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1.
J Antimicrob Chemother ; 72(1): 240-245, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27629069

RESUMO

OBJECTIVES: We assessed factors, including treatment course, associated with failure to obtain a 10 year immunological response after starting first-generation PI-containing combined ART (cART). PATIENTS AND METHODS: In the prospective COPILOTE cohort of HIV-infected patients started on a first-generation PI-containing regimen in 1997-99, the impact of cART history on the failure to achieve immunological response measured at 10 years was assessed by multivariate logistic regression models in the 399 patients with clinical and virological success of cART. RESULTS: Failure of CD4 response (CD4 >500/mm3) was associated with age ≥40 years at baseline (P < 0.001), CD4 cell counts ≤500/mm3 at month 4 (P = 0.016) or month 12 (P < 0.001) and ≥3 months of cART interruption (P = 0.016). Factors associated with failure to achieve complete immunological response (CD4 >500/mm3 and CD4:CD8 ratio >1) were CD4:CD8 ratio ≤0.8 at month 8 (P < 0.001) or month 12 (P < 0.001), ≥3 months of cumulative cART interruption (P = 0.011), ≥3 antiretroviral regimens (P = 0.009) and ≤4 treatment lines (P = 0.015). Baseline CD4 and CD4:CD8 ratio were not predictors of the 10 year immunological outcomes. CONCLUSIONS: In this therapeutic cohort of patients starting first-generation PI-containing cART in 1997-99, poor initial immunological response had a negative impact on 10 year CD4 and CD4 plus CD4:CD8 ratio response, despite prolonged virological success. Lack of treatment interruption may improve long-term immunological outcome in HIV infection.


Assuntos
Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Infecções por HIV/tratamento farmacológico , Adulto , Contagem de Linfócito CD4 , Relação CD4-CD8 , Feminino , Infecções por HIV/imunologia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Falha de Tratamento
2.
Clin Infect Dis ; 61(8): 1328-35, 2015 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-26105170

RESUMO

BACKGROUND: Rifampicin (RIF) induces UGT1A1, an enzyme involved in raltegravir (RAL) elimination, thereby potentially lowering RAL exposure. We examined the pharmacokinetics of RAL in human immunodeficiency virus (HIV)-infected patients on RIF-based antitubercular therapy in the French National Agency for HIV/AIDS and Viral Hepatitis Research 12 180 Reflate Tuberculosis trial. METHODS: Patients started RAL in combination with tenofovir disoproxil fumarate and lamivudine after initiation of RIF (10 mg/kg/day). In arm 1 (n = 21), they received 400 mg RAL twice daily; in arm 2 (n = 16), they received RAL 800 mg twice daily initially then 400 mg twice daily 4 weeks after RIF discontinuation. Pharmacokinetic sampling was performed over 12-hour periods, 4 weeks after initiation of RAL together with RIF (period 1), 4 weeks after RIF discontinuation (period 2), and after the RAL dose reduction in arm 2 (period 3). RESULTS: In arm 1, the geometric mean ratio (GMR) between period 1 and period 2 was 0.94 (90% confidence interval [CI], .64-1.37) for the 12-hour area under the time-concentration curve (AUC0-12), and 0.69 (90% CI, .42-1.13) for the concentration at 12 hours (C12). In arm 2, the corresponding GMRs were 0.75 (90% CI, .48-1.17) and 1.10 (90% CI, .61-2.00) for period 1 vs period 2, and 1.10 (90% CI, .78-1.55) and 1.68 (90% CI, .88-3.23) for period 1 vs period 3. CONCLUSIONS: The double dose of RAL overcompensated for RIF induction, but the standard dose was associated with only small decreases in AUC0-12 and C12 during RIF coadministration, warranting further evaluation in patients with HIV/tuberculosis coinfection. CLINICAL TRIALS REGISTRATION: NCT0082231.


Assuntos
Fármacos Anti-HIV/farmacocinética , Antibióticos Antituberculose/uso terapêutico , Infecções por HIV/tratamento farmacológico , Raltegravir Potássico/farmacocinética , Rifampina/uso terapêutico , Tuberculose/tratamento farmacológico , Adulto , Fármacos Anti-HIV/administração & dosagem , Fármacos Anti-HIV/uso terapêutico , Coinfecção , Esquema de Medicação , Quimioterapia Combinada , Feminino , Infecções por HIV/complicações , HIV-1/efeitos dos fármacos , Humanos , Lamivudina/administração & dosagem , Lamivudina/uso terapêutico , Masculino , Raltegravir Potássico/administração & dosagem , Tenofovir/administração & dosagem , Tenofovir/uso terapêutico
3.
PLoS One ; 11(12): e0168640, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27977797

RESUMO

OBJECTIVE: To assess whether higher 25-hydroxyvitamin D (25OHD) levels are associated with subsequent better immune responses to hepatitis B and Streptococcus pneumoniae vaccination in HIV-infected patients. METHODS: 25OHD was measured on stored baseline plasma samples from two randomized vaccine trials in HIV-infected adults: the ANRS HB03 VIHVAC B trial and an immunological sub-study of the ANRS 114-PNEUMOVAC trial. In ANRS HB03 VIHVAC B, participants received three or four doses of recombinant HBV vaccine strategies. Anti-HBs IgG titers were measured four weeks after the last injection. Associations between baseline 25OHD levels and ordered IgG response categories were analyzed in multivariable proportional odds models. In the ANRS 114-PNEUMOVAC sub-study, two strategies of pneumococcal vaccination were tested, cellular immune responses were measured at repeated time points, and IgG responses four weeks after the last vaccine injection. Exploratory statistical analyses were performed on this sub-study data set. RESULTS: Three hundred and thirty-nine ANRS HB03 VIHVAC B and 25 ANRS 114-PNEUMOVAC sub-study participants were included in the analyses. Median age in each of the two studies was 43 years, 68% were male, and 77-92% on antiretroviral treatment. Median 25OHD level was 18 ng/mL (IQR: 12-25) and 24 ng/mL (IQR: 13-32) in the two trial populations, respectively. In the multivariable model, there was no significant association between baseline 25OHD level and vaccine responses in ANRS HB03 VIHVAC B (proportional odds ratio 0.83 per 10 ng/mL 25OHD increase; 95% confidence interval 0.65-1.07, p = 0.14). Exploratory analyses of ANRS 114-PNEUMOVAC showed consistent results. CONCLUSION: This study does not support a positive association between 25OHD and immune responses to hepatitis B or pneumococcal vaccination in HIV-infected patients.


Assuntos
Hepatite B/sangue , Hepatite B/imunologia , Vacinas Pneumocócicas/uso terapêutico , Vitamina D/sangue , Adulto , Feminino , Hepatite B/prevenção & controle , Anticorpos Anti-Hepatite B/sangue , Vacinas contra Hepatite B/uso terapêutico , Humanos , Imunoglobulina G/sangue , Masculino , Pessoa de Meia-Idade , Streptococcus pneumoniae/imunologia , Streptococcus pneumoniae/patogenicidade , Vitamina D/análogos & derivados
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