RESUMO
BACKGROUND: Previous studies have demonstrated the efficacy of treatment for latent tuberculosis infection (TLTBI) in persons infected with the human immunodeficiency virus, but few studies have investigated the operational aspects of implementing TLTBI in the co-infected population.The study objectives were to describe eligibility for TLTBI as well as treatment prescription, initiation and completion in an HIV-infected Spanish cohort and to investigate factors associated with treatment completion. METHODS: Subjects were prospectively identified between 2000 and 2003 at ten HIV hospital-based clinics in Spain. Data were obtained from clinical records. Associations were measured using the odds ratio (OR) and its 95% confidence interval (95% CI). RESULTS: A total of 1242 subjects were recruited and 846 (68.1%) were evaluated for TLTBI. Of these, 181 (21.4%) were eligible for TLTBI either because they were tuberculin skin test (TST) positive (121) or because their TST was negative/unknown but they were known contacts of a TB case or had impaired immunity (60). Of the patients eligible for TLTBI, 122 (67.4%) initiated TLTBI: 99 (81.1%) were treated with isoniazid for 6, 9 or 12 months; and 23 (18.9%) with short-course regimens including rifampin plus isoniazid and/or pyrazinamide. In total, 70 patients (57.4%) completed treatment, 39 (32.0%) defaulted, 7 (5.7%) interrupted treatment due to adverse effects, 2 developed TB, 2 died, and 2 moved away. Treatment completion was associated with having acquired HIV infection through heterosexual sex as compared to intravenous drug use (OR:4.6; 95% CI:1.4-14.7) and with having taken rifampin and pyrazinamide for 2 months as compared to isoniazid for 9 months (OR:8.3; 95% CI:2.7-24.9). CONCLUSIONS: A minority of HIV-infected patients eligible for TLTBI actually starts and completes a course of treatment. Obstacles to successful implementation of this intervention need to be addressed.
Assuntos
Antituberculosos/uso terapêutico , Infecções por HIV/complicações , Tuberculose Latente/tratamento farmacológico , Adulto , Feminino , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha , Resultado do TratamentoRESUMO
INTRODUCTION: Tuberculin skin testing (TST) for tuberculosis (TB) is recommended for all patients with HIV infection because of the known relationship between these two conditions. In this report we analyze the incidence and variables associated with non-prescription of TST in a cohort of HIV-infected people. PATIENTS AND METHODS: Longitudinal study conducted between 2000 and 2002 at 10 HIV hospital-based clinics. All HIV-infected patients who had not been regularly followed-up previously in dedicated clinics were identified. Data about TST and other variables related to TB were obtained from the clinical records. We calculated the percentage of patients who did not undergo TST and the associated factors, using odds ratios (ORs) and the 95% CI to investigate associations. A multivariate logistic regression analysis was performed. RESULTS: A total of 1242 patients met the inclusion criteria. TST was not performed in 185 patients (17.6% of those eligible). The fact of being an intravenous drug abuser was associated with a higher probability of TST non-prescription (OR: 2.6, 95% CI 1.1-6.5), whereas being unemployed (OR: 0.6, 95% CI 0.3-1.0), having a CD4 cell count >200 (CD4 200-499: OR 0.5, 95% CI 0.3-0.9. CD4> or =500: OR 0.3, 95% CI 0.2-0.6), and contact with persons with TB (OR 0.2, 95% CI 0.1-0.5) were associated with a lower probability. CONCLUSIONS: In this study, the percentage of TST non-prescription was quite high. The results suggest that TST non-prescription in this population is related to the clinicians' expectations regarding the results of the test and the patients' adherence to treatment for latent TB infection.
Assuntos
Infecções por HIV/complicações , Teste Tuberculínico/estatística & dados numéricos , Tuberculose/diagnóstico , Adulto , Estudos de Coortes , Comorbidade , Diagnóstico Tardio , Testes Diagnósticos de Rotina/estatística & dados numéricos , Emigrantes e Imigrantes/estatística & dados numéricos , Feminino , Fidelidade a Diretrizes , Infecções por HIV/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Comportamento Sexual , Fatores Socioeconômicos , Espanha/epidemiologia , Abuso de Substâncias por Via Intravenosa/epidemiologia , Reação Transfusional , Tuberculose/complicações , Tuberculose/epidemiologia , Adulto JovemRESUMO
The effect of hepatic impairment on lopinavir/ritonavir pharmacokinetics was investigated. Twenty-four HIV-1-infected subjects received lopinavir 400 mg/ritonavir 100 mg twice daily prior to and during the study: 6 each with mild or moderate hepatic impairment (and hepatitis C virus coinfected) and 12 with normal hepatic function. Mild and moderate hepatic impairment showed similar effects on lopinavir pharmacokinetics. When the 2 hepatic impairment groups were combined, lopinavir Cmax and AUC12 were increased 20% to 30% compared to the controls. Hepatic impairment increased unbound lopinavir AUC12 by 68% and Cmax by 56%. The effect of hepatic impairment on low-dose ritonavir pharmacokinetics was more pronounced in the moderate impairment group (181% and 221% increase in AUC12 and Cmax, respectively) than in the mild impairment group (39% and 61% increase in AUC12 and Cmax, respectively). While lopinavir/ritonavir dose reduction is not recommended in subjects with mild or moderate hepatic impairment, caution should be exercised in this population.
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Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/farmacocinética , Hepatite C/complicações , Hepatopatias/metabolismo , Pirimidinonas/farmacocinética , Ritonavir/farmacocinética , Adulto , Área Sob a Curva , Disponibilidade Biológica , Combinação de Medicamentos , Monitoramento de Medicamentos , Feminino , Infecções por HIV/complicações , HIV-1 , Humanos , Hepatopatias/complicações , Lopinavir , Masculino , Pessoa de Meia-Idade , Ensaio RadioliganteRESUMO
OBJECTIVE: This study evaluated maintenance with lopinavir/ritonavir monotherapy vs. continuing lopinavir/ritonavir and 2 nucleosides in HIV-infected patients with suppressed HIV replication. DESIGN: Randomized, controlled, open-label, multicenter, pilot clinical trial. METHODS: Adult patients were eligible if they had no history of virologic failure while receiving a protease inhibitor, were receiving 2 nucleosides + lopinavir/ritonavir (400/100 mg b.i.d.) for >1 month and had maintained serum HIV RNA <50 copies/mL for >6 months prior to enrollment. RESULTS: Forty-two patients were randomly assigned 1:1 to continue or stop the nucleosides. At baseline there were no significant differences between groups in median CD4 cells/muL (baseline or nadir), pre-HAART (highly active antiretroviral therapy) HIV log10 viremia, or time with HIV RNA <50 copies/mL prior to enrollment. After 48 weeks of follow-up, percentage of patients remaining at <50 HIV RNA copies/mL (intention to treat, M = F) was 81% for the monotherapy group (95% CI: 64% to 98%) vs. 95% for the triple-therapy group (95% CI: 86% to 100%); P = 0.34. Patients in whom monotherapy failed had significantly worse adherence than patients who remained virally suppressed on monotherapy. Monotherapy failures did not show primary resistance mutations in the protease gene and were successfully reinduced with prerandomization nucleosides. Mean change in CD4 cells/microL: +70 (monotherapy) and +8 (triple) (P = 0.27). Mean serum fasting lipids remained stable in both groups. No serious adverse events were observed. CONCLUSION: Most of the patients maintained with lopinavir/ritonavir monotherapy remain with undetectable viral load after 48 weeks. Failures of lopinavir/ritonavir monotherapy were not associated with the development of primary resistance mutations in the protease gene and could be successfully reinduced adding back prior nucleosides.
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Infecções por HIV/tratamento farmacológico , HIV-1 , Pirimidinonas/uso terapêutico , Ritonavir/uso terapêutico , Adulto , Feminino , Infecções por HIV/virologia , HIV-1/genética , HIV-1/isolamento & purificação , Humanos , Lopinavir , Masculino , Projetos Piloto , Pirimidinonas/administração & dosagem , RNA Viral/análise , Ritonavir/administração & dosagem , EspanhaRESUMO
OBJECTIVES: The aim of this study was to evaluate the frequency, characteristics and risk factors of lipid changes associated with lopinavir/ritonavir treatment in antiretroviral-naive patients. METHODS: A prospective cohort of 107 antiretroviral-naive HIV-infected patients was followed for 12 months after starting lopinavir/ritonavir-based highly active antiretroviral therapy. RESULTS: At 12 months, percentages of patients with hypercholesterolaemia and hypertriglyceridaemia were 17.4% and 40%, respectively. Mean increases in total cholesterol and triglycerides were 40.7 and 73.3 mg/dL. There was a significant increase in both low-density and high-density (HDL) cholesterol, and no increase in the total cholesterol/HDL ratio (from 4.16 at baseline to 4.49 after 12 months). Baseline cholesterol > 200 mg/dL and triglycerides > 150 mg/dL were independent risk factors for dyslipidaemia, while hepatitis C coinfection appeared to be protective. CONCLUSIONS: Patients with elevated lipid values at baseline have the greatest risk of developing hypercholesterolaemia and hypertriglyceridaemia after starting lopinavir/ritonavir. Antiretroviral-naive patients coinfected with hepatitis C have a low risk of developing hyperlipidaemia after starting lopinavir/ritonavir.
Assuntos
Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Inibidores da Protease de HIV/efeitos adversos , Hiperlipidemias/induzido quimicamente , Pirimidinonas/efeitos adversos , Ritonavir/efeitos adversos , Adulto , Idoso , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Feminino , Infecções por HIV/complicações , Inibidores da Protease de HIV/uso terapêutico , Hepatite C/complicações , Humanos , Hipercolesterolemia/induzido quimicamente , Hipertrigliceridemia/induzido quimicamente , Lipídeos/sangue , Lopinavir , Masculino , Pessoa de Meia-Idade , Pirimidinonas/uso terapêutico , Fatores de Risco , Ritonavir/uso terapêutico , Triglicerídeos/sangueRESUMO
OBJECTIVE: To compare the clinical, immunologic, and virologic outcomes of efavirenz (EFV)-based versus protease inhibitor (PI)-based highly active antiretroviral therapy (HAART) in severely immunosuppressed HIV-1-infected patients. DESIGN: Retrospective observational cohort study. METHODS: Responses were analyzed according to the intent-to-treat principle among antiretroviral-naive patients with < 100 CD4 cells/muL who started EFV (n = 92) or a PI (n = 218) plus 2 nucleoside reverse transcriptase inhibitors. The primary end point was time to treatment failure. Secondary end points were percentage of patients with a viral load < 400 copies/mL, time to virologic failure, time to CD4 lymphocyte count > 200 cells/microL, and incidence of opportunistic events or death. RESULTS: The median baseline CD4 cell count and viral load were 34 cells/microL and 5.54 log10 copies/mL (EFV group) and 38 cells/microL and 5.40 log10 copies/mL (PI group). Time to treatment failure was shorter with a PI-based regimen than with an EFV-based regimen (adjusted relative hazard [RH] = 2.19, 95% confidence interval [CI]: 1.23-3.89). After 12 months of therapy, a significantly higher proportion of patients receiving EFV reached a viral load < 400 copies/mL (69.4 vs. 45.1%; P < 0.05). The probability of virologic failure was higher with a PI than with EFV (adjusted HR = 2.52, 95% CI: 1.14-5.61; P = 0.024). There was no difference in time to CD4 cell count > 200 cells/microL or in incidence of opportunistic events or death. CONCLUSION: : In severely immunosuppressed, antiretroviral-naive, HIV-1-infected patients, treatment with an EFV-based regimen compared with a nonboosted PI-based regimen resulted in a superior virologic response with no difference in immunologic or clinical effectiveness.