Usefulness of calcaneal quantitative ultrasound stiffness for the evaluation of bone health in HIV-1-infected subjects: Comparison with dual X-ray absorptiometry

Objectives: With the development of effective treatments and the resulting increase in life expectancy, bone mineral density (BMD) alteration has emerged as an important comorbidity in human immunodeficiency virus type-1 (HIV-1)-infected individuals. The potential contributors to the pathogenesis of osteopenia/osteoporosis include a higher prevalence of risk factors, combined antiretroviral therapy (cART)-exposure, HIV-1 itself and chronic immune activation/inflammation. Dual-energy X-ray absorptiometry (DXA) is the “gold standard” technique for assessing bone status in HIV-1 population. Methods: We conducted a cross-sectional study to investigate bone mineral status in a group of 158 HIV-1-infected subjects. The primary endpoint was the feasibility of calcaneal quantitative ultrasound (QUS) as a screening tool for BMD. All subjects were receiving stable cART and were virologically suppressed (HIV-RNA <37 copies/mL) from at least 12 months. Calcaneal QUS parameters were analyzed to obtain information on bone mass and microarchitecture. The results were compared with those obtained by DXA. Results: No correlations were found between DXA/QUS parameters and demographic or HIV-1-specific characteristics, also including cART strategies. In the univariate analyses BMD, QUS indexes, and Fracture Risk Assessment Tool scores conversely showed significant associations with one or more demographic or HIV-1-related variables. Moreover, a significant relationship between calcaneal quantitative ultrasound index/stiffness and femoral/lumbar BMD values from DXA was described. The multivariate analysis showed an independent association between calcaneal quantitative ultrasound index/stiffness and body mass index, higher CD4+T-cell numbers and low 25-OH D2/D3 vitamin D levels <10 ng/mL (P-values: 0.004, 0.016, and 0.015, respectively). Conclusion: As an alternative and/or integrative examination to DXA, calcaneal QUS could be proposed as a useful screening in HIV-1-infected patients for assessing bone health impairment. In fact, the results obtained confirm that calcaneal QUS may be useful for monitoring bone status, being a noninvasive and inexpensive technique, especially in those subjects with the classical traditional risk factors for bone damage that were observed earlier in HIV-1 population

Backbone switch to abacavir/lamivudine fixed-dose combination: implications for antiretroviral therapy optimization

Current guidelines recommend treatment optimization in virologically suppressed patients through switching/ simplification strategies to minimize long-term toxicities and improve adherence. The assessment of inflammation/ coagulation profiles may support therapeutic decisions. We undertook a prospective, non-randomized study to evaluate the efficacy and safety of switching to ABC/3TC from ZDV/3TC or TDF/FTC backbones, in 40 HIV-1 infected patients with HIV-RNA levels 24 months). Main endpoints were viral load levels, CD4+ T cells and toxicities after 48 weeks. Serum inflammation/coagulation markers (ESR, CRP, D-dimer and fibrinogen) and pro-inflammatory cytokines (IL-6, TNF-α, adiponectin, resistin) were evaluated. Baseline characteristics were similar in the two arms, with significantly lower values of e-GFR in patients on TDF/FTC. Markers of inflammation/ coagulation and cytokine profile were also similar, except for higher values of resistin in patients on TDF/ FTC. During follow up, CD4+ T cells increased and viral load remained undetectable in both groups. Patient from ZDV/3TC had significantly greater changes in total cholesterol and serum creatinine. Markers of inflammation/ coagulation remained unchanged. Adiponectin significantly increased in patients from ZDV/3TC. Switching to ABC/3TC was effective and safe. Inflammatory markers remained low in both groups. Some changes in metabolic, kidney and cytokine profiles were apparently specific for baseline cART treatment

Management of HIV-1 associated hepatitis in patients with acquired immunodeficiency syndrome: role of a successful control of viral replication

In HIV-1 infected patients, increase of liver enzymes may be mainly due to viral coinfections, alcohol intake, hepatotoxic drugs or autoimmune diseases. Three cases of aminotransferase elevation occurred during a phase of uncontrolled viral replication combined with a severe immunodeficiency and resolved by an effective HAART are described, focusing on the etio-pathogenetic role possibly played by HIV-1 infection

HIV-1 induces in vivo platelet activation by enhancing platelet NOX2 activity.

OBJECTIVES: 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. METHODS: 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). RESULTS: sCD40L was increased both in HIV-1 naïve and cART patients compared to HS (p &lt; 0.001). 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, p &lt; 0.001). A stepwise multivariable linear regression analysis showed that platelet sNOX2-dp (β: 0.803, p &lt; 0.001), HIV-1 infection (β: 0.146, p = 0.014) and age (β: 0.166, p = 0.001) were independently associated to sCD40L levels. CONCLUSIONS: 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

Reduced Plasma Levels of sCD14 and I-FABP in HIV-infected Patients with Mesalazine-treated Ulcerative Colitis

BACKGROUND: Microbial translocation (MT) is a shared feature of HIV infection and inflammatory bowel disease (IBD). AIMS: This study was conducted to assess the impact of IBD (and particularly ulcerative colitis, UC) on plasma markers of MT and immune activation in HIV+ subjects. METHODS: A cross-sectional study was conducted in 3 groups of patients: HIV+/UC+(group HIV/UC); HIV+/UC- (group HIV); HIV-/UC+(group UC). Plasma levels of soluble CD14 (sCD14), intestinal fatty acid-binding protein (I-FABP), and endotoxin core antibodies (endoCAB) were measured as plasma markers of MT. Inflammation and immune activation were evaluated by measuring plasma levels of IL-6, IL-21, TNF-alpha, and high-sensitivity C-reactive protein (hs-CRP). T- and B-cells subpopulations were characterized by FACS analysis. RESULTS: Seven patients were enrolled in group HIV/UC, 9 in HIV, and 10 in UC. All HIV-positive patients had plasma values of HIV-1 RNA < 37 copies/mL for at least 12 months and good immunological recovery. All patients with UC were treated with oral mesalazine. Markers of MT, immune activation, and inflammation were not increased in subjects with HIV/UC. In fact, they had lower levels of I-FABP (p = 0.001) and sCD14 (p = 0.007) when compared to other patients groups. Positive correlations were found between I-FABP and sCD14 (r = .355, p = 0.076). Frequency of T- and B-cell subsets did not differ among groups. CONCLUSIONS: Our results suggest that UC does not worsen MT, inflammation, or immune activation in HIV-infected subjects. The anti-inflammatory activity of chronic mesalazine administration on intestinal mucosa may contribute to this finding

Evaluation of HIV-DNA and inflammatory markers in HIV-infected individuals with different viral load patterns

Abstract Background: Persistent residual viremia (RV) and low grade inflammation and immune activation have been associated with non-AIDS defining events. The impact of persistent RV and HIV-DNA load on immune activation/ inflammation remains unclear. The purpose of this study was to gain new insights into the relation between viremia, markers of inflammation and HIV-DNA levels. Methods: Three hundred and twenty-one HIV-infected patients were studied. A retrospective analysis of viremia values, prospectively collected for 48 months, was performed. Patients were separated into three groups: 113 TND (Target Not Detected, patients with sustained undetectable viremia); 113 RV (Residual Viremia, patients who had at least three detectable viral load (VL) values <37 copies/ml); 95 LLV (Low Level Viremia, patients with at least two VL values >37 but <200 copies/ml). HIV-DNA, TNF-α, IL-6 and sCD14 were analyzed. Results: HIV-DNA, sCD14 and TNF-α were significantly lower in the TND group than in the RV and LLV groups. In addition, RV patients showed lower levels of HIV-DNA and sCD14 than LLV individuals. HIV-DNA load was not related to markers of inflammation. The ordinal logistic analysis showed that two independent variables were significantly associated with VL pattern: sCD14, HIV-DNA. In addition NRTIs plus NNRTIs and NRTIs plus PIs were negatively associated to VL pattern compared to INI-containing regimen. Conclusions: Persistent undetectable viremia was associated with lower levels of inflammatory markers and HIVDNA. However, the lack of normalization of these biomarkers in the TND group and the fact that HIV-DNA load was not associated with inflammation strongly suggest that other mechanisms play a major role in maintaining inflammation over time

Breastfeeding and transmission of cytomegalovirus to preterm infants. Case report and kinetic of CMV-DNA in breast milk

<p>Abstract</p> <p>Background</p> <p>Breastfeeding has a major impact on CMV epidemiology. Postnatal CMV reactivation's incidence during lactation is nearby the maternal seroprevalence. Although perinatal CMV infection has practically no consequences in term newborn, it may cause, in some cases, a severe symptomatic disease in preterm newborns.</p> <p>The aims of the present study are to evaluate the rate and clinical expression of CMV infection breast milk transmitted in preterm infants and to check the safety of the freezing treated breast milk.</p> <p>Methods</p> <p>The study included fifty-seven preterm infants and their CMV seropositive mothers. Fresh breast milk samples have been collected from 1^stto 9^thpostpartum week. Both fresh breast milk and 72, 96, 120 hours frozen samples have been examined, checking the presence of CMV; urine samples have been tested too.</p> <p>Results</p> <p>70.2% of tested mothers showed reactivation of the infection, and CMV-positive breast milk during the six weeks postpartum has been found. However, only one infant was infected by CMV, developing hepatic affection concomitantly with a multi-system involvement, as shown CMV DNA detection in urine, saliva, blood, gastric aspirate, and stools.</p> <p>Conclusion</p> <p>Freezing breast milk at -20°C and pasteurization may respectively reduce or eliminate the viral load.</p

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-Week results of a randomized trial

Objectives Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. Methods Patients on 3-drug ART with stable HIV-1 RNA &lt;50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm).Results In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm. Conclusion Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therap

Switch to maraviroc with darunavir/r, both QD, in patients with suppressed HIV-1 was well tolerated but virologically inferior to standard antiretroviral therapy: 48-Week results of a randomized trial

Objectives: Primary study outcome was absence of treatment failure (virological failure, VF, or treatment interruption) per protocol at week 48. Methods: Patients on 3-drug ART with stable HIV-1 RNA &lt;50 copies/mL and CCR5-tropic virus were randomized 1:1 to maraviroc with darunavir/ritonavir qd (study arm) or continue current ART (continuation arm). Results: In June 2015, 115 patients were evaluable for the primary outcome (56 study, 59 continuation arm). The study was discontinued due to excess of VF in the study arm (7 cases, 12.5%, vs 0 in the continuation arm, p = 0.005). The proportion free of treatment failure was 73.2% in the study and 59.3% in the continuation arm. Two participants in the study and 10 in the continuation arm discontinued therapy due to adverse events (p = 0.030). At VF, no emergent drug resistance was detected. Co-receptor tropism switched to non-R5 in one patient. Patients with VF reported lower adherence and had lower plasma drug levels. Femoral bone mineral density was significantly improved in the study arm. Conclusion: Switching to maraviroc with darunavir/ritonavir qd in virologically suppressed patients was associated with improved tolerability but was virologically inferior to 3-drug therapy

Comparative Analysis of Real-Time Polymerase Chain Reaction Methods to Typing HLA-B*57:01 in HIV-1-Positive Patients

The HLA-B*57:01 allele is strongly associated with the hypersensitivity reaction to Abacavir (ABC). Therefore, treatment guidelines recommend that patients initiating ABC are preventively tested for the presence of this allele. To date, four different commercial assays based on the real-time quantitative polymerase chain reaction (Q-PCR) technique are available for the detection of HLA-B*57:01: Duplicα-RealTime Reagent Set HLA-B*57:01 by Euroclone, HLA-B*57:01 Real-TM by Sacace Biotechnologies, COBAS AmpliPrep/COBAS TaqMan HLA-B*57:01 Screening Test by Roche Diagnostic, and HLA-B*57:01 by Nuclear Laser Medicine. The study was carried out to compare the performance of the first three commercially available Q-PCR kits in a routine clinical setting. A total of 98 samples from Policlinico Umberto I Hospital were tested. Results obtained by the Duplicα-RealTime Genotyping kit and AmpliPrep/TaqMan system were 100% concordant. In contrast, genotyping by the HLA-B*57:01 Real-TM kit showed poor agreement with the other systems, that is, 12 out of 33 positive samples were detected as HLA-B*57:01 negative. To confirm the correct genotype of these discordant samples, two additional methods with rapid turnaround times and already implemented into routine clinical practice were used, that is, a PCR-based microsequence-specific primer DNA typing test and a laboratory-developed screening test in Q-PCR. All 12 discordant samples were genotyped as HLA-B*57:01-positive samples using these two additional methods in a single-blinded manner, thus confirming the low sensitivity of HLA-B*57:01 Real-TM test. These findings underline the need to compare results obtained with commercial assays before choosing a test suitable for use in a routine clinical laboratory