Objective: The aim of this study was to investigate introductions and spread of different HIV-1 subtypes in the Netherlands. Design: We identified distinct HIV-1 transmission chains in the... Show moreObjective: The aim of this study was to investigate introductions and spread of different HIV-1 subtypes in the Netherlands. Design: We identified distinct HIV-1 transmission chains in the Netherlands within the global epidemic context through viral phylogenetic analysis of partial HIV-1 polymerase sequences from individuals enrolled in the ATHENA national HIV cohort of all persons in care since 1996, and publicly available international background sequences. Methods: Viral lineages circulating in the Netherlands were identified through maximum parsimony phylogeographic analysis. The proportion of HIV-1 infections acquired in-country among heterosexuals and MSM was estimated from phylogenetically observed, national transmission chains using a branching process model that accounts for incomplete sampling. Results: As of 1 January 2019, 2589 (24%) of 10 971 (41%) HIV-1 sequenced individuals in ATHENA had non-B subtypes (A1, C, D, F, G) or circulating recombinant forms (CRF01AE, CRF02AG, CRF06-cpx). The 1588 heterosexuals were in 1224, and 536 MSM in 270 phylogenetically observed transmission chains. After adjustments for incomplete sampling, most heterosexual (75%) and MSM (76%) transmission chains were estimated to include only the individual introducing the virus (size = 1). Onward transmission occurred mostly in chains size 2-5 amongst heterosexuals (62%) and in chains size at least 10 amongst MSM (64%). Considering some chains originated in-country from other risk-groups, 40% (95% confidence interval: 36-44) of non-B-infected heterosexuals and 62% (95% confidence interval: 49-73) of MSM-acquired infection in-country. Conclusion: Although most HIV-1 non-B introductions showed no or very little onward transmission, a considerable proportion of non-B infections amongst both heterosexuals and MSM in the Netherlands have been acquired in-country. Show less
Reitsema, M.; Hoek, A.J. van; Loeff, M.S. van der; Hoornenborg, E.; Sighem, A. van; Wallinga, J.; ... ; Xiridou, M. 2020
Objectives: To assess the impact of a preexposure prophylaxis (PrEP) programme for high-risk men who have sex with men (MSM), which includes gonorrhoea testing and treatment, on the transmission of... Show moreObjectives: To assess the impact of a preexposure prophylaxis (PrEP) programme for high-risk men who have sex with men (MSM), which includes gonorrhoea testing and treatment, on the transmission of HIV and Neisseria among MSM in the Netherlands and the cost-effectiveness of such programme with and without risk compensation (in the form of reduced condom use). Methods: We developed a stochastic agent-based transmission model of HIV and gonorrhoea. We simulated a capped (max 2.5% of MSM) and uncapped (5.5% of MSM in 2018 declining to 3% in 2027) daily PrEP programme for high-risk MSM, with 3-monthly HIV and gonorrhoea testing, with and without risk compensation. Epidemiological outcomes were calculated from the transmission model and used in an economic model to calculate costs, quality-adjusted life-years (QALY), and incremental cost-effectiveness ratios (ICER), over 2018-2027, taking a healthcare payer perspective. Results: Without risk compensation, PrEP can lead to a reduction of 61 or 49% in the total number of new HIV infections in 2018-2027, if the programme is uncapped or capped to 2.5% of MSM, respectively. With risk compensation, this reduction can be 63 or 46% in the uncapped and capped programmes, respectively. In all scenarios, gonorrhoea prevalence decreased after introducing PrEP. Without risk compensation, 92% of simulations were cost-effective (of which 52% cost-saving). With risk compensation, 73% of simulations were cost-effective (of which 23% was cost-saving). Conclusion: A nationwide PrEP programme for high-risk MSM can result in substantial reductions in HIV and gonorrhoea transmission and be cost-effective, even with risk compensation. Show less
Objective:Successful treatment of people infected with HIV requires that patients are retained in HIV care, use combination antiretroviral therapy (cART) and ultimately reach and sustain viral... Show moreObjective:Successful treatment of people infected with HIV requires that patients are retained in HIV care, use combination antiretroviral therapy (cART) and ultimately reach and sustain viral suppression. Our aim was to identify health facility characteristics associated with these steps in the cascade of HIV care.Design:Retrospective cohort study.Methods:We included data from all adult HIV-1-infected patients who entered care in the Netherlands between 2007 and 2013 (N=7120). Multivariate logistic regression was used to examine the associations between health facility characteristics and the outcomes currently in care', initiated cART', and viral suppression'.Results:The proportion of patients currently in care' was high in all 26 treatment centres. cART initiation was positively associated with the accreditation of the health facility [OR (odds ratio): 1.62; 95% CI (confidence interval): 1.18-2.23] and the performance of an internal audit in the preceding 3 years (OR: 1.36; 95% CI: 1.02-1.81). The odds of cART initiation were higher in middle-sized (OR: 2.00; 95% CI: 1.25-3.21) and large HIV treatment centres (OR: 1.80; 95% CI: 1.14-2.84) compared with small centres (<300 HIV-infected patients). Viral suppression was negatively associated with the presence of a social worker in the HIV treatment team (OR: 0.62; 95% CI: 0.43-0.91).Conclusions:Our results confirm that appointing expert HIV treatment centres facilitates retention in care and that a minimum volume requirement may be desirable. Our findings suggest that quality assessment through accreditation and the measurement of performance benefits the delivery of HIV care. Copyright (C) 2016 Wolters Kluwer Health, Inc. All rights reserved. Show less
Background: Early diagnosis of HIV-1 infection will probably beneficially impact onward transmission and life expectancy. We compared mortality rates and CD4 cell counts at start of combination... Show moreBackground: Early diagnosis of HIV-1 infection will probably beneficially impact onward transmission and life expectancy. We compared mortality rates and CD4 cell counts at start of combination antiretroviral therapy (cART) in patients with different frequencies of diagnostic testing for HIV. Methods: Patients infected with HIV-1 through sexual contact and in follow-up anytime from 2004 through 2008 were selected from the AIDS Therapy Evaluation in the Netherlands national observational HIV cohort and stratified into three groups: patients without a prior negative HIV antibody test (i.e., with a positive first-test result); patients with 1-2 years between the last negative and first positive test; and patients with less than 1 year between tests. Outcome measures were mortality from 2004 through 2008 and CD4 cell count at cART initiation. Results: Of 5494 patients, the mortality rate was highest among the 4067 patients with a positive first test (1.33/100 person-years) and the adjusted relative risk of mortality was 0.50 in 561 patients with tests 1-2 years apart (P = 0.04 compared to patients with a positive first test) and 0.49 (P = 0.02) when tests were less than 1 year apart (n = 866). In patients with a positive first test, 48% had CD4 cell counts less than 200 cells/mu l at cART initiation; this proportion was 23-26% in the two groups of repeatedly tested patients (adjusted odds ratio compared to patients with a positive first test 0.43 and 0.37, respectively; both P < 0.0001). Conclusion: Frequent repeated testing for HIV may improve the rate of timely diagnosis and treatment, thereby preventing disease progression. (c) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins Show less
Sighem, A. van; Gras, L.; Reiss, P.; Brinkman, K.; Wolf, F. de; ATHENA Natl Observational Cohort S 2010
Objective: To compare life expectancies between recently diagnosed HIV-infected patients and age and sex-matched uninfected individuals from the general population. Design: National observational... Show moreObjective: To compare life expectancies between recently diagnosed HIV-infected patients and age and sex-matched uninfected individuals from the general population. Design: National observational HIV cohort in the Netherlands. Methods: Four thousand, six hundred and twelve patients diagnosed with HIV between 1998 and 2007 and still antiretroviral therapy-naive as of 24 weeks after diagnosis were selected. Progression to death compared to the age and sex-matched general population was studied with a multivariate hazards model in 4174 (90.5%) patients without AIDS events at 24 weeks. Life expectancy and number of life years lost were calculated using the predicted survival distribution. Results: During 17 580 person-years of follow-up since 24 weeks after diagnosis [median follow-up 3.3 years, interquartile range (IQR) 1.6-5.8], 118 deaths occurred, yielding a mortality rate of 6.7 [95% confidence interval (CI) 5.5-8.0] per 1000 person-years. Median CD4 cell counts at 24 weeks were 480 cells/mu l (IQR 360-650). According to the model, the median number of years lived from age 25 was 52.7 (IQR 44.2-59.3; general population 53.1) for men and 57.8 (49.2-63.7; 58.1) for women without CDC-B event. The number of life years lost varied between 0.4 if diagnosed with HIV at age 25 and 1.4 if diagnosed at age 55; for patients with a CDC-B event this range was 1.8-8.0 years. Conclusion: The life expectancy of asymptomatic HIV-infected patients who are still treatment-naive and have not experienced a CDC-B or C event at 24 weeks after diagnosis approaches that of non-infected individuals. However, follow-up time is short compared to the expected number of years lived. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins Show less
Luin, M. van; Ende, M.E. van der; Richter, C.; Visser, M.; Faraj, D.; Ven, A. van der; ... ; Burger, D.M. 2010
HIV-infected travellers frequently use atovaquone/ proguanil as malaria prophylaxis. We compared atovaquone/ proguanil pharmacokinetics between healthy volunteers and HIV-infected patients taking... Show moreHIV-infected travellers frequently use atovaquone/ proguanil as malaria prophylaxis. We compared atovaquone/ proguanil pharmacokinetics between healthy volunteers and HIV-infected patients taking efavirenz, lopinavir/ ritonavir or atazanavir/ritonavir. The geometric mean ratio (95% confidence interval) area under the curve (AUC)(0 -> t) for atovaquone relative to the healthy volunteers was 0.25 (0.16-0.38), 0.26 (0.17-0.41) and 0.54 (0.350.83) for patients on efavirenz, lopinavir/ ritonavir and atazanavir/ ritonavir, respectively. Proguanil plasma concentrations were also significantly lower (38-43%). Physicians should be alert for atovaquone/ proguanil prophylaxis failures in patients taking efavirenz, lopinavir/ ritonavir or atazanavir/ ritonavir. Show less
Bezemer, D.; Sighem, A. van; Lukashov, V.V.; Hoek, L. van der; Back, N.; Schuurman, R.; ... ; ATHENA Observational Cohort 2010
Objective: To obtain insight in the HIV-1 transmission networks among men having sex with men (MSM) in the Netherlands. Design: A phylogenetic tree was constructed from polymerase sequences... Show moreObjective: To obtain insight in the HIV-1 transmission networks among men having sex with men (MSM) in the Netherlands. Design: A phylogenetic tree was constructed from polymerase sequences isolated from 2877 HIV-1 subtype B-infected patients monitored as part of the AIDS Therapy Evaluation in the Netherlands (ATHENA) nationwide observational cohort. Methods: For MSM with a known date of infection, the most similar sequences were selected as potential transmission pairs when they clustered with bootstrap value of at least 99%. Time from infection to onward transmission was estimated as the Median time between dates of infection for each transmission pair. The source of infections with a resistant strain was traced using the entire phylogenetic tree. Results: Of sequences from 403 MSM with a known date of infection between 1987 and 2007, 175 (43%) formed 63 clusters. Median time to onward transmission was 1.4 years (interquartile range 0.6-2.7). Twenty-four (6%) MSM carried a virus with resistance-related mutations, 13 of these were in eight clusters together with sequences from 28 other patients in the entire phylogenetic tree. Six clusters contained sequences obtained from 29 men all presenting the same resistance-related mutations. Conclusion: From our selection of likely transmission pairs, we conclude that onward transmission of HIV-1 from infected MSM in the Netherlands happens both during and after primary infection. Transmission of resistant strains from the antiretroviral therapy-treated population is limited, but strains with resistance-related mutations have formed subepidemics. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins Show less
Worm, S.W.; Friis-Moller, N.; Bruyand, M.; Monforte, A.D.; Rickenbach, M.; Reiss, P.; ... ; DAD Study Grp 2010
Introduction: This study describes the characteristics of the metabolic syndrome in HIV-positive patients in the Data Collection on Adverse Events of Anti-HIV Drugs study and discusses the impact... Show moreIntroduction: This study describes the characteristics of the metabolic syndrome in HIV-positive patients in the Data Collection on Adverse Events of Anti-HIV Drugs study and discusses the impact of different methodological approaches on estimates of the prevalence of metabolic syndrome over time. Methods: We described the prevalence of the metabolic syndrome in patients under follow-up at the end of six calendar periods from 2000 to 2007. The definition that was used for the metabolic syndrome was modified to take account of the use of lipid-lowering and anti hypertensive medication, measurement variability and missing values, and assessed the impact of these modifications on the estimated prevalence. Results: For all definitions considered, there was an increasing prevalence of the metabolic syndrome over time, although the prevalence estimates themselves varied widely. Using our primary definition, we found an increase in prevalence from 19.4% in 200012001 to 41.6% in 2006/2007. Modification of the definition to incorporate antihypertensive and lipid-lowering medication had relatively little impact on the prevalence estimates, as did modification to allow for missing data. In contrast, modification to allow the metabolic syndrome to be reversible and to allow for measurement variability lowered prevalence estimates substantially. Discussion: The prevalence of the metabolic syndrome in cohort studies is largely based on the use of nonstandardized measurements as they are captured in daily clinical care. As a result, bias is easily introduced, particularly when measurements are both highly variable and may be missing. We suggest that the prevalence of the metabolic syndrome in cohort studies should be based on two consecutive measurements of the laboratory components in the syndrome definition. (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins Show less
OBJECTIVE To estimate the effect of combined antiretroviral therapy (cART) on mortality among HIV-infected individuals after appropriate adjustment for time-varying confounding by indication.... Show moreOBJECTIVE To estimate the effect of combined antiretroviral therapy (cART) on mortality among HIV-infected individuals after appropriate adjustment for time-varying confounding by indication. DESIGN A collaboration of 12 prospective cohort studies from Europe and the United States (the HIV-CAUSAL Collaboration) that includes 62 760 HIV-infected, therapy-naive individuals followed for an average of 3.3 years. Inverse probability weighting of marginal structural models was used to adjust for measured confounding by indication. RESULTS Two thousand and thirty-nine individuals died during the follow-up. The mortality hazard ratio was 0.48 (95% confidence interval 0.41-0.57) for cART initiation versus no initiation. In analyses stratified by CD4 cell count at baseline, the corresponding hazard ratios were 0.29 (0.22-0.37) for less than 100 cells/microl, 0.33 (0.25-0.44) for 100 to less than 200 cells/microl, 0.38 (0.28-0.52) for 200 to less than 350 cells/microl, 0.55 (0.41-0.74) for 350 to less than 500 cells/microl, and 0.77 (0.58-1.01) for 500 cells/microl or more. The estimated hazard ratio varied with years since initiation of cART from 0.57 (0.49-0.67) for less than 1 year since initiation to 0.21 (0.14-0.31) for 5 years or more (P value for trend <0.001). CONCLUSION We estimated that cART halved the average mortality rate in HIV-infected individuals. The mortality reduction was greater in those with worse prognosis at the start of follow-up. Show less
Burg, S.H. van der; Klein, M.R.; Velde, C.J.H. van de; Kast, W.M.; Miedema, F.; Melief, C.J.M. 1995
