Introduction
Advancements in and accessibility to effective antiretroviral therapy has improved the life expectancy of people living with HIV, increasing the proportion of people living with HIV ...reaching older age (≥60 years), making this population's health‐related quality of life (HRQoL) more relevant. Our aim was to identify the determinants of poor HRQoL in people living with HIV aged ≥60 years and compare them with those of their younger counterparts.
Methods
We used data from the ‘Vive+’ study, a cross‐sectional survey conducted between October 2019 and March 2020, nested within the PISCIS cohort of people living with HIV in Catalonia and the Balearic Islands, Spain. We used the 12‐item short‐form survey (SF‐12), divided into a physical component summary (PCS) and a mental component summary (MCS), to evaluate HRQoL. We used the least absolute shrinkage and selection operator for variable selection and used multivariable regression models to identify predictors.
Results
Of the 1060 people living with HIV (78.6% males) who participated in the study, 209 (19.7%) were aged ≥60 years. When comparing older people living with HIV (≥60 years) and their younger counterparts, older people exhibited a worse PCS (median 51.3 interquartile range {IQR} 46.0–58.1 vs. 46.43 IQR 42.5–52.7, p < 0.001) but a similar MCS (median 56.0 IQR 49.34–64.7 vs. 57.0 IQR 48.9–66.3, p = 0.476). In the multivariable analysis, cognitive function correlated with a PCS (β correlation factor β −0.18, p = 0.014), and depressive symptoms and satisfaction with social role correlated with an MCS (β 0.61 and β −0.97, respectively, p < 0.001) in people living with HIV aged ≥60 years.
Conclusion
Depressive symptoms, poor cognitive function, and lower satisfaction with social roles predict poorer HRQoL in older people living with HIV. These factors need to be considered when designing targeted interventions.
The long-term non-progressors (LTNPs) are a heterogeneous group of HIV-positive individuals characterized by their ability to maintain high CD4+ T-cell counts and partially control viral replication ...for years in the absence of antiretroviral therapy. The present study aims to identify host single nucleotide polymorphisms (SNPs) associated with non-progression in a cohort of 352 individuals.
DNA microarrays and exome sequencing were used for genotyping about 240 000 functional polymorphisms throughout more than 20 000 human genes. The allele frequencies of 85 LTNPs were compared with a control population. SNPs associated with LTNPs were confirmed in a population of typical progressors. Functional analyses in the affected gene were carried out through knockdown experiments in HeLa–P4, macrophages and dendritic cells.
Several SNPs located within the major histocompatibility complex region previously related to LTNPs were confirmed in this new cohort. The SNP rs1127888 (UBXN6) surpassed the statistical significance of these markers after Bonferroni correction (q = 2.11 × 10−6). An uncommon allelic frequency of rs1127888 among LTNPs was confirmed by comparison with typical progressors and other publicly available populations. UBXN6 knockdown experiments caused an increase in CAV1 expression and its accumulation in the plasma membrane. In vitro infection of different cell types with HIV-1 replication-competent recombinant viruses caused a reduction of the viral replication capacity compared with their corresponding wild-type cells expressing UBXN6.
A higher prevalence of Ala31Thr in UBXN6 was found among LTNPs within its N-terminal region, which is crucial for UBXN6/VCP protein complex formation. UBXN6 knockdown affected CAV1 turnover and HIV-1 replication capacity.
Display omitted
Objectives
To compare the prevalence of carotid atherosclerosis in virologically suppressed HIV patients with that of a community sample, and to evaluate the capacity of various cardiovascular risk ...(CVR) equations for predicting carotid atherosclerosis.
Methods
This was a cross‐sectional study with two randomly selected groups: HIV patients from an HIV unit and a control group drawn from the community. Participants were matched by age (30–80 years) and sex without history of cardiovascular disease. Carotid plaque, common carotid intima–media thickness (cc‐IMT) and subclinical atherosclerosis (carotid plaque and/or cc‐IMT > 75th percentile) were assessed by carotid ultrasound. The Systematic Coronary Risk Evaluation (SCORE), Framingham, REGICOR, reduced Data Collection on Adverse Effects of Anti‐HIV Drugs (D:A:D), and COMVIH equations were applied, and their abilities to predict carotid plaque were compared using the area under the curve (AUC).
Results
Each group included 379 subjects (77.8% men, age 49.7 years). Duration of antiretroviral therapy was 15.5 years. There were no differences between the groups for carotid plaque (HIV, 33.2%; control, 31.3%), mean cc‐IMT (HIV, 0.63 mm; control, 0.61 mm) or subclinical atherosclerosis (HIV, 42.9%; control, 47.9%). Thymidine analogues were independently associated with subclinical atherosclerosis in HIV‐infected patients. CVR equations revealed AUCs between 0.715 and 0.807 for prediction of carotid plaque; prediction was better in the control group and did not improve when HIV‐adapted scales were used.
Conclusions
The features of carotid atherosclerosis did not differ between the HIV‐infected and the control group, although CVR equations were more predictive for carotid plaque in controls than in HIV‐infected patients. HIV‐specific equations did not improve prediction.
Objective
The aim of the study was to investigate changes in plasma biomarkers of cardiovascular risk and lipids in a CD4‐guided antiretroviral therapy interruption study.
Methods
This was a substudy ...of a prospective, randomized, multicentre treatment interruption study. At months 12, 24 and 36, monocyte chemotactic protein‐1 (MCP‐1), soluble vascular cell adhesion molecule‐1 (sVCAM‐1), interleukin‐6 (IL‐6), interleukin‐8 (IL‐8), soluble CD40 ligand (sCD40L), soluble P‐selectin (sP‐selectin), and tissue plasminogen activator (t‐PA) were measured using a multiplex cytometric bead‐based assay. Total cholesterol (total‐c), high‐density lipoprotein cholesterol (HDL‐c) and triglycerides (TG) were determined using standard methods.
Results
Fifty‐four patients were included in the study 34 in the treatment continuation (TC) arm and 20 in the treatment interruption (TI) arm. There were no differences at baseline between the groups, except in CD4 cell count, which was higher in the TI arm (P = 0.026), and MCP‐1, which was higher in the TC arm (P = 0.039). MCP‐1 and sVCAM‐1 were increased relative to baseline at the three study time‐points in the TI arm, with no changes in the TC arm. Soluble CD40L and sP‐selectin were increased at month 36 in both arms, with a greater increase in the TI arm (P = 0.02). t‐PA was increased in both arms at the three time‐points. Total‐c, HDL‐c and low‐density lipoprotein cholesterol (LDL‐c) were decreased in the TI arm at the three time‐points, with no changes in the total‐c/HDL‐c ratio. HIV viral load positively correlated with MCP‐1 at months 12 and 24. Regression analysis showed a significant negative association of HDL‐c with MCP‐1 and sVCAM‐1.
Conclusions
A significant increase in cardiovascular risk biomarkers persisting over the prolonged study period was seen in the TI arm. This factor may contribute to the increased cardiovascular risk observed in previous studies.
Objective
The aim of the study was to evaluate the efficacy of fosamprenavir/ritonavir (FPV/r) monotherapy in plasma and reservoirs in virologically suppressed patients.
Methods
A 48‐week, ...prospective, single‐arm pilot trial was carried out (trial registration: ISRCTN78584791). Patients receiving triple therapy FPV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) for at least the previous month, with viral load (VL) <40 HIV‐1 RNA copies/mL and no previous virological failure (VF) on protease inhibitors (PIs), were included in the trial and received FPV/r monotherapy (700/100 mg/12 h). VL and FPV/r levels by liquid chromatography‐tandem mass spectrometry (LC/MS/MS); limit of detection (LOD) 0.5 ng/mL in cerebrospinal fluid (CSF) were determined at week 24. VF was defined as VL >40 copies/mL in three consecutive samples or >500 copies/mL in two samples.
Results
Enrolment was prematurely stopped because of a high percentage of VF. Twenty patients (45% men; median age 43.5 years) were included in the trial. Nine patients (45%) presented therapeutic failure seven (35%) had VF, and two discontinued therapy. Resistance testing was available in five patients. One patient presented major PI mutations (54L, 32I and 47V) in addition to one minor mutation (13V), whereas two patients had minor PI mutations (10V+36I and 71T, respectively). The patient with major PI mutations switched from FPV/r to darunavir/r and VL was re‐suppressed. In the other six patients with VF, VL was re‐suppressed after the reintroduction of NRTIs. VL was <40 copies/mL in all CSF samples (n=10). Median amprenavir plasma levels were 2.5 μg/mL (range 0.7–8.6 μg/mL) at week 24 and 2.5 μg/mL (range 0.4–3.8 μg/mL) at VF. The CSF amprenavir concentration was 28.1 ng/mL (range 6.39–83.6 ng/mL), exceeding the reported 50% inhibitory concentration (IC50) range for CSF in nine of 11 patients.
Conclusions
The high percentage of patients with VF in our study suggests that the use of FPV/r in a simplification monotherapy strategy should be discouraged. Adequate amprenavir levels and undetectable VL in CSF were documented in all samples evaluated.
Switching to raltegravir in selected patients treated with ritonavir-boosted protease inhibitors may result in similar efficacy and lower plasma lipids.
SPIRAL is a 48-week multicentre, open-label ...trial in which HIV-infected adults with less than 50 copies/ml of plasma HIV RNA for at least the previous 6 months on ritonavir-boosted protease inhibitor-based therapy were randomized (1: 1) to switch from the ritonavir-boosted protease inhibitor to raltegravir or to continue on ritonavir-boosted protease inhibitor-based therapy. Primary endpoint was the proportion of patients free of treatment failure (noncompleter = failure) at 48 weeks. SPIRAL study was powered to show noninferior efficacy of raltegravir-based therapy with a margin of -12.5%.
Two hundred and seventy-three patients assigned to switch to raltegravir (n = 139) or to continue ritonavir-boosted protease inhibitor (n = 134) were included in the efficacy analysis. At 48 weeks, 89.2% (raltegravir-based therapy) and 86.6% (ritonavir-boosted protease inhibitor-based therapy) of the patients remained free of treatment failure difference 2.6%; 95% confidence interval (CI) -5.2 to 10.6. A total of 96.9% (raltegravir-based therapy) and 95.1% (ritonavir-boosted protease inhibitor-based therapy) of the patients remained free of virological failure (difference 1.8%; 95% CI -3.5 to 7.5). Switching to raltegravir was associated with significant decreases in plasma lipids and total-to-HDL cholesterol ratio relative to continuing ritonavir-boosted protease inhibitor. Severe adverse events and study drug discontinuations due to any adverse event occurred in 4 and 2% of the patients in each group.
In patients with sustained virological suppression on ritonavir-boosted protease inhibitor-based therapy, switching from ritonavir-boosted protease inhibitor to raltegravir demonstrated noninferior efficacy and resulted in a better lipid profile at 48 weeks than continuing ritonavir-boosted protease inhibitor.
Summary Background Our objective was to assess therapeutic non-inferiority of dual treatment with lopinavir–ritonavir and lamivudine to triple treatment with lopinavir–ritonavir plus two ...nucleos(t)ides for maintenance of HIV-1 viral suppression. Methods In this randomised, open-label, non-inferiority trial, we recruited patients from 32 HIV units in hospitals in Spain and France. Eligible patients were HIV-infected adults (aged ≥18 years) with HIV-1 RNA of less than 50 copies per mL, for at least 6 months on triple treatment with lopinavir–ritonavir (twice daily) plus lamivudine or emtricitabine and a second nucleos(t)ide, with no resistance or virological failure to these drugs, and no positive hepatitis B serum surface antigen. Investigators at each centre randomly assigned patients (1:1; block size of four; stratified by time to suppression <1 year or >1 year and nadir CD4 cell count <100 cells per μL or >100 cells per μL; computer-generated random sequence) to continue triple treatment or switch to dual treatment (oral lopinavir 400 mg and oral ritonavir 100 mg twice daily plus oral lamivudine 300 mg once daily). The primary endpoint was response to treatment in the intention-to-treat population (all randomised patients) at 48 weeks. The non-inferiority margin was 12%. This study is registered with ClinicalTrials.gov , number NCT01471821. Findings Between Oct 1, 2011, and April 1, 2013, we randomly assigned 250 participants to continue triple treatment (127 51% patients) or switch to dual treatment (123 49% patients). In the intention-to-treat population, 110 (86·6%) of 127 patients in the triple-treatment group responded to treatment versus 108 (87·8%) of 123 in the dual-treatment group (difference −1·2% 95% CI −9·6 to 7·3; p=0·92), meeting the criteria for non-inferiority. Serious adverse events occurred in eight (7%) patients in the triple-treatment group and five (4%) in the dual-treatment group (p=0·515), and study drug discontinuations due to adverse events occurred in four (3%) in the triple-treatment group and one (1%) in the dual-treatment group (p=0·223). Interpretation Dual treatment with lopinavir–ritonavir plus lamivudine has non-inferior therapeutic efficacy and is similarly tolerated to triple treatment. Funding AbbVie and Red Temática Cooperativa de Investigación en Sida.
IntroductionAdvancements in and accessibility to effective antiretroviral therapy has improved the life expectancy of people living with HIV, increasing the proportion of people living with HIV ...reaching older age (≥60 years), making this population's health‐related quality of life (HRQoL) more relevant. Our aim was to identify the determinants of poor HRQoL in people living with HIV aged ≥60 years and compare them with those of their younger counterparts.MethodsWe used data from the ‘Vive+’ study, a cross‐sectional survey conducted between October 2019 and March 2020, nested within the PISCIS cohort of people living with HIV in Catalonia and the Balearic Islands, Spain. We used the 12‐item short‐form survey (SF‐12), divided into a physical component summary (PCS) and a mental component summary (MCS), to evaluate HRQoL. We used the least absolute shrinkage and selection operator for variable selection and used multivariable regression models to identify predictors.ResultsOf the 1060 people living with HIV (78.6% males) who participated in the study, 209 (19.7%) were aged ≥60 years. When comparing older people living with HIV (≥60 years) and their younger counterparts, older people exhibited a worse PCS (median 51.3 interquartile range {IQR} 46.0–58.1 vs. 46.43 IQR 42.5–52.7, p < 0.001) but a similar MCS (median 56.0 IQR 49.34–64.7 vs. 57.0 IQR 48.9–66.3, p = 0.476). In the multivariable analysis, cognitive function correlated with a PCS (β correlation factor β −0.18, p = 0.014), and depressive symptoms and satisfaction with social role correlated with an MCS (β 0.61 and β −0.97, respectively, p < 0.001) in people living with HIV aged ≥60 years.ConclusionDepressive symptoms, poor cognitive function, and lower satisfaction with social roles predict poorer HRQoL in older people living with HIV. These factors need to be considered when designing targeted interventions.
To compare 48-week changes in body fat distribution and bone mineral density (BMD) between patients switching from a ritonavir-boosted protease inhibitor (PI/r) to raltegravir (RAL) and patients ...continuing with PI/r.
Substudy of the prospective, randomized, open-label, multicenter SPIRAL study.
Patients were randomized (1 : 1) to continue with the PI/r-based regimen or switch to RAL, maintaining the rest of the treatment unchanged. Dual-energy X-ray absorptiometry and computed tomography scans were performed at baseline and after 48 weeks to measure body fat and bone composition, analyzing intragroup and intergroup differences.
Eighty-six patients were included and 74 patients (39 RAL, 35 PI/r) completed the substudy. Significant increases in median interquartile range (IQR) visceral adipose tissue (VAT) 20.7 (-2.4 to 45.6) cm(2), P = 0.002 and total adipose tissue (TAT) 21.4 (-1.3 to 55.4) cm(2), P = 0.013 were seen within the PI/r group. No significant changes in body fat were seen with RAL or between treatment groups. Regarding bone composition, total BMD 0.01 (0 to 0.02) g/cm(2), P = 0.002, total hip BMD 0.01 (0 to 0.03) g/cm(2), P = 0.015 and total hip T score 0.12 (-0.05 to 0.21) SD, P = 0.004 significantly increased with RAL, with no significant changes within the PI/r group. Differences between treatment groups were significant in femoral neck BMD 0.01 (-0.02 to 0.02) g/cm(2), P = 0.032 and T score 0.01 (-0.18 to 0.18) SD, P = 0.016.
Although there were no significant changes in body fat between groups, maintaining a PI/r-based regimen was associated with a significant increase in VAT and TAT. Switching to RAL led to a significant increase in femoral neck BMD when comparing between groups.
PDF
