In our study population, CMV/HIV coinfection was associated with the risk of severe non-AIDS-defining events/non-AIDS-related death, especially with cardiovascular and cerebrovascular events, independently of other prognostic factors. This finding supports a potential independent role of CMV coinfection in vascular/degenerative organ disorders in HIV-infected subjects.

BackgroundHIV-1 non-B subtypes have recently entered Western Europe following immigration from other regions. The distribution of non-B clades and their association with demographic factors, over the entire course of the HIV-1 epidemic, have not been fully investigated in Italy. MethodsWe carried out a phylogenetic analysis of HIV-1 pol sequences derived from 3670 patients followed at 50 Italian clinical centres over nearly three decades. ResultsOverall, 417 patients (11.4%) carried non-B subtypes. The prevalence of non-B strains increased from 2.6% in 1980 -1992 to 18.9% in 1993) in a subset of 2479 subjects with a known year of diagnosis. A multivariate analysis on a subset of 1364 patients for whom relevant demographic data were available indicated that African ethnicity, heterosexual route of infection and year of diagnosis were independently associated with non-B HIV-1 infection (P 0.0001). All pure subtypes, except for clade K, and seven circulating recombinant forms were detected, accounting for 56.6 and 34.1% of the non-B infections, respectively. The F1 subtype was the most prevalent non-B clade among Europeans and was acquired heterosexually in half of this patient population. Unique recombinant forms accounted for 9.4% of the non-B sequences and showed a B/F1 recombination pattern in one-third of cases. ConclusionsThe circulation of non-B clades has significantly increased in Italy in association with demographic changes. Spread of the F1 subtype and B/F recombinants appears to predominate, which may result in a redistribution of the relative proportions of the different strains, and this could lead to overlapping epidemics. Thus, the HIV-1 landscape in Italy may in future be distinct from that of the rest of Europe. IntroductionNine discrete lineages of group M HIV-1 (A-D, F-H, J and K) have differentiated during the global pandemic as a result of massive virus replication, the very high error rate of reverse transcriptase (RT) and the selective pressure exerted by the immune system. The highly recombinogenic activity of HIV-1 RT has added further complexity to the global diversity of HIV-1 as 43 circulating recombinant forms (CRFs) have already been characterized and a number of unique recombinant forms (URFs) have been identified world-wide [1][2][3]. Most subtypes and CRFs were originally restricted to specific geographical regions or populations, but their distribution is constantly evolving [4]. In order to monitor the evolution of the global pandemic, it is convenient and effective to assign viral clades, which allow evaluation of the local epidemiological trends that result from social changes and migration flows. [6][7][8][9][10][11][12][13]. The recent epidemiology of HIV-1 infection in Western European countries with large immigrant communities has been characterized by increasing genetic diversity and a marked rise in non-B subtype strains among newly diagnosed individuals [14][15][16][17]. It has been assumed that most non-B subtype infections in Western Europe are linked to migration ...

Migrant and Italian HIV-infected patients (n = 5773) enrolled in the ICONA cohort in 2004-2014 were compared for disparities in access to an initial antiretroviral regimen and/or risk of virologic failure (VF), and determinants of failure were evaluated. Variables associated with initiating antiretroviral therapy (ART) were analysed. Primary endpoint was time to failure after at least 6 months of ART and was defined as: VF, first of two consecutive virus loads (VL) >200 copies/mL; treatment discontinuation (TD) for any reason; and treatment failure as confirmed VL >200 copies/mL or TD. A Poisson multivariable analysis was performed to control for confounders. Migrants presented significantly lower CD4 counts and more frequent AIDS events at baseline. When adjusting for baseline confounders, migrants presented a lower likelihood to begin ART (odds ratio 0.80, 95% confidence interval (CI) 0.67-0.95, p 0.012). After initiating ART, the incidence VF rate was 6.4 per 100 person-years (95% CI 4.8-8.5) in migrants and 2.7 in natives (95% CI 2.2-3.3). Multivariable analysis confirmed that migrants had a higher risk of VF (incidence rate ratio 1.90, 95% CI 1.25-2.91, p 0.003) and treatment failure (incidence rate ratio 1.16, 95% CI 1.01-1.33, p 0.031), with no differences for TD. Among migrants, variables associated with VF were age, unemployment and use of a boosted protease inhibitor-based regimen versus nonnucleoside reverse transcriptase inhibitors. Despite the use of more potent and safer drugs in the last 10 years, and even in a universal health care setting, migrants living with HIV still present barriers to initiating ART and an increased risk of VF compared to natives.

Fluvastatin showed anti-hepatitis C virus (HCV) activity in vitro, through the inhibition of geranylgeranylation of cellular proteins, and a synergistic effect with interferon (IFN)-alpha. Nevertheless statins up-regulate low-density lipoprotein (LDL) receptor, required for HCV cell entry, and the closely related scavenger receptors SRBI and CD36; moreover they reduce class II major histocompatibility complex expression on antigen presenting cell, modulating T-cell activation. In vivo LDL levels have been identified as prognostic indicator of sustained viral response to IFN in patients with HCV infection, suggesting that lipid-lowering agents might conversely favour HCV entry into the hepatocytes and translate into higher viral replication. We evaluated the effect of fluvastatin on HCV-RNA levels, CD36 expression and T-cell homeostasis in HCV-RNA positive patients. HCV-RNA was measured at baseline and after 4 weeks in 42 HCV/HIV-1 co-infected patients, randomized to receive either fluvastatin 80 mg qd or no treatment. CD36 expression and markers of T-cell activation were evaluated by means of flow cytometry. Plasma interleukin (IL)-10, IFN-gamma and IL-7 were measured by ELISA. Serum cholesterol and LDL decreased significantly in the treatment group (P = 0.0001 and 0.01, respectively). Surprisingly a significant increase of HCV-RNA levels was seen after 4 weeks of fluvastatin (P = 0.03). The percentages of naive/activated/apoptotic cells and CD36 expression remained unchanged. Fluvastatin did not inhibit HCV-RNA replication in vivo; conversely we observed a significant increase of HCV-RNA levels. CD36 expression on monocytes were not up-regulated by statins as previously reported in vitro. The correlation between HCV infectivity, oxidized-LDL receptor and statins in HCV infection need further evaluation.