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3.
J Med Virol ; 85(1): 8-15, 2013 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23024008

RESUMEN

The objective of this study was to evaluate the switch to once-daily darunavir/ritonavir 800/100 mg in treatment-experienced patients with suppressed HIV-1 replication on a twice-daily ritonavir-boosted protease-inhibitor (bid PI/r) containing regimen, that is in a setting where genotypic resistance test cannot be performed. In this open label, non-comparative, multicenter study, patients on a bid PI/r-containing triple combination, with suppressed viral replication, were switched to once-daily darunavir/r 800/100 mg containing triple combination. The primary endpoint was the proportion of patients with plasma HIV-RNA < 50 copies/ml 24 weeks after the switch. Intensive darunavir pharmacokinetic evaluation was performed at Week 4 (W4) in 11 patients. Eighty-five patients were enrolled. All had HIV-RNA < 50 copies/ml at screening with a pre-exposure to a median of 2 PI/r (1-5). By intent-to-treat analysis (missing = failure), 78/85 patients (92%, 95% CI [83;96]) maintained an HIV-RNA < 50 copies/ml at W24. Seven patients experienced protocol-defined treatment failure between baseline and W24: Two had confirmed low-level viral rebound, one discontinued study treatment for adverse event, three withdrew their consent, and one was lost to follow-up. By on-treatment analysis, 78/80 patients (97%, 95% CI [91;99]) maintained an HIV-RNA < 50 copies/ml at W24. Results were similar at Week 48. The median area under the darunavir plasma concentration-time curve measured in 11 patients was 61,380 ng hr/ml; darunavir median trough concentration 1,340 ng/ml and darunavir half-life was 12.2 hr. Tolerability of once-daily darunavir/r 800/100 mg was excellent. Optimally suppressed, treatment-experienced patients can switch safely from a twice-daily PI/r regimen to a once-daily darunavir/r 800/100 mg containing regimen.


Asunto(s)
Fármacos Anti-VIH/administración & dosificación , Terapia Antirretroviral Altamente Activa/métodos , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/virología , VIH-1/aislamiento & purificación , Ritonavir/administración & dosificación , Sulfonamidas/administración & dosificación , Adulto , Anciano , Fármacos Anti-VIH/farmacocinética , Darunavir , Femenino , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Sulfonamidas/farmacocinética , Resultado del Tratamiento , Carga Viral , Adulto Joven
4.
Antivir Ther ; 13(1): 67-76, 2008.
Artículo en Inglés | MEDLINE | ID: mdl-18389900

RESUMEN

BACKGROUND: Although thiazolidinediones have been shown to increase subcutaneous fat in congenital lipodystrophy, rosiglitazone did not show convincing results in HIV lipoatrophy. We assess a potential specific effect of pioglitazone in this setting. METHODS: One-hundred and thirty HIV-1-infected adults with self-reported lipoatrophy confirmed by physical examination were randomized to receive pioglitazone 30 mg once daily (n=64) or placebo (n=66) for 48 weeks. Changes in limb fat between weeks 0 and 48 were measured using dual-energy Xray absorptiometry. Subcutaneous and visceral fat was measured by single-slice computed tomography; fasting plasma measurements of glucose, insulin and lipids levels were recorded. RESULTS: Limb fat increased by 0.38 kg in the pioglitazone group and 0.05 kg in the placebo group at week 48 (mean difference 0.33 kg, 95% confidence interval [CI] 0.10-0.56; P=0.051) by intention-to-treat analysis. In patients not receiving stavudine, an increase of 0.45 kg versus 0.04 kg was observed (mean difference, 0.40 kg, 95% CI 0.12-0.69; P=0.013), but this was not seen in patients on stavudine (n=36; P=0.404). Overall, there was no significant difference in subcutaneous abdominal fat or in visceral fat areas on computed tomography at L4 vertebra. The lipid profile was not significantly different at week 48 except for levels of high-density lipoprotein cholesterol, which was improved in the pioglitazone group (+0.08 mmol/l versus -0.08; P=0.005). CONCLUSIONS: Pioglitazone 30 mg once daily for 48 weeks improved limb fat atrophy in antiretroviral-treated HIV-1-infected patients, although clinical benefits were not perceived by the patients. Treatment did lead to a favourable lipid profile, however, suggesting that this thiazolidinedione should be considered in the context of HIV-related lipoatrophy.


Asunto(s)
Síndrome de Lipodistrofia Asociada a VIH/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Tiazolidinedionas/uso terapéutico , Adulto , Método Doble Ciego , Femenino , VIH-1 , Humanos , Masculino , Persona de Mediana Edad , Pioglitazona
5.
Vaccine ; 23(34): 4292-301, 2005 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-15927325

RESUMEN

This open single-arm study evaluated whether the administration of an HIV-recombinant canarypox vaccine (vCP1433) in highly active antiretroviral therapy (HAART)-treated patients chronically infected with HIV was safe, immunogenic and associated with prolongation of treatment discontinuation: 48 patients received four monthly vCP1433 injections and stopped HAART. Immunization was safe. HIV-p24-specific lymphoproliferative responses (LPR), significantly increased in the whole group after two injections but decreased thereafter, HIV-gag-specific CD8 T cells were boosted in 55% patients tested. Altogether, 11% patients with at least one HIV-specific LPR during immunization remained off therapy after 44 weeks of interruption. Detection of such LPR response at the time of treatment interruption was significantly associated with the probability of remaining off therapy. These results provide rationale for future randomized trials exploring this strategy.


Asunto(s)
Vacunas contra el SIDA/inmunología , Virus de la Viruela de los Canarios/inmunología , Infecciones por VIH/terapia , VIH-1/inmunología , Vacunas Sintéticas/inmunología , Vacunas contra el SIDA/efectos adversos , Adulto , Linfocitos T CD8-positivos/inmunología , Femenino , Proteína p24 del Núcleo del VIH/inmunología , Infecciones por VIH/inmunología , Humanos , Inmunización , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Estudios Prospectivos
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