[Show abstract][Hide abstract] ABSTRACT: PREVALEAT II (PREmature VAscular LEsions and Antiretroviral Therapy II) is an ongoing multicenter, longitudinal cohort study aimed to the evaluation of cardiovascular (CV) risk in advanced HIV-infected antiretroviral (ARV) naïve patients starting their first antiretroviral therapy (ART).
Journal of the International AIDS Society 01/2014; 17(4 Suppl 3):19545. · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: In the present study, we investigated the ability of anti-HIV drugs to interfere with normal cell cycle progression and to induce oxidative stress by perturbing the redox environment. Our results provide evidence that anti-HIV drugs have a differential effect on adipocyte cell cycle and differentiation, being able to modify the response to oxidative stress through an increase of reactive oxygen species (ROS) that compromises the induction of phase-2 and antioxidant enzymes. In detail, saquinavir, efavirenz, and stavudine exert antiadipogenic influences on the model 3T3-L1 cell line, perturbing the oxidative response and inducing of apoptosis. When considered together, the effects of anti-HIV drugs on 3T3-L1 pre adipocytes are distinct but commonly antiadipogenic, thus suggesting another additional possible mechanism by which antiretroviral therapies could contribute to lipoatrophy.
In vivo (Athens, Greece) 03/2012; 26(2):287-91. · 1.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Highly active antiretroviral therapy (HAART therapy) for HIV-1 infection has significantly increased the survival and quality of life of patients with this disease. However, in several epidemiological studies the onset of metabolic syndrome is a phenomenon reported to be extremely frequent. In the present study, genes involved in the molecular cascade responsible for the alteration of fat tissue and of lipid and glucose metabolism in patients with HIV-1 infection treated with antiretroviral therapy were identified. Towards this goal, hybridization using Atlas cDNA Expression Arrays allowed simultaneous monitoring of the expression levels of approximately 250 genes and identification of a panel of changes in relation to different therapeutic groups and in the presence of metabolic syndrome, with some genes being up-regulated, while others are down-regulated in the different subgroups of patients. The results of this analysis have shown a panel of transcriptional changes associated with oxidative stress mechanisms that provide a basis for further studies on understanding of mechanisms that, in vivo, are the foundation the metabolic disorders in patients with HIV infection.
In vivo (Athens, Greece) 03/2012; 26(2):237-42. · 1.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: PREVALEAT II (PREmature VAscular LEsions and Antiretroviral Therapy II) is an ongoing multicenter, longitudinal cohort study aimed to the evaluation of cardiovascular risk in advanced naïve HIV-infected patients starting their first HAART. It includes all consecutive naïve pts with <200 CD4 cells/ml who start any PI/r-based or NNRTI-based+2 NRTIs regimen. Pts are subjected to epi-aortic vessels ultrasonography, brachial artery flow mediated dilation (FMD), endothelial cytokine inflammatory markers value at time 0 and after 3, 6 and 12 months. Data about independent risk factors for CV disease are taken at time 0. Viral load, CD4+ counts, serum lipid values, glucose, body mass index (BMI) are recorded at every control. We enrolled 47 pts: 76,6% males, 87,2% caucasians, 40,4% cigarette smokers, 10,6% HCV co-infected, 6,4% had lipodystrophy. 29,8% homosexuals, 12,8% drug addicts, 51,1% heterosexuals. At baseline, 23,4% of pts had pathologic BMI, 31,91% had a epi-aortic vessels lesion (IMT and/or plaque), 27,65% had pathologic FMD; ICAM1 was pathologic in 46,80%, VCAM1 in 53,19%, IL-6 in 51,06%, D-dimers in 29,79%, hsCRP in 23,40%. 27 pts completed stage T1 of the study (after 3 months); percentages and significance level of variations are the following: 44,44% had a lesion of the epi-aortic vessels (p=0,28), 48,14% had a pathologic FMD (p=0,08), ICAM1 was pathologic in 59,26% (p=0,30), VCAM1 in 70,37% (p=0,15), IL-6 in 74,07% (p=0,05), D-dimers in 14,81% (p=0,12), hsCRP in 25,92% (p=0,80). 27 pts completed stage T2 of the study (6 months). Percentages and significance level of variations in regard of baseline are the following: 51,85% had a epi-aortic vessels lesion (p=0,462); 25,92% had pathologic FMD (p=0,37). 10 pts completed stage T3 of the study (12 months): 60% had a epi-aortic vessels lesion (p=0,07); 40% had pathologic FMD (p=0,49). No significant change has been showed in the trend of variation of inflammatory cytokines at T2 and T3. Our data, at baseline, evidence that advanced naïve pts show a relevant deterioration of CV conditions in terms of US data, FMD and cytokine markers. At T1, US and FMD seem to further worsen; cytokines, except D-dimers, show a worsening trend, too. At T1 and T2, prevalence of vessel lesion and pathologic FMD is yet higher, with a p value closer to significance level. Further data deriving from the follow-up of missing pts are warranted to better understand the evolution of the CV risk profile in this setting of pts.
Journal of the International AIDS Society 01/2012; 15(6):18153. · 3.94 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The hypothesis that fosamprenavir-including highly active antiretroviral therapy (HAART) regimens would be associated with few metabolic and hepatic side-effects was investigated.
An observational single-arm retrospective study was set up on a cohort of 139 human immunodeficiency virus (HIV)-infected patients, followed up at A.O.R.N. Cotugno Hospital, Naples, Italy, treated with antiretroviral regimens including fosamprenavir, in order to evaluate the safety of these regimens in relationship to hepatic and metabolic side-effects, also considering co-morbidities and other risk factors.
Only seven patients met the criteria to reach the primary end-point (grade ≥ 3 adverse event) and none of them discontinued HAART therapy during the follow-up period. Eighty percent of the patients reached viral load <50 cp/μl at 48 weeks of observation. At the end of follow-up, no patient with fasting serum total cholesterol and/or fasting serum triglycerides above grade 3 was found, while 1 out of 114 (0.88%) cases presented aspartate transaminase and alanine transaminase ≥ grade 3 and 1 out of 114 (0.88%) cases had fasting serum glucose ≥ grade 3. One out of 137 patients developed a malignant neoplasm (0.73%) and 4 (2.92%) displayed newly diagnosed hypertension.
Fosamprenavir-based regimens caused a low number of serious metabolic adverse events during a 48 week follow-up period, with a low incidence of co-morbidities and satisfying results in terms of viro-immunological response including for patients with already existing co-morbidities requiring other therapies.
In vivo (Athens, Greece) 01/2011; 25(5):813-9. · 1.15 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: The pathogenetic bases of HAART-associated lipodystrophy are still poorly known, even if it is clear that adipose tissue and its metabolism are sensitive to antiretroviral therapy alone and/or in combination with HIV infection. The NEDD8 system is essential for the regulation of protein degradation pathways involved in cell cycle progression, morphogenesis and tumorigenesis. We investigated the possible involvement of NEED8 in adipogenesis and, consequently, in HIV-related lipodystrophy. One hundred HIV-1-infected patients were included in the study. Using an in vitro model of adipogenesis we evaluated the effects on adipogenesis of the forced expression of NEDD8 together with efavirenz, stavudine, saquinavir, amprenavir and indinavir, belonging to the three main classes of anti-HIV medications. We showed that NEDD8 expression level is higher in the peripheral blood of HIV patients developing lipodystrophy. Coherently, forced expression of NEDD8 in an in vitro model of adipogenesis was able to perturb expression of some key proteins involved in adipogenesis, such as C/EBPalpha and PPARgamma, possibly acting throughout the NEDD8/p27/beta-catenin pathway. Moreover, three out of five evaluated drugs were able to affect adipocyte differentiation: efavirenz, stavudine and saquinavir. Finally, we have shown that NEDD8 was expressed in the fat tissue of lipodystrophic patients, being significantly higher in the lipodystrophic patients with respect to the controls, thus further confirming the altered NEDD8 expression in the fat tissue of HIV-infected patients affected by lipodystrophy. Taken together, our data support the hypothesis of an implication of NEDD8 through p27 and beta-catenin pathways in the disruption of adipogenesis and consequent lipodystrophy in patients affected by HIV infection under HAART therapy with qualitative and quantitative differences according to diverse antiretroviral treatments. These evidences indicate the NEDD8/beta-catenin/p27 pathway as a possible molecular target for prevention of lipodystrophy development in patients under HAART therapy.
[Show abstract][Hide abstract] ABSTRACT: Cryptococcus neoformans CNS infection frequently affects HIV-infected patients and is often lethal, despite antifungal therapy. The most recent treatment guidelines for Cryptococcal meningitis recommend therapy with lyposomal amphotericin B and possible association with flucitosine. However, clinical response rates in HIV-infected patients are not satisfactory, with a persistent high mortality rate and long term therapy is affected by a high risk of major side effects. Posaconazole, the latest broad-spectrum azole, with both in vitro- and in vivo-documented potent activity against C. neoformans, clearly showed no antagonism with amphotericin B, echinocandins or flucytosine and it has both in vitro and in vivo agonistic activity with flucytosine against C. neoformans. We report two cases of successful salvage therapy based on the addition of posaconazole to a standard treatment based on liposomal amphotericin B and Flucytosine. In addition we used posaconazole also in a maintenance therapeutic regimen with no evidence of recurrences in the follow up of these patients. Our report confirms that posaconazole has clinical activity in the CNS against C. neoformans infection. In addition posaconazole showed no antagonism with any other currently available antifungal agent, and was in fact synergistic to some of them (flucytosine); consequently, it seems to be an ideal candidate for antimicrobial combination salvage therapies. Finally posaconazole represents a good alternative to parenteral therapy and an ideal candidate for long-term maintenance therapy due to its competent toxicity profile and oral bioavailability.
In vivo (Athens, Greece) 23(3):465-8. · 1.15 Impact Factor