Suchergebnisse

IntroductionLow bone mineral density (BMD) and osteoporosis are prevalent in HIV‐infected patients and were associated with HIV infection and tenofovir‐containing ART.Materials and MethodsThe GUSTA study (GUided Simplification with Tropism Assay) is a two‐arm, prospective, multicenter, 1:1 randomized controlled trial designed to demonstrate the non‐inferiority of therapeutic switch to maraviroc+darunavir/ritonavir (MVC+DRV/r) 300/800/100 mg QD against the continuation of previous triple cART in patients with stable virological suppression. Enrolment criteria include HIV1‐RNA <50 copies/mL for >6 months, R5 tropism and CD4>200 cells/µL for >3 months. Dual energy X‐ray absorptiometry scans of proximal femur and lumbar spine were performed at baseline and week 48. Bone composition was evaluated using L2‐L4 lumbar column and proximal femoral BMD, T‐score and the Z‐score. At the same timepoints, plasma bone metabolism biomarkers were measured. Linear regression was used to compare means of differences between arms. The association between BMD changes and the baseline variables was assessed by linear regression.Results27 patients were included, 13 from study group and 14 from control group, 74.1% were males, 44.4% heterosexuals, 81.5% Caucasian, median age was 47 years (IQR 41–53), time from HIV diagnosis 13.4 years (9–19), CD4 553/µL (406–739), nadir CD4 201/µL (76–283). At baseline, median ART duration was 10.5 years (5.7–15.3), the majority of patients (70.4%) was on tenofovir, 63% was on a PI‐based regimen and 14,8% on an NNRTI‐based regimen. Mean proximal femur BMD from baseline increased over 48 weeks by 2.06% (SD 2.24) in the study arm and decreased by −2.77% (SD 4.63) in control arm (p=0.003). The change over 48 weeks in proximal femur T‐score was significantly different between the study (+0.11, SD 0.22) and control arm (−1.14, SD 0.27, p=0.016). Also the changes in total alkalin phosphatase (−20 U/L vs −1.5, p=0.003) was significant between the two groups. After adjusting for time from HIV diagnosis and years of ART, study group was the only factor associated to higher mean percentage change from baseline femoral BMD (MVC+DRV/r +4.83, p=0.044).ConclusionsThe study demonstrated a significant improvement in femoral BMD and T‐score after treatment simplification with MVC+DRV/r.

IntroductionRaltegravir intensification is associated with an increase in 2‐LTR episomal HIV DNA= circles, indicating a persistent low‐level replication, in some individuals in ART with suppressed HIV RNA. We aimed at monitoring residual plasma HIV RNA and cellular HIV DNA in virologically suppressed patients switching to a raltegravir‐based regimen.Materials and MethodsForty‐six HIV‐infected subjects on PI or NNRTI based‐regimens, with plasma HIV RNA level <40 copies/mL for ≥6 months and CD4 >200 cells/µL for ≥12 months were enrolled. Thirty‐four patients switched to raltegravir‐based regimen (RASTA study group) and 12 continued a PI or NNRTI based‐regimen (control group). Ultrasensitive HIV residual viremia and total PBMC HIV DNA were assessed at baseline (W0), 24 (W24) and 48 (W48) weeks. HIV RNA levels were determined by an ultrasensitive test derived from a commercial real time PCR (limit of detection 5 copies/ml). A real time PCR was used to quantify HIV DNA copy numbers in PBMCs.ResultsAt W0, HIV DNA was detected in all patients while at W48 it was detectable in 82.3% of RASTA group vs 100% of controls (p=0.01). The difference between the average values of HIV DNA log10 copies/10°6 CD4 at W0 (median 3.11, IQR 2.70–3.45) and W48 (median 2.87, IQR 2.24–3.38) was statistically significant for RASTA group (p=0.035). Male gender (mean difference −0.37 log10 copies/10°6 PBMC, p=0.023) and previous PI based‐ART (mean difference +0.39 log10 copies/10°6 PBMC, p=0.036) were predictive of HIV DNA level at W0. After adjusting for previous PI based‐ART, male gender was the only variable independently associated with HIV DNA size at W0 (mean difference −0.326 log10 copies/10°6 PBMC, 95% CI −0.641, −0.011 p=0.043). Ultrasensitive HIV‐1 RNA was detectable at W0 in 50% of RASTA group versus 66.7% of controls and at W48 in 32.4% versus 45.5%, respectively. No differences were found between HIV RNA levels at W0 and W48 within and between the two groups.ConclusionsSwitching to raltegravir‐based regimens may be associated with a decrease of HIV reservoir, as measured by total PBMC HIV DNA. A larger sample size is required to confirm this finding.

IntroductionHIV/HCV coinfection is a risk factor for hepatic injury in patients receiving HAART and previous studies support a favourable effect of antiretroviral regimens including maraviroc (MVC) on the course of coinfection compared with other antiretroviral drugs. There are few observations about MVC use in simplified treatment of coinfected patients.Objective: To evaluate the efficacy and the safety of simplification to darunavir (DRV)/ritonavir (r)/maraviroc (MVC) in virologically HIV‐suppressed patients and to explore the effect of simplified treatment on coinfected patients.Material and MethodsGUSTA study is a randomized two arms trial that compares the switch to DRV/r/MVC with standard HAART with three drugs. The study enrols patients with HIV‐1 RNA<50cp/mL>6 months, R5 tropism, CD4>200 cells/mm. Survival analysis was used to analyze factors associated to time‐to a single viral load (VL) over 50cp/mL and FIB‐4>1.45.ResultsWe included 62 patients with at least the 24 week follow‐up for FIB‐4 analysis: males 75.8%, heterosexuals 48.4%, HCV+12.9% median age 48.3 years (IQR41.1;53.5), time from HIV diagnosis 11.0 years (IQR7.3;16.7), CD4 cells 659/mm (IQR478;882), nadir CD4 203/mm (IQR115;286), FPR 46 (IQR30;70), baseline (BL) FIB‐4 1.11 (IQR0.75;1.35). At BL no differences were observed in the two arms, except for platelets (−34.96 109/L, in the study arm, p=0.028) and CD4 at nadir (−70cell/µL, p0.051). After 24 weeks a significant reduction in total bilirubin (TB) (−0.55 mg/dL, p=0.025) and alkaline phosphatase(AP) (−12.96 UI/L, p=0.002) was observed in the study group. A statistically significant difference in mean change of TB (0.61 mg/dL, p=0.016) and AP (13.23 UI/L, p=0.04) at 24 week between control and study group was observed. No grade 3/4 transaminase elevation was observed for any patient even if HIV/HCV coinfected and receiving MVC. A single HCV negative patient in the control arm had grade 3 bilirubin increase. Including all patients with at least one follow‐up HCV status was not associated with an increased risk of detectable VL (n=114, 4072 person‐week‐follow‐up [IQR12;51.6]), nor with FIB‐4>1.45 (n=98, 3513 person‐week‐follow‐up [IQR11.4;50.9]).ConclusionsThe initial results from GUSTA study show that ART‐regimen including MVC did not increase the incidence of adverse events or severe laboratory liver abnormalities in HIV‐1‐infected patients with or without HCV coinfection. Coinfected patients did not show an increased risk of failure on simplification treatment with MVC/DRV/r.