bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rate of viral load failure over time in people on ART in the UK Collaborative HIV Cohort (CHIC) study
Authors: O'Connor Jemma , Smith Colette , Lampe Fiona , Johnson Margaret , Sabin Caroline , Phillips Andrew 
Published: November 2014

IntroductionMost people achieve and maintain viral load (VL) suppression on first‐line antiretroviral therapy (ART) but for a minority this does not happen. It is unclear whether those who have maintained VL suppression for several years will be able to continue to do so, or if rates of VL failure – due to poor adherence, ART interruption and/or resistance – remain at appreciable levels.MethodsEligible participants were ART‐naïve and started treatment after 1st January 2000, with ≥3 antiretrovirals and ≥9 months follow‐up. VL failure was defined as failure to achieve VL suppression (≤50 copies/mL) by 9 months on ART or a single VL >200 copies/mL after 9 months after start of ART. Kaplan‐Meier estimates were used to examine the cumulative probability of experiencing a VL >200 copies/mL over time, irrespective of treatment interruption (Figure 1). Follow‐up was censored at last VL assessment but not at treatment interruption. In a sensitivity analysis, VL failure was instead defined as two consecutive VL >1000 copies/mL.ResultsA total of 13,556 participants were included. Median (IQR) age at start of ART was 37 (32–43), median follow‐up 4.1 (2.3–6.7) years, pre‐ART VL 71,400 (17,400–221,900) copies/mL and pre‐ART CD4 count 204 (110–290) cells/mm3. Fifty‐one percent were white, 71% male and 50% MSM. Of which, 5,351 (39%) participants experienced a VL >200 copies/mL. In sub‐groups of participants the proportion experiencing a VL >200 copies/mL by one year after start of ART were: <50 years 22%, ≥50 years 17%, men 20%, women 26%, MSM 19%, black heterosexuals 23%, white heterosexuals 26% and other 23%. The median time to VL >200 copies/ml was 8 years. In sensitivity analyses based on 12,811 participants, 4274 (33%) experienced two consecutive VL >1000 copies/mL. Table 1 presents the rate of experiencing a VL >200 copies/mL (two consecutive VL >1000 copies/mL) by time since start of ART. The rate of VL >200 copies/mL declines over time, from 30 per 100 person‐years after up to two years after ART, to two per 100 person‐years after up to 11.5 years after ART. A sum of 2,047 (15%) participants stopped ART at some point (10, 14 and 17% had stopped ART by 1, 3, and 5 years, respectively).ConclusionsAlthough resistance will often not be present and, even if present, several drug options will likely remain, first occurrence of VL > 200 copies/mL after having attained viral suppression continues to occur after 10 years on ART.
HIV‐1 attachment inhibitor prodrug BMS‐663068 in antiretroviral‐experienced subjects: week 24 sub‐group analysis
Authors: Brinson Cynthia , Lalezari Jacob , Gulam Latiff H , Thompson Melanie , Echevarria Juan , Treviño‐Pérez Sandra , Stock David , Samit Joshi R , George Hanna J , Lataillade Max 
Published: November 2014

IntroductionBMS‐663068 is a prodrug of BMS‐626529, an attachment inhibitor that binds directly to HIV‐1 gp120, preventing initial viral attachment and entry into the host CD4+ T‐cell. AI438011 is a Phase IIb, randomized, active‐controlled trial investigating the safety, efficacy and dose–response of BMS‐663068 versus atazanavir/ritonavir (ATV/r) in treatment‐experienced (TE), HIV‐1‐positive subjects.Materials and MethodsAntiretroviral TE subjects (exposure to ≥1 antiretroviral for ≥1 week) with susceptibility to all study drugs (BMS‐626529 IC50 100 nM), were randomized equally to four BMS‐663068 arms (400 or 800 mg, BID; 600 or 1200 mg, QD) and a control group (ATV/r 300/100 mg QD) with tenofovir disoproxil fumarate (TDF) + raltegravir (RAL). A sub‐group analysis of viral efficacy and immunologic reconstitution is presented.ResultsA total of 251 subjects were treated. Median age was 39 years, 60% were male and 38% were white. Median baseline (BL) viral load (VL) was 4.85 log10 c/mL (43%; 100,000 c/mL) and median CD4+ T‐cell count was 230 cells/mm3 (38%; 200 CD4 cells/mm3). Through Week 24, response rates (HIV‐1 RNA 50 c/mL) were comparable across all BMS‐663068 arms and the ATV/r arm regardless of gender, age and race. Response rates for subjects with BL VL 100,000 c/mL (BMS‐663068, 82‐96%; ATV/r, 93%) were higher than those for subjects with BL VL ≥100,000 c/mL (BMS‐663068, 70‐87%; ATV/r, 73%); however, there were no substantial differences in response across the BMS‐663068 and ATV/r arms in either sub‐group. Response rates for subjects with BL CD4+ cell counts ≥200 cells/mm3 (87‐96%) were higher than those for subjects with BL CD4+ cell counts 200 cells/mm3 (62–82%); however, no substantial differences in response were seen across the BMS‐663068 and ATV/r arms in either sub‐group. Mean changes in CD4+ T‐cell counts from BL were similar across all arms regardless of gender, age and BL CD4+ T‐cell count.ConclusionVirologic response rates were similar across the BMS‐663068 and ATV/r arms in TE subjects, regardless of BL demographic characteristics (gender, race, age), BL HIV‐1 RNA, or BL CD4+ T‐cell count. Mean increases in CD4+ T‐cell counts across the BMS‐663068 arms were consistent with ATV/r, regardless of gender, age and BL CD4+ T‐cell count. These results support continued development of BMS‐663068.NotePreviously submitted at IDWeek, Philadelphia, PA, 8 October 2014.
Safety profile of HIV‐1 attachment inhibitor prodrug BMS‐663068 in antiretroviral‐experienced subjects: week 24 analysis
Authors: Lalezari Jacob , Latiff Gulam H , Brinson Cynthia , Echevarria Juan , Treviño‐Pérez Sandra , Bogner Johannes R , Stock David , Joshi Samit R , Hanna George J , Lataillade Max 
Published: November 2014

IntroductionBMS‐663068 is a prodrug of BMS‐626529, an attachment inhibitor that binds directly to HIV‐1 gp120, preventing initial viral attachment and entry into the host CD4+ T‐cell. AI438011 is an ongoing, Phase IIb, randomized, active‐controlled trial investigating the safety, efficacy and dose–response of BMS‐663068 vs. atazanavir/ritonavir (ATV/r) in treatment‐experienced (TE), HIV‐1‐positive subjects. At Week 24, response rates across the BMS‐663068 arms were consistent with ATV/r.Materials and MethodsAntiretroviral TE subjects (exposure to ≥1 antiretroviral for ≥1 week) with susceptibility to all study drugs (including BMS‐626529 IC50 100 nM) were randomized equally to four BMS‐663068 arms (400 or 800 mg, BID; 600 or 1200 mg, QD) and a control arm (ATV/r 300/100 mg QD), with tenofovir disoproxil fumarate (TDF) + raltegravir (RAL). The complete safety profile through Week 24 is reported.ResultsIn total, 251 subjects were treated (BMS‐663068, 200; ATV/r, 51). No BMS‐663068‐related adverse events (AEs) led to discontinuation. Grade 2–4 drug‐related AEs occurred in 17/200 (8.5%) subjects across the BMS‐633068 arms; however, these events were mostly single instances and no dose‐relationship was seen. Similarly, no noticeable trend for Grade 3–4 laboratory abnormalities was seen and Grade 3–4 hematologic changes and liver chemistry elevations were uncommon (neutropenia, 2.5%; AST/ALT elevations, 1% (n=196)). In the ATV/r arm, Grade 2–4 drug‐related AEs occurred in 14/51 (27.5%) subjects and were mostly secondary to gastrointestinal and/or hepatobiliary disorders. Serious adverse events (SAEs) occurred in 13/200 (6.5%) and 5/51 (9.8%) subjects receiving BMS‐663068 and ATV/r, respectively; most were secondary to infections and none were related to study drugs. The most common AE reported for BMS‐663068 was headache (28/200, 14%), occurring in 5/51 (10%) subjects in the ATV/r arm; in the BMS‐663068 arms, this was not dose‐related. There were no deaths.ConclusionsBMS‐663068 was generally well tolerated across all arms, with no related SAEs or AEs leading to discontinuation and no dose‐related safety signals. There were no trends for Grade 2–4 AEs or clinical laboratory abnormalities. These results support continued development of BMS‐663068.NotePreviously submitted at IDWeek, Philadelphia, PA, 8 October 2014.
Rates of cardiovascular events and deaths are associated with advanced stages of HIV‐infection: results of the HIV HEART study 7, 5 year follow‐up
Authors: Esser Stefan , Eisele Lewin , Schwarz Birte , Schulze Christina , Holzendorf Volker , Brockmeyer Nobert H , Hower Martin , Kwirant Friedhelm , Rudolph Roland , Neumann Till , Reinsch Nico 
Published: November 2014

IntroductionCardiovascular diseases are increasing in aging HIV‐positive patients (HIV+). Impact of traditional cardiovascular risk factors, HIV‐specific parameters and antiretroviral therapy (ART) on the incidence of cardiovascular events (CVE) and on the mortality rate are investigated in different HIV+ cohorts.MethodsThe HIV HEART (HIVH) study is an ongoing prospective observational cohort study in the German Ruhr area to assess the frequency and clinical course of cardiac disorders in 1481 HIV+ by standardized non‐invasive cardiovascular screening. CVE were defined as diagnosed or documented myocardial infarction, coronary heart disease, arterial coronary intervention, stent implantation, bypass operation and stroke.Results1481 HIV+ subjects (mean age: 49.3±10.7 years (y), female: 15.6%) were included. 130 CVE and 90 deaths were documented until the end of 7, 5 year follow‐up of HIVH. Mean duration of the HIV‐infection was 12.9±6.8 y. HIV+ were treated with ART on average for 8.6±6.8 y. According to the CDC classification of the HIV‐infection, HIV+ were distributed over the clinical categories (A:34.6%; B:31.4% and C:33.9%) while more than the half had an advanced immunodeficiency (I:8.3%; II:41.1%; III:50.7%). Advanced clinical and immunological stages were significantly (p<0.001) associated with higher incidences of deaths (A:16.7%; B:26.7%; C:56.7% and I:6.7%; II:27.7%; III:65.6%) and CVE (A:17.7%; B:33.1%; C:49.2% and I:3.1%; II:32.3%; III:64.6%) but not with the duration of HIV‐infection (per y: Hazard ratio (HR): 0.91 [0.88–0.94]) and ART (per y: HR: 0.81 [0.79–0.84]) adjusted for age. The proportion of deceased HIV+ with HIV‐RNA ≥50 copies/mL and lower CD4‐cell counts at their last visit is significantly higher compared with living HIV+ without CVE (HIV‐RNA ≥50 copies/mL: 25.6% vs 14.7%). Median CD4‐cells: 286.5 cells/µL (IQR: 168.8–482.8) versus 574 cells/µL (IQR: 406–786). 96.1% of the living HIV+ with CVE had HIV‐RNA<50 copies/mL and median CD4‐cells 542.5 cells/µL (IQR: 370–793.5).ConclusionsAdvanced clinical and immunological stages of HIV‐infection, but not the duration of ART, were associated with higher incidences of CVE and deaths in the HIVH cohort. These observations support an earlier initiation of ART in HIV+. Special cardiovascular risk calculations for HIV+ should consider immunological and clinical categories of the HIV‐infection.
Cardiovascular markers of inflammation and serum lipid levels in HIV‐infected patients with undetectable viraemia
Authors: Viskovic Klaudija , Zidovec‐Lepej Snjezana , Gorenec Lana , Grgic Ivana , Lukas Davorka , Zekan Sime , Dragobratovic Anja , Begovac Josip 
Published: November 2014

IntroductionSuccessfully treated HIV‐infected patients may still have an increased risk for cardiovascular morbidity and mortality, which might be related not only to traditional risks, but also to inflammation and dyslipidemia induced by HIV and/or antiretroviral therapy [1, 2]. We examined the relationship of serum lipid levels with plasma biomarkers of inflammation using a composite inflammatory burden score (IBS) from the following seven markers of inflammation: CD40L, tPA, MCP‐1, IL‐8, IL‐6, hCRP and P‐selectin.Materials and MethodsSubjects were selected among consecutive HIV‐infected males ≥18 years of age with an undetectable viral load (<50 copies/mL of HIV1‐RNA), seen at the University Hospital for Infectious Diseases, Zagreb, Croatia, in the period from January 2012 to March 2013. Plasma inflammatory biomarkers (CD40L, tPA, MCP‐1, IL‐8, IL‐6, hCRP and P‐selectin, quantified by bead‐based cytometry) >75th percentile were considered elevated and an IBS was constructed as the presence of zero, one, two, or three or more elevated biomarkers. Correlations between the IBS and lipid parameters were examined using Spearman's Rho and by ordered logistic regression proportional odds model to estimate the odds of more elevated (>75th percentile) biomarkers.Results181 male patients were included into the study, the median age was 46.7 (Q1–Q3, 39.9–55.0) years and the median current CD4 cell count was 553.0 (Q1–Q3, 389–729) per microliter. The patients were mainly treated with two nucleoside reverse transcriptase inhibitor (NRTI) plus one non‐NRTI (NNRTI) (N=100, 60.8%) or two NRTI plus lopinavir (N=50, 27.6%). There was a significant correlation between the IBS and serum cholesterol (Rho=0.23, 95% CI, 0.09–0.37), triglycerides (Rho=0.30, 95% CI, 0.16–0.42) and cholesterol/HDL‐cholesterol ratio (Rho=0.25, 95% CI 0.11–0.38). In the multivariable model a one unit increase in cholesterol/HDL‐cholesterol ratio was associated with a 1.72‐fold (95% CI, 1.27–2.33) increased odds of having a greater IBS. One unit increase (mmol/L) of cholesterol and triglycerides was associated with a 1.41‐fold (95% CI, 1.13–1.76) and 1.37‐fold (95% CI, 1.18–1.60) increased odds of having a greater IBS, respectively.ConclusionsOur study suggests that in virologically suppressed patients there is a significant association between markers of inflammation and serum levels of cholesterol and triglycerides as well as the cholesterol/HDL‐cholesterol ratio.
Prevalence and concordance of high cardiovascular disease scores in HIV/AIDS patients from Croatia and Serbia with four international algorithms
Authors: Begovac Josip , Dragovic Gordana , Viskovic Klaudija , Kusic Jovana , Perovic Mihanovic Marta , Lukas Davorka , Jevtovic Djordje 
Published: November 2014

IntroductionWe evaluated cardiovascular risks in HIV‐infected patients from Croatia and Serbia and the eligibility for statin therapy as recommended by the 2013 American College of Cardiology/American Heart Association (ACC/AHA) guidelines, European AIDS Clinical Society (EACS) Guidelines and European Society of Cardiology and the European Atherosclerosis Society (ESC/EAS) guidelines for cardiovascular disease (CVD) prevention [1–3].Materials and MethodsA cross‐sectional analysis of consecutive patients between 40 and 79 years old who had received antiretroviral therapy for at least 12 months was performed.ResultsOf 254 (132 from Croatia and 122 from Serbia) persons included in the study, 76% were male; median age was 49 years. Up to 51.6% of persons had a high CVD risk. The prevalence of current smoking was 42.9%, hypertension 31.5% and hypercholesterolaemia (>6.2 mmol/L) 35.4%. Statins would be recommended to 21.3% (95% CI, 16.3% to 27.4%) of persons by the EACS, 25.6% (95% CI, 20.2% to 31.9%) by ESC/EAS and 37.9% (95% CI, 31.6 to 44.6%) by the ACC/AHA guidelines. A high 5‐year data collection on adverse effects of anti‐HIV drugs study risk score (>5%) had a moderate agreement with the high (≥20%) 10‐year CVD Framingham risk score (kappa=0.47) and high (≥5%) 10‐year European systematic coronary risk evaluation score algorithm (kappa=0.47), and substantial agreement with the elevated (≥7.5%) 10‐year Pooled Cohort Atherosclerotic CVD risk equation score (kappa=0.63).ConclusionWe found a high prevalence of CVD risks in patients from Croatia and Serbia. The ACC/AHA guideline would recommend statins more often than ESC/EAS and EACS guidelines.
Lipid‐lowering agents for dyslipidemia in patients who were infected with HIV in Taoyuan, Taiwan
Authors: Cheng Shu‐Hsing , Cheng Chien‐Yu , Sun Na‐Lee 
Published: November 2014

IntroductionThere is no doubt that highly active antiretroviral therapy (ART) has decreased the total mortality of HIV‐infected populations drastically, and HIV has become a chronic and manageable condition. However, complications after long‐term treatment of ART tarnished the great efforts. We aimed to study the effects of add‐on lipid‐lowering agents on ART for patients who developed hyperlipidemia after HIV treatment. The risk factors for failure to normalize lipid profile were analyzed.Materials and MethodsHIV‐infected patients who visited outpatient clinics of Taoyuan General Hospital between July 2013 and January 2014 were retrospectively reviewed. Subjects who needed the management of dyslipidemia were enrolled. Total cholesterol (TC), triglyceride (TG), high‐density lipoprotein (HDL) and low‐density lipoprotein (LDL) were regularly followed up for at least 6 months. ART modification and add‐on lipid‐lowering agents for dyslipidemia were analyzed.ResultsThere were 926 HIV‐infected patients undertaking ART in the hospital during the study period. Among them, 23.2% of patients undergoing lopinavir‐based regimen, 8.4% efavirenz‐based regimen, 4.2% darunavir‐based regimen, 3.3% nevirapine‐based regimen, 2.4% raltegravir‐based regimen and 2.3% atazanavir‐based regimen developed dyslipidemia. There were 76 patients (8.2%) who needed management of dyslipidemia (Table 1). Among them, 97% received lipid‐lowering agents, and 17% switched to lipid‐friendly ART (atazanavir, boosted atazanavir, boosted darunavir, nevirapine or raltegravir) despite statins or fibrates used. Mean values (mg/dL) of TC/ TG/LDL were, respectively, 279/422/139 before enrolment, 209/270/114 at 4–12 weeks and 206/250/121 at 48 weeks (p<0.05 for baseline compared to 4–12 weeks and 1 year, respectively). No obvious changes in HDL were noted. In Cox proportional hazard model, patients who received lopinavir (adjusted hazard ratio [aHR], 0.293; 95% confidence interval [CI], 0.110–0.784; p=0.015) or efavirenz (aHR, 0.185; 95% CI, 0.072–0.447; p=0.005) were less likely to achieve normalization of TC (<200 mg/dL) and TG (<200 mg/dL). Modification of ART (aHR, 1.807; 95% CI, 0.828–3.944; p=0.137) did not change the outcome (Figure 1).ConclusionsEfavirenz and lopinavir were independent factors for the persistence of dyslipidemia despite adding lipid‐lowering agents. ART associated with a favourable lipid profile would be considered in the modern era, and this certainly leaves the question of cost versus benefit.
Estimation of the true incidence of lactic acidosis within the Lighthouse Clinic cohort, and the likely magnitude of missed diagnoses in the region
Authors: Speight Colin , Gabriel Layout , Phiri Sam , Tweya Hannock , Sutherland Rebecca 
Published: November 2014

IntroductionLactic acidosis is one of the most serious side effects associated with ART, most commonly associated with stavudine. Clinical features are non‐specific and specialist laboratory capabilities are essential to confirm the diagnosis, making under‐diagnosis likely in resource‐constrained settings. Lighthouse Trust is a tertiary referral ART centre with over 23,500 patients on ART. The adjacent University of North Carolina Project laboratory, also serving Kamuzu Central Hospital, has been the only site processing lactate tests in Central Zone for many years. Our objective was to quantify the true incidence within our cohort, and estimate the likely degree of historical missed diagnoses from less central ART clinics.MethodsAll high lactate results between June 2010 and June 2013 were treated as cases, and cross referenced with the Lighthouse database. Patients transferring in to Lighthouse within one month prior to diagnosis were assumed to have been referred due to their lactic acidosis, and moved to the Central Zone cohort to avoid referral bias. Routinely collected quarterly ART cohort data for both Lighthouse and the entire Central Zone were analyzed.ResultsOver the three‐year period, from within the Lighthouse cohort, there were 138 cases: 74% were female, median duration on ART was 14 months (IQR 10–26), and 98.5% were attributable to stavudine (only two cases to zidovudine). Over this period, the average number of patients taking stavudine at Lighthouse was 10,960 (3,600 on zidovudine). For the whole Central Zone (minus Lighthouse patients) there were 61,000 on stavudine (4,830 on zidovudine), yet only 124 cases of lactic acidosis were apparently diagnosed from within this cohort.ConclusionsAlthough cases may, of course, also have been missed at Lighthouse, as a tertiary referral centre the rate observed is likely to be closer to the true incidence. Over the three years, with 138 cases from the 10,960 patients taking stavudine at Lighthouse, it is likely that somewhere in the region of 700 additional cases occurred amongst the 61,000 patients elsewhere in the Central Zone. This equates to somewhere in the region of 550 missed diagnoses or 80% of all cases. Given that the clinical sequelae of undiagnosed lactic acidosis are either death or at best ART default, this provides further vindication for the decision to phase out stavudine in Malawi.
Lipohypertrophy and metabolic disorders in HIV patients on antiretroviral therapy: a systematic multidisciplinary clinical approach
Authors: Sculier Delphine , Toutous‐Trellu Laurence , Verolet Charlotte , Matthes Nicolas , Lecompte Thanh , Calmy Alexandra 
Published: November 2014

IntroductionMorphological and metabolic complications in HIV patients on antiretroviral therapy remain a challenge. While new cases of lipoatrophy (LA) disappear, irreducible central lipohypertrophy (LH) and metabolic complications require highly specialized management. We described a day hospital dedicated to lipodystrophy (LD) and metabolic disorders in HIV patients on treatment in Geneva, Switzerland, with a focus on LH.Materials and MethodsThe “Groupe Lipo & Metabolism” is a multidisciplinary consultation where patients undergo a standard evaluation including questionnaire, physical examination, dual‐energy x‐ray absorptiometry (DEXA) and L5‐level CT scans, blood tests and consultations with various specialists. Based on prospectively maintained data, we describe clinical, biological and radiological characteristics of patients ≥18 years who attended the consultation between 2008 and 2013. We defined LH by CT scan, the gold standard method, as abdominal visceral adipose tissue (VAT) ≥130 cm2, value associated with increased risk of cardiovascular event.ResultsA total of 195 patients attended the consultation during study period. Reasons for referral included LH in 28.3%, LA in 25% and mixed syndrome in 15.5% of cases. Metabolic disorders accounted for 19% of referrals with or without LD features. Among patients with a CT scan performed (n=183), 46 (25%) had LH with a VAT ≥130 cm2. In this population, mean age was 49.1 years and 53.6% were male. HIV viral load was <50 cp/ml in 87% of patients. Mean body mass index was 24.6 kg/m2. Mean waist to hip ratio (WHR) was 0.98 for males and 0.89 for females. A total of 9.8%, 29.5% and 35% of patients had abnormal levels of total cholesterol (≥6.5 mmol/L), triglycerides (≥2.0 mmol/L) and HDL cholesterol (≤1.0 mmol/L), respectively. Mean fasting glycaemia was 5.7 mmol/L and HbA1c was >6% in 10.5% of patients. Vitamin‐D level was <75 nmol/L in 70.7% of patients. Respectively 31.2% and 12.1% of patients had osteopenia and osteoporosis on the spine and 44.8% and 6.6% on the hip neck. Factors associated with a VAT≥130 cm2 included male gender (OR 3.7 [95% CI 1.7–8.2] p<0.001), triglycerides ≥2 mmol/L (OR 2.6 [95% CI 1.3–5.4] P<0.01) and increase in BMI category (OR 1.8 [95% CI 1.2–2.8] p<0.01).ConclusionsLipohypertrophy is a prevalent feature of fat redistribution among HIV patients on treatment. Risk factors for LH include male gender, dyslipidemia and overweight. Glucose impairment and bone disorders are also common. A multidisciplinary approach is important to identify and promptly address these disorders.AcknowledgmentsThe “Groupe Lipo & Metabolism” team.