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2.
Medicina (B Aires) ; 82(6): 830-835, 2022.
Artigo em Espanhol | MEDLINE | ID: mdl-36571520

RESUMO

INTRODUCTION: The clinical presentation of pregnant women with COVID-19 varied according to the time of the pandemic. OBJECTIVE: The clinic, complications and lethality were described, as well as a comparative analysis of the clinical presentation during the first two pandemic waves of pregnant and postpartum women with COVID-19. METHODS: An observational prospective cohort study of pregnant women assisted in the Municipal Maternity of San Isidro was carried out between 04/01/2020 and 07/31/21. RESULTS: The infection was confirmed in 103 pregnant women, 76.7% had a mild condition, 18.4% moderate and 4.8% severe. 59% were assisted by telemedicine, 41% were admitted and 2.9% required mechanical ventilation. Most had a good evolution and the case fatality rate was < 1% (n = 1). At the time of this analysis, 78% of the women had completed pregnancy. 41% of them presented some type of complication, the most frequent being: premature rupture of the membrane 42%, arterial hypertension and other associated pathologies (including a patient with preeclampsia) 27% and preterm delivery 18%. In the comparative analysis between the first two pandemic waves, there was a higher proportion of moderate/severe cases (p = 0.016) and the indication for mechanical ventilation was significantly higher (p = 0.048) in 2021. DISCUSSION: These findings support the need for prioritize this group of patients to implement preventive strategies.


Introducción: La presentación clínica de las gestantes con COVID-19 fue variando según el momento de la pandemia. Objetivo: Se describió la clínica, complicaciones y letalidad, así como un análisis comparativo de la presentación clínica durante las dos primeras olas pandémicas de las gestantes y puérperas con COVID-19. Métodos: Se realizó un estudio de cohorte prospectivo observacional de las gestantes asistidas en la Maternidad Municipal de San Isidro entre el 01/04/2020 al 31/07/21. Resultados: Se confirmó la infección de 103 gestantes, de las cuales el 76.7% cursó un cuadro leve, 18.4% moderado y 4.8% grave. El 59% fueron asistidas por telemedicina, el 41% se internó, de las cuales el 2.9% requirieron asistencia respiratoria mecánica (ARM). La mayoría tuvo buena evolución y la tasa de letalidad fue < 1% (n = 1). Al momento del presente análisis el 78% de las mujeres habían finalizado la gestación. El 41% de ellas, presentó algún tipo de complicación, siendo lo más frecuente: ruptura prematura de membrana 42%, hipertensión arterial y otras patologías asociadas (incluyendo una paciente con preeclampsia) el 27% y parto pretérmino el 18%. En el análisis comparativo entre las dos primeras olas pandémicas, hubo una mayor proporción de casos moderados/graves (p=0.016) y fue significativamente mayor la indicación de ARM (p=0.048) en el 2021. Discusión: Estos hallazgos avalan la necesidad de priorizar a este grupo de pacientes para implementar estrategias preventivas.


Assuntos
COVID-19 , Complicações Infecciosas na Gravidez , Nascimento Prematuro , Recém-Nascido , Feminino , Gravidez , Humanos , COVID-19/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Estudos Prospectivos , Pandemias/prevenção & controle , Período Pós-Parto , Nascimento Prematuro/epidemiologia
3.
J Infect Dis ; 226(10): 1717-1720, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-35723970

RESUMO

Infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron variant is usually asymptomatic or mild and appears to be poorly immunogenic at least in unvaccinated individuals. Here, we found that health care workers vaccinated with 2 doses of Sputnik V and a booster dose of ChAdOx1 mount a vigorous neutralizing-antibody response after Omicron breakthrough infection.


Assuntos
Formação de Anticorpos , COVID-19 , Humanos , SARS-CoV-2 , COVID-19/prevenção & controle , Vacinação , Anticorpos Neutralizantes , Anticorpos Antivirais
4.
Clin Drug Investig ; 35(3): 211-9, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25637061

RESUMO

BACKGROUND AND OBJECTIVES: Long-term use of antiretroviral therapy (ART) to treat HIV infection has been associated with dyslipidemia and metabolic and cardiovascular complications. Available options for patients at risk of cardiovascular disease include antiretroviral drugs with improved lipid profiles. Dolutegravir is one of a new generation of HIV integrase inhibitors recently incorporated into the US Department of Health and Human Services, German, Spanish, and Italian HIV treatment guidelines as a preferred first-line third agent in combination with dual nucleoside reverse transcriptase inhibitor (NRTI) backbone therapies. To understand the lipid profile of dolutegravir in the context of combination ART, we analyzed the lipid outcomes at 48 weeks in ART-naive participants in four phase IIb-IIIb clinical trials. METHODS: Variables included in this analysis were total cholesterol (TC), low-density lipoprotein (LDL) cholesterol (LDL-C), high-density lipoprotein (HDL) cholesterol (HDL-C), TC/HDL ratio, and triglycerides at baseline and week 48. RESULTS: In a comparative analysis, dolutegravir demonstrated a broadly neutral effect on lipids versus efavirenz or ritonavir-boosted darunavir; in both comparisons, patients taking dolutegravir exhibited smaller increases in TC, LDL-C, and triglyceride levels. In comparison with raltegravir, dolutegravir exhibited a similar lipid profile, including small increases in TC, LDL-C, and triglyceride levels for both agents. In the pooled dolutegravir analysis, minimal increases in LDL-C and triglycerides were observed but mean values at 48 weeks remained below National Cholesterol Education Program target levels. HDL-C levels increased at 48 weeks, and the mean TC/HDL-C ratio was 0.6 at 48 weeks; these values are associated with a lower risk of cardiovascular disease. CONCLUSIONS: Together, these data show that dolutegravir has a safer lipid profile in combination ART and provides an important treatment option for older patients who may have other risk factors for metabolic syndrome or cardiovascular disease.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/sangue , Infecções por HIV/tratamento farmacológico , Lipídeos/sangue , Adulto , Alcinos , Benzoxazinas/administração & dosagem , Benzoxazinas/uso terapêutico , Ensaios Clínicos como Assunto , Ciclopropanos , Darunavir/administração & dosagem , Darunavir/uso terapêutico , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Infecções por HIV/virologia , Compostos Heterocíclicos com 3 Anéis/administração & dosagem , Compostos Heterocíclicos com 3 Anéis/uso terapêutico , Humanos , Masculino , Oxazinas , Piperazinas , Piridonas , Raltegravir Potássico/administração & dosagem , Raltegravir Potássico/uso terapêutico , Ritonavir/administração & dosagem , Ritonavir/uso terapêutico , Fatores de Tempo , Resultado do Tratamento
5.
BMC Infect Dis ; 12: 147, 2012 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-22742573

RESUMO

BACKGROUND: Changes in CD4 cell counts are poorly documented in individuals with low or moderate-level viremia while on antiretroviral treatment (ART) in resource-limited settings. We assessed the impact of on-going HIV-RNA replication on CD4 cell count slopes in patients treated with a first-line combination ART. METHOD: Naïve patients on a first-line ART regimen with at least two measures of HIV-RNA available after ART initiation were included in the study. The relationships between mean CD4 cell count change and HIV-RNA at 6 and 12 months after ART initiation (M6 and M12) were assessed by linear mixed models adjusted for gender, age, clinical stage and year of starting ART. RESULTS: 3,338 patients were included (14 cohorts, 64% female) and the group had the following characteristics: a median follow-up time of 1.6 years, a median age of 34 years, and a median CD4 cell count at ART initiation of 107 cells/µL. All patients with suppressed HIV-RNA at M12 had a continuous increase in CD4 cell count up to 18 months after treatment initiation. By contrast, any degree of HIV-RNA replication both at M6 and M12 was associated with a flat or a decreasing CD4 cell count slope. Multivariable analysis using HIV-RNA thresholds of 10,000 and 5,000 copies confirmed the significant effect of HIV-RNA on CD4 cell counts both at M6 and M12. CONCLUSION: In routinely monitored patients on an NNRTI-based first-line ART, on-going low-level HIV-RNA replication was associated with a poor immune outcome in patients who had detectable levels of the virus after one year of ART.


Assuntos
Contagem de Linfócito CD4 , Infecções por HIV/imunologia , Adulto , Fármacos Anti-HIV/uso terapêutico , Feminino , Infecções por HIV/tratamento farmacológico , Humanos , Masculino , RNA Viral/genética
6.
Antimicrob Agents Chemother ; 56(5): 2570-5, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-22314532

RESUMO

GSK2248761 is a novel, once-daily (QD), next-generation nonnucleoside reverse transcriptase inhibitor (NNRTI) with activity against efavirenz-resistant strains. Two phase I/IIa, double-blind, randomized, placebo-controlled studies investigated the antiviral activity, safety, and pharmacokinetics (PK) of several doses of GSK2248761 monotherapy in treatment-naive HIV-infected subjects. In the initial study, 10 subjects (8 active and 2 placebo) per dose received sequentially descending GSK2248761 monotherapy regimens of 800, 400, 200, and 100 mg QD for 7 days. Because a dose-response relationship was not identified, a second study examined a lower, 30-mg QD dose in 8 subjects (6 active and 2 placebo). Adverse events, viral load (VL), PK, and reverse transcriptase mutations were assessed and combined for analysis. Treatment with GSK2248761 for 7 days was well tolerated with no serious adverse events or discontinuations. The mean VL reductions from baseline on day 8 were 0.97, 1.87, 1.84, 1.81, and 1.78 log(10) copies/ml for GSK2248761 doses of 30, 100, 200, 400, and 800 mg QD, respectively. GSK2248761 PK (maximum drug concentration in serum [C(max)], area under the plasma concentration-time curve from 0 h to the end of the dosing interval [AUC(0-τ)], and concentration at the end of the dosing interval [C(τ)]) increased proportionally over the dose range of 30 to 800 mg QD. The relationship between short-term VL change and GSK2248761 PK was best described by a maximum-effect (E(max)) model using C(τ) (E(max) = 2.0; 50% effective concentration [EC(50)] = 36.9 ng/ml). No NNRTI resistance mutations emerged during the study. GSK2248761 at 100 to 800 mg QD for 7 days was well tolerated, demonstrated potent antiviral activity in treatment-naive HIV-infected subjects, and had favorable PK and resistance profiles. GSK2248761 is no longer in clinical development.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Transcriptase Reversa do HIV/antagonistas & inibidores , HIV-1/efeitos dos fármacos , Indóis/uso terapêutico , Ácidos Fosfínicos/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Adulto , Alcinos , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/síntese química , Argentina , Benzoxazinas , Ciclopropanos , Método Duplo-Cego , Esquema de Medicação , Farmacorresistência Viral , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Feminino , Infecções por HIV/virologia , HIV-1/enzimologia , HIV-1/genética , Humanos , Indóis/administração & dosagem , Indóis/síntese química , Masculino , Mutação , Ácidos Fosfínicos/administração & dosagem , Ácidos Fosfínicos/síntese química , Placebos , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/síntese química , Carga Viral/efeitos dos fármacos
7.
Trials ; 12: 70, 2011 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-21388549

RESUMO

BACKGROUND: Swine origin influenza A/H1N1 infection (H1N1) emerged in early 2009 and rapidly spread to humans. For most infected individuals, symptoms were mild and self-limited; however, a small number developed a more severe clinical syndrome characterized by profound respiratory failure with hospital mortality ranging from 10 to 30%. While supportive care and neuraminidase inhibitors are the main treatment for influenza, data from observational and interventional studies suggest that the course of influenza can be favorably influenced by agents not classically considered as influenza treatments. Multiple observational studies have suggested that HMGCoA reductase inhibitors (statins) can exert a class effect in attenuating inflammation. The Collaborative H1N1 Adjuvant Treatment (CHAT) Pilot Trial sought to investigate the feasibility of conducting a trial during a global pandemic in critically ill patients with H1N1 with the goal of informing the design of a larger trial powered to determine impact of statins on important outcomes. METHODS/DESIGN: A multi-national, pilot randomized controlled trial (RCT) of once daily enteral rosuvastatin versus matched placebo administered for 14 days for the treatment of critically ill patients with suspected, probable or confirmed H1N1 infection. We propose to randomize 80 critically ill adults with a moderate to high index of suspicion for H1N1 infection who require mechanical ventilation and have received antiviral therapy for ≤ 72 hours. Site investigators, research coordinators and clinical pharmacists will be blinded to treatment assignment. Only research pharmacy staff will be aware of treatment assignment. We propose several approaches to informed consent including a priori consent from the substitute decision maker (SDM), waived and deferred consent. The primary outcome of the CHAT trial is the proportion of eligible patients enrolled in the study. Secondary outcomes will evaluate adherence to medication administration regimens, the proportion of primary and secondary endpoints collected, the number of patients receiving open-label statins, consent withdrawals and the effect of approved consent models on recruitment rates. DISCUSSION: Several aspects of study design including the need to include central randomization, preserve allocation concealment, ensure study blinding compare to a matched placebo and the use novel consent models pose challenges to investigators conducting pandemic research. Moreover, study implementation requires that trial design be pragmatic and initiated in a short time period amidst uncertainty regarding the scope and duration of the pandemic. TRIAL REGISTRATION NUMBER: ISRCTN45190901.


Assuntos
Anti-Inflamatórios/uso terapêutico , Antivirais/uso terapêutico , Fluorbenzenos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Vírus da Influenza A Subtipo H1N1/patogenicidade , Influenza Humana/tratamento farmacológico , Pirimidinas/uso terapêutico , Projetos de Pesquisa , Sulfonamidas/uso terapêutico , Doença Aguda , Argentina , Austrália , Canadá , Comportamento Cooperativo , Cuidados Críticos , Estado Terminal , Quimioterapia Combinada , Estudos de Viabilidade , Humanos , Influenza Humana/diagnóstico , Influenza Humana/virologia , Consentimento Livre e Esclarecido , México , Nova Zelândia , Seleção de Pacientes , Projetos Piloto , Respiração Artificial , Rosuvastatina Cálcica , Arábia Saudita , Resultado do Tratamento
8.
Antivir Ther ; 15(2): 185-92, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-20386073

RESUMO

BACKGROUND: Amdoxovir acts synergistically with zidovudine in vitro and the combination prevents or delays the selection of thymidine analogue and K65R mutations. In silico studies have shown that a reduced dose of zidovudine (200 mg) results in decreased zidovudine-monophosphate levels, associated with toxicity, while maintaining zidovudine-triphosphate levels, which are associated with antiviral effects. Here, we aimed to assess the short-term tolerability and antiviral activity of amdoxovir in combination with reduced and standard doses of zidovudine. METHODS: The study was a double-blind, placebo-controlled study in HIV-1-infected patients not receiving antiretroviral therapy and with plasma HIV-1 RNA > or =5,000 copies/ml. Patients were randomized to 10 days of twice-daily treatment with 200 mg zidovudine, 300 mg zidovudine, 500 mg amdoxovir, 500 mg amdoxovir plus 200 mg zidovudine or 500 mg amdoxovir plus 300 mg zidovudine. The mean change in viral load (VL) log(10) and area under the virus depletion curve (AUC(VL)) from baseline to day 10 were determined. Laboratory and clinical safety monitoring were performed. RESULTS: Twenty-four patients were enrolled. The mean VL log(10) change was 0.10 with placebo, -0.69 with zidovudine 200 mg, -0.55 with zidovudine 300 mg, -1.09 with amdoxovir, -2.00 with amdoxovir plus zidovudine (200 mg) and -1.69 with amdoxovir plus zidovudine (300 mg). Amdoxovir plus zidovudine (200 mg) was significantly more potent than amdoxovir monotherapy in AUC(VL) and mean VL decline (P=0.019 and P=0.021, respectively), suggesting synergy. There was markedly decreased VL variability with the combination compared with amdoxovir alone. All adverse events were mild to moderate. CONCLUSION: The combination of amdoxovir plus zidovudine appeared synergistic with reduced VL variability. This combined therapy, including the use of a lower zidovudine dosage, warrants further development for the therapy of HIV infection.


Assuntos
Fármacos Anti-HIV/uso terapêutico , Dioxolanos/uso terapêutico , Infecções por HIV/tratamento farmacológico , HIV-1/efeitos dos fármacos , Nucleosídeos de Purina/uso terapêutico , Inibidores da Transcriptase Reversa/uso terapêutico , Zidovudina/uso terapêutico , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/efeitos adversos , Fármacos Anti-HIV/farmacologia , Dioxolanos/administração & dosagem , Dioxolanos/efeitos adversos , Dioxolanos/farmacologia , Método Duplo-Cego , Quimioterapia Combinada , Feminino , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Nucleosídeos de Purina/administração & dosagem , Nucleosídeos de Purina/efeitos adversos , Nucleosídeos de Purina/farmacologia , RNA Viral/sangue , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/efeitos adversos , Inibidores da Transcriptase Reversa/farmacologia , Resultado do Tratamento , Carga Viral , Adulto Jovem , Zidovudina/administração & dosagem , Zidovudina/efeitos adversos , Zidovudina/farmacologia
9.
AIDS ; 24(6): 885-90, 2010 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-19952712

RESUMO

OBJECTIVE: Protease inhibitors and other antiretroviral drugs have been associated with dyslipidemia, endothelial dysfunction, and increased cardiovascular disease risk. The protease inhibitor atazanavir has an advantageous lipid profile; we studied its effects on arterial function and other metabolic and inflammatory cardiovascular disease risk factors. DESIGN: Prospective, randomized, multinational trial in HIV-infected patients receiving stable protease inhibitor-based therapy with plasma HIV RNA less than 500 copies/ml and fasting low-density lipoprotein cholesterol more than 130 mg/dl, or triglycerides more than 200 mg/dl. METHODS: Patients were randomized to continue their current protease inhibitor or switch the protease inhibitor to atazanavir and continue ritonavir if given as a protease inhibitor booster for 24 weeks. Brachial artery flow-mediated dilation, lipoproteins, and inflammatory and metabolic markers were measured at baseline, week 12, and week 24. Median changes within (signed rank test) and between (Wilcoxon test) arms were calculated. RESULTS: Twenty-six patients switched to atazanavir (all continued on ritonavir); 24 remained on their protease inhibitor regimen. Median CD4 cell count was 499 cells/mul, total cholesterol 204 mg/dl, low-density lipoprotein cholesterol 122 mg/dl, and triglycerides 244 mg/dl. There were no significant changes in flow-mediated dilation after 12 and 24 weeks. At 24 weeks, significant changes in the atazanavir vs. continued protease inhibitor group were observed for total cholesterol (-25 vs. +1.5 mg/dl, P = 0.009), triglycerides (-58 vs. +3.5 mg/dl, P = 0.013), and nonhigh-density lipoprotein cholesterol (-27 vs. -0.5 mg/dl, P = 0.014). CONCLUSION: In dyslipidemic individuals with suppressed HIV RNA on stable therapy, changing the protease inhibitor to atazanavir/ritonavir for 24 weeks improved lipids; however, endothelial function, inflammatory, and metabolic markers did not change.


Assuntos
Doenças Cardiovasculares/tratamento farmacológico , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/administração & dosagem , HIV-1/efeitos dos fármacos , Oligopeptídeos/administração & dosagem , Piridinas/administração & dosagem , Ritonavir/administração & dosagem , Adulto , Idoso , Terapia Antirretroviral de Alta Atividade , Sulfato de Atazanavir , Contagem de Linfócito CD4 , Doenças Cardiovasculares/metabolismo , Feminino , Infecções por HIV/metabolismo , Inibidores da Protease de HIV/efeitos adversos , Humanos , Lipídeos , Masculino , Pessoa de Meia-Idade , Oligopeptídeos/efeitos adversos , Piridinas/efeitos adversos , Ritonavir/efeitos adversos
12.
J Gen Virol ; 89(Pt 11): 2773-2782, 2008 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-18931075

RESUMO

Mother-to-child transmission (MTCT) of human immunodeficiency virus type 1 (HIV-1) as described for women with an established infection is, in most cases, associated with the transmission of few maternal variants. This study analysed virus variability in four cases of maternal primary infection occurring during pregnancy and/or breastfeeding. Estimated time of seroconversion was at 4 months of pregnancy for one woman (early seroconversion) and during the last months of pregnancy and/or breastfeeding for the remaining three (late seroconversion). The C2V3 envelope region was analysed in samples of mother-child pairs by molecular cloning and sequencing. Comparisons of nucleotide and amino acid sequences as well as phylogenetic analysis were performed. The results showed low variability in the virus population of both mother and child. Maximum-likelihood analysis showed that, in the early pregnancy seroconversion case, a minor viral variant with further evolution in the child was transmitted, which could indicate a selection event in MTCT or a stochastic event, whereas in the late seroconversion cases, the mother's and child's sequences were intermingled, which is compatible with the transmission of multiple viral variants from the mother's major population. These results could be explained by the less pronounced selective pressure exerted by the immune system in the early stages of the mother's infection, which could play a role in MTCT of HIV-1.


Assuntos
Aleitamento Materno/efeitos adversos , Infecções por HIV/transmissão , HIV-1/genética , Transmissão Vertical de Doenças Infecciosas , Leite Humano/virologia , Complicações na Gravidez/virologia , Sequência de Aminoácidos , Primers do DNA , Feminino , HIV-1/classificação , HIV-1/patogenicidade , Humanos , Lactente , Recém-Nascido , Dados de Sequência Molecular , Filogenia , Gravidez , Seleção Genética , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Proteínas do Envelope Viral/genética
13.
Medscape J Med ; 10(4): 78, 2008 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-18504475

RESUMO

OBJECTIVE: To report emerging data on the use of highly active antiretroviral therapy (HAART) in Argentina by assessing patterns of HAART access and late vs early treatment initiation in a population-based cohort of adults infected with HIV type-1. DESIGN: The Prospective Study on the Use and Monitoring of Antiretroviral Therapy (PUMA) is a study of 883 HIV-positive individuals enrolled in the Argentinean drug treatment program. Individuals were 16 years of age and older and were recruited from 10 clinics across Argentina. METHODS: Sociodemographic and clinical characteristics were examined using contingency tables (Pearson chi-square test and Fisher exact test) for categoric variables and Wilcoxon rank-sum test for continuous variables. To analyze time to initiation of HAART we used Kaplan-Meier methods and Cox regression. RESULTS: Patients who initiated HAART were more likely to be older, have an AIDS-defining illness, be an injection drug user (IDU), have a lower median CD4 cell count, have a higher median viral load, and be less likely to be men who have sex with men (MSM). In multivariate analysis, AIDS-defining illness and plasma viral load were significantly associated with time to starting therapy. Patients who received late access were more likely to be diagnosed with AIDS and have higher median plasma viral loads than those receiving early access. CONCLUSION: Our results indicate that despite free availability of treatment, monitoring, and care in Argentina, a significant proportion of men and women are accessing HAART late in the course of HIV disease. Further characterization of the HIV-positive population will allow for a more comprehensive evaluation of the impact of HAART within the Argentinean drug treatment program.


Assuntos
Terapia Antirretroviral de Alta Atividade/estatística & dados numéricos , Infecções por HIV/epidemiologia , Infecções por HIV/prevenção & controle , HIV-1 , Acesso aos Serviços de Saúde/estatística & dados numéricos , Medição de Risco/métodos , Adulto , Argentina/epidemiologia , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Fatores Socioeconômicos
15.
J Int AIDS Soc ; 10(4): 78, 2008 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-19825142

RESUMO

OBJECTIVE: To report emerging data on the use of highly active antiretroviral therapy (HAART) in Argentina by assessing patterns of HAART access and late vs early treatment initiation in a population-based cohort of adults infected with HIV type-1. DESIGN: The Prospective Study on the Use and Monitoring of Antiretroviral Therapy (PUMA) is a study of 883 HIV-positive individuals enrolled in the Argentinean drug treatment program. Individuals were 16 years of age and older and were recruited from 10 clinics across Argentina. METHODS: Sociodemographic and clinical characteristics were examined using contingency tables (Pearson chi-square test and Fisher exact test) for categoric variables and Wilcoxon rank-sum test for continuous variables. To analyze time to initiation of HAART we used Kaplan-Meier methods and Cox regression. RESULTS: Patients who initiated HAART were more likely to be older, have an AIDS-defining illness, be an injection drug user (IDU), have a lower median CD4 cell count, have a higher median viral load, and be less likely to be men who have sex with men (MSM). In multivariate analysis, AIDS-defining illness and plasma viral load were significantly associated with time to starting therapy. Patients who received late access were more likely to be diagnosed with AIDS and have higher median plasma viral loads than those receiving early access. CONCLUSION: Our results indicate that despite free availability of treatment, monitoring, and care in Argentina, a significant proportion of men and women are accessing HAART late in the course of HIV disease. Further characterization of the HIV-positive population will allow for a more comprehensive evaluation of the impact of HAART within the Argentinean drug treatment program.

16.
J Acquir Immune Defic Syndr ; 41(4): 425-9, 2006 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-16652049

RESUMO

OBJECTIVE: To evaluate clinical, immunologic, and virologic performance of patients with nadir CD4 counts of >350 cells/microL upon treatment interruption. DESIGN: Randomized, open-label clinical trial of 48 weeks' duration. METHODS: Patients on effective highly active antiretroviral therapy, with nadir CD4 counts of >350 cells/microL and peak viral loads of <50,000 copies/mL were randomized to continue therapy or to interrupt antiretroviral medication. End points for patients with treatment interruption were CD4 counts of <350 cells/microL, viral loads of >1 log above the pretherapy values, or clinical symptoms attributable to HIV, at which point treatment was restarted. In the continuation group, the end points were virologic failure, opportunistic infections, and treatment discontinuation due to toxicities. RESULTS: Twenty patients were randomized to stop therapy and 16 patients to continue. Median CD4 counts at baseline were 643 cells/microL for the interruption group and 633 cells/microL for the continuation group. No end points were reached in the interruption group. By week 8, viral load returned to values comparable to those of pretherapy in all patients in the interruption group and remained stable until week 48. CD4 counts dropped in the interruption group (median loss of 156 cells/microL) at week 48. Significant decreases in venous lactate were observed in the interruption group. CONCLUSIONS: Treatment interruptions in patients with nadir CD4 counts of >350 cells/microL seem safe for at least 48 weeks. Pretherapy viral load appears as a valuable tool to predict its level at week 48.


Assuntos
Fármacos Anti-HIV/administração & dosagem , Contagem de Linfócito CD4 , Infecções por HIV/tratamento farmacológico , Adulto , Fármacos Anti-HIV/farmacologia , Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Feminino , Infecções por HIV/imunologia , Humanos , Ácido Láctico/sangue , Masculino , Pessoa de Meia-Idade , Carga Viral
17.
J Infect Dis ; 193(2): 259-68, 2006 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-16362890

RESUMO

BACKGROUND: We sought to characterize the impact that hepatitis C virus (HCV) infection has on CD4 cells during the first 48 weeks of antiretroviral therapy (ART) in previously ART-naive human immunodeficiency virus (HIV)-infected patients. METHODS: The HIV/AIDS Drug Treatment Programme at the British Columbia Centre for Excellence in HIV/AIDS distributes all ART in this Canadian province. Eligible individuals were those whose first-ever ART included 2 nucleoside reverse transcriptase inhibitors and either a protease inhibitor or a nonnucleoside reverse transcriptase inhibitor and who had a documented positive result for HCV antibody testing. Outcomes were binary events (time to an increase of > or = 75 CD4 cells/mm3 or an increase of > or = 10% in the percentage of CD4 cells in the total T cell population [CD4 cell fraction]) and continuous repeated measures. Statistical analyses used parametric and nonparametric methods, including multivariate mixed-effects linear regression analysis and Cox proportional hazards analysis. RESULTS: Of 1186 eligible patients, 606 (51%) were positive and 580 (49%) were negative for HCV antibodies. HCV antibody-positive patients were slower to have an absolute (P<.001) and a fraction (P = .02) CD4 cell event. In adjusted Cox proportional hazards analysis (controlling for age, sex, baseline absolute CD4 cell count, baseline pVL, type of ART initiated, AIDS diagnosis at baseline, adherence to ART regimen, and number of CD4 cell measurements), HCV antibody-positive patients were less likely to have an absolute CD4 cell event (adjusted hazard ratio [AHR], 0.84 [95% confidence interval [CI], 0.72-0.98]) and somewhat less likely to have a CD4 cell fraction event (AHR, 0.89 [95% CI, 0.70-1.14]) than HCV antibody-negative patients. In multivariate mixed-effects linear regression analysis, HCV antibody-negative patients had increases of an average of 75 cells in the absolute CD4 cell count and 4.4% in the CD4 cell fraction, compared with 20 cells and 1.1% in HCV antibody-positive patients, during the first 48 weeks of ART, after adjustment for time-updated pVL, number of CD4 cell measurements, and other factors. CONCLUSION: HCV antibody-positive HIV-infected patients may have an altered immunologic response to ART.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Síndrome de Imunodeficiência Adquirida/imunologia , Terapia Antirretroviral de Alta Atividade , Contagem de Linfócito CD4 , Hepatite C/complicações , Síndrome de Imunodeficiência Adquirida/complicações , Adulto , Relação CD4-CD8 , Estudos de Coortes , Feminino , Inibidores da Protease de HIV/administração & dosagem , Inibidores da Protease de HIV/uso terapêutico , Hepatite C/imunologia , Anticorpos Anti-Hepatite C/sangue , Humanos , Masculino , Inibidores da Transcriptase Reversa/administração & dosagem , Inibidores da Transcriptase Reversa/uso terapêutico
19.
J Clin Virol ; 30(3): 271-5, 2004 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-15135748

RESUMO

BACKGROUND: Prolonged therapy with ganciclovir (GCV) can result in the development of GCV-resistant strains due to mutations in the viral phosphotransferase (UL97 gene) and/or in the viral DNA polymerase (UL54 gene). OBJECTIVES: The purpose of this study was to detect by molecular methods the most prevalent UL97 mutants which confer ganciclovir-resistance in immunocompromised populations. STUDY DESIGN: Patients from two populations were selected: (a) renal transplant patients with active cytomegalovirus (CMV) infection and more than one cycle of GCV; (b) HIV-infected patients with retinitis due to CMV, who were under GCV induction, maintenance therapy or withdrawal. Patients were followed up by pp65 antigenemia and by viral isolation from blood or/and urine samples. Two fragments (133 and 255pb) of the UL97 gene were amplified by polymerase chain reaction (PCR) from CMV isolates. RESULTS: Nine from 12 isolates obtained were sequenced, three from two renal transplant patients and six from five HIV-infected patients. A UL97 mutation, known to confer GCV resistance, was found in two isolates from a renal transplant patient. A methionine to valine mutation at codon 460 (M460V) was detected. These isolates exhibited another mutation at codon 605, whose amino acid changed from aspartic acid (D) to glutamic acid (E). These findings were observed after treatment with IV-GCV/ O-GCV/ IV-GCV for 151 days. The 605 mutation was also detected in leukocytes from the same patient previous to the beginning of the treatment with GCV. CONCLUSIONS: Although a known resistant mutation appeared in a renal transplant patient, it was not associated with CMV disease. We suggest that the D605E mutation could "partially or totally compensate" for the effect of GCV resistance conferred by the 460 mutation. Further studies should be performed to confirm this hypothesis.


Assuntos
Antivirais/farmacologia , Citomegalovirus/efeitos dos fármacos , Farmacorresistência Viral , Ganciclovir/farmacologia , Hospedeiro Imunocomprometido , Mutação , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Infecções Oportunistas Relacionadas com a AIDS/virologia , Argentina , Infecções por Citomegalovirus/diagnóstico , Infecções por Citomegalovirus/tratamento farmacológico , Infecções por Citomegalovirus/virologia , Retinite por Citomegalovirus/diagnóstico , Retinite por Citomegalovirus/tratamento farmacológico , Retinite por Citomegalovirus/virologia , Humanos , Transplante de Rim/efeitos adversos , Dados de Sequência Molecular , Reação em Cadeia da Polimerase , Análise de Sequência de DNA
20.
Ann Intern Med ; 139(2): 81-9, 2003 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-12859157

RESUMO

BACKGROUND: Mathematical modeling has suggested that alternating antiretroviral regimens while patients' viral load remains suppressed would minimize HIV resistance mutations. OBJECTIVE: To compare alternation of antiretroviral regimens with the current standard of switching regimens after viral load rebound. DESIGN: Randomized, multicenter, open-label, pilot trial. SETTING: 15 outpatient HIV clinics in Spain and Argentina. PATIENTS: 161 HIV-1-infected, antiretroviral-naive persons. INTERVENTION: Patients were assigned to continuously receive stavudine, didanosine, and efavirenz (standard of care, regimen A) or zidovudine, lamivudine, and nelfinavir (standard of care, regimen B) until virologic failure, or to alternate between those two regimens every 3 months while viral load was suppressed (regimen C). MEASUREMENTS: Time to virologic failure, percentage of patients with undetectable plasma viremia over 48 weeks, CD4 and CD8 cell counts, adverse events, emergence of drug resistance, drug adherence, and quality of life. RESULTS: Patients receiving standard-of-care regimens A and B did not differ. Virologic failure over 48 weeks was delayed in the alternating therapy group compared with the pooled standard-of-care group (incidence rate, 1.2 events/1000 person-weeks [95% CI, 0.3 to 3.6 events/1000 person-weeks] vs. 4.8 events/1000 person-weeks [CI, 2.9 to 7.4 events/1000 person-weeks]; P = 0.01). Genotypic drug resistance emerged in 79% of patients in the standard-of-care group who experienced on-therapy treatment failure. Patients in the standard-of-care and alternating therapy groups had similar CD4 cell counts, frequency of adverse events, reported drug adherence, and quality of life. CONCLUSIONS: Virologic outcome was better with alternating therapy than with the current standard of care, while adverse events and adherence were similar. The strategy of alternating therapy merits further investigation.


Assuntos
Síndrome de Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade/métodos , Síndrome de Imunodeficiência Adquirida/virologia , Adulto , Terapia Antirretroviral de Alta Atividade/efeitos adversos , Contagem de Linfócito CD4 , Relação CD4-CD8 , Progressão da Doença , Esquema de Medicação , Farmacorresistência Viral , Feminino , Humanos , Masculino , Cooperação do Paciente , Projetos Piloto , Qualidade de Vida , Falha de Tratamento , Carga Viral
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