ritonavir in a cohort of HIV-1-infected patients. METHODS: A retrospective, multicentre cohort study, including all consecutive adult HIV-1-infected patients who started abacavir/lamivudineâ+âdarunavir/ritonavir from April 2008 to December 2010 and had at least one follow-up visit. The primary endpoint was HIV-1 viral load (VL) <40 copies/mL at week 48. RESULTS: One hundred and eighty-three patients (42 naive and 141 experienced) from 19 hospitals in Spain were studied. The median follow-up was 26.7 (0.5-58.6) months, 79.8% were men, the median age was 47.1 (21.4-80.5) years, 26.2% had AIDS and 38.8% were positive for hepatitis C virus. At baseline, the median CD4 count was 246 cells/mm(3) in naive patients and 393 cells/mm(3) in experienced patients and the median VL was 4.80 and <1.59 log copies/mL, respectively. At week 48, 81.8% of naive patients and 84.2% of experienced patients receiving the regimen reached a VL <40 copies/mL, whereas at 96 weeks this occurred in 90.5% and 92.8%, respectively. CD4 cell count increases at 48 and 96 weeks were +176.5 and +283.5 cells/mm(3) in naive patients and +74.9 and +93 cells/mm(3) in experienced patients, respectively. Overall, 86 (47%) patients discontinued the study regimen, in many cases possibly related to non-medical reasons, such as drug switches to reduce cost or changes in address due to economic constraints. Three patients died of causes unrelated to therapy and 19 (10.4%) discontinued the regimen due to adverse events. CONCLUSIONS: In our cohort, abacavir/lamivudineâ+âdarunavir/ritonavir was safe, well tolerated and achieved high rates of virological suppression. In a proportion of patients, discontinuation of this effective regimen was possibly due to non-medical reasons.
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Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Didesoxinucleosídeos/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Ritonavir/uso terapêutico , Sulfonamidas/uso terapêutico , Adulto , Idoso , Idoso de 80 Anos ou mais , Fármacos Anti-HIV/efeitos adversos , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Estudos de Coortes , Darunavir , Didesoxinucleosídeos/efeitos adversos , Combinação de Medicamentos , Feminino , HIV-1/isolamento & purificação , Humanos , Lamivudina/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Ritonavir/efeitos adversos , Espanha , Sulfonamidas/efeitos adversos , Resultado do Tratamento , Carga Viral , Adulto JovemRESUMO
PURPOSE: To determine whether immigrant status is associated with late initiation of highly active antiretroviral treatment (HAART) and/or poor response to antiretrovirals. METHODS: GESIDA 5808 is a multicenter, retrospective cohort study (inclusion period January 2005 through December 2006) of treatment-naïve patients initiating HAART that compares HIV-infected patients who are immigrants with Spanish-born patients. A late starter (LS) was defined as any patient starting HAART with a CD4+ lymphocyte count <200 cells/µL and/or diagnosis of an AIDS-defining illness before or at the start of therapy. The primary endpoint was time to treatment failure (TTF), defined as virological failure (VF), death, opportunistic infection, treatment discontinuation/switch (D/S), or missing patient. Secondary endpoints were time to treatment failure as observed data (TTO; censoring missing patients) and time to virological failure (TVF; censoring missing patients and D/S not due to VF). RESULTS: LS accounted for 56% of the patients. Lower educational and socioeconomic level and intravenous drug use (IVDU) were associated with categorization as LS, but immigrant status was not. Cox regression analysis (hazard ratio [HR]; 95% CI) between LS and non-LS patients showed no differences in TTF (0.97; 0.78-1.20) or TTO (1.18; 0.88-1.58), although it did reveal a difference in TVF (1.97; 1.18-3.29). CD4+ lymphocyte recovery was equivalent for both LS and non-LS patients (159 vs 173). CONCLUSIONS: In our cohort, immigrant status was not shown to be related to late initiation of HAART. Although LS patients did not have a longer TTF for any reason, TVF was significantly shorter. Despite universal free access to HAART in Spain, measures to ensure early diagnosis and treatment of HIV infection are necessary.
Assuntos
Fármacos Anti-HIV/administração & dosagem , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , HIV/crescimento & desenvolvimento , Adulto , Estudos de Coortes , Emigrantes e Imigrantes , Feminino , Infecções por HIV/imunologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Espanha , Falha de Tratamento , Carga ViralRESUMO
BACKGROUND AND AIMS: Dietary counseling and oral supplementation have unclear results in preventing the progressive weight loss in human deficiency virus (HIV)-infection. The aim of the study was to compare the progression of nutritional indicators with or without a formula enriched with n-3 fatty acids. PATIENTS AND METHODS: 30 HIV patients were enrolled. 15 were randomized to group I (standard formula) and 15 were randomized to group II (formula enriched with n-3 fatty acids). A nutritional evaluation was realized at basal time and at 3 months. RESULTS: An increase in protein and calories intakes was detected in both. There was a significant increase in n3 fatty acid intake from baseline in group II, without statistical changes in group I. Treatment with both supplements resulted in a significant and sustained increase in weight (4.5% in group I and 5.4%, in group II). This increase was mostly due to fat free mass in group I. In group II it was due to an increase in fat free mass and fat mass. CONCLUSIONS: Oral nutritional supplements for a 3-months period were well tolerated and resulted in body weight gain in HIV-infected patients with previous weight loss.
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Nutrição Enteral/métodos , Ácidos Graxos Ômega-3/uso terapêutico , Infecções por HIV/complicações , Redução de Peso/efeitos dos fármacos , Adulto , Assistência Ambulatorial , Proteínas Alimentares/administração & dosagem , Suplementos Nutricionais , Ingestão de Energia , Ácidos Graxos Ômega-3/administração & dosagem , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Tempo , Resultado do Tratamento , Aumento de Peso/efeitos dos fármacosRESUMO
BACKGROUND: The intestinal wall integrity is central to the barrier function and depends on the balance of proliferation/apoptosis. Short bowel (SB) or Parenteral Nutrition (PN) induce high bacterial translocation (BT) probably by the intestinal barrier bug. Probiotics or minimal enteral nutrition (MEN) have reduced BT in animal models. OBJECTIVE: Determine in two BT animal models (SB or PN) the effect of MEN or probiotics on proliferation and apoptosis rates of the intestinal wall. METHODS: Seventy-one Wistar rats, divided into 4 groups: 1) PN (N = 23): parenteral nutrition; 2) PNMEN (N = 16): PN + MEN (2.9 g/100 g/day standard diet); 3) RES (N = 15): 80% bowel resection and standard oral diet; 4) RESPROB (N = 17): RES + probiotics (7 X 10(9) CFU Bifidobacterium lactis). After 10 days in metabolic cages, mesenteryc lymph nodes, portal blood and peripheral blood were cultured. By immunohistochemistry, proliferation and apoptosis index were calculated as well as the proliferation-apoptosis rate. RESULTS: BT: decreased in PNMEN (45%) and RESPROB groups (35%) versus PN (65%) and RES (67%) groups (p<0.05). Proliferation index: was better in PNMEN (12,07) and RESPROB (13,93) groups than PN (7,45) and RES (5,54) groups. (p0.05). Apoptosis index: PNMEN group had 7,81 and PN group 14,90. (p<0,05). Proliferation-apoptosis rate: was higher in PNMEN (1,54) and RESPROB (1,67) groups than PN (0,50) ans RES (0,71) groups. (p<0.01). CONCLUSIONS: MEN and probiotics reduce BT and improve cellular renewal by encouraging the proliferation. MEN also prevents apoptosis.
Assuntos
Apoptose/fisiologia , Translocação Bacteriana , Proliferação de Células , Nutrição Enteral , Intestino Delgado/fisiologia , Probióticos/farmacologia , Adaptação Fisiológica , Animais , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Nutrição Enteral/métodos , Intestino Delgado/citologia , Intestino Delgado/microbiologia , Masculino , Ratos , Ratos Wistar , Síndrome do Intestino Curto/microbiologia , Síndrome do Intestino Curto/patologia , Síndrome do Intestino Curto/terapiaRESUMO
BACKGROUND: Bacterial overgrowth occuring after massive bowel resection, facilitates Gram-negative intestinal Bacterial Translocation (TB). Probiotic agents might have beneficial effects on TB. On the other hand, polymerase chain-reaction (PCR) has better sensitivity than conventional methods for bacterial detection and has not been investigated in experimental models of short bowel syndrome and TB. OBJECTIVE: To test the hypothesis that the administration of Bifidobacterium lactis (BL) decreases Escherichia coli Bacterial Translocation (ECTB) in experimental short bowel syndrome and to confirm the better sensitivity of PCR technique to detect ECTB. METHODS: Adult Wistar rats, orally fed with standard rat chow and tap water "ad libitum", were maintained in individual metabolic cages for ten days and divided into three groups: Control (n = 15): non-manipulated animals. RES (n = 15): 80% gut resection. Daily administration 1 ml of sterile water, after orogastric intubation. RES-PRO (n = 18): same resection and daily administration of 7.8 x10(9) Bifidobacterium lactis Colony Forming Units (CFU). At the end of the experiment, mesenteric lymph nodes (MLN), and both peripheral and portal blood samples were recovered and cultured by standard procedures. Also, genomic DNA from E. coli was detected by PCR technique. RESULTS: By conventional cultures ECTB was detected in 0% in the control group, 73% in the RES group and 33% in the RES-PRO group. PCR technique detected ECTB in 47% of the control group, 87% of the RES group and 33% of RES-PRO group, showing higher sensitivity. By both methods, animals receiving BL (RES-PRO group) showed less ECTB. By conventional culture, the relative risk (RR) was 0.45 (95% CI 0,22-0,79) and the number needed to treat (NNT) was 3 (95% CI 0-11). By PCR technique, the RR was 0.38 (95% CI 0.19-0.76), and the NNT 2 (95% CI 0-4). CONCLUSIONS: 1) Administration of Bifidobacterium lactis reduces the incidence of ECTB. 2) PCR technique is a more sensitive method for ECTB detection.
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Translocação Bacteriana , Reação em Cadeia da Polimerase , Síndrome do Intestino Curto/microbiologia , Animais , Ratos , Ratos WistarRESUMO
The fight against infection and liver disease associated with parenteral nutrition (PN) are surely two of the most problematic aspects in the management of paediatric patients with short bowel syndrome (SBS). In the Research Unit of Donostia Hospital, we have spent the past 15 years investigating different ways of reducing these complications in an experimental model of short bowel in the Wistar rat (resection of 80% of the small bowel, with and without PN). All the experiments had a duration of 10 days and 323 animals reached the end of the study period. Nine groups were established in which some type of intervention was performed, and there were 8 control groups. The interventions were: 3 dietary (minimal enteral nutrition [MEN] with low or high dose probiotics); 5 pharmacological (administration of growth hormone [GH], epidermal growth factor [EGF], insulin, cholecystokinin [CCK], and selective intestinal decontamination [SID]); and 1 surgical (resection of the ileocaecal valve). Infection due to bacterial translocation (BT) was detected by culture of mesenteric lymph nodes, portal blood and peripheral blood, and liver damage by the levels of proinflammatory cytokines (IL-1 and TNF-alpha). In summary, our results are: Probiotics, MEN and SID reduce BT. Liver damage was milder in the groups with MEN, SID and CCK. The groups receiving GH, EGF or insulin presented a higher incidence of BT. BT was lower after resection of the ileocaecal valve. In conclusion, the probiotics, MEN and CCK could be useful in the management of children with SBS. These data confirm the utility of this experimental model of short bowel for the investigation of different aspects of SBS.
Assuntos
Síndrome do Intestino Curto/prevenção & controle , Animais , Translocação Bacteriana , Masculino , Ratos , Ratos Wistar , PesquisaRESUMO
INTRODUCTION: Total parenteral nutrition (TPN) is not free of complications. One of the most serious is cholestasis; the cause of this complication is unclear but it may be due to a lack of an enteral stimulus for cholecystokinin (CCK) production. CCK is essential for contraction of the gallbladder and also stimulates intrahepatic bile flow. Its absence may contribute to cholestasis. After any hepatic aggression, the Kupffer cells respond and release proinflammatory cytokines, such as interleukin-1 (IL-1) and tumour necrosis factor alpha (TNF-alpha), which increase the hepatic damage. The objective of this experimental study has been to observe the effect that the exogenous administration of CCK could have on hepatic damage in experimental short bowel with and without TPN, determined using the serum levels of IL-1 and TNF-alpha. MATERIAL AND METHODS: A resection of 80% of the small bowel was performed on 53 Wistar rats and a continuous infusion of saline or TPN was initiated. The rats were divided into the following groups: SHAM (N = 14): normal saline infusion and free access to food and water. TPN (N = 15): Standard TPN. SHAM-CCK (N = 14): same as the SHAM group but with a daily dose of CCK. TPN-CCK (N = 10): same as the TPN group but with a daily dose of CCK. At the end of the experiment, the animals were sacrificed and blood samples were obtained to determine the IL-1 and TNF-alpha values by ELISA. RESULTS: The IL-1 and TNF-alpha levels were higher in the TPN group (7.537 and 5.899 pg/mL, respectively) than in the SHAM group (6.509 and 4.989 pg/mL, respectively) (p > 0.05). The TNF-alpha values were higher in the SHAM group (4.989 pg/mL) than in the SHAM-CCK group (4.583 pg/mL) (p < 0.001). The IL-1 and TNF-alpha levels were higher in the TPN group than in the TPN-CCK group (6.709 and 4.794 pg/mL, respectively) (p < 0.001 for TNF-alpha). CONCLUSIONS: 1. There is a rise in the serum levels of the pro-inflammatory cytokines IL-1 and TNF-alpha in animals with short bowel on TPN or enteral nutrition. 2. The administration of CCK causes a fall in the IL-1 and TNF-alpha levels, and could be used such as a further measure to prevent TPN-associated cholestasis.
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Colecistocinina/uso terapêutico , Colestase/etiologia , Colestase/prevenção & controle , Nutrição Parenteral Total/efeitos adversos , Animais , Colestase/sangue , Interleucina-1/sangue , Ratos , Ratos Wistar , Síndrome do Intestino Curto , Fator de Necrose Tumoral alfa/sangueRESUMO
Selective intestinal decontamination (SID) has been useful restraining Bacterial translocation (BT) in both animal models and human clinics. The not well known parenteral nutrition-related liver disease is a serious problem associated to short bowel and long-term parenteral nutrition (PN) use, and BT is also frequent in those patients. Germs reach liver through portal vein and activate Kupffer cells, which release cytokines as IL-1 or TNF-alpha. The aim of this study was to test the use of SID restraining BT in a PN undergoing experimental short bowel model, and its possible favourable consequences on hepatic injury determined by IL-1 and TNF-alpha levels. Twenty-five 240-280 g Wistar rats were divided into two groups and maintained in individual metabolic cages for ten days: Resection-PN group (n=15): animals with a bowel resection of the 80% and a continuous PN infusion. Resection-PN-SID (n=10) group: similar to previous group and a daily oral administration of Tobramycine (20mg/kg/day) and Polymyxine-E (25mg/kg/day). Animals were sacrificed and mesenteric lymph nodes (MLN), and both peripheral and portal blood samples were recovered for TB determination in bacterial culture. Determination of both IL-l and TNF-alpha seric levels were carried out by ELISA. Bacterial translocation incidence was higher in RES-NPT group (66.6%) than RES-NPT-SID group (30%) (P>0,05). The relative risk was 2.22 (IC 95% 0,81-6,11) and the number needed to treat was 3 (IC 95% 2-235). Seric levels of IL-1 and TNF-alpha were also higher in RES-NPT group (7,537 and 5,399 pg/ml, respectively) than in RES-NPT-SID group (6,397 and 5,032 pg/ml respectively) (p<0,001). 1. SID reduces TB in a PN undergoing experimental short bowel resection murine model. 2. Parenteral nutrition-related liver disease decreases in DIS receiving animals.
Assuntos
Translocação Bacteriana/fisiologia , Intestino Delgado/microbiologia , Hepatopatias/etiologia , Nutrição Parenteral/efeitos adversos , Animais , Ensaio de Imunoadsorção Enzimática , Ratos , Ratos WistarRESUMO
INTRODUCTION: Both necrotizing enterocolitis (NEC) and bacterial translocation (BT) have in common that bacterial overgrowth, a decrease in immunity and intestinal mucosal damage, followed by a barrier failure, can act as trigger factors. The main objectives in NEC treatment are to reduce mortality due to sepsis and to promote feeding tolerance. To achieve that, Minimal Enteral Nutrition (MEN) (less than 25% of the calories provided by enteral route) is a more and more used technique in newborns who receive Parenteral Nutrition (PN) to slow down fasting related villi atrophy and to attenuate its consequences. AIM: To test the hypothesis that MEN decreases BT in an experimental model of PN. METHODS: Twenty-four adult Wistar male rats received a continuous infusion of all-in-one PN solution through a jugular vein catheter. The animals were randomly divided in two groups and maintained in individual metabolic cages for ten days. * Control group (N= 1): fasting rats receiving, standard PN (300 mL/kg/ 24 h, 280 kcall kg/24 h). * MEN group (N=13): standard PN and rat chow (15 g /24 h, 3,1 kcal/g). At the end of the experiment animals were sacrificed and mesenteric lymph nodes (MLN), and both peripheral and portal blood samples were recovered and cultured. Bacterial identification in blood was carried out by conventional methods and MLN culture was considered positive with a growth over 100 Colony Forming Units/g. RESULTS: Weight curve was better in MEN group and BT was also significantly reduced. Translocation was found in 45% of control group and 8% of MEN group (p < 0,05). The relative risk (RR) was 5,9 (IC 95% 0,81-43,71) and the number needed to treat (NNT) was 3 (95% CI 2-20). CONCLUSIONS: 1. MEN reduces the incidence of BT in an experimental model of parenteral nutrition. 2. BT reduction could decrease NEC-related sepsis risk.
Assuntos
Translocação Bacteriana/fisiologia , Nutrição Enteral/métodos , Enterocolite Necrosante/microbiologia , Animais , Cateterismo Venoso Central/métodos , Enterocolite Necrosante/cirurgia , Veias Jugulares/cirurgia , Masculino , Ratos , Ratos WistarRESUMO
OBJECTIVES: Polyunsaturated fatty acids are immunomodulatory agents. These agents could develop a main role in patients with HIV infection. The aim of our study was to analyse the relation between polyunsaturated fatty acid intake and CD4 count in HIV infected patients. PATIENTS AND METHODS: Forty patients with HIV infections were enrolled. In all patients, the next variables were recorded; age, sex, drugs, anthropometric evaluation (weight, height, tricipital skinfold, midarm circumference, body mass index) and a biochemical evaluation (albumin, prealbumin, trasferrin, total proteins, total lymphocytes and CD4 count). A 3 day dietary intake questionnaire was performed, too. RESULTS: The mean age was (24 males and 16 females) 37.6 +/- 9.4 years, mean weight 65.6 +/- 12.2 kg and body mass index 23.2 +/- 3.25. Anthropometric evaluation showed a mean tricipital skinfold of 15.1 +/- 5.3 mm, midarm circumference 27.5 +/- 3.1 cm. Caloric intake and macronutrient distribution were normal (carbohydrates 48%, proteins 18% and lipids 34%). Dietary intake of polyunsaturated fatty acids was omega 3 (1.22 +/- 3.1 g/day) and omega 9 (31.5 +/- 11 g/day). Multivariante analysis, with CD4 count as a dependent variable, showed omega 3 intake as a independent variable (F = 6.2; p < 0.05), with an increase of 32 (IC95%: 9.86-52.14) CD4+ (count/uL) with each 1 g of omega 3 dietary intake adjusted by age, sex, and drugs. CONCLUSION: In patients with HIV infection, dietary intake of omega 3 fatty acids increase CD4 count.
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Dieta , Ácidos Graxos Ômega-3/farmacologia , Infecções por HIV/imunologia , Adulto , Contagem de Linfócito CD4 , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
The introduction of the so-called highly active antiretroviral therapies has had an impact on the natural history of the HIV infection. The aim of this contribution is to assess the differences in terms of plasma viral load (VL), as a reflection of therapy success or failure. A retrospective study was made of the changes in VL in two cohorts of patients depending on the drugs included in the triple therapy prescribed to them. The comparison of the triple therapies containing any reverse transcriptase inhibitor and different protease inhibitors, indinavir (IDV) (239 patients) versus saquinavir (SQV) or ritonavir (RTV) (138 subjects), showed a significantly higher percentage of patients reaching a 'non-detectable' VL among those receiving indinavir (67.8% versus 54.3%; P = 0.011). The interval before VL levels rose above 30,000 RNA copies/ml was different in the two groups: 385 days (276-495 days) for therapies including indinavir, and 239 days (86-391 days) for saquinavir or ritonavir. This seems to support the excellent behaviour of indinavir when its efficiency is compared with other protease inhibitors acting as potential competitors.
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Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , Indinavir/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Estudos de Coortes , Infecções por HIV/imunologia , Infecções por HIV/virologia , Inibidores da Protease de HIV/administração & dosagem , Humanos , Indinavir/administração & dosagem , Estudos Retrospectivos , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico , Saquinavir/administração & dosagem , Saquinavir/uso terapêuticoRESUMO
OBJECTIVE: To establish the impact of a pharmaceutical care program on the improvement of adherence to antiretroviral therapy, and on patient immunologic and virologic outcome. MATERIALS AND METHODS: A multicenter, observational, prospective study in a HIV-infected patient cohort under treatment with antiretrovirals selected by random sampling in 19 Spanish hospitals. The study lasted 12 months, in which the program was applied through a baseline preprocedural visit and 4 quarterly visits. Adherence estimation was based on pill counting. An adherence > or = 90, or > or = 95% was considered adequate (in two time points). RESULTS: 541 patients were included, most of them were males (68.8%) between 20 and 78 years of age. Major risk groups included injecting drug users (43.4%) and heterosexuals (29.4%). Sixty percent had already received treatment for more than 3 years. Mean baseline viral load and CD4 count values were 32,866 copies/ml and 485 cells/mm3, respectively. Throughout the study a slight increase in the percentage of adherent patients was seen; however, statistical significance was not reached (64.3 and 79.2% of patients showed an adherence > 95 and > 90%, respectively, during the fourth quarter, versus 59.8 and 75.5% at baseline). A statistically significant decrease in viral load and increase in CD4 cells was seen following program application. The percentage of patients with a viral load < 200 copies/ml was 72.2, 76.7, and 75.0% at the 2nd, 3rd, and 4th quarters, respectively, versus 64.2% at baseline. CD4 cell counts increased by 50 cells/mm3 on average from the start to the end of follow-up. CONCLUSIONS: Patients included in the program had a good immunologic and virologic outcome, and a trend towards an increased percentage of patients with good adherence was also seen. These results confirm the need to implement follow-up programs for patients receiving antiretrovirals in order to ensure maximum therapeutic benefits.
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Antirretrovirais/uso terapêutico , Cooperação do Paciente/estatística & dados numéricos , Serviço de Farmácia Hospitalar , Avaliação de Programas e Projetos de Saúde , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosAssuntos
Anticolesterolemiantes/uso terapêutico , Inibidores da Protease de HIV/efeitos adversos , Hiperlipidemias/tratamento farmacológico , Pravastatina/uso terapêutico , Adulto , Feminino , Fenofibrato/farmacologia , Fenofibrato/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/uso terapêutico , HIV-1/enzimologia , Humanos , Hiperlipidemias/induzido quimicamente , Hipolipemiantes/farmacologia , Masculino , Resultado do TratamentoRESUMO
UNLABELLED: The outcome of patients with short bowel syndrome is influenced for factors such as the length of remnant intestine or the presence or absence of ileocecal valve (ICV). Gram-negative sepsis, the main cause of mortality in this group of children, is probably due to bacterial translocation (BT), because after gut resection there are a number of circumstances that favour its occurrence, being the most known intestinal dismotility, bacterial overgrowth, loss of gut-associated lymphoid tissue, total parenteral nutrition (TPN) and fasting related mucosal atrophy. The aim of this experimental controlled study was to test the incidence of BT after four different types of gut resection, in animals fed orally or receiving TPN. Hundred and three adult Wistar rats bred and raised in our facilities according to European Union Regulations were randomly divided in six groups:--Group 1 (n = 26): non-manipulated animals, served as a control.--Group 2 (n = 14): 80% non-lethal small bowel resection, fed orally.--Group 3 (n = 15): same resection as group 2 but including ICV. Rat chow ad libitum.--Group 4 (n = 27): non-resected fasting animals receiving all-in-one TPN solution.--Group 5 (n = 11): same resection as group 2, but fasting and receiving TPN--Group 6 (n = 10): 90% small bowel resection, including cecum and ICV, fasting and TPN. The animals were maintained for 10 days in individual metabolic cages, and, at the end of the experiment, were bled by portal and cardiac puncture. Mesenteric lymph nodes, peripheral and portal blood samples were cultured for BT. Non-manipulated rats (group 1) had lower BT incidence (8%) than resected ones (groups 2, 3, 5 and 6, 93%, 60%, 91%, 60%, p < 0.05) or animals non-resected, receiving TPN (group 4.51%, p < 0.05). When resection included ICV in orally fed rats BT index was also lower (group 3 vs group 2.60% vs 91%, p < 0.05). In TPN resected animals a drop was also found in BT when ICV and cecum were added to small bowel resection (group 6 vs group 5.60% vs 91%, p < 0.05). IN CONCLUSION: 1. Gut resection is associated to a high degree of BT, even if the animals are fed orally. 2. Resection including ICV, produced less BT. 3. TPN-related BT was shown in half of the animals non resected. 4. TPN-resected rats had also less BT when ICV and cecum were removed.
Assuntos
Translocação Bacteriana/fisiologia , Valva Ileocecal/microbiologia , Intestino Delgado/microbiologia , Síndrome do Intestino Curto/microbiologia , Animais , Incidência , Masculino , Modelos Animais , Nutrição Parenteral Total , Ratos , Ratos WistarRESUMO
The aims of this retrospective study were to assess the prevalence of primary genotypic resistance to antiretroviral drugs in untreated HIV patients in Spain using the line probe assay and to determine its possible relationship to several epidemiological variables. The global prevalence of primary resistance was 12.5%. Primary mutations in the reverse transcriptase gene were found in two (2.2%) samples: M41L, K70R and M184 V were found in one sample and K70R in another. Primary mutations in the protease gene were detected in 12% of cases; V82A was the mutation most frequently detected (11/12, 91.6%). No statistical significance was found for any of the epidemiological variables studied. In conclusion, the prevalence of primary resistance detected is similar to that found by other authors.
Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral Múltipla , Infecções por HIV/virologia , HIV/efeitos dos fármacos , HIV/fisiologia , Adolescente , Adulto , Idoso , Criança , Feminino , Variação Genética , HIV/enzimologia , HIV/genética , Infecções por HIV/epidemiologia , Transcriptase Reversa do HIV/genética , Transcriptase Reversa do HIV/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação/genética , Estudos Retrospectivos , Espanha/epidemiologiaRESUMO
Alterations in the antioxidant system (AS) has been observed during total parenteral nutrition (TPN). Light exposure or changes in the composition of TPN may affect this deleterious effect. On the other hand, bacterial translocation (BT) is frequent under TPN and may be related to AS. The aim of the study was to determine the adverse effect of standard and glutamine-enriched (GE) TPN, with or without light exposure, on the AS, and its relationship to BT. Forty-nine adult Wistar rats underwent central venous cannulation and were randomly assigned to one of five groups: Sham (n = 16): chow and water ad libitum and saline i.v. TPN (n = 10): had standard TPN. TPN(-) (n = 8): standard TPN without light-exposure. GTPN (n = 8): GE TPN. GTPN(-) (n = 7): GE TPN without light exposure. After 10 days, glutation reduced (GSH) was determined in liver and kidney. Mesenteric lymph nodes, peripheral and portal blood samples were cultured for BT. Comparing to Sham rats, TPN groups had statistically significant lower GSH levels, but there were no differences between standard or GE groups nor with or without light exposure groups. Sham animals had 12% BT. Significantly higher BT (p < 0.05) was found in TPN rats: 70% in TPN group, 88% in TPN(-) group, 86% in GTPN(-) animals and only 50% in GTPN group (p = 0.06 vs TPN group). To conclude: 1. TPN reduces antioxidant capacity and induces BT. 2. Glutamine supplementation or light protection do not improve tissue antioxidant capacity under TPN. 3. Glutamine supplementation tends to reduce BT only in the presence of light. 4. Absence of light exposure does not improve BT TPN-related.
Assuntos
Translocação Bacteriana , Nutrição Parenteral , Animais , Antioxidantes , Masculino , Ratos , Ratos WistarRESUMO
INTRODUCTION: The impact of micronutrients on HIV disease progression has been an area of great interest. Several studies have shown an association between disease progression and micronutrient status. The aim of our study was to assess the correlation between micronutrients intakes and immune status in HIV infected patients. MATERIAL AND METHODS: A total of 119 patients were evaluated. Nobody dropped out. In all patients the following parameters were assessed; age, sex, treatment with anti-retroviral drugs, performed an anthropometric evaluation (weight, tricipital skinfold, midarm circumference, and body mass index (BMI)) and a biochemical evaluation (glucose, albumin, prealbumin, transferrin, total proteins, limphocytes and count of CD4). All patients received instruction in 24-hour written food record keeping. RESULTS: Patients had an average age 37.9 +/- 9.9 years, weight 64.5 +/- 13.2 kg and body mass index 22.5 +/- 3.5. Levels of total proteins, albumin, prealbumin y transferrin were normal. Percentile distribution of anthropometric parameters showed a deep depletion in muscular protein compartiment, 53.1% of patients had tricipital skinfold under P 50, 91.8% had midarm muscle circumference under P 50. The correlation analysis among dietary intake and immune status, showed a positive association among vitamin A intake and vitamin D with CD4+ (r = 0.35; p < 0.01) and (r = 0.51; p < 0.001), respectively. In the multivariant analysis with dependent variable (CD4 count), only vitamin D remained in the model (F = 16.99; p < 0.001), with an increase of 34 (CI 95%: 5.81-167.3) CD4+ (count/uL) with each microgram of vitamin D intake, adjusted by age, sex, energy and protein intake, and anti-retroviral drugs. CONCLUSION: Vitamin A, and D intakes were correlated with CD4 count, only vitamin D remained as a independent predictor parameter in a in multivariant model.
Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , HIV-1/fisiologia , Micronutrientes/administração & dosagem , Estado Nutricional , Oligoelementos/sangue , Adulto , Antropometria , Contagem de Linfócito CD4 , Ingestão de Energia , Feminino , Humanos , Masculino , Vitamina A/administração & dosagem , Vitamina D/administração & dosagemRESUMO
Alterations in the antioxidative system have been observed during total parenteral nutrition (TPN). Light exposure or changes in the composition of TPN formulas may affect this system. Bacterial translocation (BT) is frequent under TPN and may be related to oxidative status. The aim of this study was to determine the adverse effects of standard and glutamine-enriched TPN, with or without light exposure, on oxidative status (liver and kidney-reduced glutathione, GSH) and its relationship to BT. Thirty-three adult Wistar rats underwent central-venous cannulation and were randomly assigned to one of four groups receiving different TPN regimes for 10 days. The TPN group (n = 10) had standard TPN, the TPN(-) group (n = 8) standard TPN without light exposure, the GTPN group (n = 8) glutamine-enriched TPN, and the GTPN(-) group (n = 7) glutamine-enriched TPN without light exposure. A sham group (n = 16) receiving chow and water ad libitum and saline i.v. served as controls. At the end of the experiment, GSH was determined in liver and kidney tissue. Mesenteric lymph nodes and peripheral and portal blood samples were cultured for BT. Compared to sham rats, TPN groups had statistically significant lower GSH levels, but there were no differences between standard or glutamine-enriched groups or light-exposure groups. Sham animals had 12% BT. Significantly higher BT (P < 0.05) occurred in TPN rats: 70% in the TPN group, 88% in the TPN(-) group, 86% in GTPN (-) animals, and only 50% in the GTPN group (P = 0.06 vs TPN group). In conclusion, (1) TPN reduces antioxidant capacity; (2) glutamine supplementation or light protection does not improve tissue antioxidant capacity under TPN; (3) the absence of light exposure does not improve TPN-related BT; and (4) glutamine supplementation tends to reduce BT only in the presence of light.