Associations between HIV-RNA-based indicators and virological and clinical outcomes

OBJECTIVES: To evaluate and compare the performance of six HIV-RNA-based quality of care indicators for predicting short-term and long-term outcomes. DESIGN: Multinational cohort study. METHODS: We included EuroSIDA patients on antiretroviral therapy (ART) with ≥3viral load (VL) measurements after baseline (the latest of 01/01/2001 or entry into EuroSIDA). Using multivariate Poisson regression we modelled the association between short-term (resistance, triple-class failure) and long-term (all-cause mortality, any AIDS/non-AIDS clinical event) outcomes and the indicators: (i)viraemia copy years (VCY), (ii) Consecutive months with VL ≥50 copies/mL, (iii) percentage of time on ART spent fully suppressed (%FS), (iv) stable on ART, (v)48 weeks snapshot, and (vi) current VL. Indicators were compared using area under the ROC curve (AUC) and different measures of model fit. RESULTS: Adjusted incidence rate ratios for all outcomes tended to increase with increasing VCY, number of consecutive months with VL ≥50 copies/mL, current VL and with lower %FS, but the gradient of increased risk was weak across strata. None of the indicators reliably identified those at risk of long-term outcomes (AUC 0.54-0.58), but performed consistently better with short-term outcomes (triple class failure [AUC 0.67-0.76]) and resistance [AUC 0.64-0.79]). Goodness of fitvariedwith the outcome evaluated, but differences between indicators were small. CONCLUSIONS: Differences between quality of care indicators were small and no indicator performed consistently better than current VL. Given the simplicity in assessing and interpreting this indicator, wepropose to use current VL when HIV-RNA-based indicators are used to evaluate the efficacy of ART programs

Predictive value of prostate specific antigen in a European HIV-positive cohort: does one size fit all?

Background: It is common practice to use prostate specific antigen (PSA) ≥4.0 ng/ml as a clinical indicator for men at risk of prostate cancer (PCa), however, this is unverified in HIV+ men. We aimed to describe kinetics and predictive value of PSA for PCa in HIV+ men. Methods: A nested case control study of 21 men with PCa and 40 matched-controls within EuroSIDA was conducted. Prospectively stored plasma samples before PCa (or matched date in controls) were measured for the following markers: total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG). Conditional logistic regression models investigated associations between markers and PCa. Mixed models were used to describe kinetics. Sensitivity and specificity of using tPSA >4 ng/ml to predict PCa was calculated. Receiver operating characteristic curves were used to identify optimal cutoffs in HIV+ men for total PSA. Results: 61 HIV+ men were included with a median 6 (IQR 2–9) years follow-up. Levels of tPSA increased by 13.7% per year (95% CI 10.3, 17.3) in cases, but was stable in controls (-0.4%; 95% CI -2.5, 1.7). Elevated PSA was associated with higher odds of PCa at first (OR for twofold higher 4.7; 95% CI 1.7, 12.9; P4 ng/ml had 99% specificity and 38% sensitivity. The optimal PSA cutoff was 1.5 ng/ml overall (specificity =84%, sensitivity =81%). Conclusions: PSA was highly predictive of PCa in HIV+ men; however, the commonly used PSA>4 ng/ml to indicate high PCa risk was not sensitive in our population and use of the lower cutoff of PSA>1.5 ng/ml warrants consideration

Predictive value of prostate-specific antigen for prostate cancer: a nested case-control study in EuroSIDA

INTRODUCTION: Although prostate cancer (PCa) incidence is lower in HIV+ men than in HIV- men, the usefulness of prostate-specific antigen (PSA) screening in this population is not well defined and may have higher false negative rates than in HIV- men. We aimed to describe the kinetics and predictive value of PSA in HIV+ men. METHODS: Men with PCa (n=21) and up to two matched controls (n=40) with prospectively stored plasma samples before PCa (or matched date in controls) were selected. Cases and controls were matched on date of first and last sample, age, region of residence and CD4 count at first sample date. Total PSA (tPSA), free PSA (fPSA), testosterone and sex hormone binding globulin (SHBG) were measured. Conditional logistic regression models investigated associations between markers and PCa. Sensitivity and specificity of using tPSA >4 µg/L to predict PCa was calculated. Mixed models were used to describe kinetics. RESULTS: Sixty-one men were included with a median six (IQR 2-9) years follow-up. Time between last sample and PCa was seven (4-11) months. Cases and controls were well matched at first sample, with a median age of 51 (IQR 48-57) and CD4 of 437 (243-610) cells/mm(3). Median tPSA [2.8 (IQR: 1.6-4.6) and 0.8 (0.5-1.2) µg/L] and fPSA [0.4 (0.2-0.8) and 0.3 (0.2-0.4) µg/L] levels were higher in cases than controls at first sample. Both tPSA and fPSA increased significantly over time in cases (Figure 1), to a median at last sample of 6.1 (4.7-9.5) and 0.9 (0.6-1.3) µg/L, respectively, but were stable in controls, with a median at last sample of 0.8 (0.5-1.4) and 0.2 (0.2-0.4) µg/L (Figure). Higher levels of tPSA and fPSA were associated with higher odds of PCa at first sample [OR for 2-fold higher 4.7 (CI: 1.7-12.9) and 5.4 (1.7-17.4)]. Elevated tPSA values in cases were detectable ≥5 years before PCa (p0.7). The most informative predictor of PCa was tPSA (AUC=0.9), followed by fPSA (0.8). Testosterone (AUC = 0.5) and SHBG (0.5) were poor predictors of PCa. Overall, tPSA level >4 µg/L had 99% specificity and 37% sensitivity. Performance was best in the year prior to PCa (specificity: 99%, sensitivity: 88%). CONCLUSIONS: PSA was highly predictive of PCa in HIV+ men. Our results indicate that PSA screening in HIV+ men may be useful, and further work is needed to identify potentially age-related cut-offs to maximize sensitivity and specificity to identify those for further evaluation at early stages of PCa

The cardiovascular risk management for people living with HIV in Europe:how well are we doing?

Objectives: HIV has become a chronic condition associated with comorbidities. We investigated cardiovascular risk and risk modification in a European HIV cohort. Methods: EuroSIDA patients (from 1 January 2000) for whom cardiovascular risk could be calculated (DAD risk equation) were included in the analysis. Moderate-to-high risk was defined as 5-year cardiovascular risk more than 5% and risk modification as two measurements meeting the EuropeanAIDSClinicalSocietyguidelines. Factorsassociated with risk development and modifications were investigated using Poisson regression. Results: Of 8762 individuals, 32.1% were hypertensive, 45.0% had high cholesterol, 47.4% were current smokers, and 27.1% were overweight. A total of 1504 (17.2%) had a 5-year cardiovascular risk of more than 5%. Of 7258 individuals with a 5-year risk less than 5%, 1905 (26.2%) developed cardiovascular risk more than 5% (6.53/100 personyears). These patients were more likely to be older, men, living in East Europe, with traditional cardiovascular risk factors. MSM with longer exposure to antiretroviral therapy, low CD4 nadir, higher current CD4 and prior AIDS events were more likely to develop cardiovascular risk. Those on antihypertensive treatment and living in central Europe were less likely to develop cardiovascular risk. Of those clinically indicated for risk modification, 1205 of 2077 (58.0%) successfully modified BP; 1283 of 3919 (32.8%) stopped smoking; 277 of 1394 (19.9%) modified cholesterol and 543 of 2163 (25.1%) reduced their BMI. There was variation in modification of individual risk factors, by sex, age, HIV-related factors and region of follow-up. Risk modification for BP and smoking improved over time (P < 0.001). Conclusion: Cardiovascular risk was common. More than half modified their cardiovascular risk, and this improved over time.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

An Analysis Of Cephalometric Criteria Used For The Diagnosis Of Skeletal Open Bite

ATRIPLA is licensed for use only in HIV-positive persons whose viral loads <50 for ≥3 months. We investigated the use of ATRIPLA as first-line antiretroviral therapy (ART) in EuroSIDA using a web-based survey performed in Autumn 2012. 96/112 clinics (85.7 %) completed the survey. Recommendations when initiating first-line ART was TRUVADA plus efavirenz in 36 (37.5 %), ATRIPLA in 35 (36.5 %), a different first-line regimen in 12 clinics (12.5 %), and no recommendation in 7 clinics (7.3 %). ATRIPLA was commonest in Northern (15/21 clinics; 71.4 %), and least common in Eastern Europe (2/31 clinics; 6.5 %; p < 0.0001). Over one-third of the participating clinics in this survey were using ATRIPLA as first-line antiretroviral therapy, despite EMA recommendations

Does hepatitis C viremia or genotype predict the risk of mortality in individuals co-infected with HIV?

The influence of HCV-RNA levels and genotype on HCV disease progression is not well studied. The prognostic value of these markers was investigated in HIV/HCV co-infected individuals from the EuroSIDA cohort. EuroSIDA is a prospective cohort of 18,295 HIV-1 infected patients in 105 centres across Europe, Israel, and Argentina. All subjects with known HCV antibody (HCVAb) status (n=13,025) were enrolled in the present study. 4044 (31.0%) patients had detectable HCVAb. After adjustment, HCVAb+ patients had an increased incidence of liver-related death (LRD) compared to HCVAb- individuals (IRR 8.90; 95% CI 5.60-14.14, p <0.0001). Information on HCV-RNA was available for 2709 (67.0%) HCVAb+ patients and 2010 (74.2%) were HCV-RNA+. Of 1907 patients with measured HCV genotype, 1008 (52.9%), 62 (3.3%), 567 (29.7%), and 270 (14.2%) were infected with genotype 1, 2, 3 and 4, respectively. Patients with detectable HCV-RNA had similar incidence of non-LRD, but higher incidence of LRD compared to HCVAb+ aviremic patients (adjusted IRR 1.18; 95% CI 0.93-1.50, p=0.17) and (adjusted IRR 2.11; 95% CI 1.30-3.42, p=0.0025), respectively. In patients with HCV viremia, HCV-RNA levels and HCV genotype did not influence the risk of non-LRD or LRD. HCV seropositive HIV patients had a 9-fold increased risk of LRD compared to patients who were HCV seronegative. Risk of death from any cause or LRD was not influenced by level of HCV viremia or HCV genotyp

Plasma HIV-1 Tropism and the Risk of Short- Term Clinical Progression to AIDS or Death

Objective To investigate if plasma HIV-1 tropism testing could identify subjects at higher risk for clinical progression and death in routine clinical management. Design Nested case-control study within the EuroSIDA cohort. Methods Cases were subjects with AIDS or who died from any cause, with a plasma sample with HIV-1 RNA >1000 copies/mL available for tropism testing 3 to 12 months prior to the event. At least 1 control matched for age, HIV-1 RNA and HCV status at the time of sampling were selected per each case. Conditional logistic regression was used to investigate exposures associated with clinical progression to AIDS or death. A linear mixed model with random intercept was used to compare CD4+T-cell slopes by HIV tropism over the 12 months following the date of sampling. Results The study included 266 subjects, 100 cases and 166 controls; one quarter had X4 HIV; 26% were ART-naïve. Baseline factors independently associated with clinical progression or death were female gender (OR = 2.13 vs. male, 95CI = 1.04, 4.36), p = 0.038), CD4+T-cell count (OR = 0.90 (95CI = 0.80, 1.00) per 100 cells/mm3 higher, p = 0.058), being on ART (OR = 2.72 vs. being off-ART (95CI = 1.15, 6.41), p = 0.022) and calendar year of sample [OR = 0.84 (95CI = 0.77, 0.91) per more recent year, p<0.001). Baseline tropism was not associated with the risk of clinical progression or death. CD4+T-cell slopes did not differ within or between tropism groups

Portrait of Keneth Thornett, actor in the J.C. Williamson production of Pommy 2 copies [picture]

From: Pommy / W. P. Liscomb and John Watson.; Part of the collection: J.C. Williamson collection of photographs.; Also available in an electronic version via the internet at: http://nla.gov.au/nla.pic-vn3805446; Seasons in Australasia recorded in programs and ephemera held in J C Williamson collection, PROMPT Collection: 1954 commencing 9 October Theatre Royal, Sydney