bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nevirapine vs efavirenz in virologically supressed patients: differences in lipoprotein subclasses and inflammatory biomarkers
Authors: Estrada V , Gómez‐Garre M , Santos J , Gutiérrez F , Labarga P , Palacios R , Masiá M , López‐Vázquez M , Isernia V , Vispo E , Fernández‐Cruz A 
Published: November 2012

BackgroundThe interaction between lipid disturbances and inflammatory markers is not well known in patients on antiretroviral therapy (ART). As nevirapine (NVP) is associated with a better lipid profile than efavirenz (EFV), we investigated the relationships between lipid profiles, lipoprotein subclasses and inflammatory biomarkers in patients with prolonged viral suppression with either NVP or EFV and no obvious clinical inflammation.Methods122 clinically stable HIV‐infected patients with HIV‐1 RNA <20 copies longer than 6 months on NNRTI therapy were studied. 72 (59%) were on EFV and 50 (41%) on NVP. Any potentially inflammatory co‐morbid diseases (concurrent viral hepatitis, diabetes, hypertension, chronic liver or renal diseases), or statin treatment, were exclusion criteria. Inflammatory biomarkers included hsCRP, LpPLA2, sCD40L, IL‐6, IL‐8, t‐PA, MCP‐1, p‐selectin and VCAM‐1. Lipoprotein subclass measures (VLDL, LDL, IDL and HDL particle number and size) were obtained by the use of proton nuclear magnetic resonance spectroscopy.Results82% were male; median age 45 years. Median CD4 count 550/μL (IQR 324). Median time since HIV diagnosis 96 months (IQR 102) and accumulated time on ART 50 months (IQR 101). Patients on NVP had higher time since HIV diagnosis (126.9 [66.7] vs. 91.3 [6.6] months, p=0.008) a prolonged time on ART (89.6 [54.6] vs. 62.3 [52.2] months, p=0.01) and were older (47.7 vs. 40.7 years, p=0.001) than those on EFV. NVP‐treated patients presented increased HDL‐c (55.8 [16] vs. 48.8 [10.7] mg/dL, p=0.007) and apoA1 levels (153.4 [31.9] vs. 141.5 [20.5] mg/dL, p=0.02), and reduced apoB/apoA1 ratio (0.68 [0.1] vs 0.61 [0.1], p=0.003) than EFV‐treated patients. No differences in inflammatory markers or lipoprotein subclasses were found between NVP and EFV. In patients with extreme lipid values (less favorable: 75th percentiles of LDL, small/dense LDLp and small HDLp, or more favorable: HDL p75 and apoB/apoA1 ratio p25), no consistent differences in inflammatory biomarkers were found.ConclusionsPatients with prolonged viral suppression on NVP present significantly higher HDL and apoA1 levels and reduced apoB/apoA1 ratios than those on EFV, but no differences were found in lipoprotein particles nor inflammatory biomarkers. Relationships between lipid parameters and inflammatory biomarkers in NNRTI‐treated patients are complex and do not show a linear relationship in this study.
Too old too soon? Heart age compared with actual age in HIV‐positive individuals
Authors: Davies T , May M , Gompels M 
Published: November 2012

Absolute risk of cardiovascular disease (CVD) may be calculated using the Framingham equation. Since risk increases with age, a useful measure of excess risk adjusted for age is ‘heart age’, the age of a reference person with the same estimated risk, but based on ideal values of risk factors defined as non‐smoker, non‐diabetic, untreated SBP of 125 mmHg, total cholesterol of 180 mg/dL and HDL cholesterol of 45 mg/dL [1]. Patients attended the Bristol HIV Cohort between 2008–11. HDL and total cholesterol, SBP, CD4 count and viral load measured within a period of 6 months were available for 749/1013 (74%) patients. The median age was 42 years, 33% were female and 82% were on ART. We calculated heart‐age deviation (heart age‐actual age) by sex and age group. Smoking status was not available and therefore we did all calculations twice assuming all a) non‐smokers b) smokers. We used fractional polynomials to model change in heart‐age deviation with actual age. We used mutually adjusted multivariable linear regression to determine whether sex, age, CD4, viral load, treatment status and year of starting ART were associated with heart‐age deviation. The mean heart‐age deviation in males was 3.4 years (females 1.7) for non‐smokers, and 14.8 years (females 12.5) for smokers. The figure shows that deviation increased with age; eg for male smokers it was 9.7, 15.0, 20.4 and 23.3 years at ages 16–39, 40–49, 50–59 and ≥60 years respectively. On average a 45‐year‐old male smoker had a heart age of 60 years. Compared with males, deviation was lower in younger females, but became higher after age 48 years. Compared with treated patients (assuming non‐smoker) with viral suppression, untreated patients had similar heart age (0.33 [95% CI 1.67, 2.33]) and treated patients with unsuppressed viral replication had higher heart age (3.01 [0.61, 5.42]). Higher CD4 count was associated with higher heart age: those with CD4 between 500–750 and >750 (v.<500) had an increase of 2.25 (0.61, 3.89) and 4.39 (2.41, 6.36) years respectively.HIV+ve individuals have a considerably increased risk of CVD compared with the ideal reference values, although we do not know if estimated risk translates to CVD events. Heart‐age deviation increases with age and is greater for smokers. Deviation increases more sharply in women, possibly due to lower CVD risk at younger ages or to increased risk postmenopause. Heart age could be a useful communication tool in attempts to reduce CVD risk in HIV+ve individuals.Heart age deviation by actual age by sex and smoking status (95% CI shown shaded)image
Role of maraviroc in a dyslipidemic murine model of atherosclerosis RTV‐induced
Authors: Cipriani S , Mencarelli A , Francisci D , Renga B , Schiaroli E , D'Amore C , Fiorucci S , Baldelli F 
Published: November 2012

PurposeChemokines and their receptors play a crucial role in the development of atherosclerosis. CCR5 is considered to be crucial to monocyte recruitment during development of atherosclerosis. CCR5, known as a co‐receptor of HIV‐1, is the target of the approved CCR5 antagonist maraviroc (MVC). Therefore we investigated whether MVC reduces inflammation and atherosclerosis in a rodent model of dyslipidemia (ApoE‐/‐mice) treated or not with Ritonavir (RTV).MethodsTwo‐month‐old mice (8 per group): wild type, ApoE‐/‐ plus vehicle; ApoE‐/‐ plus RTV; ApoE‐/‐ plus RTV in combination with MVC. Nine‐month‐old mice (13 per group): wild type; Apo E‐/‐ + vehicle; and Apo E‐/‐ + MVC. Animals were sacrificed after 3 months treatments and plasma, aortas and epididymal fat were collected. Areas of aortas plaque were measured. Immunohistochemistry was performed to evaluate macrophages infiltration, and protein levels of cytokines/chemokines (i.e. ICAM, PAI, VCAM, IL‐10, IL‐17, MCP1, Rantes, TNFα, INFγ) were evaluated in aorta lysates.Summary of resultsRTV enhances the plaque areas percentage in two month old ApoE‐/‐ mice and is significantly reduced by MVC. The ritonavir‐enhanced Mac3 expression on plaques is also reduced by MVC. Treatment with MVC lowers aortic concentration of cytokines/chemokines and plasmatic level of CRP that are increased by RTV. Ritonavir, enhancing mRNA expression of IL‐6, Rantes and Mip1α, induces lipoatrophy in epididymal fat; MVC revertes this lipoatrophy and reduces mRNA levels of these cytokines‐chemokines. Moreover, in ApoE‐/‐ mice 9 months old, MVC significantly reduces the percentage of plaque areas (from 16.6±3.35% to 7.13±1.44%) (en‐face coloration), lowers aortic MAC3 staining and reduces the aortic concentration of cytokines/chemokines.ConclusionsIn a dyslipidemic rodent model the CCR5 inhibitor Maraviroc significantly reduces the percentage of aortic plaque areas, aortic inflammation and lipoatrophy of the epididymal fat. Therefore, the current use of CCR5 antagonists to treat HIV infection, a condition associated with an increased occurrence of cardiovascular disease, should also be exploited to determine any beneficial cardiovascular effects [1,2].
Findings from the WHO/PAHO early warning indicators of HIV drug resistance monitoring system performed in Argentina
Authors: Bissio E , Balleri C , Falistocco C , Curras V , Vila M 
Published: November 2012

BackgroundIn the last years, WHO developed a Global Strategy for HIV Drug Resistance Prevention and Assessment using a public health approach. This strategy supports optimal functioning of treatment programs to minimize emergence of preventable HIV drug resistance and to maintain effectiveness of first‐ and second‐line ART regimens. Since 2011, Argentina has been monitoring some of the indicators of this strategy (called early warning indicators [EWIs]). The aim of this study was to analyze the outcomes measured during the mentioned year.MethodsBased on the availability of information in the hospitals’ pharmacies, where the data collection took place, and on the relevance for Argentina, some of the EWIs proposed by WHO were selected and adapted. The information is being collected since beginning of 2011, and a first analysis was performed at the end of that year. Since this was a pilot phase, 6 representative hospitals’ pharmacies participated.ResultsData are available for 4 of the sites. The data produced the following indicators: EWI 1a: Percentage of adult patients initiating ART who are prescribed a non‐recommended first‐line ART regimen (goal 0%). Site A: 22.5%; Site B: 11.1%; Site C: 0%; Site D: 2.7%. EWI 1b: Percentage of adult patients initiating ART who withdraw a non‐recommended first‐line ART regimen (goal 0%). Site A: 22.5%; Site B: 25.8%; Site C: 15.5%; Site D: 16.1%. EWI 2: Percentage of patients lost to follow‐up 12 months after ART initiation (goal less than 20%): Site A: 41.6%; Site B: 9.3%; Site C: 22.2%; Site D: 0%. EWI 4: percentage of patients who picked up prescribed ARV drugs on time (goal:>90%): Site A: 39.1%; Site B: 72.4%; Site C: 44.5%; Site D: N/DConclusionsThere is a high proportion of patients in Argentina which are prescribed non‐recommended regimens, and a higher proportion withdraw these regimens from pharmacies: 75% of sites do NOT reach the goal of EWI 1a; 100% do NOT reach the goal for EWI 1b. There is also a high proportion of patients lost to follow up during the first year after treatment initiation: 50% of sites reach the goal of EWI 2. A very high proportion of patients do NOT pick‐up ART on time: none of the sites reach EWI 4 goal. The use of these indicators allowed us to visualize that there is a high proportion of patients that would be nonadherent. With these data the Directorate of AIDS will improve efforts to know better the situation, understand the causes and implement strategies to increase adherence.
Community viral load in patients harboring HIV drug‐resistant strains and new cases of TDR in Northern Greece‐a retrospective cohort study
Authors: Pilalas D , Metallidis S , Skoura L , Haidich A , Chrysanthidis T , Tsachouridou O , Papadimitriou E , Kollaras P , Malisiovas N , Nikolaidis P 
Published: November 2012

Purpose of the studyRecent studies suggest an association between community viral load and new diagnoses of HIV infection. Aim of our study was to explore a potential association between the pattern of new cases of transmitted drug resistance (TDR) in Northern Greece and the community viral load in the subset of patients who harbored HIV drug‐resistant strains during 2000–2007.MethodsData on viral load measurements and genotypic HIV drug resistance were extracted from the respective databases of the Infectious Diseases Division of the AHEPA University Hospital and the National Reference Laboratory for AIDS of Northern Greece which provide healthcare services free of charge for the majority of HIV‐positive individuals in Northern Greece. Patients who had undergone at least once genotypic resistance testing were included in the study. The 2009 SDRM list was used to categorize patients in subsets with regard to genotypic resistance results. Community viral load (CVL) was calculated as follows: The per‐year weighed mean viral load was calculated for each individual patient and the median value of this set was defined as the community viral load. Poisson log‐linear regression models with robust estimators were employed to examine the association between new cases of TDR and CVL of patients with genotypic drug resistance, patient number and year.Results512 patients out of 701 ever recorded had undergone genotypic HIV drug resistance testing at least once (73%). Overall, 202 out of 512 patients (39.4%) were identified with at least one resistance mutation (106/512 NNRTI, 175/512 NRTI, 104/512 PI). Poisson log‐linear multivariate models correlated new cases of TDR with either log CVL (p = 0.068, RR: 7.59, 95% CI: 0.863–66.71) and year (p = 0.013, RR: 2.19, 95% CI: 1.18–4.08) or log CVL (p = 0.030, RR: 5.08, 95% CI: 1.17–22.06) and number of patients with drug resistance (p = 0.0001, RR: 1.03, 95% CI: 1.01–1.06).ConclusionsOur results indicate that the community viral load of patients with HIV drug resistance may affect the number of new patients with TDR, underline the need for successful viral suppression in patients with resistant HIV strains from a public health standpoint and, should they be supported by further studies, suggest that community viral load could be used as a biomarker for TDR surveillance.
Cholecalciferol supplementation, vitamin D status and T‐cell immune phenotype in HIV‐infected children: a randomised controlled trial
Authors: Vigano A , Giacomet V , Manfredini V , Bedogni G , Mora S , Cerini C , Borelli M , Trabattoni D , Zuccotti G 
Published: November 2012

Purpose of the studyBesides its known effects on bone metabolism, vitamin D may regulate immune function. We performed a randomized controlled trial (RCT) to test whether cholecalciferol supplementation can improve vitamin D status and modulate immune responses in HIV‐infected children and youth.MethodsCaucasian vertically HIV‐infected patients (aged 8 to 26 years) with vitamin D deficiency and normal parathormone (PTH) levels were randomized into an experimental (n=25) and control (n=25) group to receive 100,000 IU of oral cholecalciferol every 3 months for a total of 4 doses, or placebo. A pre‐randomization period (−3 months) was also taken into account to better model within‐individual variability. Mixed linear regression models were used to evaluate the between‐group changes in the outcomes of interest. The analysis was intention to treat.Summary of results47 subjects completed the RCT. Cholecalciferol supplementation produced an early decrease in PTH levels (3 months) and a later concomitant increase in 25(OH)D and 1,25(OH)2D levels (6 months), both persisting up to 12 months.The supplementation had no effect on CD4+T‐cell numbers or percentage while was associated with a decreased loge Th1, an increased loge Th2 (*p<0.05), an increased loge Treg (**p<0.01), and and a decreased loge Th17:Treg(*p<0.05).

Loge VDR
Loge Th1
Loge Th2
Loge (Th1:Th2)
Loge Th17
Loge Treg
Loge (Th17:Treg)

Month 3
0.5 (−0.1 to 1.2)
−1.6 (−3.6 to 0.5)
−0.1 (−0.6 to 0.5)
−1.4 (−3.5 to 0.7)
−1.5 (−3.2 to 0.2)
0.6 (−0.3 to 1.6)
−2.5 (−4.5 to−0.4)*

Month 12
0.7 (−3.0 to 1.7)
−0.7 (−2.5 to 1.1)
1.1* (0.02 to 2.1)
−1.6 (−3.7 to 0.5)
0.3 (−1.2 to 1.8)
1.7** (0.6 to 2.7)
−1.3 (−3.3 to 0.7)

ConclusionsIn our cohort, supplementation with oral cholecalciferol was effective in increasing serum 25(OH)D and 1–25(OH)2D while decreasing serum PTH levels, had no effect on CD4+T‐cell count, but was associated with T‐cell phenotype changes mainly favoring Tregulatory subset.
VERxVE 144 week results: nevirapine extended‐release (NVP XR) QD versus NVP immediate‐release (IR) BID with FTC/TDF in treatment‐naïve HIV‐1 patients
Authors: Brinson C , Bogner J , Nelson M , Podzamczer D , Quinson A , Drulak M , Gathe J 
Published: November 2012

BackgroundHere we report 96‐ and 144‐week follow‐up data from VERxVE, which demonstrated that NVP XR (400 mg QD) was non‐inferior to NVP IR (200 mg BID), each on a backbone of emtricitabine/tenofovir at 48 weeks.MethodsVERxVE was a double‐blind, double‐dummy, non‐inferiority study in adults with screening viral‐load (VL) >1000 copies/mL and CD4+ cell count <400 cells/mm3 (males) and <250 cells/mm3 (females). Randomization was stratified by baseline VL (copies/mL), ≤100,000 or >100,000. Primary endpoint was confirmed virologic response (<50 copies/mL) at Week 48. Cochran's statistic incorporating baseline‐VL strata tested non‐inferiority of XR efficacy to IR. Secondary endpoints included 144‐week sustained virologic response and safety.Results1011 patients were randomized and treated; 736 (NVP XR: 378, NVP IR: 358) completed 144 weeks. Virologic response was 63.6% for NVP XR and 58.5% for NVP IR (adjusted difference of 4.8% [95% CI: −1.1%, 10.8%] favoring NVP XR). No significant differences were seen in changes in CD4+ T cell counts from baseline, virologic failures, and total discontinuation rates between treatment arms regardless of demographic or baseline characteristics.

48 Weeks
96 Weeks
144 Weeks

NVP IR 200 mg BID
NVP XR 400 mg QD
NVP IR 200 mg BID
NVP XR 400 mg QD
NVP IR 200 mg BID
NVP XR 400 mg QD

% Virologic response
75.9
81.0
66.6
69.3
58.5
63.6

Change from baseline in CD4+ Count (cells/mm3)
207
213
257
275
286
317

Virologic failures (%)
5.9
3.2
10.7
11.1
15.8
15.1

Discontinuation rate (%)
19.2
16.6
26.1
23.6
29.2
25.1

Discontinuations due to AEs
8.3
6.3
9.5
8.3
10.7
8.5

ConclusionsNVP XR continued to demonstrate non‐inferior virologic efficacy to NVP IR in prior treatment‐naïve HIV infected patients out to week 144. NVP XR continued to be well‐tolerated with a safety profile similar to NVP IR.
Low plasma zinc level and response to zinc supplement in HIV‐infected patients who have immunological discordance after antiretroviral therapy
Authors: Asdamongkol N , Phanachet P , Sungkanuparph S 
Published: November 2012

Purpose of the studyImmunological discordance in HIV‐infected patients is associated with the higher risk of mortality and disease progression. Zinc is an essential micronutrient for immune function. We aimed to determine plasma zinc level and immunological response after zinc supplementation in HIV‐infected patients with immunological discordance after antiretroviral therapy (ART).MethodsA pilot study of 2 phases including a cross‐sectional study to determine plasma zinc level in patients with immunological discordance and a prospective, randomized, open‐label, placebo‐controlled trial was conducted in HIV‐infected patients with immunological discordance in a medical‐school hospital. Immunological discordance was defined as patients who received ART, had complete virological response (HIV RNA<40 copies/ml), and had immunological response with CD4 cell count<200 cell/mm3 and increased less than 30% from baseline after ART with undetectable HIV RNA for at least 6 months. Plasma zinc level was measured and stratified into low (<75 µg/dL) and normal plasma zinc level. Patients were randomly assigned to receive zinc or placebo supplementation for 6 months. CD4 cell count was monitored every 3 months.Summary of resultsOf 31 patients, median (IQR) plasma zinc level was 76 (66–88) µg/dL (IQR) and 12 (38.7%) patients had low plasma zinc level. Five of 12 patients with low plasma zinc level and 8 of 19 patients with normal plasma zinc level were randomized to receive zinc supplementation. Median (IQR) change of plasma zinc level after zinc supplementation in patients with low and normal plasma zinc level were 29 (−2–50) and−8 (−17–10) µg/dL, respectively. Significant increase of CD4 cell count after zinc supplementation was observed in patients with low plasma zinc level. Median (IQR) CD4 cell count at baseline and after zinc supplementation were 176 (161–200) and 250 (192–262) cells/mm3. The effect of zinc supplementation compared to placebo on the rising of CD4 cell count was not significantly different in both patients with low and normal plasma zinc level.ConclusionsLow plasma zinc level is observed over one‐third of patients with immunological discordance. Zinc supplementation increases plasma zinc level and CD4 cell count in patients with low zinc level but the effect was not significant different from placebo. Further large‐scale study to determine long‐term benefit of zinc supplementation in patients with immunological discordance is needed.
A phase 4, single‐arm, open‐label, pilot study of maraviroc, raltegravir and darunavir/r in HIV‐1 adults with triple class failure: TERCETO study
Authors: Patterson P , Magneres C , Sued O , Fink V , Figueroa M , Cesar C , Gun A , Cahn P , Krolewiecki A 
Published: November 2012

The purpose of this phase 4, single‐arm, open‐label study was to evaluate the safety, tolerability, efficacy, antiviral and immunological activity of maraviroc (MVC) in combination with raltegravir (RGV) and darunavir/r (DRV/r) in adult HIV‐1 infected patients (pts) with limited treatment options. HIV‐1 pts with documented virologic triple class failure or multi‐drug class resistance defined as the presence of Q151 complex, 69 insertion complex and/or≥3 TAMs for NRTIs and K103N, G190S+Y181C or Y188L mutants for NNRTIs and≥3 RAMs (L10F/I/R/V; M46I/L; I54V/M/L; V82A/F/T/S; I84V; L90M) for protease inhibitors (PIs) were offered a triple drug regimen consisting of MVC 150 mg BID, RGV 400 mg BID and DRV/r 600/100 mg BID. Safety, lipid profile and virologic efficacy were evaluated at week 4, 12, 24, 36 and 48. Between January 2010 and March 2012, 27 pts were enrolled. Screening failure rate was 52% due to undetectable viral load (pVL) or non R5 tropism type (Trofile™). Despite being heavily pre‐treated pts, only 26% had negative tropism test at SCR. Baseline characteristics of 13 included pts were: 77% male, median age 43 years (IQR: 40.1–48.6), 38% had a prior AIDS‐defining condition. Median BSL pVL was 23,350 cps/mL (4.4 log10) (IQR: 11,236–55,785) and median CD4 was 222 cells/mm3 (IQR: 179–318). Median time on NRTIs, NNRTIs and PIs were 10.7 (8.6–13.7), 1.7 (1.3–7.6) and 5.4 (4.7–10) years respectively. Pts had received a median of 2 PIs (IQR: 2–3). 8/13 pts showed thymidine analogue‐associated mutations (TAMs), and≥2 were present in 5/13. Detectable NNRTI resistance‐associated mutations (RAMs) were present in 10/13 patients. 9/13 had≥4 primary PI RAMs. At 48 weeks, 2 pts had discontinued therapy (OIs related death (cryptococcal meningitis)=1, withdrawn from the study on W36 due to blips despite not achieving criteria for virologic failure=1) and the remaining pts (11/13) achieved undetectable pVL and increased CD4 in 133 cell/mm3 from BSL (IQR: 81–174.5). Median total cholesterol levels increased from 162 mg/dL (IQR: 135‐188) to 215 mg/dL (IQR: 182–237) between BSL/W48; median change in cholesterol levels: 40 mg/dL (IQR: 6.5‐66). Salvage therapy including MVC, RGV and DRV/r achieved sustained reductions in pVL (<50 copies/mL) through 48 weeks of therapy in this pilot study with no treatment limiting toxicity.AcknowledgementsTERCETO study was sponsored through an investigator‐initiated research (IIR) grant from Pfizer Inc. Merck provided raltegravir.