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Plasma extracellular vesicle (EV)-associated cytokines were quantified in people with HIV (PWH) with different virological control status, including elite controllers (EC) who maintain persistent control (PC) or not (TC). Cytokine signatures and pathways were determined for each group. Median EV-associated cytokine levels were higher among PWH than HIV-uninfected. EC showed the highest levels of EV-associated cytokines among PWH with PC levels higher than TC levels. IL-18 levels best distinguished PWH from uninfected controls, and EC from ART-treated, and IL-3 distinguished PC from TC. The role of EV-cytokines in intercellular communication and endogenous control of HIV expression should be investigated further.

Objectives: To describe the pattern of drug resistance at virological failure in the NEAT001/ANRS143 trial (first-line treatment with ritonavir-boosted darunavir plus either tenofovir/emtricitabine or raltegravir). Methods: Genotypic testing was performed at baseline for reverse transcriptase (RT) and protease genes and for RT, protease and integrase (IN) genes for patients with a confirmed viral load (VL) >50 copies/mL or any single VL >500 copies/mL during or after week 32. Results: A resistance test was obtained for 110/805 (13.7%) randomized participants qualifying for resistance analysis (61/401 of participants in the raltegravir arm and 49/404 of participants in the tenofovir/emtricitabine arm). No resistance-associated mutation (RAM) was observed in the tenofovir/emtricitabine plus darunavir/ritonavir arm, and all further analyses were limited to the raltegravir plus darunavir arm. In this group, 15/55 (27.3%) participants had viruses with IN RAMs (12 N155H alone, 1 N155H + Q148R, 1 F121Y and 1 Y143C), 2/53 (3.8%) with nucleotide analogue RT inhibitor RAMs (K65R, M41L) and 1/57 (1.8%) with primary protease RAM (L76V). The frequency of IN mutations at failure was significantly associated with baseline VL: 7.1% for a VL of

To assess the effectiveness and safety of antiretroviral therapy with unboosted atazanavir (400 mg once daily) plus co-formulated abacavir/lamivudine as a treatment simplification strategy in HIV-infected patients with sustained viral suppression in routine clinical practice.We performed a retrospective study including patients who were switched to unboosted atazanavir plus abacavir/lamivudine and whose HIV-1 RNA was50 copies/mL. The primary endpoint was the percentage of subjects who maintained viral suppression after 48 weeks of follow-up. Secondary endpoints included the percentage of subjects who maintained viral suppression after 96 weeks of follow-up, the incidence of adverse events, changes in CD4+ T-cell count and in lipid profile, and the percentage of patients with subtherapeutic atazanavir trough concentrations during follow-up.Forty-six patients were included. None had a prior history of resistance to protease inhibitors or to lamivudine or abacavir. The percentage of patients with viral suppression at Week 48 was 73.9% when all the included patients were considered (full dataset analysis) and 85.0% when only subjects on treatment were considered. There was a continuous immune recovery and an improvement in lipid profile during follow-up. Two thirds of the patients had subtherapeutic atazanavir trough concentrations in plasma in at least one determination during follow-up.Antiretroviral therapy with unboosted atazanavir plus abacavir/lamivudine is safe and effective in the long term as a treatment simplification strategy in HIV-infected patients with sustained virological suppression in routine clinical practice.

Objectives: The aim of this study was to assess the influence of hepatitis B virus or hepatitis C virus co-infection and the extent of liver fibrosis on saquinavir and ritonavir pharmacokinetics in HIV-infected subjects without liver function impairment. Methods: A cross-sectional, comparative study enrolling HIV-infected adults receiving saquinavir/ ritonavir 1000/100 mg twice daily or 1500/100 mg once daily was conducted. Patients with chronic viral hepatitis (HEP+) were grouped as having advanced liver fibrosis (HEP+/FIB+) or not (HEP+/FIB-) based on the FIB-4 index. Saquinavir and ritonavir trough concentrations (C trough ) in plasma were determined by HPLC. The geometric mean ratio (GMR) was used to compare saquinavir and ritonavir C trough between HEP― and HEP+ patients, and the influence of the extent of liver fibrosis on saquinavir and ritonavir pharmacokinetics was explored using analysis of variance. Results: One hundred and thirty-eight patients on twice-daily saquinavir/ritonavir (67 HEP―, 71 HEP+) and 36 patients on once-daily saquinavir/ritonavir (12 HEP―, 24 HEP+) were included. Saquinavir C trough was comparable between HEP― and HEP+ patients receiving either saquinavir/ritonavir 1000/ 100 mg twice daily [GMR 0.91, 95% confidence interval (CI) 0.60―1.37; P=0.655] or 1500/100 mg once daily (GMR 0.88, 95% CI 0.39―1.97; P=0.752). Similarly, ritonavir C trough was also comparable between HEP― and HEP+ patients. The extent of liver fibrosis was not significantly related to saquinavir or ritonavir C trough in patients receiving either of the two studied doses. Conclusions: Saquinavir C trough was not increased in HIV-infected patients with chronic viral hepatitis in the absence of liver function impairment. These results confirm that no specific dose modification of saquinavir/ritonavir should be recommended in this setting.

Objetivo Estimar el impacto de la toxicidad asociada a los inhibidores de la transcriptasa inverse analogos de nucleosidos (ITIAN) en el coste total del tratamiento de pacientes con infeccion por el virus de la inmunodeficiencia humana tipo 1 (VIH-1). Metodos Se ha disenado un modelo farmacoeconomico a partir de datos obtenidos de un estudio prospectivo, multicentrico, observacional realizado en Espana (Estudio Recover). Los pacientes del estudio habian desarrollado un acontecimiento adverso (AA) asociado a un ITIAN que motivaba su suspension. En el analisis se incluyen todos los costes derivados de la toxicidad inducida por los ITIAN en los tratamientos antirretrovirales durante un ano. Los costes (valores del ano 2005) incluidos han sido: medicos directos (farmacos y manejo de AA) e indirectos (perdidas de productividad). La estimacion de los recursos relacionados con el manejo de los AA se ha realizado a traves de un panel de consenso de expertos clinicos. Resultados El incremento en el uso y coste de recursos sanitarios se correlaciona con la gravedad de todos los AA evaluados. El coste promedio total estimado por paciente ha sido de 4.012 €: 1.789 € por costes farmacologicos (ITIAN asociados con la discontinuacion de la terapia por AA) y 2.223 € por costes directos e indirectos del manejo de los AA (45 y 55%, respectivamente, de los costes totales). El 73% de los costes por paciente asociados a AA se deben a la lipoatrofia (560 €), lipodistrofia mixta (535 €) y neuropatia periferica (533 €). Conclusion En pacientes que desarrollan toxicidades asociadas a ITIAN, el coste economico de su manejo es superior al coste de adquisicion de los ITIAN y produce un incremento significativo en los costes totales del tratamiento de la infeccion por VIH-1. El coste del manejo de estas toxicidades deberia tenerse en cuenta en el diseno de estrategias de tratamiento antirretroviral mas eficientes.

To estimate the impact of toxicity related to nucleoside analogue reverse transcriptase inhibitors (NRTI) on the total cost of medical care in HIV-1-infected patients.. A pharmacoeconomic model was developed from the data obtained by a prospective, observational, multicenter study performed in Spain (Recover). The study patients had developed one NRTI-associated adverse event (AE) that justified discontinuation of treatment with the drug. All costs derived from NRTI-associated AEs in the HAART regimens of HIV-1-infected patients over a period of one year were assessed. The cost assessment (2005 values) included direct medical costs (drugs and AE management) and indirect costs (loss of productivity). The healthcare resources used in AE management were estimated by an expert panel of clinicians.The use and cost of resources rose with increasing severity of all the AE. The average total cost per patient was estimated to be 4012 euro, which included 1789 euro in drug costs (NRTI associated with therapy discontinuation due to AE), and 2223 euro in direct and indirect costs of AE management (45% and 55% of total cost, respectively). Seventy-three per cent of AE-associated costs per patient came from lipoatrophy (560 euro), lipodystropy (535 euro) and peripheral neuropathy (533 euro).Management of NRTI-related toxicities is more costly than NRTI acquisition and produces a significant increase in the overall healthcare expenditure for HIV-1-infected patients. This fact should be taken into account when designing the most efficient antiretroviral treatment strategies.