bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of age on symptom burden, mental health and quality of life amongst people with HIV in the UK
Authors: McGowan Jennifer , Sherr Lorraine , Rodger Alison , Fisher Martin , Miners Alec , Johnson Margaret , Elford Jonathan , Collins Simon , Hart Graham , Phillips Andrew , Speakman Andrew , Lampe Fiona 
Published: November 2014

IntroductionThe evolving HIV epidemic, coupled with advances in HIV treatment, has resulted in an ageing HIV‐diagnosed population. It has been suggested that adverse physical and psychological effects of HIV may be higher among older people. However, few studies have examined the effect of older age on well‐being for people with HIV.Materials and MethodsThe ASTRA study included 3258 HIV‐diagnosed individuals (2248 MSM; 373 heterosexual men; 637 women) recruited from eight UK clinics in 2011–12 (64% response rate). Participants completed a questionnaire that included standard inventories on symptoms and health‐related quality of life (HrQoL). Associations of age group with: physical symptom distress (reporting significant distress for ≥1 of 26 symptoms), depression and anxiety (score ≥10 on PHQ‐9 and GAD‐7, respectively) and HrQoL problem (reporting problems on ≥1 of 5 Eurqol‐5D domains) were assessed; adjustment was made for gender/sexuality and time with diagnosed HIV.ResultsOf all participants, 87% were taking ART, 76% had VL ≤50c/mL and 19% had CD4 <350/mm3. Mean age was 45 years (range 18–88) with 5% <30, 23% 30–39, 43% 40–49, 22% 50–59 and 7% ≥60 years. The most prevalent distressing physical symptoms were: lack of energy/tiredness (26%), difficulty sleeping (24%), muscle‐ache/joint pain (21%) and pain (18%). With older age, there was no clear trend in prevalence of physical symptom distress, but prevalence of depression and anxiety decreased, while prevalence of HrQoL problems increased. This pattern remained after adjustment for gender/sexuality and time diagnosed with HIV. The increase with age in overall prevalence of HrQoL problem was due to increased problems for “mobility,” “self‐care” and “performing usual activities” domains, not an increase in “depression/anxiety.” Longer time with diagnosed HIV was strongly associated with higher prevalence of all symptoms measures and HrQoL problem (p<0.001 for trend, adjusted models).ConclusionsPhysical and psychological symptoms are common among people living with HIV, but the burden of these symptoms is not highest among the older age group. While HrQoL tended to worsen with older age, physical symptom distress did not, and mental health improved. This may reflect greater resilience in older adults, or the potential for “successful ageing”: maintaining mental health despite age‐related health losses.
First prospective comparison of genotypic vs phenotypic tropism assays in predicting virologic responses to Maraviroc (MVC) in a phase 3 study: MODERN
Authors: Heera Jayvant , Valluri Srinivas , Craig Charles , Fang Annie , Thomas Neal , Dan Meyer Ralph , Demarest James 
Published: November 2014

IntroductionMODERN (A4001095) was the first prospective phase 3 study comparing genotype vs phenotype (Trofile™) tropism assessments.Materials and MethodsTreatment‐naïve adults with HIV‐1 RNA >1000 copies/mL were randomized 1:1 at screening to either genotype or Trofile for tropism assessment. Genotype was determined using the geno2pheno algorithm to assess triplicate HIV‐1 gp120 V3 loop sequences (plasma); false‐positive rate=10%. R5‐virus‐infected subjects were then randomized 1:1 to receive Maraviroc (MVC) 150 mg QD or Truvada 200/300 mg QD each with DRV/r 800/100 mg QD. Tropism of screening samples from enrolled subjects was also retrospectively determined using the alternate testing method. Positive predictive values (PPV) were estimated by%R5 subjects with Week 48 HIV‐1 RNA < 50 c/mL. PPV for each assay was estimated using the response rate among those randomized to that assay and using model‐based response estimates in those with R5 by that assay (at screening or retest).ResultsThe observed response rate was 146/181 (80.7%) for genotype vs 160/215 (74.4%) for Trofile (stratification adjusted difference=6.9%, 95% CI 1.3% to 15%). The model‐based estimates of PPV (±SE) were 79.1% (±2.42) and 76.3% (±2.38), respectively (difference = 2.8%, 95% CI −2.1% to 7.2%). There was no difference in response rate between assays in the Truvada arm (observed difference=− 0.1%, 95% CI −6.8% to 6.6%). Most enrolled subjects had R5 results at screening using both assays (285/396 (72%)), and of these subjects, 79.3% (226/285) had HIV‐1 RNA <50 c/mL at week 48 (Table 1). The few subjects classified as non‐R5 by the alternate assay had similar virologic responses to the concordant R5 group.ConclusionThere was a higher MVC response rate and model‐based positive predictive value with genotype compared to Trofile, but this difference did not reach statistical significance. The majority of subjects had concordant R5 tropism results. Either phenotype or genotype can effectively predict MVC response.
Effectiveness of a reduced dose of efavirenz plus 2 NRTIs as maintenance antiretroviral therapy with the guidance of therapeutic drug monitoring
Authors: Yang Shang‐Ping , Liu Wen‐Chun , Lee Kuan‐Yeh , Wu Bing‐Ru , Su Yi‐Ching , Wu Pei‐Ying , Zhang Jun‐Yu , Luo Yu‐Zhen , Sun Hsin‐Yun , Chang Sui‐Yuan , Lin Shu‐Wen , Hung Chien‐Ching 
Published: November 2014

IntroductionWide inter‐patient variation of plasma efavirenz (EFV) concentrations has been observed, and a substantial proportion of HIV‐positive patients may have unnecessarily higher plasma EFV concentrations than recommended while receiving EFV‐containing combination antiretroviral therapy (cART) at the currently recommended daily dose of 600 mg. A lower daily dose (400 mg) of EFV has recently been demonstrated to be as efficacious as the recommended 600 mg when combined with tenofovir/mtricitabine in a multinational clinical trial, with a lower incidence of adverse effects. We aimed to use a therapeutic drug monitoring (TDM)‐guided strategy to optimize the EFV dose in HIV‐positive Taiwanese patients.Materials and MethodsThe plasma EFV concentrations at 12 hours (C12) after taking the previous dose were determined among HIV‐positive adults who had received EFV‐containing cART with viral suppression (plasma HIV RNA load (PVL) <200 copies/mL). For those with EFV C12 >2.0 mg/L, EFV (Stocrit, MSD) was reduced to half a tablet daily. Determinations of EFV C12 were repeated 4–12 weeks after switch using high‐performance liquid chromatography. CYP2B6 G516T polymorphisms were determined using polymerase‐chain‐reaction restriction fragment‐length polymorphism.ResultsBetween April 2013 and June 2014, 111 patients (95.5% male; mean age, 39 years; 96.4% with PVL <40 copies/ml; 26.4% HBsAg‐positive and 7.5% anti‐HCV‐positive) with plasma C12 efavirenz >2.0 mg/L were switched to a reduced dose (1/2# hs) of EFV; 45.5% of them had CYP2B6 G516T or TT genotypes; and 32.4% weighed 60 kg or less. The mean baseline EFV C12 before switch was 3.65 mg/L (interquartile range (IQR), 2.62–4.17) for 111 patients, which decreased to 1.96 mg/L (IQR, 1.53–2.33) for 64 patients who had completed follow‐up of C12 EFV 4 weeks after switch, with a reduction of 49.4% (IQR, 38.9–57.0%). As of 10 July, 2014, all of the 38 patients (100%) who had completed at least one follow‐up of PVL achieved undetectable PVL (<40 copies/ml) following switch to a reduced dose of EFV after a mean observation of 13 weeks (IQR, 7–15 weeks).ConclusionsSwitch to cART containing a half tablet of EFV (1/2#) in HIV‐positive Taiwanese patients with higher plasma EFV concentrations who had achieved viral suppression could maintain successful viral suppression with the guidance of TDM.
Analysis of neurocognitive function and CNS endpoints in the PROTEA trial: darunavir/ritonavir with or without nucleoside analogues
Authors: Clarke Amanda , Johanssen Veronika , Gerstoft Jan , Clotet Bonaventura , Ripamonti Diego , Murungi Andrew , Bicer Ceyhun , Blanca Hadacek Maria , Moecklinghoff Christiane 
Published: November 2014

IntroductionDuring treatment with protease inhibitor monotherapy, the number of antiretrovirals with therapeutic concentrations in the cerebrospinal fluid (CSF) is lower, compared to standard triple therapy. However, the clinical consequences are unclear.MethodsA total of 273 patients with HIV RNA <50 copies/mL for over 24 weeks on current antiretrovirals randomized to darunavir/ritonavir (DRV/r) 800/100 mg once‐daily, either as monotherapy (n=137) or with 2NRTIs (n=136). Neurocognitive function was evaluated in all patients by the Hopkins Verbal Learning Tests, the Colour Trail Tests and the Grooved Pegboard Test at screening, baseline and at Week 48. A global neurocognitive score (NPZ‐5) was derived by averaging the standardized results of the five domains. In a central nervous system (CNS) sub‐study (n=70), HIV RNA levels in the CNS were evaluated at baseline and Week 48. Clinical adverse events related to the CNS were collected at each visit.ResultsPatients were 83% male and 88% White, with median age 43 years. There were more patients with nadir CD4 count below 200 cells/µL in the DRV/r monotherapy arm (41/137, 30%) than the triple therapy arm (30/136, 22%). At Week 48, there was no difference between the treatment arms for the five combined domains of the neurocognitive score. At Week 48, the percentage of patients with an abnormal neurocognitive score among the five domains was 12.2% for DRV/r monotherapy and 14.9% for triple therapy. However, one patient on DRV/r monotherapy with a CD4 nadir of 17 cells/µL was hospitalized with HIV encephalomyelitis at Week 24, with HIV RNA 2500 copies/mL in the CSF and 125 copies/mL in the plasma. Symptoms resolved after intensification with high dose zidovudine. A second patient on DRV/r monotherapy with CD4 nadir of 166 cells/µL had a rise in HIV RNA in CSF from <40 copies/mL at baseline to 654 copies/mL at Week 48, with concurrent plasma HIV RNA of 77 copies/mL.ConclusionsIn this study for patients with HIV RNA <50 copies/mL at baseline, there was no difference in neurocognitive function between the treatment arms. However two patients on PI monotherapy with CD4 nadir <200 cells/µL developed viraemia in both CSF and plasma, with one symptomatic case. DRV/r monotherapy should be used with caution in patients with nadir CD4 counts below 200 cells/µL.
Evolution of Framingham cardiovascular risk score in HIV‐infected patients initiating EFV‐ and LPV/r‐based HAART in a Latin American cohort
Authors: Cecchini Diego , Ines Mattioli Maria , Cassetti Julia , Chan Debora , Cassetti Isabel 
Published: November 2014

IntroductionEpidemiological studies suggest that some antiretroviral drugs may contribute to increase cardiovascular risk in HIV‐infected patients. However, data from Latin American countries are limited, as impact of HAART on cardiovascular risk remains understudied. In this context, we aimed to evaluate if 10‐year Framingham Cardiovascular Risk Score (FCRS) increases in patients following exposure to EFV‐ and LPV/r‐based HAART in a Latin American cohort.Materials and MethodsRetrospective 48‐week cohort study. We reviewed clinical charts of randomly selected samples of patients initiating (according to national guidelines) EFV first‐line HAART and LPV/r first‐ or second‐line (but first PI‐based) HAART assisted at a reference HIV centre in Buenos Aires, Argentina (period 2004–2012). Each patient could only be included in one arm. FCRS was calculated according to National Institutes of Health risk assessment tool (http://cvdrisk.nhlbi.nih.gov/).ResultsA total of 357 patients were included: 249 in EFV arm and 108 in LPV/r arm (80 as first line and 28 as second line, but first PI‐based HAART). Baseline characteristics (median, interquartile range): age, 38 (33–45) years; male, 247 (69%); viral load, 98200 (20550–306000) copies/mL; CD4 T‐cell count, 115 (60–175) cel/µL; total cholesterol, 159 (135–194) mg/dL; HDL: 39 (31–41) mg/dL; LDL: 94 (72–123) mg/dL; current smoker, 29%; on antihypertensive drugs: 14 (4%), diabetic: 4 (1%). Most frequent accompanying nucleoside reverse transcriptase inhibitors (NRTIs) were 3TC (92%) and zidovudine (AZT; 76%). Baseline FCRS was low, moderate and high for 93%, 7% and 0% of patients on EFV arm and 96.7%, 1.7% and 1.7% on LPV/r arm. On EFV arm, an increase in FCRS category (low to moderate or moderate to high) was observed in 1 patient (0.9%) at 24 weeks and 6 (5,6%) at 48 weeks; 5 (4.7%) decreased category. On LPV/r arm no one varied FCRS category at 24 weeks and 2 (3.4%) increased from low to moderate at 48 weeks (no patient decreased FCRS category). Cumulative incidence of overall cardiovascular events was 1.6% on EFV and 1.8% on LPV/r arms respectively. Probability of increasing FCRS category or having a cardiovascular event did not differ between arms at a significance level of 5%.ConclusionsProbability of increasing FCRS category and cardiovascular events was low and similar in patients exposed to EFV versus LPV/r‐based HAART in a Latin American cohort. ClinicalTrials.gov Identifier: NCT01705873.
Impact of NRTI backbone on renal, bone and cardiovascular markers in HIV‐infected individuals receiving a boosted protease inhibitor
Authors: Barber Tristan , Hill Andrew , Jagjit Singh Gurmit , Boffito Marta , Nelson Mark , Moyle Graeme 
Published: November 2014

IntroductionWe have previously shown in the SSAT 044 study that unconjugated hyperbilirubinaemia in subjects receiving a boosted protease inhibitor (PI/r) has limited impact on renal, cardiovascular (CV) and bone biomarkers, as well as on neurocognitive performance, relative to those receiving PI/r with a normal bilirubin. We present here a secondary analysis comparing markers in those receiving abacavir‐ vs tenofovir‐ based antiretroviral therapy (ART).Materials and MethodsThis cross‐sectional study included 101 HIV‐1 infected individuals stable (HIV RNA<50 cps/ml, >6 months) on antiretroviral regimens including tenofovir (TDF)/emtricitabine or abacavir/lamivudine plus a ritonavir boosted PI.ResultsForty‐three subjects had normal bilirubin (NBR) levels and 35 had high bilirubin (>2.5 times upper limit); the remaining 23 patients had intermediate bilirubin levels or violated the protocol. The mean age of participants was 48 years; 93% were male and 84% Caucasian; 22 received ABC‐based therapy and 78 TDF. No differences were seen in cardiovascular markers: Framingham (10‐year risk % median, IQR): ABC 8.1, 5.6–15.3; TDF 9.5, 4.8–13.4 (p=ns); pulse wave velocity and carotid intimal thickness also showed no significant differences. No differences were seen in bone parameters: Calcaneal Stiffness Index (median score, IQR): ABC −0.5, −0.8 to 0.8; TDF −0.5, 1.4–0.4 (p=ns); 10 year FRAX score (% median, IQR): ABC 5.0, 2.4–6.2; TDF 3.6, 2.5–5.8 (p=ns). There were differences in renal parameters as shown in Table 1. We show statistically significant differences in urine protein/creatinine ratio (uPCR) (10 vs 7; p=0.004) and urine albumin/creatinine ratio (uACR) (15 vs 8; p=0.002), with both being higher in the TDF group.ConclusionsTenofovir use is associated with excess loss of proteins including those typically resorbed in the renal tubule. Abacavir use was not associated with an increase in biomarkers of CV risk or vascular dysfunction.
Attitudes of serodiscordant couples towards antiretroviral‐based HIV prevention strategies in Kenya: a qualitative study
Authors: Fowler Nikola , Arkell Paul , Abouyannis Michael , James Catherine , Roberts Lesley 
Published: November 2014

IntroductionTransmission in serodiscordant couples (SDCs) accounts for approximately half of all new HIV infections, both in Kenya and the wider sub‐Saharan region [1]. With evidence to suggest inconsistent condom use within this population [2], the World Health Organization has recommended two new methods of HIV prevention for SDCs: Treatment as Prevention (TasP) and Pre‐Exposure Prophylaxis (PrEP). However, there has been little research about the attitudes of SDCs towards these strategies [3, 4]; knowledge that is paramount for successfully predicting the acceptability and efficacy of each method, as well as for informing decisions regarding HIV policy changes in Kenya.MethodsAn exploratory, qualitative study was conducted in the Muhoroni constituency of Nyando district, Kenya from January to March 2013. Purposive sampling was predominately used to recruit 21 HIV‐positive and 17 HIV‐negative individuals in a serodiscordant relationship from four hospitals and health centres. During face‐to‐face semi‐structured interviews, topic guides were used to elicit information about participants’ attitudes and preferences towards TasP and PrEP. Collected data underwent framework analysis, allowing the development of overarching categories, sub‐themes and inductive interpretation.ResultsThe majority of participants, irrespective of gender and HIV status, found TasP more acceptable than PrEP. A key factor influencing this decision was HIV‐negative participants’ limited motivation to take and adhere to antiretrovirals (ARVs), primarily due to a predominantly external health locus of control, a lack of cultural acceptance of prophylactic medication and concerns about side effects. In addition to this, the likely health improvements TasP offers HIV‐positive partners, as well as the attitude that the sick individual should be the first to receive HIV medication, also contributed to this conclusion. Issues of risk compensation were raised, with some HIV‐negative partners indicating a desire to stop using condoms if ARV‐based prevention methods were available.ConclusionsFindings from the study indicate that TasP may represent a more viable approach to HIV prevention in Kenya than PrEP. Couples’ preferences, however, may differ depending on local attitudes towards prophylaxis and health locus of control.
Prevalence of low bone mineral density among HIV patients on long‐term suppressive antiretroviral therapy in resource limited setting of western India
Authors: Dravid Ameet , Kulkarni Milind , Borkar Amit , Dhande Sachin 
Published: November 2014

IntroductionBone mineral density (BMD) assessment in HIV patients is sparsely done in resource limited settings.Materials and MethodsWe conducted a cross‐sectional study of BMD amongst HIV patients following up in our clinic from 1 June to 1 December 2013 by performing dual‐energy X‐ray absorptiometry scan (Lunar Prodigy Advanced DXA System, GE Healthcare) of lumbar spine and hip. Patients on long term (≥12 months), virologically suppressive antiretroviral therapy (ART) were included. Patients who were ART naïve were included as control population. Virologic failures were excluded. Low BMD was defined by WHO T‐score criteria (normal: T score ≥−1;osteopenia: T score between −1 and −2.5 SD; osteoporosis: T score ≤−2.5 SD). Baseline risk factors associated with low BMD like age, low BMI, lipoatrophy, diabetes mellitus, current smoking, current alcohol intake, steroid exposure and menopause were recorded. ART‐related factors associated with low BMD like ART duration, exposure to tenofovir and exposure to protease inhibitors (PI) were studied.ResultsA total of 536 patients (66% males, 496 ART experienced and 40 ART naïve) were included in this analysis. Median age was 42 years, mean BMI 23.35 kg/m2 and median CD4 count 146 cells/mm3. All ART experienced patients had plasma viral load<400 copies/ml.Prevalence of low BMD amongst ART naive and ART experienced patients was 67% (osteopenia: 70.4%, osteoporosis: 29.6%) and 80.4% (osteopenia: 63.4%, osteoporosis: 36.6%), respectively (p=0.05). Mean T scores at lumbar spine and hip for ART naive and ART experienced patients were −1.37 and −0.9 versus −1.56 and −1.48 (p=0.05), respectively. Age, low BMI, current smoking, menopause, baseline CD4 count and exposure to ART were factors significantly associated with low overall BMD on univariate regression analysis. On multivariable logistic regression analysis age (p<0.001), low BMI (p<0.001), current smoking (0.05) and menopause (0.03) were associated with low BMD. BMI decrease of 1 kg/m2 and baseline CD4 decline of 50 cells/mm3 lead to 14% and 4% increased probability of low BMD, respectively. Choice of antiretroviral use (tenofovir vs non‐tenofovir, PI vs No PI) did not influence loss of BMD.ConclusionsExtremely high prevalence of accelerated BMD loss amongst ART naïve and ART experienced patients in our cohort is a matter of deep concern due to its association with pathological fractures. Bone mineral loss was seen irrespective of ART used. Association of low BMD with low baseline CD4 count strengthens the case for early ART.
Acceptance rate of clinical study endpoints and adequacy of source documentation: experience from clinical study endpoint review in NEAT001/ANRS143
Authors: Berenguer Juan , Wit Ferdinand , Jansson Per O , Schwimmer Christine , Kowalska Justyna D , Saillard Juliette , Diallo Alpha , Pozniak Anton L , Raffi François , Grarup Jesper 
Published: November 2014

IntroductionNEAT001/ANRS143 was an open‐label, randomized, non‐inferiority study comparing raltegravir+darunavir/r(RGV+DRV/r) vs. tenofovir/emtricitabine+darunavir/r (TDF/FTC+DRV/r) in HIV‐infected antiretroviral naïve adults. Primary efficacy outcome was a composite of virological and clinical events by week 96.Materials and MethodsClinical trial units collected and translated supporting documentation (SD) related to the investigator‐reported events. A coordinator checked events and SD for consistency and completeness. The Endpoint Review Committee (ERC) determined if clinical events met pre‐defined diagnostic criteria in categories “confirmed” or “probable”. The ERC of 12 experienced, independent clinicians served in groups of three conducting individual reviews in writing, blinded to treatment arm. Differences of opinion were adjudicated in a second review by direct dialogue between reviewers. “Confirmed” events required adequate SD like laboratory, radiographic or pathology diagnostic reports. “Probable” events were typically based on clinical criteria.ResultsOf the 164 serious and 3,964 adverse events reported in the study, 133 qualified for endpoint review, for a total of 153 adjudications:Sixty of 111 per protocol endpoints were confirmed (n=53) or probable (n=7), which equals an acceptance rate of 54%. In two confirmed cases, SD was partly adequate and evaluation uncertain. Of 51 rejected events, 13 had insufficient SD, two were recurrent events. The rate of rejected events was comparable between treatments with 41% rejected events in the RGV+DRV/r arm compared to 52% in the TDF/FTC+DRV/r arm. The IRIS acceptance rate was low (3 of 18), demonstrating the difference in perception of IRIS in daily patient management and the stricter protocol definition.ConclusionsBlinded endpoint review prevented unacceptably high false positive event rates documenting that real‐time ascertainment of clinical endpoints is crucial for appropriateness of the overall results. Non‐confirmed events jeopardize the statistical power in this and probably all kinds of clinical studies. The rejection rate was not indicative of poor study conduct – on the contrary over‐reporting prevented missing events, which would have adversely impacted the trial. Adequacy of SD and investigator training on possible differences in event criteria in daily pragmatic clinical management compared to protocol defined criteria is essential.