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1.
Int J Infect Dis ; 53: 46-51, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27815225

RESUMO

INTRODUCTION: Boceprevir (BOC) was one of the first oral inhibitors of hepatitis C virus (HCV) NS3 protease to be developed. This study assessed the safety and efficacy of BOC+pegylated interferon-α2a/ribavirin (PEG-IFN/RBV) in the retreatment of HIV-HCV co-infected patients with HCV genotype 1. METHODS: This was a phase III prospective trial. HIV-HCV (genotype 1) co-infected patients from 16 hospitals in Spain were included. These patients received 4 weeks of PEG-IFN/RBV (lead-in), followed by response-guided therapy with PEG-IFN/RBV plus BOC (a fixed 44 weeks was indicated in the case of cirrhosis). The primary endpoint was the sustained virological response (SVR) rate at 24 weeks post-treatment. Efficacy and safety were evaluated in all patients who received at least one dose of the study drug. RESULTS: From June 2013 to April 2014, 102 patients were enrolled, 98 of whom received at least one treatment dose. Seventy-three percent were male, 34% were cirrhotic, 23% had IL28b CC, 65% had genotype 1a, and 41% were previous null responders. The overall SVR rate was 67%. Previous null-responders and cirrhotic patients had lower SVR rates (57% and 51%, respectively). Seventy-six patients (78%) completed the therapy scheme; the most common reasons for discontinuation were lack of response at week 12 (12 patients) and adverse events (six patients). CONCLUSIONS: Response-guided therapy with BOC in combination with PEG-IFN/RBV led to an overall SVR rate of 67%, but an SVR rate of only 51% in patients with cirrhosis. The therapy was generally well tolerated. Although the current standards of care do not include BOC+PEG-IFN/RBV, the authors believe that this combination can be beneficial in situations where new HCV direct antiviral agent interferon-free therapies are not available yet.


Assuntos
Antivirais/uso terapêutico , Infecções por HIV/tratamento farmacológico , Hepacivirus/efeitos dos fármacos , Hepatite C/tratamento farmacológico , Adulto , Coinfecção , Quimioterapia Combinada , Feminino , Genótipo , Infecções por HIV/complicações , Hepacivirus/genética , Hepatite C/complicações , Humanos , Interferon-alfa/uso terapêutico , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/uso terapêutico , Prolina/análogos & derivados , Prolina/uso terapêutico , Estudos Prospectivos , Proteínas Recombinantes/uso terapêutico , Retratamento , Ribavirina/uso terapêutico , Espanha , Resultado do Tratamento , Proteínas não Estruturais Virais/antagonistas & inibidores
2.
Clin Microbiol Infect ; 21(1): 104.e1-5, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25636936

RESUMO

We characterized transmitted drug resistance to rilpivirine and the predicted efficacy of first-line rilpivirine-containing regimens in antiretroviral-naive Spanish patients. International Antiviral Society-USA mutations were detected in 138 of 2781 patients (4.9%), E138A (3.4%) being the most prevalent. Using the Stanford Algorithm, 121 patients (4.4%) showed low-level or intermediate resistance. No differences in the predicted efficacy of first-line non-nucleoside reverse transcriptase inhibitor-based regimens were observed. As rilpivirine becomes more widely used in clinical practice, the evolution of its transmitted drug resistance will need to be monitored. In addition, the exact role of E138A singletons on rilpivirine activity as part of first-line regimens merits further evaluation.


Assuntos
Fármacos Anti-HIV/farmacologia , Farmacorresistência Viral/genética , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , Nitrilas/farmacologia , Pirimidinas/farmacologia , Adulto , Infecções por HIV/epidemiologia , HIV-1/genética , Humanos , Mutação/genética , Prevalência , Rilpivirina
3.
J Antimicrob Chemother ; 69(9): 2536-40, 2014 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-24833755

RESUMO

OBJECTIVES: To present clinical experience with a regimen including abacavir/lamivudine + darunavir/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/lamivudine + darunavir/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/lamivudine + darunavir/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.


Assuntos
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 Jovem
4.
Curr HIV Res ; 10(6): 513-20, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22716109

RESUMO

OBJECTIVE: To evaluate long-term outcomes in patients maintaining a nevirapine (NVP)-based regimen. METHODS: Retrospective, multicenter, cohort study including patients currently receiving an NVP regimen that had been started at least 5 years previously. Demographic, clinical, and analytical variables were recorded. RESULTS: Median follow-up was 8.9 (5.7-11.3) years. Baseline characteristics: 74% men, 47 years old, 36% drug users, 40% AIDS, 40% HCV+, 51.4% detectable HIV-1 viral load, CD4 count 395 (4-1,421)/µL, 19% CD4 < 200/µL, 27% ALT grade 1-2, 36% AST grade 1-2. Thirty percent ART-naive, 83%received NVP associated with 2 nucleoside analogues during the study period, and 17% a protease inhibitor. A significant improvement was observed in general health status markers, including hemoglobin, platelets, and albumin, regardless of HCV coinfection. CD4 cell gain was +218 and +322/µL after 6 and 9 years, respectively (+321 and +391 in naive patients). Triglycerides significantly decreased in pretreated patients, whereas the percentage of patients with HDLc < 1.03 mmol/L and LDL-c > 3.37 mmol/L significantly decreased in a subsample with available values. A significant decrease in transaminases, alkaline phosphatase, and Fib4 score was observed, mainly in HCV+ and ARV-naive patients. CONCLUSIONS: In patients who tolerate NVP therapy, (even those with HCV coinfection), long term benefits may be significant in terms of a progressive improvement in general health status markers and CD4 response, a favorable lipid profile, and good liver tolerability.


Assuntos
Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Fármacos Anti-HIV/administração & dosagem , Hepatite C/tratamento farmacológico , Fígado/efeitos dos fármacos , Nevirapina/administração & dosagem , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Síndrome da Imunodeficiência Adquirida/sangue , Síndrome da Imunodeficiência Adquirida/epidemiologia , Contagem de Linfócito CD4 , Colesterol/sangue , Estudos de Coortes , Coinfecção , Quimioterapia Combinada , Feminino , Seguimentos , Hepatite C/sangue , Hepatite C/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Espanha/epidemiologia , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/sangue , Carga Viral
5.
Int J Tuberc Lung Dis ; 12(12): 1393-400, 2008 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-19017448

RESUMO

OBJECTIVE: To estimate incidence rates and risk factors for tuberculosis (TB) in human immunodeficiency virus seroprevalent subjects. METHODS: Multicentre, hospital-based cohort study of patients presenting to 10 Spanish hospitals from 1 January 1997 to 31 December 2003. Poisson regression was used and highly active antiretroviral treatment (HAART) was modelled as a time-dependent covariate. RESULTS: A total of 4268 patients were followed for a median of 3.8 years; 221 TB cases were diagnosed over 16 464 person-years (py). TB rates were higher in HAART-naïve subjects (1.56 per 100 py, 95%CI 1.36-1.79) than those on HAART (0.5/100 py, 95%CI 0.31-0.80). Among HAART-naïves, TB risk factors were: being male, being an injecting drug user (IDU) (RR 2.01, 95%CI 1.28-3.16), having low CD4 counts (P < 0.001) and high viral loads (P < 0.001). HAART was protective (RR 0.26, 95%CI 0.16-0.40) and reductions in TB rates were observed in the last calendar period (RR 0.74, 95%CI 0.55-1.00). For patients on HAART, no differences were observed by category of transmission. Low CD4 counts at entry were associated with higher TB rates (P < 0.001). CONCLUSIONS: HAART was associated with lower TB rates, and TB risk factors differed according to whether or not patients had received HAART. To further reduce TB rates, additional strategies are needed, such as timely access and adherence to HAART, especially in IDUs.


Assuntos
Terapia Antirretroviral de Alta Atividade , Soropositividade para HIV/complicações , Soropositividade para HIV/tratamento farmacológico , Tuberculose/epidemiologia , Adulto , Estudos de Coortes , Feminino , Humanos , Masculino , Fatores de Risco , Tuberculose/etiologia
6.
An Sist Sanit Navar ; 29 Suppl 1: 127-38, 2006.
Artigo em Espanhol | MEDLINE | ID: mdl-16721423

RESUMO

Diarrhoeic diseases caused by water and food contaminated by enteropathogens continue to be an important cause of morbidity in countries with a low level of development. Some 50,000 cases of diarrhoea in travellers are estimated in the world every day, and this is the main cause of consultation by travellers who return from undeveloped zones. The principal determinant of risk is the place of destination; there are significant differences between different regions with respect to risk and to the aetiology of the diarrhoea. The most frequent cause of diarrhoeas is of bacterial origin, which represents between 60 and 85% of the cases, while parasites represent 10% and some 5% are produced by viruses. Although it normally follows a benign course, complications can arise, with mortality being only exceptionally associated to this disease. Prevention is essentially based on strictly following elemental hygienic measures and avoiding the ingestion of foodstuffs and drinks with a risk of contamination. Prophylaxis with antibiotics is only advisable in journeys of short duration, in which the risk and/or seriousness of diarrhoeas, above all in immunosuppressed patients, are higher than the possible collateral effects. The treatment of diarrhoea in the traveller is based on adequate hydration, and the use of microbians is reserved for moderate and serious situations, with quinolones being the drug of choice. Rifaximine is a new drug approved for the treatment of diarrhoeas in the traveller, above all in areas with enteropathogens that are resistant to quinolones.


Assuntos
Diarreia , Viagem , Diarreia/diagnóstico , Diarreia/epidemiologia , Diarreia/etiologia , Diarreia/terapia , Humanos , Fatores de Risco
7.
An. sist. sanit. Navar ; 29(supl.1): 127-138, ene.-abr. 2006. ilus
Artigo em Es | IBECS | ID: ibc-048526

RESUMO

Las enfermedades diarreicas causadas por la contaminación de agua y alimentos por enteropatógenos continúan siendo causa de importante morbilidad en los países con escaso nivel de desarrollo. Se estima alrededor de unos 50.000 casos diarios de diarreas del viajero en el mundo, siendo el principal motivo de consulta de los viajeros que regresan de zonas no desarrolladas. El principal determinante de riesgo es el lugar de destino, existiendo diferencias importantes entre las distintas regiones en cuanto al riesgo y la etiología de la diarrea. La causa más frecuente de diarreas es la bacteriana, que representa del 60 al 85% de los casos, los parásitos representan el 10% y un 5% están producidas por virus. Aunque habitualmente cursa de forma benigna, pueden aparecer complicaciones, siendo excepcional la mortalidad asociada esta enfermedad. La prevención se basa fundamentalmente en seguir estrictamente las medidas higiénicas elementales y evitar la ingesta de alimentos y bebidas con riesgo de contaminación. La profilaxis con antibióticos sólo se aconseja en viajes de corta duración, en los que el riesgo y/o gravedad de las diarreas, sobre todo en pacientes inmunosuprimidos, sean superiores a los posibles efectos colaterales. El tratamiento de la diarrea del viajero se basa en una adecuada hidratación y se reserva el uso de antimicrobianos para situaciones clínicas moderadas y graves, siendo las quinolonas el fármaco de elección. La rifaximina es un nuevo fármaco aprobado para el tratamiento de las diarreas del viajero, sobre todo en áreas con enteropatógenos resistentes a las quinolonas


Diarrhoeic diseases caused by water and food contaminated by enteropathogens continue to be an important cause of morbidity in countries with a low level of development. Some 50,000 cases of diarrhoea in travellers are estimated in the world every day, and this is the main cause of consultation by travellers who return from undeveloped zones. The principal determinant of risk is the place of destination; there are significant differences between different regions with respect to risk and to the aetiology of the diarrhoea. The most frequent cause of diarrhoeas is of bacterial origin, which represents between 60 and 85% of the cases, while parasites represent 10% and some 5% are produced by viruses. Although it normally follows a benign course, complications can arise, with mortality being only exceptionally associated to this disease. Prevention is essentially based on strictly following elemental hygienic measures and avoiding the ingestion of foodstuffs and drinks with a risk of contamination. Prophylaxis with antibiotics is only advisable in journeys of short duration, in which the risk and/or seriousness of diarrhoeas, above all in immunosuppressed patients, are higher than the possible collateral effects. The treatment of diarrhoea in the traveller is based on adequate hydration, and the use of microbians is reserved for moderate and serious situations, with quinolones being the drug of choice. Rifaximine is a new drug approved for the treatment of diarrhoeas in the traveller, above all in areas with enteropathogens that are resistant to quinolones


Assuntos
Humanos , Diarreia/diagnóstico , Diarreia/epidemiologia , Diarreia/etiologia , Diarreia/terapia , Viagem , Fatores de Risco
8.
Cytokine ; 15(4): 232-6, 2001 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-11563884

RESUMO

We studied 174 patients with SIRS criteria, 45 with sepsis, eight with severe sepsis and 13 with septic shock. Serum TNF-alpha, IL-6, IL-8 and IL-10 levels were raised in SIRS patients, even in those cases in which an infection could not be documented, and more intensely in severe sepsis and in patients who died (11%). The slope of the regression line between IL-10 and TNF-alpha was sharper in patients with severe sepsis and in those who died; an imbalance between pro- and anti-inflammatory cytokines may be related to poor prognosis. Increased IL-6 and IL-10, decreased muscle mass, raised BUN and low body temperature were all independently related to prognosis.


Assuntos
Inflamação/imunologia , Sepse/diagnóstico , Sepse/imunologia , Choque Séptico/diagnóstico , Choque Séptico/imunologia , Fatores Etários , Idoso , Temperatura Corporal , Citocinas/biossíntese , Feminino , Humanos , Interleucina-10/biossíntese , Interleucina-10/sangue , Interleucina-6/sangue , Interleucina-8/sangue , Cinética , Masculino , Pessoa de Meia-Idade , Músculos/patologia , Prognóstico , Sepse/mortalidade , Choque Séptico/mortalidade , Resultado do Tratamento , Fator de Necrose Tumoral alfa/biossíntese
9.
J Acquir Immune Defic Syndr ; 25(1): 26-35, 2000 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-11064501

RESUMO

The objective of antiretroviral therapy is to obtain an almost complete and durable suppression of viral replication in all compartments to facilitate recovery of the immune system. We assessed the virologic effect in plasma, tonsillar tissue, and cerebrospinal fluid (CSF) in 94 HIV-1-infected patients with CD4 counts >500 x 106 cells per liter and viral load >5000 copies/ml randomly assigned to triple antiretroviral therapy (two nucleoside reverse transcriptase inhibitors (NRTIs) plus one protease inhibitor) versus double therapy (two NRTIs). We also analyzed the immunologic recovery in this cohort of patients. Lymphoid tissue and cerebrospinal fluid viral load, development of genotypic resistance, proliferative responses to HIV-1 specific antigens, and other immunophenotypic markers were analyzed. The proportion of patients who achieved a decrease in HIV RNA levels to <200 copies/ml was significantly greater in the triple therapy group than in the two drug groups (p =.0002 for each pair-wise difference). At week 52, tonsillar tissue HIV RNA from 5 patients treated with triple therapy was lower than the limit of detection, whereas the mean +/- standard error in patients with double therapy (n = 5) was 5.03 +/- 0.34 copies/mg/tissue. In all 10 patients, CSF viral load (VL) was <20 HIV-1 RNA copies/ml at week 52. CSF cell counts and protein levels tended to decrease after 52 weeks of antiretroviral therapy. After 1 year of therapy, 13 of 21 patients (62%) in the double-therapy groups (zidovudine plus lamivudine [n = 9] and stavudine plus lamivudine [n = 12]) had evidence of M184V mutation. None of the 10 samples of patients receiving triple therapy could be amplified because of low HIV RNA levels. The mean increase in CD4 cells at week 52 was greater in the stavudine and lamivudine and indinavir group than in the double-treatment arms (186 versus 67 and 102, respectively; p =.03). In patients treated with triple therapy, the increase in naive T cells (CD4 and CD8) was greater than in patients treated with double therapy. Markers of activation decreased further in patients treated with the regimen that included protease inhibitors. Proliferative responses to HIV-1 p24 antigen were never recovered after double or triple therapy. Our study suggests that even in very early stages of HIV-1 disease only therapy with two NRTIs and one protease inhibitor reduces plasma, lymphoid tissue, and CSF VL to undetectable levels. HIV-1-related immune system abnormalities improved but were still defective after 1 year of antiretroviral therapy.


Assuntos
Infecções por HIV/tratamento farmacológico , HIV-1 , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Sangue/virologia , Contagem de Linfócito CD4 , Contagem de Células , Líquido Cefalorraquidiano/química , Líquido Cefalorraquidiano/citologia , Líquido Cefalorraquidiano/virologia , Proteínas do Líquido Cefalorraquidiano/análise , Estudos de Coortes , Quimioterapia Combinada , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Inibidores da Protease de HIV/uso terapêutico , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Lamivudina/uso terapêutico , Masculino , Tonsila Palatina/virologia , Mutação Puntual , RNA Viral/análise , Espanha , Estavudina/uso terapêutico , Fatores de Tempo , Carga Viral , Zidovudina/uso terapêutico
10.
Med Clin (Barc) ; 115(13): 481-6, 2000 Oct 21.
Artigo em Espanhol | MEDLINE | ID: mdl-11093869

RESUMO

BACKGROUND: The natural history of HIV infection and its related diseases has changed after the introduction of new potent antiretroviral therapies (HAART). We have performed this study to analyse in our hospital the natural history of HIV infection in relation to the therapeutics advances. PATIENTS AND METHODS: We have exhaustively revised the clinic records of all the 807 adult HIV-infected patients followed at the HUC from January 1985 to December 1999. RESULTS: The incidence of most opportunistic diseases, new AIDS cases, hospital admissions and deaths decreased as from 1997. Patients who started antiretroviral therapy with HAART had lower incidence of AIDS, hospital admissions and deaths than patients with other therapy modalities. Survival of patients placed on HAART was better than that of patients who received different therapy modalities (p < 0.001), independently on the intensity of immunosuppression and AIDS diagnosis. Multivariate analysis showed that HAART therapy was the best protector factor, decreasing the risk of progression to death (p < 0.001). CONCLUSIONS: HAART therapy leads an important improvement of survival of HIV infected patients, independently an the intensity of immunosuppression and slows HIV progression, decreasing the number of new AIDS cases, hospital admissions and deaths.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1 , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/mortalidade , Síndrome da Imunodeficiência Adquirida/epidemiologia , Adulto , Terapia Antirretroviral de Alta Atividade/métodos , Feminino , Infecções por HIV/mortalidade , Humanos , Incidência , Masculino , Análise Multivariada , Espanha/epidemiologia , Fatores de Tempo
11.
AIDS ; 14(16): 2485-94, 2000 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-11101059

RESUMO

OBJECTIVES: To evaluate the safety and effectiveness of once-daily didanosine and nevirapine plus twice-daily stavudine versus twice-daily administration of all three drugs. METHODS: This open-label, randomized, multicentre study enrolled 94 antiretroviral-naive patients with chronic HIV infection, CD4+ cell counts > 500 x 10(6) cells/l, and viral loads > 5000 copies/ml. Patients were treated with either 40 mg stavudine (twice daily) plus 400 mg didanosine (once daily) and 400 mg nevirapine (once daily) or 40 mg stavudine (twice daily) plus 200 mg didanosine (twice daily) and 200 mg nevirapine (twice daily). RESULTS: After 12 months, 68% of patients who received twice-daily didanosine and nevirapine had viral loads < 200 copies/ml in the intention-to-treat and 79% in the on-treatment analysis, respectively. The corresponding values for patients treated with didanosine and nevirapine, taken once-daily, were 73 and 85%. The percentages of patients in each group with viral loads < 5 copies/ml at 12 months were 40% (once daily ) and 45% (twice daily) for the intention-to-treat analysis. Five of 11 patients (45%) with plasma viral loads < 5 copies/ml at 12 months had detectable virus in tonsillar tissue. Genotypic resistance to nevirapine was noted in seven of the 14 patients with detectable viral load at month 12. Mean changes in CD4+ cell counts for patients treated with stavudine plus once- or twice-daily didanosine and nevirapine were 154 and 132 x 10(6) cells/l, respectively. Treatment was interrupted due to adverse events in seven patients (8%) (four who received once-daily didanosine and nevirapine and three treated with twice-daily doses). CONCLUSIONS: The combination of twice-daily stavudine plus once-daily didanosine and nevirapine was as safe and well tolerated as twice-daily administration of all three agents. Both regimens were equally effective in reducing viral loads and in increasing CD4+ cell counts.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Didanosina/uso terapêutico , Infecções por HIV/tratamento farmacológico , Nevirapina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Estavudina/uso terapêutico , Contagem de Linfócito CD4 , Resistência Microbiana a Medicamentos/genética , Quimioterapia Combinada , Infecções por HIV/virologia , HIV-1/efeitos dos fármacos , HIV-1/genética , HIV-1/fisiologia , Humanos , Tonsila Palatina/virologia , Projetos Piloto , RNA Viral/análise , RNA Viral/sangue , Subpopulações de Linfócitos T/imunologia , Carga Viral
12.
AIDS ; 13(17): 2377-88, 1999 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-10597779

RESUMO

BACKGROUND: Most current guidelines state that antiretroviral therapy should be considered for HIV-infected patients with plasma HIV RNA > 5000-10000 copies/ml and CD4 cells > 500 x 10(6) cells/l. However, there is increasing concern about whether this is the optimal point to begin treatment or whether it is better to delay the initiation to more advanced stages. OBJECTIVE: To study the immunological and virological benefits of starting antiretroviral therapy at these early stages. METHODS: A total of 161 HIV-infected asymptomatic patients with CD4 cell count > 500 x 10(6) cells/l and viral load > 10000 copies/ml were randomly assigned to one of five treatment groups: no treatment, twice daily zidovudine and thrice daily zalcitabine (ZDV-ddC), twice daily zidovudine and didanosine (ZDV-ddI), twice daily stavudine and didanosine (D4T-ddI), or a twice daily three-drug regimen with stavudine and lamivudine and ritonavir. The endpoints were progression to < 350 x 10(6) cells/l CD4 cells, to < 500 x 10(6) cells/l with either two Centers for Disease Control class B symptoms or an increase of viral load > 0.5 log10 copies/ml above baseline, or to AIDS or death. In various substudies, the lymphoid tissue and cerebrospinal fluid viral load, development of genotypic resistance, proliferative responses to mitogens and cytomegalovirus, and HIV-1 specific antigens and other immunophenotypic markers were also analysed. RESULTS: Progression rates to study endpoints within 1 year were greater in the control group (31%) than in all groups receiving antiretroviral therapy pooled together (5%; estimated hazard ratio 7.41; 95% confidence interval 5.72-74.55; P < 0.001). The peak mean viral load decrease was greater in the three-drug group when compared with any of the three groups with a two-drug regimen (2.32, 1.65, 1.72 and 1.84, respectively; P < or = 0.001). At 1 year, viral load remained below 20 copies/ml in 30 out of 33 patients in the three-drug group (91%) and in only eight out of 94 patients (9%) in two-drug groups (P = 0.001). The peak mean increase in CD4 cells was also greater in the three-drug group than in the double treatment arms (259 versus 85, 144 and 145 x 10(6) cells/l, respectively; P = 0.001). By comparison, 36% of patients in the three-drug group regimen had to change the therapy as a result of adverse events. Substudies were performed in 60 patients recruited at two sites. Tonsillar tissue HIV RNA was measured in seven patients (two in the two-drug groups and five in the three-drug group) in whom plasma HIV RNA was < 20 copies/ml at 1 year. It was 15151 and 133333 copies/mg tissue in the two patients from the two-drug group, < 40 copies/mg tissue in four patients in the three-drug group, and 485 copies/mg in one patient in the three-drug group. At 1 year there was a mean increase of 4.21+/-2.94% in CD8+CD38+ cells in the control group and a decrease of 9.48+/-3.36% in the two-drug groups (P = 0.01), and 19.87+/-3.64 in the three-drug group (P = 0.001 and P = 0.05, for comparisons with control group and two-drug groups, respectively). Although proliferative responses to cytomegalovirus antigens were significantly greater in those receiving antiretroviral therapy, response to HIV-1 p24 antigen was not detected in any patient in either treatment group. CONCLUSIONS: This study supports the recommendation to start antiretroviral therapy with a three-drug combination during very early stages of HIV-1 disease, at least if viral load is above a cut-off point (10000 copies/ml in our study). The risk of progression was sevenfold higher in non-treated patients at 8 months of follow-up. Some immune system parameters improved toward normal values after 1 year of antiretroviral therapy, but the proliferative response of CD4 T lymphocytes against the p24 HIV-1 antigen was not recovered. Therapeutic approaches with more potent, better-tolerated and more convenient regimens will increasingly favour early intervention with antiretroviral t


Assuntos
Fármacos Anti-HIV/administração & dosagem , Infecções por HIV/tratamento farmacológico , HIV-1 , Adulto , Fármacos Anti-HIV/efeitos adversos , Contagem de Linfócito CD4 , Relação CD4-CD8 , Didanosina/administração & dosagem , Quimioterapia Combinada , Feminino , Infecções por HIV/imunologia , Infecções por HIV/virologia , Humanos , Lamivudina/administração & dosagem , Masculino , Tonsila Palatina/virologia , RNA Viral/sangue , RNA Viral/líquido cefalorraquidiano , Ritonavir/administração & dosagem , Espanha , Estavudina/administração & dosagem , Viremia/tratamento farmacológico , Viremia/imunologia , Viremia/virologia , Zalcitabina/administração & dosagem , Zidovudina/administração & dosagem
14.
Enferm Infecc Microbiol Clin ; 15(2): 61-4, 1997 Feb.
Artigo em Espanhol | MEDLINE | ID: mdl-9101748

RESUMO

BACKGROUND: An approach of daily or 5 days per week treatment as maintenance therapy is mandatory among HIV patients with CMV retinitis. We evaluate the efficacy and tolerance of thrice weekly maintenance therapy for CMV retinitis in AIDS patients. METHODS: Sixty nine consecutive patients with CMV disease were eligible for a prospective open clinical trial. Thirty three completed the induction treatment of CMV retinitis, agreed on maintenance thrice weekly and were included. Twenty nine received Ganciclovir (10 mg/kg/day) and 4 foscarnet (100 mg/kg/day) thrice weekly. RESULTS: The mean age was 34 years. Twenty nine of the 33 (87%) were males and 13 (39%) drug addicts. Mean CD4+ lymphocyte count at inclusion was 44 cells per relapsed and 22 (66%) died. The median time to relapse, survival free of CMV retinitis and the median survival was 18, 14 and 34 weeks respectively. CONCLUSION: Since the outcome of our patients with thrice weekly maintenance therapy was similar to historical controls our study at least provides the rational for this hypothesis to be tested in a future randomised trial.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Antivirais/uso terapêutico , Retinite por Citomegalovirus/tratamento farmacológico , Foscarnet/uso terapêutico , Ganciclovir/uso terapêutico , Adulto , Antivirais/administração & dosagem , Retinite por Citomegalovirus/complicações , Esquema de Medicação , Feminino , Foscarnet/administração & dosagem , Ganciclovir/administração & dosagem , Infecções por HIV/complicações , Infecções por HIV/mortalidade , HIV-1 , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Taxa de Sobrevida
15.
Alcohol ; 12(6): 581-7, 1995.
Artigo em Inglês | MEDLINE | ID: mdl-8590623

RESUMO

To investigate the androgen, weak androgen, estrogen, and gonadotrophin response to clomiphene in alcoholics, we determined in 63 male patients (25 with and 38 without liver cirrhosis) serum testosterone, sexual hormone binding protein (SHBG), dehidroepiandrosterone, androstenedione, LH, FSH, prolactin, and estradiol levels, on the first and the sixth day after admission, and after a course of 8 days of clomiphene 200 mg/day. The same test was performed on 15 healthy volunteers. Cirrhotic patients showed decreased basal testosterone levels and a loss of the circadian rhythm with recovery after clomiphene. Although basal testosterone levels in noncirrhotic alcoholics did not differ from those of the controls, there was a significant improvement after withdrawal. SHBG levels were higher in both groups of alcoholics than in controls, pointing to a worse degree of hypogonadism, because only the free hormone is active. Before the clomiphene test, serum LH and FSH levels were nonsignificantly higher in both groups of alcoholics than in the control group. After clomiphene both LH and FSH increased. Androstenedione and estradiol showed a (parallelism) similar behavior in alcoholic and in cirrhotic groups, showing in both cases higher levels than in the control group, and an increase after clomiphene, perhaps reflecting peripheral conversion of androgens to estrogens. Because clomiphene has no effect on the adrenal cortex, the increase of androstenedione after clomiphene points to its testicular origin (directly or after testosterone conversion) and not to an adrenal one. The highest serum estradiol levels were observed in cirrhotics with ascites or gynecomastia. We have not found any relation between serum hormone levels and alcohol intake nor with nutritional status.


Assuntos
Alcoolismo/complicações , Clomifeno/farmacologia , Hipogonadismo/etiologia , Adulto , Síndrome de Resistência a Andrógenos/etiologia , Androgênios/sangue , Androstenodiona/sangue , Estradiol/sangue , Humanos , Hipogonadismo/sangue , Cirrose Hepática Alcoólica/sangue , Cirrose Hepática Alcoólica/complicações , Testes de Função Hepática , Masculino , Pessoa de Meia-Idade , Estado Nutricional , Testosterona/sangue
16.
Drug Alcohol Depend ; 38(1): 11-8, 1995 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-7648992

RESUMO

OBJECTIVE: To discern if factors such as organic pathology, sex, duration and/or intensity of drug addiction, alcohol abuse, hepatitis B infection, anorexia with poor food and drink consumption, or disturbance of social and familial networks, are related to an impaired nutritional status in hospitalized drug addicts. DESIGN: Cross-sectional prospective study. SETTING: Detoxication unit and internal medicine unit of a university hospital. PATIENTS: 140 drug addicts without acute organic pathology and 18 with acute organic pathology related to drug addiction. The immunological study was compared with a control group composed of 50 healthy and well-nourished individuals (26 women and 24 men), age-matched with our patients. RESULTS: Drug addicts without organic pathology were under-nourished: 92.4% weighed under the mean weight for the population and 55.7% had had a weight loss above 5%. The distribution of mid-upper arm circumference (MUAC), triceps skinfold (TSF) measurement and mid-arm muscle area (MAMA) compared with the percentiles for the population showed a shift towards lower values. We found a high percentage of patients with a high lymphocyte count (55%). Despite the high lymphocyte count, delayed hypersensitivity was depressed in our patients. Of our patients, 66.4% exhibited anorexia at admission. The mean calorific intake was 978 +/- 89 kcal/day in females and 1265 +/- 64 kcal/day in males. However, in most cases, malnutrition (usually marasmus-like malnutrition) was not very severe; only 30% of the drug addicts weighed less than 80% of the mean weight for the population, or admitted to a weight loss above 10%, and by subjective nutritional assessment, only 18% were deeply malnourished. Otherwise, the nutritional status was very poor in drug addicts with acute organic pathology. We also found a worse nutritional status in our patients related to female sex, intensity of drug addiction, anorexia with poor food and drink consumption, and disturbance of the social and familial networks. CONCLUSIONS: Many drug addicts suffer from calorie and protein malnutrition. This mainutrition is related to female sex, intensity of drug addiction, anorexia and poor food and drink consumption, and disturbance of the social and familial links. Acute organic pathology leads to a significant worsening of the nutritional status of drug addicts.


Assuntos
Alcoolismo/fisiopatologia , Avaliação Nutricional , Desnutrição Proteico-Calórica/fisiopatologia , Abuso de Substâncias por Via Intravenosa/fisiopatologia , Transtornos Relacionados ao Uso de Substâncias/fisiopatologia , Adulto , Alcoolismo/psicologia , Alcoolismo/reabilitação , Anorexia/fisiopatologia , Anorexia/psicologia , Anorexia/reabilitação , Cocaína , Ingestão de Energia/fisiologia , Metabolismo Energético/fisiologia , Feminino , Soropositividade para HIV/fisiopatologia , Soropositividade para HIV/psicologia , Soropositividade para HIV/reabilitação , Hepatite B/fisiopatologia , Hepatite B/psicologia , Hepatite B/reabilitação , Dependência de Heroína/fisiopatologia , Dependência de Heroína/psicologia , Dependência de Heroína/reabilitação , Humanos , Contagem de Linfócitos , Masculino , Infecções Oportunistas/fisiopatologia , Infecções Oportunistas/psicologia , Infecções Oportunistas/reabilitação , Estudos Prospectivos , Desnutrição Proteico-Calórica/psicologia , Desnutrição Proteico-Calórica/reabilitação , Abuso de Substâncias por Via Intravenosa/psicologia , Abuso de Substâncias por Via Intravenosa/reabilitação , Transtornos Relacionados ao Uso de Substâncias/psicologia , Transtornos Relacionados ao Uso de Substâncias/reabilitação , Redução de Peso/fisiologia
18.
Clin Nutr ; 12(2): 75-80, 1993 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-16843291

RESUMO

OBJECTIVE: To assess the nutritional status of drug addicts without acute organic pathology, in order to determine the prevalence of malnutrition and to discern if early HIV infection is associated with a poor nutritional status in this group of patients. DESIGN: Prospective study. SETTING: Detoxication unit of a university hospital. PATIENTS: 140 drug addicts without acute organic pathology. 31 patients were HIV+. No one fulfilled the definition of AIDS. RESULTS: We found that drug addicts were undernourished: 92.4% weighed under the mean populational weight and 55.7% had a weight loss above 5%. The distribution of mid upper arm circumference (MUAC), triceps skinfold (TSF) and mid arm muscle area (MAMA) was lower than a reference normal population. Food intakes were poor; 66.4% of our patients complained of anorexia on admission. The mean caloric intake was 978 +/- 89 kcal/day in females and 1265 +/- 64 kcal/day in males. The mean protein intakes were 39.3 +/- 3.3 g/day in females (0.76 +/- 0.07 g/kg/day) and 49.7 +/- 2.7 g/day in males (0.77 +/- 0.04 g/kg/day). When we compared nutritional parameters between HIV+ and HIV- patients we found no differences. CONCLUSIONS: Nutritional impairment in drugs abusers with early stages of HIV infection should be attributed to drug abuse rather than to HIV infection.

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