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HIV Seropositivity: HELP
Articles by Jens D. Lundgren
Based on 25 articles published since 2008
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Between 2008 and 2019, J. Lundgren wrote the following 25 articles about HIV Seropositivity.
 
+ Citations + Abstracts
1 Editorial Aging with HIV in Africa: the challenges of living longer. 2012

Negin, Joel / Bärnighausen, Till / Lundgren, Jens D / Mills, Edward J. · ·AIDS · Pubmed #22713477.

ABSTRACT: -- No abstract --

2 Review Conclusions from the HIV in Europe Copenhagen 2012 Conference and ways forward: working together for optimal HIV testing and earlier care. 2013

Raben, D / Delpech, V / de Wit, J / Sullivan, A / Lazarus, J V / Dedes, N / Coenen, T / Lundgren, J / Anonymous4170769. ·Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark. ·HIV Med · Pubmed #24033894.

ABSTRACT: The objective of this article is to set the scene for this supplement by presenting and discussing the overall outcomes of the HIV in Europe Copenhagen 2012 Conference and how the HIV in Europe initiative intends to further address challenges and themes raised during the conference.

3 Article Gender differences in the use of cardiovascular interventions in HIV-positive persons; the D:A:D Study. 2018

Hatleberg, Camilla I / Ryom, Lene / El-Sadr, Wafaa / Mocroft, Amanda / Reiss, Peter / De Wit, Stephane / Dabis, Francois / Pradier, Christian / d'Arminio Monforte, Antonella / Kovari, Helen / Law, Matthew / Lundgren, Jens D / Sabin, Caroline A / Anonymous3331107. ·Department of Infectious Diseases Section 2100, CHIP, University of Copenhagen, Finsencentret, Rigshospitalet, Copenhagen, Denmark. · ICAP-Columbia University and Harlem Hospital, New York, NY, USA. · Institute for Global Health, UCL, London, United Kingdom. · Academic Medical Center, Department of Global Health and Division of Infectious Diseases, University of Amsterdam, HIV Monitoring Foundation, Amsterdam, The Netherlands. · Division of Infectious Diseases, Saint Pierre University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · CHU de Bordeaux and INSERM U897, Université de Bordeaux, Talence, France. · Department of Public Health, Nice University Hospital, Nice, France. · Dipartimento di Scienze della Salute, Clinica di Malattie Infettive e Tropicali, Azienda Ospedaliera-Polo Universitario San Paolo, Milan, Italy. · Division of infectious diseases and hospital epidemiology, University hospital Zurich, University of Zurich, Zurich, Switzerland. · Kirby Institute, UNSW Sydney, Sydney, Australia. ·J Int AIDS Soc · Pubmed #29509305.

ABSTRACT: INTRODUCTION: There is paucity of data related to potential gender differences in the use of interventions to prevent and treat cardiovascular disease (CVD) among HIV-positive individuals. We investigated whether such differences exist in the observational D:A:D cohort study. METHODS: Participants were followed from study enrolment until the earliest of death, six months after last visit or February 1, 2015. Initiation of CVD interventions [lipid-lowering drugs (LLDs), angiotensin-converting enzyme inhibitors (ACEIs), anti-hypertensives, invasive cardiovascular procedures (ICPs) were investigated and Poisson regression models calculated whether rates were lower among women than men, adjusting for potential confounders. RESULTS: Women (n = 12,955) were generally at lower CVD risk than men (n = 36,094). Overall, initiation rates of CVD interventions were lower in women than men; LLDs: incidence rate 1.28 [1.21, 1.35] vs. 2.40 [2.34, 2.46]; ACEIs: 0.88 [0.82, 0.93] vs. 1.43 [1.39, 1.48]; anti-hypertensives: 1.40 [1.33, 1.47] vs. 1.72 [1.68, 1.77] and ICPs: 0.08 [0.06, 0.10] vs. 0.30 [0.28, 0.32], and this was also true for most CVD interventions when exclusively considering periods of follow-up for which individuals were at high CVD risk. In fully adjusted models, women were less likely to receive CVD interventions than men (LLDs: relative rate 0.83 [0.78, 0.88]; ACEIs: 0.93 [0.86, 1.01]; ICPs: 0.54 [0.43, 0.68]), except for the receipt of anti-hypertensives (1.17 [1.10, 1.25]). CONCLUSION: The use of most CVD interventions was lower among women than men. Interventions are needed to ensure that all HIV-positive persons, particularly women, are appropriately monitored for CVD and, if required, receive appropriate CVD interventions.

4 Article Cardiovascular disease (CVD) and chronic kidney disease (CKD) event rates in HIV-positive persons at high predicted CVD and CKD risk: A prospective analysis of the D:A:D observational study. 2017

Boyd, Mark A / Mocroft, Amanda / Ryom, Lene / Monforte, Antonella d'Arminio / Sabin, Caroline / El-Sadr, Wafaa M / Hatleberg, Camilla Ingrid / De Wit, Stephane / Weber, Rainer / Fontas, Eric / Phillips, Andrew / Bonnet, Fabrice / Reiss, Peter / Lundgren, Jens / Law, Matthew. ·Kirby Institute, University of New South Wales, Sydney, Australia. · Faculty of Health and Medical Sciences, University of Adelaide, Adelaide, South Australia, Australia. · Department of Infection and Population Health, University College London, London, United Kingdom. · Centre of Excellence for Health, Immunity and Infections, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. · Dipartimento di Scienze della Salute, Clinica di Malattie Infettive e Tropicali, Azienda Ospedaliera-Polo Universitario San Paolo, Milan, Italy. · ICAP at Columbia University, New York, New York, United States of America. · Division of Infectious Diseases, Saint-Pierre University Hospital, Université Libre de Bruxelles, Brussels, Belgium. · Department of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. · Department of Public Health, Nice University Hospital, Nice, France. · Centre Hospitalier Universitaire de Bordeaux, Université de Bordeaux, Bordeaux, France. · Bordeaux Population Health, INSERM U1219, Université de Bordeaux, Bordeaux, France. · Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · HIV Monitoring Foundation, Amsterdam, The Netherlands. ·PLoS Med · Pubmed #29112958.

ABSTRACT: BACKGROUND: The Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study has developed predictive risk scores for cardiovascular disease (CVD) and chronic kidney disease (CKD, defined as confirmed estimated glomerular filtration rate [eGFR] ≤ 60 ml/min/1.73 m2) events in HIV-positive people. We hypothesized that participants in D:A:D at high (>5%) predicted risk for both CVD and CKD would be at even greater risk for CVD and CKD events. METHODS AND FINDINGS: We included all participants with complete risk factor (covariate) data, baseline eGFR > 60 ml/min/1.73 m2, and a confirmed (>3 months apart) eGFR < 60 ml/min/1.73 m2 thereafter to calculate CVD and CKD risk scores. We calculated CVD and CKD event rates by predicted 5-year CVD and CKD risk groups (≤1%, >1%-5%, >5%) and fitted Poisson models to assess whether CVD and CKD risk group effects were multiplicative. A total of 27,215 participants contributed 202,034 person-years of follow-up: 74% male, median (IQR) age 42 (36, 49) years, median (IQR) baseline year of follow-up 2005 (2004, 2008). D:A:D risk equations predicted 3,560 (13.1%) participants at high CVD risk, 4,996 (18.4%) participants at high CKD risk, and 1,585 (5.8%) participants at both high CKD and high CVD risk. CVD and CKD event rates by predicted risk group were multiplicative. Participants at high CVD risk had a 5.63-fold (95% CI 4.47, 7.09, p < 0.001) increase in CKD events compared to those at low risk; participants at high CKD risk had a 1.31-fold (95% CI 1.09, 1.56, p = 0.005) increase in CVD events compared to those at low risk. Participants' CVD and CKD risk groups had multiplicative predictive effects, with no evidence of an interaction (p = 0.329 and p = 0.291 for CKD and CVD, respectively). The main study limitation is the difference in the ascertainment of the clinically defined CVD endpoints and the laboratory-defined CKD endpoints. CONCLUSIONS: We found that people at high predicted risk for both CVD and CKD have substantially greater risks for both CVD and CKD events compared with those at low predicted risk for both outcomes, and compared to those at high predicted risk for only CVD or CKD events. This suggests that CVD and CKD risk in HIV-positive persons should be assessed together. The results further encourage clinicians to prioritise addressing modifiable risks for CVD and CKD in HIV-positive people.

5 Article Sexual Activity Without Condoms and Risk of HIV Transmission in Serodifferent Couples When the HIV-Positive Partner Is Using Suppressive Antiretroviral Therapy. 2016

Rodger, Alison J / Cambiano, Valentina / Bruun, Tina / Vernazza, Pietro / Collins, Simon / van Lunzen, Jan / Corbelli, Giulio Maria / Estrada, Vicente / Geretti, Anna Maria / Beloukas, Apostolos / Asboe, David / Viciana, Pompeyo / Gutiérrez, Félix / Clotet, Bonaventura / Pradier, Christian / Gerstoft, Jan / Weber, Rainer / Westling, Katarina / Wandeler, Gilles / Prins, Jan M / Rieger, Armin / Stoeckle, Marcel / Kümmerle, Tim / Bini, Teresa / Ammassari, Adriana / Gilson, Richard / Krznaric, Ivanka / Ristola, Matti / Zangerle, Robert / Handberg, Pia / Antela, Antonio / Allan, Sris / Phillips, Andrew N / Lundgren, Jens / Anonymous251097. ·Research Department of Infection and Population Health, University College London, London, United Kingdom. · Department of Infectious Diseases/CHIP, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. · Division of Infectious Diseases and Hospital Epidemiology, Cantonal Hospital, St Gallen, Switzerland. · HIV i-Base, London, United Kingdom. · University Medical Center Hamburg-Eppendorf, Hamburg-Eppendorf, Germany. · European AIDS Treatment Group, Bruxelles, Belgium. · Hospital Clinico San Carlos and Universidad Complutense, Madrid, Spain. · Institute of Infection and Global Health, University of Liverpool, Liverpool, United Kingdom. · Chelsea and Westminster NHS Foundation Trust, London, United Kingdom. · Hospital Virgen del Rocío, Sevilla, Spain. · Hospital General de Elche & Universidad Miguel Hernández, Alicante, Spain. · IrsiCaixa Foundation, UAB, UVIC-UCC, Hospital Universitari "Germans Trias i Pujol," Badalona, Catalonia, Spain. · Department of Public Health, Nice University Hospital and EA 6312, University Nice Sophia-Antipolis, France. · Rigshospitalet, Copenhagen, Denmark. · Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland. · Unit of Infectious Diseases and Dermatology, Department of Medicine, Karolinska Institutet, and Department of Infectious Diseases, Karolinska University Hospital, Stockholm, Sweden. · Department of Infectious Diseases, Bern University Hospital, University of Bern, Bern, Switzerland. · Academic Medical Center, Amsterdam, the Netherlands. · Medical University of Vienna, Vienna, Austria. · Division of Infectious Diseases and Hospital Epidemiology, University Hospital Basel, Basel, Switzerland. · Department of Internal Medicine 1, University Hospital of Cologne, Cologne, Germany. · Ospedal San Paolo, Milan, Italy. · Ospedale L. Spallanzani, Roma, Italy. · Praxis Driesener Straße, Berlin, Germany. · Helsinki University Central Hospital, Helsinki, Finland. · Medical University Innsbruck, Innsbruck, Austria. · Hvidovre Universitets Hospital, Hvidovre, Denamrk. · Hospital Clínico Universitario de Santiago de Compostela, Santiago de Compostela, Spain. · Coventry and Warwickshire Hospital, Coventry, United Kingdom. ·JAMA · Pubmed #27404185.

ABSTRACT: IMPORTANCE: A key factor in assessing the effectiveness and cost-effectiveness of antiretroviral therapy (ART) as a prevention strategy is the absolute risk of HIV transmission through condomless sex with suppressed HIV-1 RNA viral load for both anal and vaginal sex. OBJECTIVE: To evaluate the rate of within-couple HIV transmission (heterosexual and men who have sex with men [MSM]) during periods of sex without condoms and when the HIV-positive partner had HIV-1 RNA load less than 200 copies/mL. DESIGN, SETTING, AND PARTICIPANTS: The prospective, observational PARTNER (Partners of People on ART-A New Evaluation of the Risks) study was conducted at 75 clinical sites in 14 European countries and enrolled 1166 HIV serodifferent couples (HIV-positive partner taking suppressive ART) who reported condomless sex (September 2010 to May 2014). Eligibility criteria for inclusion of couple-years of follow-up were condomless sex and HIV-1 RNA load less than 200 copies/mL. Anonymized phylogenetic analysis compared couples' HIV-1 polymerase and envelope sequences if an HIV-negative partner became infected to determine phylogenetically linked transmissions. EXPOSURES: Condomless sexual activity with an HIV-positive partner taking virally suppressive ART. MAIN OUTCOMES AND MEASURES: Risk of within-couple HIV transmission to the HIV-negative partner. RESULTS: Among 1166 enrolled couples, 888 (mean age, 42 years [IQR, 35-48]; 548 heterosexual [61.7%] and 340 MSM [38.3%]) provided 1238 eligible couple-years of follow-up (median follow-up, 1.3 years [IQR, 0.8-2.0]). At baseline, couples reported condomless sex for a median of 2 years (IQR, 0.5-6.3). Condomless sex with other partners was reported by 108 HIV-negative MSM (33%) and 21 heterosexuals (4%). During follow-up, couples reported condomless sex a median of 37 times per year (IQR, 15-71), with MSM couples reporting approximately 22,000 condomless sex acts and heterosexuals approximately 36,000. Although 11 HIV-negative partners became HIV-positive (10 MSM; 1 heterosexual; 8 reported condomless sex with other partners), no phylogenetically linked transmissions occurred over eligible couple-years of follow-up, giving a rate of within-couple HIV transmission of zero, with an upper 95% confidence limit of 0.30/100 couple-years of follow-up. The upper 95% confidence limit for condomless anal sex was 0.71 per 100 couple-years of follow-up. CONCLUSIONS AND RELEVANCE: Among serodifferent heterosexual and MSM couples in which the HIV-positive partner was using suppressive ART and who reported condomless sex, during median follow-up of 1.3 years per couple, there were no documented cases of within-couple HIV transmission (upper 95% confidence limit, 0.30/100 couple-years of follow-up). Additional longer-term follow-up is necessary to provide more precise estimates of risk.

6 Article Relevance of Interleukin-6 and D-Dimer for Serious Non-AIDS Morbidity and Death among HIV-Positive Adults on Suppressive Antiretroviral Therapy. 2016

Grund, Birgit / Baker, Jason V / Deeks, Steven G / Wolfson, Julian / Wentworth, Deborah / Cozzi-Lepri, Alessandro / Cohen, Calvin J / Phillips, Andrew / Lundgren, Jens D / Neaton, James D / Anonymous561060. ·School of Statistics, University of Minnesota, Minneapolis, MN, United States of America. · Hennepin County Medical Center, Minneapolis, MN, United States of America. · Department of Medicine, University of Minnesota, Minneapolis, MN, United States of America. · University of California San Francisco, San Francisco, CA, United States of America. · San Francisco General Hospital, San Francisco, CA, United States of America. · Division of Biostatistics, School of Public Health, University of Minnesota, Minneapolis, MN, United States of America. · University College London, London, United Kingdom. · Medical Affairs Department, Gilead Sciences, Foster City, CA, United States of America. · Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. ·PLoS One · Pubmed #27171281.

ABSTRACT: BACKGROUND: Despite effective antiretroviral treatment (ART), HIV-positive individuals are at increased risk of serious non-AIDS conditions (cardiovascular, liver and renal disease, and cancers), perhaps due in part to ongoing inflammation and/or coagulation. To estimate the potential risk reduction in serious non-AIDS conditions or death from any cause that might be achieved with treatments that reduce inflammation and/or coagulation, we examined associations of interleukin-6 (IL-6), D-dimer, and high-sensitivity C-reactive protein (hsCRP) levels with serious non-AIDS conditions or death in 3 large cohorts. METHODS: In HIV-positive adults on suppressive ART, associations of IL-6, D-dimer, and hsCRP levels at study entry with serious non-AIDS conditions or death were studied using Cox regression. Hazard ratios (HR) adjusted for age, gender, study, and regression dilution bias (due to within-person biomarker variability) were used to predict risk reductions in serious non-AIDS conditions or death associated with lower "usual" levels of IL-6 and D-dimer. RESULTS: Over 4.9 years of mean follow-up, 260 of the 3766 participants experienced serious non-AIDS conditions or death. IL-6, D-dimer and hsCRP were each individually associated with risk of serious non-AIDS conditions or death, HR = 1.45 (95% CI: 1.30 to 1.63), 1.28 (95% CI: 1.14 to 1.44), and 1.17 (95% CI: 1.09 to 1.26) per 2x higher biomarker levels, respectively. In joint models, IL-6 and D-dimer were independently associated with serious non-AIDS conditions or death, with consistent results across the 3 cohorts and across serious non-AIDS event types. The association of IL-6 and D-dimer with serious non-AIDS conditions or death was graded and persisted throughout follow-up. For 25% lower "usual" IL-6 and D-dimer levels, the joint biomarker model estimates a 37% reduction (95% CI: 28 to 46%) in the risk of serious non-AIDS conditions or death if the relationship is causal. CONCLUSIONS: Both IL-6 and D-dimer are independently associated with serious non-AIDS conditions or death among HIV-positive adults with suppressed virus. This suggests that treatments that reduce IL-6 and D-dimer levels might substantially decrease morbidity and mortality in patients on suppressive ART. Clinical trials are needed to test this hypothesis.

7 Article Predictive value of prostate specific antigen in a European HIV-positive cohort: does one size fit all? 2016

Shepherd, Leah / Borges, Álvaro H / Ravn, Lene / Harvey, Richard / Bower, Mark / Grulich, Andrew / Silverberg, Michael / Kronborg, Gitte / Galli, Massimo / Kirk, Ole / Lundgren, Jens / Mocroft, Amanda / Anonymous5560856. ·Research Department of Infection and Population Health, University College London, London, UK. · Centre for Health & Infectious Disease Research (CHIP), Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. · Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark. · Charing Cross Oncology Laboratory and Trophoblastic Disease Centre, Charing Cross Hospital Campus of Imperial College Healthcare National Health Service Trust, London, UK. · National Centre for HIV Malignancy, Chelsea and Westminster Hospital NHS Foundation Trust, London, UK. · Kirby Institute, The University of New South Wales, Sydney, NSW, Australia. · Kaiser Permanente Northern California, Oakland, CA, USA. · Institut for Klinisk Medicin, Hvidovre Hospital, Hvidovre, Denmark. · Clinic of Infectious Disease, Luigi Sacco Hospital, Milan, Italy. ·Antivir Ther · Pubmed #26823399.

ABSTRACT: 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; 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 >4 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.

8 Article Late presentation for HIV care across Europe: update from the Collaboration of Observational HIV Epidemiological Research Europe (COHERE) study, 2010 to 2013. 2015

Anonymous5480850 / Mocroft, Amanda / Lundgren, Jens / Antinori, Andrea / Monforte, Antonella d'Arminio / Brännström, Johanna / Bonnet, Fabrice / Brockmeyer, Norbert / Casabona, Jordi / Castagna, Antonella / Costagliola, Dominique / De Wit, Stéphane / Fätkenheuer, Gerd / Furrer, Hansjakob / Jadand, Corinne / Johnson, Anne / Lazanas, Mario / Leport, Catherine / Moreno, Santiago / Mussini, Christina / Obel, Niels / Post, Frank / Reiss, Peter / Sabin, Caroline / Skaletz-Rorowski, Adriane / Suarez-Loano, Ignacio / Torti, Carlo / Warszawski, Josiane / Wittkop, Linda / Zangerle, Robert / Chene, Genevieve / Raben, Dorthe / Kirk, Ole. ·a.mocroft@ucl.ac.uk ·Euro Surveill · Pubmed #26624933.

ABSTRACT: Late presentation (LP) for HIV care across Europe remains a significant issue. We provide a cross-European update from 34 countries on the prevalence and risk factors of LP for 2010-2013. People aged ≥ 16 presenting for HIV care (earliest of HIV-diagnosis, first clinic visit or cohort enrollment) after 1 January 2010 with available CD4 count within six months of presentation were included. LP was defined as presentation with a CD4 count < 350/mm(3) or an AIDS defining event (at any CD4), in the six months following HIV diagnosis. Logistic regression investigated changes in LP over time. A total of 30,454 people were included. The median CD4 count at presentation was 368/mm(3) (interquartile range (IQR) 193-555/mm(3)), with no change over time (p = 0.70). In 2010, 4,775/10,766 (47.5%) were LP whereas in 2013, 1,642/3,375 (48.7%) were LP (p = 0.63). LP was most common in central Europe (4,791/9,625, 49.8%), followed by northern (5,704/11,692; 48.8%), southern (3,550/7,760; 45.8%) and eastern Europe (541/1,377; 38.3%; p < 0.0001). There was a significant increase in LP in male and female people who inject drugs (PWID) (adjusted odds ratio (aOR)/year later 1.16; 95% confidence interval (CI): 1.02-1.32), and a significant decline in LP in northern Europe (aOR/year later 0.89; 95% CI: 0.85-0.94). Further improvements in effective HIV testing strategies, with a focus on vulnerable groups, are required across the European continent.

9 Article Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. 2015

Anonymous6800836 / Lundgren, Jens D / Babiker, Abdel G / Gordin, Fred / Emery, Sean / Grund, Birgit / Sharma, Shweta / Avihingsanon, Anchalee / Cooper, David A / Fätkenheuer, Gerd / Llibre, Josep M / Molina, Jean-Michel / Munderi, Paula / Schechter, Mauro / Wood, Robin / Klingman, Karin L / Collins, Simon / Lane, H Clifford / Phillips, Andrew N / Neaton, James D. · ·N Engl J Med · Pubmed #26192873.

ABSTRACT: BACKGROUND: Data from randomized trials are lacking on the benefits and risks of initiating antiretroviral therapy in patients with asymptomatic human immunodeficiency virus (HIV) infection who have a CD4+ count of more than 350 cells per cubic millimeter. METHODS: We randomly assigned HIV-positive adults who had a CD4+ count of more than 500 cells per cubic millimeter to start antiretroviral therapy immediately (immediate-initiation group) or to defer it until the CD4+ count decreased to 350 cells per cubic millimeter or until the development of the acquired immunodeficiency syndrome (AIDS) or another condition that dictated the use of antiretroviral therapy (deferred-initiation group). The primary composite end point was any serious AIDS-related event, serious non-AIDS-related event, or death from any cause. RESULTS: A total of 4685 patients were followed for a mean of 3.0 years. At study entry, the median HIV viral load was 12,759 copies per milliliter, and the median CD4+ count was 651 cells per cubic millimeter. On May 15, 2015, on the basis of an interim analysis, the data and safety monitoring board determined that the study question had been answered and recommended that patients in the deferred-initiation group be offered antiretroviral therapy. The primary end point occurred in 42 patients in the immediate-initiation group (1.8%; 0.60 events per 100 person-years), as compared with 96 patients in the deferred-initiation group (4.1%; 1.38 events per 100 person-years), for a hazard ratio of 0.43 (95% confidence interval [CI], 0.30 to 0.62; P<0.001). Hazard ratios for serious AIDS-related and serious non-AIDS-related events were 0.28 (95% CI, 0.15 to 0.50; P<0.001) and 0.61 (95% CI, 0.38 to 0.97; P=0.04), respectively. More than two thirds of the primary end points (68%) occurred in patients with a CD4+ count of more than 500 cells per cubic millimeter. The risks of a grade 4 event were similar in the two groups, as were the risks of unscheduled hospital admissions. CONCLUSIONS: The initiation of antiretroviral therapy in HIV-positive adults with a CD4+ count of more than 500 cells per cubic millimeter provided net benefits over starting such therapy in patients after the CD4+ count had declined to 350 cells per cubic millimeter. (Funded by the National Institute of Allergy and Infectious Diseases and others; START ClinicalTrials.gov number, NCT00867048.).

10 Article Development and validation of a risk score for chronic kidney disease in HIV infection using prospective cohort data from the D:A:D study. 2015

Mocroft, Amanda / Lundgren, Jens D / Ross, Michael / Law, Matthew / Reiss, Peter / Kirk, Ole / Smith, Colette / Wentworth, Deborah / Neuhaus, Jacqueline / Fux, Christoph A / Moranne, Olivier / Morlat, Phillipe / Johnson, Margaret A / Ryom, Lene / Anonymous6001162 / Anonymous6011162 / Anonymous6021162 / Anonymous6031162 / Anonymous6041162. ·Department of Infection and Population Health, University College London, London, United Kingdom. · Copenhagen HIV Programme, Department of Infectious Diseases, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark. · Division of Nephrology, Mount Sinai School of Medicine, New York, New York, United States of America. · The Kirby Institute, University of New South Wales, Sydney, New South Wales, Australia. · Division of Infectious Diseases and Department of Global Health, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. · University of Minnesota, Minneapolis, Minnesota, United States of America. · Clinic for Infectious Diseases and Hospital Hygiene, Kantonsspital Aarau, Aarau, Switzerland. · Nephrology Department, Public Health Department, Centre Hospitalier Universitaire de Nice, Nice, France. · Université de Bordeaux, INSERM U 897, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France. · Department of HIV Medicine, Royal Free London NHS Foundation Trust, London, United Kingdom. ·PLoS Med · Pubmed #25826420.

ABSTRACT: BACKGROUND: 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. METHODS AND FINDINGS: A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with ≥3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR ≤ 60 ml/min/1.73 m2. Poisson regression was used to develop a risk score, externally validated on two independent cohorts. In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1:393 chance of developing CKD in the next 5 y in the low risk group (risk score < 0, 33 events), rising to 1:47 and 1:6 in the medium (risk score 0-4, 103 events) and high risk groups (risk score ≥ 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. CONCLUSIONS: Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.

11 Article Risk factors and outcomes for late presentation for HIV-positive persons in Europe: results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE). 2013

Mocroft, Amanda / Lundgren, Jens D / Sabin, Miriam Lewis / Monforte, Antonella d'Arminio / Brockmeyer, Norbert / Casabona, Jordi / Castagna, Antonella / Costagliola, Dominique / Dabis, Francois / De Wit, Stéphane / Fätkenheuer, Gerd / Furrer, Hansjakob / Johnson, Anne M / Lazanas, Marios K / Leport, Catherine / Moreno, Santiago / Obel, Niels / Post, Frank A / Reekie, Joanne / Reiss, Peter / Sabin, Caroline / Skaletz-Rorowski, Adriane / Suarez-Lozano, Ignacio / Torti, Carlo / Warszawski, Josiane / Zangerle, Robert / Fabre-Colin, Céline / Kjaer, Jesper / Chene, Genevieve / Grarup, Jesper / Kirk, Ole / Anonymous4950772. ·Department of Infection and Population Health, University College London, London, United Kingdom. ·PLoS Med · Pubmed #24137103.

ABSTRACT: BACKGROUND: Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. METHODS AND FINDINGS: LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm(3) or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95-0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19-20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55-12.43). CONCLUSIONS: LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP.

12 Article Advanced chronic kidney disease, end-stage renal disease and renal death among HIV-positive individuals in Europe. 2013

Ryom, L / Kirk, O / Lundgren, J D / Reiss, P / Pedersen, C / De Wit, S / Buzunova, S / Gasiorowski, J / Gatell, J M / Mocroft, A / Anonymous5920755. ·Copenhagen HIV Programme, Faculty of Health & Medical Sciences, University of Copenhagen, Copenhagen, Denmark. lrn@cphiv.dk ·HIV Med · Pubmed #23590641.

ABSTRACT: OBJECTIVES: Knowledge about advanced chronic kidney disease (CKD) and end-stage renal disease (ESRD) in HIV-positive persons is limited. The aim of this study was to investigate incidence, predictors and outcomes for advanced CKD/ESRD and renal death. METHODS: Advanced CKD was defined as confirmed (two consecutive measurements ≥ 3 months apart) estimated glomerular filtration rate (eGFR) ≤ 30 mL/min/1.73 m(2) using Cockcroft-Gault, and ESRD as haemodialysis or peritoneal dialysis for ≥ 1 month or renal transplant. Renal death was death with renal disease as the underlying cause, using Coding Causes of Death in HIV (CoDe) methodology. Follow-up was from 1 January 2004 until last eGFR measurement, advanced CKD, ESRD or renal death, whichever occurred first. Poisson regression was used to identify predictors. RESULTS: Of 9044 individuals included in the study, 58 (0.64%) experienced advanced CKD/ESRD/renal death [incidence rate 1.32/1000 person-years of follow-up (PYFU); 95% confidence interval (CI) 0.98-1.66]; 52% of those who experienced the endpoint had a baseline eGFR ≤ 60 mL/min/1.73 m(2) compared with 3% of those who did not. Using Kaplan-Meier methods, at 6 years from baseline, 0.83% (95% CI 0.59-1.07%) were estimated to have experienced the endpoint overall and 11.26% (95% CI 6.75-15.78%) among those with baseline eGFR ≤ 60 mL/min/1.73 m(2) . Independent predictors of the endpoint included any cardiovascular event [incidence rate ratio (IRR) 2.16; 95% CI 1.24-3.77], lower eGFR (IRR 0.64 per 5 mL/min/1.73 m(2) ; 95% CI 0.59-0.70) and lower CD4 count (IRR 0.77 per doubling; 95% CI 0.62-0.95). One year after experiencing advanced CKD or ESRD, an estimated 19.21% (95% CI 7.84-30.58%) of patients had died, mostly from extra-renal causes. CONCLUSIONS: The incidence of advanced CKD/ESRD/renal death was low and predictors included traditional renal risk factors, HIV-related factors and pre-existing renal impairment. The prognosis following advanced CKD/ESRD was poor. Larger studies should address possible contributions of specific antiretrovirals.

13 Article Association between ALT level and the rate of cardio/cerebrovascular events in HIV-positive individuals: the D: A: D study. 2013

Sabin, Caroline A / Ryom, Lene / Kovari, Helen / Kirk, Ole / de Wit, Stephane / Law, Matthew / Reiss, Peter / Dabis, Francois / Pradier, Christian / El-Sadr, Wafaa / Monforte, Antonella d'Arminio / Kamara, David / Phillips, Andrew N / Lundgren, Jens D. ·Research Department of Infection and Population Health, UCL, London, United Kingdom. c.sabin@ucl.ac.uk ·J Acquir Immune Defic Syndr · Pubmed #23535291.

ABSTRACT: BACKGROUND: An inverse association between serum alanine aminotransferase (ALT) levels and the risk of myocardial infarction (MI) has been reported in the general population. We investigated associations between ALT levels and the risk of various cardiovascular and cerebrovascular outcomes in a large cohort study of HIV-positive individuals. METHODS: Using Poisson regression, we investigated associations between the latest ALT level and MI, coronary heart disease (CHD), and stroke, after adjusting for known confounders and cumulative/recent exposure to antiretroviral drugs. Analyses were also performed for the end points of all-cause/liver-related mortality and new-onset diabetes mellitus. RESULTS: By February 2011, participants had experienced 541 MIs, 804 CHD, and 258 stroke events. The MI rate decreased from 3.1/1000 person-years among those with ALT ≤18 U/L to 2.1/1000 person-years among those with ALT >60 U/L. After adjustment for confounders, each 2-fold increment in ALT was associated with a 19% drop in the MI rate {relative rate, 0.81 [95% confidence interval (CI): 0.74 to 0.89], P = 0.0001}. A weaker inverse association was seen for CHD with no indication of a linear association between ALT levels and stroke (P = 0.72). Adjusted relative rates were 0.88 (95% CI: 0.81 to 0.97) and 0.70 (95% CI: 0.54 to 0.92) in those who were hepatitis C virus negative and hepatitis C virus positive, respectively, and 0.72 (95% CI: 0.58 to 0.89) and 0.84 (0.77 to 0.93) in injection drug users and non-injection drug users, respectively. Liver-related mortality and diabetes both demonstrated a positive association with ALT levels, whereas all-cause mortality showed a U-shaped relationship. CONCLUSIONS: Higher ALT levels are associated with lower MI risk in HIV-positive individuals, but with higher risks of liver-related mortality and diabetes mellitus.

14 Article Feasibility and effectiveness of indicator condition-guided testing for HIV: results from HIDES I (HIV indicator diseases across Europe study). 2013

Sullivan, Ann K / Raben, Dorthe / Reekie, Joanne / Rayment, Michael / Mocroft, Amanda / Esser, Stefan / Leon, Agathe / Begovac, Josip / Brinkman, Kees / Zangerle, Robert / Grzeszczuk, Anna / Vassilenko, Anna / Hadziosmanovic, Vesna / Krasnov, Maksym / Sönnerborg, Anders / Clumeck, Nathan / Gatell, José / Gazzard, Brian / Monforte, Antonella d'Arminio / Rockstroh, Jürgen / Lundgren, Jens D. ·Directorate of Sexual Health and HIV Medicine, Chelsea and Westminster NHS Foundation Trust, London, United Kingdom. ·PLoS One · Pubmed #23341910.

ABSTRACT: Improved methods for targeting HIV testing among patients most likely to be infected are required; HIDES I aimed to define the methodology of a European wide study of HIV prevalence in individuals presenting with one of eight indicator conditions/diseases (ID); sexually transmitted infection, lymphoma, cervical or anal cancer/dysplasia, herpes zoster, hepatitis B/C, mononucleosis-like illness, unexplained leukocytopenia/thrombocytopenia and seborrheic dermatitis/exanthema, and to identify those with an HIV prevalence of >0.1%, a level determined to be cost effective. A staff questionnaire was performed. From October 2009- February 2011, individuals, not known to be HIV positive, presenting with one of the ID were offered an HIV test; additional information was collected on previous HIV testing behaviour and recent medical history. A total of 3588 individuals from 16 centres were included. Sixty-six tested positive for HIV, giving an HIV prevalence of 1.8% [95% CI: 1.42-2.34]; all eight ID exceeded 0.1% prevalence. Of those testing HIV positive, 83% were male, 58% identified as MSM and 9% were injecting drug users. Twenty percent reported previously having potentially HIV-related symptoms and 52% had previously tested HIV negative (median time since last test: 1.58 years); which together with the median CD4 count at diagnosis (400 cell/uL) adds weight to this strategy being effective in diagnosing HIV at an earlier stage. A positive test was more likely for non-white individuals, MSM, injecting drug users and those testing in non-Northern regions. HIDES I describes an effective strategy to detect undiagnosed HIV infection. All eight ID fulfilled the >0.1% criterion for cost effectiveness. All individuals presenting to any health care setting with one of these ID should be strongly recommended an HIV test. A strategy is being developed in collaboration with ECDC and WHO Europe to guide the implementation of this novel public health initiative across Europe.

15 Article Health care index score and risk of death following tuberculosis diagnosis in HIV-positive patients. 2013

Podlekareva, D N / Grint, D / Post, F A / Mocroft, A / Panteleev, A M / Miller, R F / Miro, J M / Bruyand, M / Furrer, H / Riekstina, V / Girardi, E / Losso, M H / Caylá, J A / Malashenkov, E A / Obel, N / Skrahina, A M / Lundgren, J D / Kirk, O / Anonymous2230747. ·Copenhagen HIV Programme, University of Copenhagen, Denmark. dpo@cphiv.dk ·Int J Tuberc Lung Dis · Pubmed #23317955.

ABSTRACT: OBJECTIVES: To assess health care utilisation for patients co-infected with TB and HIV (TB-HIV), and to develop a weighted health care index (HCI) score based on commonly used interventions and compare it with patient outcome. METHODS: A total of 1061 HIV patients diagnosed with TB in four regions, Central/Northern, Southern and Eastern Europe and Argentina, between January 2004 and December 2006 were enrolled in the TB-HIV study. A weighted HCI score (range 0-5), based on independent prognostic factors identified in multivariable Cox models and the final score, included performance of TB drug susceptibility testing (DST), an initial TB regimen containing a rifamycin, isoniazid and pyrazinamide, and start of combination antiretroviral treatment (cART). RESULTS: The mean HCI score was highest in Central/Northern Europe (3.2, 95%CI 3.1-3.3) and lowest in Eastern Europe (1.6, 95%CI 1.5-1.7). The cumulative probability of death 1 year after TB diagnosis decreased from 39% (95%CI 31-48) among patients with an HCI score of 0, to 9% (95%CI 6-13) among those with a score of ≥4. In an adjusted Cox model, a 1-unit increase in the HCI score was associated with 27% reduced mortality (relative hazard 0.73, 95%CI 0.64-0.84). CONCLUSIONS: Our results suggest that DST, standard anti-tuberculosis treatment and early cART may improve outcome for TB-HIV patients. The proposed HCI score provides a tool for future research and monitoring of the management of TB-HIV patients. The highest HCI score may serve as a benchmark to assess TB-HIV management, encouraging continuous health care improvement.

16 Article Platelet count kinetics following interruption of antiretroviral treatment. 2013

Zetterberg, Eva / Neuhaus, Jacqueline / Baker, Jason V / Somboonwit, Charurut / Llibre, Josep M / Palfreeman, Adrian / Chini, Maria / Lundgren, Jens D / Anonymous1180738. ·Copenhagen University Hospital/Rigshospitalet and University of Copenhagen, Denmark. ·AIDS · Pubmed #23018440.

ABSTRACT: OBJECTIVES: To investigate the mechanisms of platelet kinetics in the Strategies for Management of Antiretroviral Therapy (SMART) study that demonstrated excess mortality with CD4 guided episodic antiretroviral therapy (ART) drug conservation compared with continuous treatment viral suppression. Follow-up analyses of stored plasma samples demonstrated increased activation of both inflammatory and coagulation pathways after stopping ART. DESIGN: SMART patients from sites that determined platelets routinely. METHODS: Platelet counts were retrospectively collected from 2206 patients from visits at study entry, and during follow-up. D-dimer levels were measured at study entry, month 1, and 2. RESULTS: Platelet levels decreased in the drug conservation group following randomization, but remained stable in the viral suppression group [median (IQR) decline from study entry to month 4: -24 000/μl (-54 000 to 4000) vs. 3000 (-22 000 to 24 000), respectively, P < 0.0001)] and the rate of developing thrombocytopenia (<100 000/μl) was significantly higher in the drug conservation vs. the viral suppression arm (unadjusted drug conservation/viral suppression [HR (95%CI) = 1.8 (1.2-2.7)]. The decline in platelet count among drug conservation participants on fully suppressive ART correlated with the rise in D-dimer from study entry to either month 1 or 2 (r = -0.41; P = 0.02). Among drug conservation participants who resumed ART 74% recovered to their study entry platelet levels. CONCLUSION: Interrupting ART increases the risk of thrombocytopenia, but reinitiation of ART typically reverses it. Factors contributing to declines in platelets after interrupting ART may include activation of coagulation pathways or HIV-1 replication itself. The contribution of platelets in HIV-related procoagulant activity requires further study.

17 Article Regional differences in AIDS and non-AIDS related mortality in HIV-positive individuals across Europe and Argentina: the EuroSIDA study. 2012

Reekie, Joanne / Kowalska, Justyna D / Karpov, Igor / Rockstroh, Jurgen / Karlsson, Anders / Rakhmanova, Aza / Horban, Andrzej / Kirk, Ole / Lundgren, Jens D / Mocroft, Amanda / Anonymous5070734. ·Medical School, University College London, London, United Kingdom. j.reekie@ucl.ac.uk ·PLoS One · Pubmed #22911841.

ABSTRACT: BACKGROUND: Differences in access to care and treatment have been reported in Eastern Europe, a region with one of the fastest growing HIV epidemics, compared to the rest of Europe. This analysis aimed to establish whether there are regional differences in the mortality rate of HIV-positive individuals across Europe, and Argentina. METHODS: 13,310 individuals under follow-up were included in the analysis. Poisson regression investigated factors associated with the risk of death. FINDINGS: During 82,212 person years of follow-up (PYFU) 1,147 individuals died (mortality rate 14.0 per 1,000 PYFU (95% confidence interval [CI] 13.1-14.8). Significant differences between regions were seen in the rate of all-cause, AIDS and non-AIDS related mortality (global p<0.0001 for all three endpoints). Compared to South Europe, after adjusting for baseline demographics, laboratory measurements and treatment, a higher rate of AIDS related mortality was observed in East Europe (IRR 2.90, 95%CI 1.97-4.28, p<.0001), and a higher rate of non-AIDS related mortality in North Europe (IRR 1.51, 95%CI 1.24-1.82, p<.0001). The differences observed in North Europe decreased over calendar-time, in 2009-2011, the higher rate of non-AIDS related mortality was no longer significantly different to South Europe (IRR 1.07, 95%CI 0.66-1.75, p = 0.77). However, in 2009-2011, there remained a higher rate of AIDS-related mortality (IRR 2.41, 95%CI 1.11-5.25, p = 0.02) in East Europe compared to South Europe in adjusted analysis. INTERPRETATIONS: There are significant differences in the rate of all-cause mortality among HIV-positive individuals across different regions of Europe and Argentina. Individuals in Eastern Europe had an increased risk of mortality from AIDS related causes and individuals in North Europe had the highest rate of non-AIDS related mortality. These findings are important for understanding and reviewing HIV treatment strategies and policies across the European region.

18 Article Hepatitis B and C co-infection are independent predictors of progressive kidney disease in HIV-positive, antiretroviral-treated adults. 2012

Mocroft, Amanda / Neuhaus, Jacqueline / Peters, Lars / Ryom, Lene / Bickel, Markus / Grint, Daniel / Koirala, Janak / Szymczak, Aleksandra / Lundgren, Jens / Ross, Michael J / Wyatt, Christina M / Anonymous5030734 / Anonymous5040734. ·Research Department of Infection and Population Health, University College London Medical School, London, United Kingdom. ·PLoS One · Pubmed #22911697.

ABSTRACT: TRIAL REGISTRATION: ClinicalTrials.gov NCT00027352; NCT00004978.

19 Article Hepatitis C virus viremia increases the incidence of chronic kidney disease in HIV-infected patients. 2012

Peters, Lars / Grint, Daniel / Lundgren, Jens D / Rockstroh, Jürgen K / Soriano, Vincent / Reiss, Peter / Grzeszczuk, Anna / Sambatakou, Helen / Mocroft, Amanda / Kirk, Ole / Anonymous1560731. ·Copenhagen HIV Programme, University of Copenhagen, Copenhagen, Denmark. lpe@cphiv.dk ·AIDS · Pubmed #22781222.

ABSTRACT: BACKGROUND: Several studies have reported on an association between hepatitis C virus (HCV) antibody status and the development of chronic kidney disease (CKD), but the role of HCV viremia and genotype are not well defined. METHODS: Patients with at least three serum creatinine measurements after 1 January 2004 and known HCV antibody status were included. Baseline was defined as the first eligible estimated glomerular filtration rate (eGFR) (Cockcroft-Gault equation), and CKD was either a confirmed (>3 months apart) eGFR of 60 ml/min per 1.73 m or less for patients with a baseline eGFR more than 60 ml/min per 1.73 m or a confirmed 25% decline in eGFR for patients with a baseline eGFR of 60 ml/min per 1.73 m or less. Incidence rates of CKD were compared between HCV groups (anti-HCV-negative, anti-HCV-positive with or without viremia) using Poisson regression. RESULTS: Of 8235 patients with known anti-HCV status, 2052 (24.9%) were anti-HCV-positive of whom 983 (47.9%) were HCV-RNA-positive, 193 (9.4%) HCV-RNA-negative and 876 (42.7%) had unknown HCV-RNA. At baseline, the median eGFR was 97.6 (interquartile range 83.8-113.0) ml/min per 1.73 m. During 36123 person-years of follow-up (PYFU), 495 patients progressed to CKD (6.0%) with an incidence rate of 14.5 per 1000 PYFU (95% confidence interval 12.5-14.9). In a multivariate Poisson model, patients who were anti-HCV-positive with HCV viremia had a higher incidence rate of CKD, whereas patients with cleared HCV infection had a similar incidence rate of CKD compared with anti-HCV-negative patients. There was no association between CKD and HCV genotype. CONCLUSION: Compared with HIV-monoinfected patients, HIV-positive patients with chronic rather than cleared HCV infection were at increased risk of developing CKD, suggesting a contribution from active HCV infection toward the pathogenesis of CKD.

20 Article Partners of people on ART - a New Evaluation of the Risks (The PARTNER study): design and methods. 2012

Rodger, Alison / Bruun, Tina / Weait, Matthew / Vernazza, Pietro / Collins, Simon / Estrada, Vicente / Lunzen, Jan Van / Corbelli, Giulio Maria / Lampe, Fiona / Phillips, Andrew / Lundgren, Jens / Anonymous670724. ·Research Department of Infection & Population Health, University College London, London, UK. alison.rodger@ucl.ac.uk ·BMC Public Health · Pubmed #22520171.

ABSTRACT: BACKGROUND: It is known that being on antiretroviral therapy reduces the risk of HIV transmission through sex. However it remains unknown what the absolute level of risk of transmission is in a person on ART with most recent measured HIV plasma viral load<50 c/mL in the absence of condom use. There are no data on risk of transmission for anal sex in MSM when the index partner is on ART. METHODS/DESIGN: The PARTNER study is an international, observational multi-centre study, taking place from 2010 to 2014 in which HIV serodifferent partnerships who at enrolment reported recently having had condom-less vaginal or anal sexual intercourse are followed over time, with 46 monthly reporting of transmission risk behaviour through a confidential self completed risk behaviour questionnaire and with 46 monthly HIV testing for the HIV negative partner. The objective is to study (i) the risk of HIV transmission to partners, in particular in partnerships that continue not to use condoms consistently and the HIV-positive partner is on therapy with a viral load<50 copies/mL and (ii) why some partnerships do not use condoms, to describe the proportion who begin to adopt consistent condom use, and factors associated with this. For any negative partner who becomes infected phylogenetic analysis will be used following anonymisation of the samples to assess if transmission had been from the HIV infected partner. DISCUSSION: This observational study will provide missing information on the absolute risk of HIV transmission for both vaginal and anal sex when the index case is on ART with a VL<50 copies/mL in the absence of condom use.

21 Article Projected life expectancy of people with HIV according to timing of diagnosis. 2012

Nakagawa, Fumiyo / Lodwick, Rebecca K / Smith, Colette J / Smith, Ruth / Cambiano, Valentina / Lundgren, Jens D / Delpech, Valerie / Phillips, Andrew N. ·HIV Epidemiology and Biostatistics Group, Research Department of Infection and Population Health, University College London, UK. f.nakagawa@ucl.ac.uk ·AIDS · Pubmed #22089374.

ABSTRACT: BACKGROUND AND OBJECTIVES: Effective antiretroviral therapy (ART) has contributed greatly toward survival for people with HIV, yet many remain undiagnosed until very late. Our aims were to estimate the life expectancy of an HIV-infected MSM living in a developed country with extensive access to ART and healthcare, and to assess the effect of late diagnosis on life expectancy. METHODS: A stochastic computer simulation model of HIV infection and the effect of ART was used to estimate life expectancy and determine the distribution of potential lifetime outcomes of an MSM, aged 30 years, who becomes HIV positive in 2010. The effect of altering the diagnosis rate was investigated. RESULTS: Assuming a high rate of HIV diagnosis (median CD4 cell count at diagnosis, 432  cells/μl), projected median age at death (life expectancy) was 75.0 years. This implies 7.0 years of life were lost on average due to HIV. Cumulative risks of death by 5 and 10 years after infection were 2.3 and 5.2%, respectively. The 95% uncertainty bound for life expectancy was (68.0,77.3) years. When a low diagnosis rate was assumed (diagnosis only when symptomatic, median CD4 cell count 140  cells/μl), life expectancy was 71.5 years, implying an average 10.5 years of life lost due to HIV. CONCLUSION: If low rates of virologic failure observed in treated patients continue, predicted life expectancy is relatively high in people with HIV who can access a wide range of antiretrovirals. The greatest risk of excess mortality is due to delays in HIV diagnosis.

22 Article Hepatitis delta in HIV-infected individuals in Europe. 2011

Soriano, Vincent / Grint, Daniel / d'Arminio Monforte, Antonella / Horban, Andrzej / Leen, Clifford / Poveda, Eva / Antunes, Francisco / de Wit, Stephane / Lundgren, Jens / Rockstroh, Juergen / Peters, Lars. ·Department of Infectious Diseases, Hospital Carlos III, Madrid, Spain. vsoriano@dragonet.es ·AIDS · Pubmed #21857493.

ABSTRACT: BACKGROUND: Hepatitis delta virus (HDV) infection results in the most aggressive form of chronic viral hepatitis. There is scarce information about the prevalence, epidemiology, virological profile and natural history of hepatitis delta in HIV patients. METHODS: From 16,597 HIV patients enrolled in EuroSIDA, 1319 (7.9%) have ever reported serum hepatitis B virus (HBV) surface antigen (HBsAg)-positive. At last follow-up, 1084 (6.5%) patients were HBsAg-positive. The HDV substudy was carried out in 422 individuals for whom stored sera were available at the time they were HBsAg-positive. Anti-HDV immunoglobulin G was assessed using a commercial enzyme immunoassay (EIA) and serum HDV-RNA was quantified using a real-time PCR method. RESULTS: A total of 61 of 422 HBsAg-positive carriers were anti-HDV-positive (prevalence: 14.5%). Hepatitis delta predominated in intravenous drug users and for this reason in south and/or east Europe. Serum HDV-RNA was detectable in 87% of tested anti-HDV-positive patients, with a median titer of 1.76×10(7) copies/ml. Overall, delta hepatitis patients showed lower serum HBV-DNA than the rest of HBsAg-positive carriers, although the inhibitory effect of HDV on HBV replication was not recognized in HBV genotype D patients. Whereas HDV was not associated with progression to AIDS, it significantly influenced the risk of death. CONCLUSION: The prevalence of anti-HDV in chronic HBsAg-positive/HIV carriers in EuroSIDA is 14.5%. Most of these patients exhibit detectable HDV viraemia. Viral interference between HBV and HDV is manifested in all but HBV genotype D carriers in whom overt coreplication of both viruses occurs which might result in enhanced liver damage. Overall, delta hepatitis increases the risk of liver-related deaths and overall mortality in HIV patients.

23 Article Estimated glomerular filtration rate, chronic kidney disease and antiretroviral drug use in HIV-positive patients. 2010

Mocroft, Amanda / Kirk, Ole / Reiss, Peter / De Wit, Stephane / Sedlacek, Dalibor / Beniowski, Marek / Gatell, Jose / Phillips, Andrew N / Ledergerber, Bruno / Lundgren, Jens D / Anonymous3220662. ·HIV Epidemiology and Biostatistics Group, Research Department of Infection and Population Health, Division of Population Health, University College London Medical School, Royal Free Campus, London, UK. a.mocroft@ucl.ac.uk ·AIDS · Pubmed #20523203.

ABSTRACT: OBJECTIVES: Chronic kidney disease (CKD) in HIV-positive persons might be caused by both HIV and traditional or non-HIV-related factors. Our objective was to investigate long-term exposure to specific antiretroviral drugs and CKD. DESIGN: A cohort study including 6843 HIV-positive persons with at least three serum creatinine measurements and corresponding body weight measurements from 2004 onwards. METHODS: CKD was defined as either confirmed (two measurements >or=3 months apart) estimated glomerular filtration rate (eGFR) of 60 ml/min per 1.73 m or below for persons with baseline eGFR of above 60 ml/min per 1.73 m or confirmed 25% decline in eGFR for persons with baseline eGFR of 60 ml/min per 1.73 m or less, using the Cockcroft-Gault formula. Poisson regression was used to determine factors associated with CKD. RESULTS: Two hundred and twenty-five (3.3%) persons progressed to CKD during 21 482 person-years follow-up, an incidence of 1.05 per 100 person-years follow-up [95% confidence interval (CI) 0.91-1.18]; median follow-up was 3.7 years (interquartile range 2.8-5.7). After adjustment for traditional factors associated with CKD and other confounding variables, increasing cumulative exposure to tenofovir [incidence rate ratio (IRR) per year 1.16, 95% CI 1.06-1.25, P < 0.0001), indinavir (IRR 1.12, 95% CI 1.06-1.18, P < 0.0001), atazanavir (IRR 1.21, 95% CI 1.09-1.34, P = 0.0003) and lopinavir/r (IRR 1.08, 95% CI 1.01-1.16, P = 0.030) were associated with a significantly increased rate of CKD. Consistent results were observed in wide-ranging sensitivity analyses, although of marginal statistical significance for lopinavir/r. No other antiretroviral drugs were associated with increased incidence of CKD. CONCLUSION: In this nonrandomized large cohort, increasing exposure to tenofovir was associated with a higher incidence of CKD, as was true for indinavir and atazanavir, whereas the results for lopinavir/r were less clear.

24 Article [Risk of virus transmission from well-treated patients with HIV?]. 2009

Gerstoft, Jan / Mathiesen, Lars / Lundgren, Jens D / Nielsen, Henrik I / Pedersen, Court / Obel, Niels / Laursen, Alex. ·Epidemiklinikken M 5132, Rigshospitalet, 2100 København Ø. gerstoft@rh.regionh.dk ·Ugeskr Laeger · Pubmed #19321080.

ABSTRACT: -- No abstract --

25 Minor Antiretroviral Therapy in Early HIV Infection. 2016

Lundgren, Jens / Babiker, Abdel G / Neaton, James D. · ·N Engl J Med · Pubmed #26816019.

ABSTRACT: -- No abstract --