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To evaluate the efficacy, safety, and tolerability of switching to a dolutegravir (DTG)-based regimen in a cohort of virological suppressed HIV-infected patients who have previously been treated with different antiretroviral combination. The dynamics of total HIV-DNA and levels of high-sensitivity c-reactive protein, interleukin-6, soluble-CD14, and D-Dimer were also analyzed. Ninety-six individuals who switched to a DTG-containing regimen were followed up for 48 weeks. HIV RNA, CD4+ T cell count, weight, and levels of laboratory parameters were recorded at baseline, after 24 and 48 weeks of treatment for all study participants. In a subgroup of patients, HIV DNA and inflammation/coagulation marker levels were also analyzed until week 24. Ninety-three out of 96 patients maintained virological suppression, including patients who switched to dual-therapy from triple-drug combination. Eighteen out of 96 patients had residual viremia at baseline, of which 13 reached the maximal viral suppression at W48. Serum creatinine levels showed a significant increase at weeks 24 and 48. A progressive reduction of total cholesterol was observed from week 24 and up to week 48. No variation in body mass index was detected. HIV DNA, inflammation, and coagulation marker levels did not significantly change during follow-up. Switching to a DTG-based regimen may be a key option for achieving and maintaining maximal virological suppression, even in patients showing residual viremia at baseline. Furthermore, the improvement in blood lipid profile and the overall tolerability observed in this study strongly support the use of these regimens in the aging HIV population.

Here we evaluated the hypothesis that resting state electroencephalographic (EEG) cortical sources correlated with cognitive functions and discriminated asymptomatic treatment-naïve HIV subjects (no AIDS).EEG, clinical, and neuropsychological data were collected in 103 treatment-naïve HIV subjects (88 males; mean age 39.8 years ± 1.1 standard error of the mean, SE). An age-matched group of 70 cognitively normal and HIV-negative (Healthy; 56 males; 39.0 years ± 2.0 SE) subjects, selected from a local university archive, was used for control purposes. LORETA freeware was used for EEG source estimation in fronto-central, temporal, and parieto-occipital regions of interest.Widespread sources of delta (4 Hz) and alpha (8-12 Hz) rhythms were abnormal in the treatment-naïve HIV group. Fronto-central delta source activity showed a slight but significant (p 0.05, corrected) negative correlation with verbal and semantic test scores. So did parieto-occipital delta/alpha source ratio with memory and composite cognitive scores. These sources allowed a moderate classification accuracy between HIV and control individuals (area under the ROC curves of 70-75%).Regional EEG abnormalities in quiet wakefulness characterized treatment-naïve HIV subjects at the individual level.This EEG approach may contribute to the management of treatment-naïve HIV subjects at risk of cognitive deficits.

This study tested a simple statistical procedure to recognize single treatment-naïve HIV individuals having abnormal cortical sources of resting state delta (4 Hz) and alpha (8-13 Hz) electroencephalographic (EEG) rhythms with reference to a control group of sex-, age-, and education-matched healthy individuals. Compared to the HIV individuals with a statistically normal EEG marker, those with abnormal values were expected to show worse cognitive status.Resting state eyes-closed EEG data were recorded in 82 treatment-naïve HIV (39.8 ys.±1.2 standard error mean, SE) and 59 age-matched cognitively healthy subjects (39 ys.±2.2 SE). Low-resolution brain electromagnetic tomography (LORETA) estimated delta and alpha sources in frontal, central, temporal, parietal, and occipital cortical regions.Ratio of the activity of parietal delta and high-frequency alpha sources (EEG marker) showed the maximum difference between the healthy and the treatment-naïve HIV group. Z-score of the EEG marker was statistically abnormal in 47.6% of treatment-naïve HIV individuals with reference to the healthy group (p0.05). Compared to the HIV individuals with a statistically normal EEG marker, those with abnormal values exhibited lower mini mental state evaluation (MMSE) score, higher CD4 count, and lower viral load (p0.05).This statistical procedure permitted for the first time to identify single treatment-naïve HIV individuals having abnormal EEG activity.This procedure might enrich the detection and monitoring of effects of HIV on brain function in single treatment-naïve HIV individuals.

Background Previous evidence showed abnormal sources of resting-state delta ( Material and methods The rsEEG, clinical, and neuropsychological data were collected in 128 naive HIV subjects with normal cognition or mild cognitive deficits and 60 control (Healthy) subjects. The eLORETA freeware estimated source connectivity by the tool called lagged linear connectivity (LLC). Area under receiver operating characteristic (AUROC) curve indexed the accuracy in the classification of Healthy and HIV individuals. Results Posterior interhemispheric and diffuse intrahemispheric LLC solutions in alpha sources were abnormally lower in both HIV subgroups with and without mild cognitive deficits subjects, compared with the Healthy group. Noteworthy, HIV subgroup with cognitive deficits showed greater abnormalities than HIV subgroup with normal cognition. Furthermore, AUROC curves of those alpha LLC solutions exhibited moderate accuracies (>0.7) in the discrimination of control vs. HIV individuals with mild cognitive deficits. Conclusions Naive HIV subjects in quiet wakefulness were characterized by abnormalities in widespread alpha source connectivity, which were greater when related to mild cognitive deficits. Widespread alpha source connectivity may reflect HIV effects on brain and cognitive functions before drug regimens. Future studies may test utility of the present approach to select HIV subjects prone to cognitive decline over time and to track brain functions after neuroprotective anti-HIV drug regimens.

Objective Cortical sources of electroencephalographic (EEG) rhythms were investigated in two sub-populations of naive HIV subjects, grouped based on clinical criteria to receive different combination anti-retroviral therapies (cARTs). These EEG sources were hypothesized to reflect beneficial effects of both regimes. Methods Eyes-closed resting state EEG data were collected in 19 (Group A) and 39 (Group B) naive HIV subjects at baseline (i.e. pre-treatment; T0) and after 5 months of cART (T5). Compared with the Group A, the Group B was characterized by slightly worse serological parameters and higher cardiovascular risk. At T0, mean viral load (VL) and CD4 count were 87,694 copies/ml and 435 cells/μl in the Group A and 187,370 copies/ml and 331 cells/μl in the Group B. The EEG data were also collected in 50 matched control HIV-negative subjects. Cortical EEG sources were assessed by LORETA software. Results Compared to the Control Group, the HIV Groups showed lower alpha (8–12 Hz) source activity at T0 while the Group B also exhibited higher delta source activity. The treatment partially normalized alpha and delta source activity in the Group A and B, respectively, in association with improved VL, CD4, and cognitive functions. Conclusions Different cART regimens induced diverse beneficial effects in delta or alpha source activity in the two naive HIV Groups. Significance These sources might unveil different neurophysiological effects of diverse cART on brain function in naive HIV Groups as a function of clinical status and/or therapeutic compounds.

Objective Here we tested the effect of combined antiretroviral therapy (cART) on deviant electroencephalographic (EEG) source activity in treatment-naïve HIV individuals. Methods Resting state eyes-closed EEG data were recorded before and after 5 months of cART in 48 male HIV subjects, who were naïve at the study start. The EEG data were also recorded in 59 age- and sex-matched healthy subjects as a control group. Frequency bands of interest included delta, theta, alpha1, alpha2 and alpha3, based on alpha frequency peak specific to each individual. They also included beta1 (13–20 Hz) and beta2 (20–30 Hz). Low-resolution brain electromagnetic tomography (LORETA) estimated EEG cortical source activity in frontal, central, temporal, parietal, and occipital regions. Results Before the therapy, the HIV group showed greater parietal delta source activity and lower spatially diffuse alpha source activity compared to the control group. Thus, the ratio of parietal delta and alpha3 source activity served as an EEG marker. The z-score showed a statistically deviant EEG marker (EEG +) in 50% of the HIV individuals before therapy (p, Highlights • A statistical z-score tested the effect of antiretroviral therapy on resting state EEG sources in naïve HIV individuals. • Many HIV individuals (50%) had abnormal EEG before the therapy, and > 40% showed its normalization after 5 months of cART. • This procedure might monitor effects of cART on brain function in HIV single individuals.

HIV-1 patients show increased platelet activation, but the mechanisms involved are not completely clarified. We speculated that HIV-1 might induce in vivo platelet activation by enhancing platelet NOX2-related oxidative stress.We measured soluble CD40 Ligand (sCD40L), a systemic marker of platelet activation, in 36 HIV-1 patients under effective combined antiretroviral therapy (cART) and in 10 naïve HIV-1 subjects. As control, 20 healthy subjects (HS) were included. Platelet oxidative stress was measured by platelet NOX2-derived peptide (sNOX2-dp), p47(phox) translocation to platelet membrane and platelet prostaglandin F2α (8-iso-PGF2α).sCD40L was increased both in HIV-1 naïve and cART patients compared to HS (p0.001). Platelet sNOX2-dp and 8-iso-PGF2α were significantly higher in HIV-1 naïve subjects compared to those on cART and to HS, and both were mutually correlated (R = 0.734, p0.001). A stepwise multivariable linear regression analysis showed that platelet sNOX2-dp (β: 0.803, p0.001), HIV-1 infection (β: 0.146, p = 0.014) and age (β: 0.166, p = 0.001) were independently associated to sCD40L levels.HIV-1 infection is associated with increased platelet oxidative stress, which was related to the activation of NOX2. The independent association between platelet NOX2 activation and plasma levels of sCD40L suggest that in vivo platelet activation may be dependent upon platelet oxidative stress.

Objective: We tested the hypothesis that 5 months of combined anti-retroviral therapy (cART) affect cortical sources of resting state cortical electroencephalographic (EEG) rhythms in naive HIV subjects. Methods: Eyes-closed resting state EEG data were recorded at baseline (i.e. pre-treatment; T0), T1 (after 4 weeks of cART), T2 (after 8 weeks of cART), and T5 (after 5 months of cART) in 38 naive HIV subjects. EEG data were also recorded in 40 age-matched cognitively normal subjects for control purposes. EEG rhythms of interest were delta (2–4 Hz), theta (4–8 Hz), alpha 1 (8–10.5 Hz), alpha 2 (10.5–13 Hz), beta 1 (13–20 Hz), and beta 2 (20–30 Hz). Cortical EEG sources were estimated by LORETA software. Results: Compared to the control group, the HIV group at T0 showed greater delta sources and lower widespread alpha sources. cART induced a global improvement of biological (viral load, CD4 count) and EEG (delta, alpha) markers, remarkable even after 4 weeks. Compared to HIV Responders (>100 cells/ll at 5-month follow up), the HIV Mild Responders (

highlights Resting-state EEG rhythms show peculiar frequency/spatial features in naive human subjects with human immunodeficiency virus (HIV). Topography and frequency of the cortical sources estimated by low-resolution electromagnetic tomog- raphy (LORETA) can distinguish groups of HIV and control subjects. The LORETA approach provides clinically useful information for an early detection of the effect of HIV infection on brain and cognitive functions. abstract Objective: The aim of the study was to test the hypothesis that cortical sources of resting-state electro- encephalographic (EEG) rhythms show peculiar frequency/spatial features in naive human subjects with human immunodeficiency virus (HIV) compared to healthy control subjects. Methods: Resting-state eyes-closed EEG data were recorded in 18 naive HIV subjects (15 males; mean age 39 years ± 2.0 standard error of mean, SEM) and in 18 age-matched cognitively normal subjects (15 males; 38.7 years ± 2.2 SEM). EEG rhythms of interest were delta (2-4 Hz), theta (4-8 Hz), alpha1 (8-10 Hz), alpha2 (10-12 Hz), beta1 (13-20 Hz) and beta2 (20-30 Hz). Cortical EEG sources were estimated by normalised, low-resolution electromagnetic tomography (LORETA). Results: Mini Mental State Evaluation (MMSE) score was lower in HIV (26.5 ± 0.7 SEM) than in healthy (29.2 ± 0.5 SEM) subjects (p < 0.05). Central and parietal delta sources showed higher amplitude in the HIV than in control subjects. Furthermore, topographically widespread, cortical sources of resting-state alpha rhythms were lower in amplitude in HIV subjects than in control subjects. Conclusions: The present results suggest that topography and frequency of the cortical sources of resting- state EEG rhythms can distinguish groups of HIV and control subjects. Significance: These results encourage future studies in an enlarged cohort of HIV subjects to test the hypothesis that the present methodological approach provides clinically useful information for an early detection of the effect of HIV infection on brain and cognitive functions.

Accelerated progression of hepatic fibrosis has been shown in patients co-infected with hepatitis C virus (HCV) and HIV. Liver fibrosis is a dynamic process in which the altered balance between matrix metalloproteinases (MMPs) and their specific inhibitors (TIMPs) may play a major role.The involvement of MMP-9 and TIMP-1 in HCV liver disease progression in patients co-infected with HIV was evaluated. Plasma concentrations of human MMP-9 and TIMP-1 were assessed in 76 HIV-infected patients; 27 were co-infected with HCV and 49 were HCV negative. 18 healthy donors were included as controls.Patients with HIV infection exhibited a striking increase in TIMP-1 levels; this is more evident in patients with advanced CD4 depletion. There was no elevation in the plasma concentrations of the MMP-9. The highest levels of TIMP-1 were found in the HIV/HCV co-infected patients. The values of TIMP-1 in HIV-infected patients with chronic HCV hepatitis were significantly higher than in HIV-positive individuals without HCV infection, even including those with low CD4 count. No significant differences were seen in the MMP-9 levels.These findings suggest that the altered balance between circulating MMP-9 and TIMP-1 during HIV infection may play an important role in exacerbating liver fibrosis progression in patients co-infected with HCV.