[Show abstract][Hide abstract]ABSTRACT: Background
In March 2008, the D:A:D study published results demonstrating an increased risk of myocardial infarction (MI) for patients on abacavir (ABC). We describe changes to the use of ABC since this date, and investigate changes to the association between ABC and MI with subsequent follow-up.
A total of 49,717 D:A:D participants were followed from study entry until the first of an MI, death, 1 February 2013 or 6 months after last visit. Associations between a person’s 10-year cardiovascular disease (CVD) risk and the likelihood of initiating or discontinuing ABC were assessed using multivariable logistic/Poisson regression. Poisson regression was used to assess the association between current ABC use and MI risk, adjusting for potential confounders, and a test of interaction was performed to assess whether the association had changed in the post-March 2008 period.
Use of ABC increased from 10 % of the cohort in 2000 to 20 % in 2008, before stabilising at 18–19 %. Increases in use pre-March 2008, and subsequent decreases, were greatest in those at moderate and high CVD risk. Post-March 2008, those on ABC at moderate/high CVD risk were more likely to discontinue ABC than those at low/unknown CVD risk, regardless of viral load (≤1,000 copies/ml: relative rate 1.49 [95 % confidence interval 1.34–1.65]; >1,000 copies/ml: 1.23 [1.02–1.48]); no such associations were seen pre-March 2008. There was some evidence that antiretroviral therapy (ART)-naïve persons at moderate/high CVD risk post-March 2008 were less likely to initiate ABC than those at low/unknown CVD risk (odds ratio 0.74 [0.48–1.13]). By 1 February 2013, 941 MI events had occurred in 367,559 person-years. Current ABC use was associated with a 98 % increase in MI rate (RR 1.98 [1.72–2.29]) with no difference in the pre- (1.97 [1.68–2.33]) or post- (1.97 [1.43–2.72]) March 2008 periods (interaction P = 0.74).
Despite a reduction in the channelling of ABC for patients at higher CVD risk since 2008, we continue to observe an association between ABC use and MI risk. Whilst confounding cannot be fully ruled out, this further diminishes channelling bias as an explanation for our findings.
[Show abstract][Hide abstract]ABSTRACT: Background Although advances in HIV medicine have yielded increasingly better treatment outcomes in recent years, HIV-positive people with access to antiretroviral therapy (ART) still face complex health challenges. The EuroSIDA Study Group surveyed its clinics to explore regional differences in clinic services. Methods The EuroSIDA study is a prospective observational cohort study that began enrolling patients in 1994. In early 2014, we conducted a 59-item survey of the 98 then-active EuroSIDA clinics. The survey covered HIV clinical care and other aspects of patient care. The EuroSIDA East Europe study region (Belarus, Estonia, Lithuania, the Russian Federation and Ukraine) was compared to a “non-East Europe” study region comprised of all other EuroSIDA countries. Results A larger proportion of clinics in the East Europe group reported deferring ART in asymptomatic patients until the CD4 cell count dropped below 350 cells/mm3 (75 % versus 25 %, p = 0.0032). Considerably smaller proportions of East Europe clinics reported that resistance testing was provided before ART initiation (17 % versus 86 %, p < 0.0001) and that it was provided upon treatment failure (58 % versus 90 %, p = 0.0040). Only 33 % of East Europe clinics reported providing hepatitis B vaccination, compared to 88 % of other clinics (p < 0.0001). Only 50 % of East Europe clinics reported having access to direct-acting antivirals for hepatitis C treatment, compared to 89 % of other clinics (p = 0.0036). There was significantly less tuberculosis/HIV treatment integration in the East Europe group (27 % versus 84 % p < 0.0001) as well as significantly less screening for cardiovascular disease (58 % versus 90 %, p = 0.014); tobacco use (50 % versus 93 %, p < 0.0001); alcohol consumption (50 % versus 93 %, p < 0.0001); and drug use (58 % versus 87 %, p = 0.029). Conclusions Study findings demonstrate how specific features of HIV clinics differ across Europe. Significantly more East Europe clinics deferred ART in asymptomatic patients for longer, and significantly fewer East Europe clinics provided resistance testing before initiating ART or upon ART failure. The East Europe group of clinics also differed in regard to hepatitis B vaccination, direct-acting antiviral access, tuberculosis/HIV treatment integration and screening for other health issues. There is a need for further research to guide setting-specific decision-making regarding the optimal array of services at HIV clinics in Europe and worldwide.
Full-text Article · Dec 2016 · BMC Infectious Diseases
[Show abstract][Hide abstract]ABSTRACT: Background
While the association between renal impairment and cardiovascular disease (CVD) is well established in the general population, the association remains poorly understood in HIV-positive individuals.
Individuals with >2 estimated glomerular filtration rate (eGFRs) after 1/2/2004 were followed until CVD, death, last visit plus six months or 1/2/2015. CVD was defined as centrally validated myocardial infarction, stroke, invasive cardiovascular procedures or sudden cardiac death.
During 8.0 years median follow-up (Interquartile range 5.4-8.9) 1,357 of 35,357 developed CVD (incidence 5.2/1000 person-years [95%confidence interval, CI [5.0-5.5]). Confirmed baseline eGFR and CVD were closely related with 1.8% [95%CI 1.6-2.0%] estimated to develop CVD at five years at eGFR>90 ml/min/1.73m2, increasing to 21.1% [95%CI 6.6-35.6%] at eGFR<30 ml/min/1.73m2. The strong univariate relationship between low current eGFR and CVD was primarily explained by increasing age in adjusted analyses, although all eGFRs<80 ml/min/1.73m2 remained associated with 30-40% increased CVD rates and particular high rates at eGFR<30 ml/min/1.73m2 (3.08 [95%CI 2.04-4.65]).
Among HIV-positive individuals in a large contemporary cohort a strong relation between confirmed impaired eGFR and CVD was observed. This finding highlights the need for renal preventive measures and intensified monitoring for emerging CVD, in particular in older individuals with continuously low eGFR.
Article · Aug 2016 · The Journal of Infectious Diseases
[Show abstract][Hide abstract]ABSTRACT: Objective:
The impact of early allograft dysfunction on the outcome after liver transplantation is yet to be established. We explored the independent predictive value of the Model for End-Stage Liver Disease (MELD) score measured in the post-transplant period on the risk of mortality or re-transplantation.
Material and methods:
Retrospective cohort study on adults undergoing orthotopic deceased donor liver transplantation from 2004 to 2014. The MELD score was determined prior to transplantation and daily until 21 days after. The risk of mortality or re-transplantation within the first year was assessed according to quartiles of MELD using unadjusted and adjusted stepwise Cox regression analysis.
We included 374 consecutive liver transplant recipients of whom 60 patients died or were re-transplanted. The pre-transplant MELD score was comparable between patients with good and poor outcome, but from day 1 the MELD score significantly diversified and was higher in the poor outcome group (MELD score quartile 4 versus quartile 1-3 at day 10: HR 5.1, 95% CI: 2.8-9.0). This association remained after adjustment for non-identical blood type, autoimmune liver disease and hepatocellular carcinoma (adjusted HR 5.3, 95% CI: 2.9-9.5 for MELD scores at day 10). The post-transplant MELD score was not associated with pre-transplant MELD score or the Eurotransplant donor risk index.
Early determination of the MELD score as an indicator of early allograft dysfunction after liver transplantation was a strong independent predictor of mortality or re-transplantation and was not influenced by the quality of the donor, or preoperative recipient risk factors.
Article · Jun 2016 · Scandinavian Journal of Gastroenterology
[Show abstract][Hide abstract]ABSTRACT: Background:
While liver-related deaths in HIV and hepatitis C virus (HCV) co-infected individuals have declined over the last decade, hepatocellular carcinoma (HCC) may have increased. We described the epidemiology of HCC and other liver events in a multi-cohort collaboration of HIV/HCV co-infected individuals.
We studied all HCV antibody-positive adults with HIV in the EuroSIDA Study, the Southern Alberta Clinic Cohort, the Canadian Co-infection Cohort, and the Swiss HIV Cohort Study from 2001 to 2014. We calculated the incidence of HCC and other liver events (defined as liver-related deaths or decompensations, excluding HCC) and used Poisson regression to estimate incidence rate ratios.
Our study comprised 7,229 HIV/HCV co-infected individuals (68% male, 90% white). During follow-up, 72 cases of HCC and 375 other liver events occurred, yielding incidence rates of 1.6 (95% confidence interval (CI): 1.3, 2.0) and 8.6 (95% CI: 7.8, 9.5) cases per 1,000 person-years of follow-up, respectively. The rate of HCC increased 11% per calendar year (95% CI: 4%, 19%) and decreased 4% for other liver events (95% CI: 2%, 7%), but only the latter remained statistically significant after adjustment for potential confounders. High age, cirrhosis, and low current CD4 cell count were associated with a higher incidence of both HCC and other liver events.
In HIV/HCV co-infected individuals, the crude incidence of HCC increased from 2001 to 2014, while other liver events declined. Individuals with cirrhosis or low current CD4 cell count are at highest risk of developing HCC or other liver events.
[Show abstract][Hide abstract]ABSTRACT: 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. Copyright (C) 2016 Wolters Kluwer Health, Inc.
[Show abstract][Hide abstract]ABSTRACT: Chronic kidney disease (CKD) has emerged as an important health concern in HIV-positive individuals. Preventing long-term kidney toxicity from an antiretroviral therapy is therefore critical. Selected antiretroviral agents, especially tenofovir disoproxil fumarate (TDF) and some ritonavir-boosted protease inhibitors (PI/rs), have been associated with increased risk of CKD. However, the CKD risk attributable to these agents is overall small, especially in those with low baseline risk of CKD and normal renal function. CKD risk in HIV-positive individuals can be further minimized by timely identification of those with worsening renal function and discontinuation of potentially nephrotoxic agents. Clinicians can use several monitoring tools, including the D:A:D risk score and routine measurements of estimated glomerular filtration (eGFR) and proteinuria, to identify high-risk individuals who may require an intervention. Tenofovir alafenamide (TAF), a TDF alternative, promises to be safer in terms of TDF-associated kidney and bone toxicity. While the short-term data on TAF does indicate lower eGFR decline and lower risk of proteinuria (vs. TDF), long-term data on renal safety of TAF are still awaited. Promising results have also emerged from recent trials on alternative dual-therapy antiretroviral regimens which exclude the nucleoside(tide) reverse transcriptase class as well as possibly the PI/rs, thereby reducing the drug burden, and possibly the toxicity. However, long-term safety or benefits of these dual-therapy regimens are still unclear and will need to be studied in future prospective studies. Finally, addressing risk factors such as hypertension and diabetes will continue to be important in this population.
[Show abstract][Hide abstract]ABSTRACT: Background:
Antiretroviral (ART) drugs have been associated with higher triglycerides (TG), higher total cholesterol (TC) and lower high density lipoprotein cholesterol (HDL-C) levels. Associations between lipid levels with HIV viraemia and immunosuppression in the presence of ART remain unclear.
Participants from the D:A:D study with at least one TG/TC/HDL-C measurement were included. Linear mixed effect models were used to determine the association of ART, viral load (VL), nadir and current CD4 count and previous AIDS diagnosis with lipids.
Of 49,717 participants, 90%, 92% and 80% contributed at least one TG/TC/HDL-C measurement (median follow-up; 6.8, 6.8 and 5.0 years), respectively. Predicted mean (95% confidence interval (CI)) baseline levels for TG, TC and HDL-C (mmol/l), were 2.10 (2.05-2.14), 4.94 (4.91-4.98) and 1.08 (1.07-1.10), respectively.Lopinavir was associated with the worst TG profile, (27.2% higher levels compared to atazanavir; 25.2%, 29.2%), and darunavir had a similar profile as atazanavir. The nucleoside pair, lamivudine/tenofovir was associated with the most favourable TG profile (-2.8%; -3.5%, -2.0%) compared to emtricitabine/tenofovir, whereas lamivudine/abacavir (+10.2%; +9.3%, +11.2%) and lamivudine/stavudine (+8.0%; +6.9%, +9.0%), were associated with the worst. Raltegravir was associated with lower TG (-5.2%; -6.4%, -3.9%), and nevirapine had a more favourable HDL-C profile (+11.3%; +10.8%, +11.7%) than efavirenz (+5.3%; 5.0%, 5.7%), compared to atazanavir. Higher VLs were associated with lower TG/TC/HDL-C, whereas higher CD4 counts were associated with higher TG/TC/HDL-C.
TG, TC and HDL-C levels, which generally improved over time, are dependent on ART, viraemia and, to a lesser extent, immunosuppression.
[Show abstract][Hide abstract]ABSTRACT: Objective:
Few studies have described mortality and clinical outcomes after myocardial infarction (MI) in the HIV-positive population. This study evaluated changes in short-term mortality after MI in HIV-positive individuals in the D:A:D Study, and investigated possible reasons for any changes seen.
Prospective cohort study.
Demographic, cardiovascular disease (CVD)/HIV-related characteristics and CVD-related interventions (invasive cardiovascular procedures and drug interventions) were summarised at the time of and following an MI. Associations between calendar year and mortality in the first month after MI were identified using logistic regression with adjustment for confounders, including interventions received in the first month after MI.
1008 HIV-positive individuals experiencing an MI over the period 1999-2014 were included. The absolute number of MIs decreased from 214 (1999-2002) to 154 (2011-2014). Whilst the CVD risk profile remained high over time, the HIV status improved. The use of CVD-related interventions after MI appeared to increase over time. The proportion of individuals who died in the first month after MI dropped from 26.6% in 1999-2002 to 8.4% in 2011-2014. Later calendar year was associated with decreased short-term mortality; this effect was attenuated after adjusting for CVD-related interventions received in the first month after MI (odds ratio changed from 0.88 [95% confidence interval 0.83, 0.93] to 0.97 [0.91, 1.02]).
Improvements in short-term survival after MI appear to be largely driven by improved medical management of CVD risk in HIV-positive individuals after MI. Efforts are still needed to treat CVD risk factors and increase access to CVD-related interventions.
[Show abstract][Hide abstract]ABSTRACT: Management of tuberculosis in patients with HIV in eastern Europe is complicated by the high prevalence of multidrug-resistant tuberculosis, low rates of drug susceptibility testing, and poor access to antiretroviral therapy (ART). We report 1 year mortality estimates from a multiregional (eastern Europe, western Europe, and Latin America) prospective cohort study: the TB:HIV study.
[Show abstract][Hide abstract]ABSTRACT: Background:
It is common practice to use PSA≥4.0 µg/L as a clinical indicator for men at risk of PCa, however this is unverified in HIV + men. We aimed to describe kinetics and predictive value of PSA for prostate-cancer (PCa) in HIV+ men.
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[SHB]. Conditional logistic regression models investigated associations between markers and PCa. Mixed models were used to describe kinetics. Sensitivity and specificity of using tPSA >4 µg/L to predict PCa was calculated. ROC curves were used to identify optimal cut-offs in HIV+ men for total PSA.
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 2-fold-higher 4.7;95%CI:1.7-12.9;P<0.01) and last sample (8.1;95%CI:1.1,58.9;P=0.04). A similar relationship was seen between fPSA and PCa. Testosterone and SHBG level were not associated with PCa. tPSA level>4ng/mL had 99% specificity and 38% sensitivity. The optimal PSA cut-off was 1.5ng/mL overall (specificity=84%, sensitivity=81%).
PSA was highly predictive of PCa in HIV+ men; however the commonly used PSA>4ng/mL to indicate high PCa risk was not sensitive in our population and use of the lower cut-off of PSA>1.5ng/mL warrants consideration.
[Show abstract][Hide abstract]ABSTRACT: Objectives:
Whilst several antiretroviral drugs (ARVs), including the d-drugs stavudine (d4T) and didanosine (ddI), may cause biomarker-defined hepatotoxicity, their association with clinically defined end-stage liver disease (ESLD) and hepatocellular carcinoma (HCC) remains unknown.
Prospective cohort study METHODS:: D:A:D participants were followed until the first of ESLD (variceal bleeding, hepatic encephalopathy, hepatorenal syndrome or liver transplantation), HCC (histology or alpha-fetoprotein plus imaging), death, 6 months after last visit or 1/2/2014. Associations between ESLD/HCC and cumulative use of individual ARVs were investigated using Poisson regression adjusting for potential confounders.
During a median follow-up of 8.4 years, 319 ESLD/HCC cases occurred (incidence 1.01/1000 person-years [95%CI 0.90-1.12]) with a 62.6% one-year mortality rate. After adjustment, cumulative (per 5 years) exposure to d4T (relative rate 1.46 [95%CI 1.20-1.77]), ddI (1.32 [1.07-1.63]), tenofovir (TDF, 1.46 [1.11-1.93]) and (fos)amprenavir (APV, 1.47 [1.01-2.15]) was associated with increased ESLD/HCC rates. Longer exposure to emtricitabine (0.51 [0.32-0.83]) and nevirapine (0.76 [0.58-0.98]) were associated with lower ESLD/HCC rates. The ddI/d4T-associated increased ESLD/HCC rate only started to decline 6 years after cessation.
Cumulative use of d4T, ddI, TDF and APV were independently associated with increased ESLD/HCC rates, and intensified monitoring of liver function should hence be considered amongst all individuals exposed for longer time-periods. The use of d-drugs should furthermore be avoided, where there are alternatives available and focus should be put on those with longer-term d-drugs exposure who remain at increased ESLD/HCC risk. The unexpected, and viral hepatitis independent, TDF association calls for further investigations.
[Show abstract][Hide abstract]ABSTRACT: Background: Whether or not the association between some antiretrovirals used in HIV infection and chronic kidney disease is cumulative is a controversial topic, especially in patients with initially normal renal function. In this study, we aimed to investigate the association between duration of exposure to antiretrovirals and the development of chronic kidney disease in people with initially normal renal function, as measured by estimated glomerular filtration rate (eGFR). Methods: In this prospective international cohort study, HIV-positive adult participants (aged ≥16 years) from the D:A:D study (based in Europe, the USA, and Australia) with first eGFR greater than 90 mL/min per 1·73 m2 were followed from baseline (first eGFR measurement after Jan 1, 2004) until the occurrence of one of the following: chronic kidney disease; last eGFR measurement; Feb 1, 2014; or final visit plus 6 months (whichever occurred first). Chronic kidney disease was defined as confirmed (>3 months apart) eGFR lower than 60 mL/min per 1·73 m2. The primary outcome was the occurrence of chronic kidney disease. Poisson regression was used to estimate the incidence rate of chronic kidney disease associated with cumulative exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, ritonavir-boosted lopinavir, other ritonavir-boosted protease inhibitors, or abacavir. Findings: Between Jan 1, 2004, and July 26, 2013, 23 905 eligible individuals from the D:A:D study were included. Participants had a median baseline eGFR of 110 mL/min per 1·73 m2 (IQR 100-125), a median age of 39 years (33-45), and median CD4 cell count of 441 cells per mm3 (294-628). During a median follow-up of 7·2 years (IQR 5·1-8·9), 285 (1%) of 23 905 people developed chronic kidney disease (incidence 1·76 per 1000 person-years of follow-up [95% CI 1·56-1·97]). After adjustment, we recorded a significant increase in chronic kidney disease associated with each additional year of exposure to tenofovir disoproxil fumarate (adjusted incidence rate ratio 1·14 [95% CI 1·10-1·19], p<0·0001), ritonavir-boosted atazanavir (1·20 [1·13-1·26], p<0·0001), and ritonavir-boosted lopinavir (1·11 [1·06-1·16], p<0·0001), but not other ritonavir-boosted protease inhibitors or abacavir. Interpretation: In people with normal renal function, the annual incidence of chronic kidney disease increased for up to 6 years of exposure to tenofovir disoproxil fumarate, ritonavir-boosted atazanavir, or ritonavir-boosted lopinavir therapy. Although the absolute number of new cases of chronic kidney disease was modest, treatment with these antiretrovirals might result in an increasing and cumulative risk of chronic kidney disease. Patients on potentially nephrotoxic antiretrovirals or at high risk of chronic kidney disease should be closely monitored. Funding: The Highly Active Antiretroviral Therapy Oversight Committee.
[Show abstract][Hide abstract]ABSTRACT: Osteopenia, osteoporosis, and low bone mineral density are frequent in patients with HIV. We assessed the 96 week loss of bone mineral density associated with a nucleoside or nucleotide reverse transcriptase inhibitor (NtRTI)-sparing regimen.
[Show abstract][Hide abstract]ABSTRACT: In the last decade, several outbreaks of sexually acquired acute hepatitis C (HCV) infection have been described in HIV-positive men who have sex with men (MSM). The aims of this study were to determine whether there has been an increase in the number of acute HCV infections in different parts of Europe.
HCV seroconversion was defined as an HCV-antibody test change from negative to positive within the observation period in EuroSIDA. Binomial regression was performed to determine factors associated with being tested for HCV and HCV seroconversion.
A total of 223 HCV seroconversions were observed from 16,188 tests [1.38% (95%CI 1.20-1.56)] among 5,736 patients between 2002 and 2013. Overall the odds of acquiring HCV infection increased by 4% per year (OR 1.04 [95%CI 0.99-1.09]; p=0.10). Overall 63.2% (141/223) of all seroconversions were seen among MSM. Similar patterns were observed across all European regions (p=0.69, test for interaction) and HIV transmission risks groups (p=0.69, test for interaction). In multivariate analysis, North, South and East Europe had higher odds of HCV seroconversion compared with Western Europe (OR 1.90 [1.28-2.81], 1.55 [0.99-2.45], and 1.86 [1.21-2.84]; p=0.0014, p=0.058, and p=0.0044, respectively).
Within EuroSIDA a significant increase in HCV seroconversions can be observed after accounting for increased levels of testing for HCV in recent years. This highlights the need for increased HCV prevention efforts among HIV-positive persons in Europe. This article is protected by copyright. All rights reserved.
This article is protected by copyright. All rights reserved.
Article · Apr 2015 · Liver international: official journal of the International Association for the Study of the Liver
[Show abstract][Hide abstract]ABSTRACT: Potent, less toxic, directly acting antivirals (DAAs) for treatment of hepatitis C virus (HCV) infection promise to improve HCV cure rates among HIV/HCV-co-infected individuals. However, the costs of treatment will necessitate prioritization of those at greatest risk of liver-related death (LRD) for therapy. This study aims to provide guidance on who should be prioritized for DAA treatment.
Three thousand nine hundred and forty-one HCV antibody-positive EuroSIDA patients with follow-up after 1 January 2000 were included, with causes of death classified using CoDe methodology. Crude death rates, competing-risks Cox proportional-hazards models and cumulative incidence functions were used to describe factors associated with LRD.
LRD accounted for 145/670 (21.6%) deaths in the study population. LRD rates peaked in those aged 35-45 years, and occurred almost exclusively in those with at least F2 fibrosis at baseline. In adjusted Cox models, risk factors for LRD included F4 or F2/F3 fibrosis [sub-distribution hazard ratio (sHR) 6.3, 95% confidence interval (CI) 4.1-9.6; and sHR 2.5, 95% CI 1.5-4.2 vs. F0/F1, respectively), CD4 cell count (sHR 0.83, 95% CI 0.73-0.95 per doubling) and hepatitis B surface antigen-positive (sHR 2.2, 95% CI 1.3-3.5 vs. hepatitis B surface antigen-negative). The 5-year probability of LRD was low in those with F0/F1 fibrosis (sHR 2.2%, 95% CI 1.7-2.9), but substantial in those with F2/F3 and F4 fibrosis (sHR 10.3%, 95% CI 7.6-13.5; and sHR 14.0%, 95% CI 10.3-18.3, respectively).
Treatment with DAAs should be prioritized for those with at least F2 fibrosis. Early initiation of cART with the aim of avoiding low CD4 cell counts should be considered essential to decrease the risk of LRD and the need for HCV treatment.
[Show abstract][Hide abstract]ABSTRACT: Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.
[Show abstract][Hide abstract]ABSTRACT: OBJECTIVE: The prevalence of overweight and obesity is increasing among HIV-infected patients. Whether standard antiretroviral drug dosage is adequate in heavy individuals remains unresolved. We assessed the virological and immunological responses to initial efavirenz (EFV)-containing regimens in heavy compared to normal-weight HIV-infected patients.
DESIGN: Observational European cohort collaboration study.
METHODS: Eligible patients were antiretroviral-naïve with documented weight prior to EFV start and follow-up viral loads after treatment initiation. Cox regression analyses evaluated the association between weight and time to first undetectable viral load (<50 copies/ml) after treatment initiation, and time to viral load rebound (two consecutive viral load >50 copies/ml) after initial suppression over 5 years of follow-up. Recovery of CD4 cell count was evaluated 6 and 12 months after EFV initiation. Analyses were stratified by weight (kg) group (I - <55; II - >55, <80 (reference); III - >80, <85; IV - >85, <90; V - >90, <95; VI - >95).
RESULTS: The study included 19 968 patients, of whom 9.1, 68.3, 9.1, 5.8, 3.5, and 4.3% were in weight groups I-VI, respectively. Overall, 81.1% patients attained virological suppression, of whom 34.1% subsequently experienced viral load rebound. After multiple adjustments, no statistical difference was observed in time to undetectable viral load and virological rebound for heavier individuals compared to their normal-weight counterparts. Although heaviest individuals had significantly higher CD4 cell count at baseline, CD4 cell recovery at 6 and 12 months after EFV initiation was comparable to normal-weight individuals.
CONCLUSION: Virological and immunological responses to initial EFV-containing regimens were not impaired in heavy individuals, suggesting that the standard 600 mg EFV dosage is appropriate across a wide weight range.