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ABSTRACT: Tuberculosis (TB) and HIV comorbidity is a major challenge in TB prevention and control but difficult to assess in Germany as in other countries, where data confidentiality precludes notifying the HIV status of TB patients. We aimed to estimate the HIV-prevalence in TB patients in Germany, 2002-2009, and to characterize the HIV/TB patients demographically. Data from the long-term observational open multicentre cohort ClinSurv HIV were used to identify incident TB in HIV-positive individuals. We assessed the cohort's coverage for the nationwide HIV-positive population by contrasting ClinSurv HIV patients under antiretroviral therapy (ART) with national HIV patient numbers derived from ART prescriptions (data by Insight Health; available for 2006-2009). The HIV-prevalence in TB patients was calculated as the number of HIV/TB cases projected for Germany over all culture-positive TB notifications. From 2002 to 2009, 298 of 15,531 HIV-positive patients enrolled in the ClinSurv HIV cohort were diagnosed with TB. A 21% cohort coverage was determined. The annual estimates of the HIV-prevalence in TB patients were on average 4.5% and ranged from 3.5% (95%CI 2.3-5.1%) in 2007 to 6.6% (95%CI 5.0-8.5%) in 2005. The most recent estimate for 2009 was 4.0% (95%CI 2.6-5.9%). The 298 HIV/TB patients were characterized by a male-to-female ratio of 2.1, by a median age of 38 years at TB diagnosis, and by 59% of the patients having a foreign origin, mainly from Subsahara Africa. We provide, to our knowledge, the first estimate of the HIV-prevalence in TB patients for Germany by joint evaluation of anonymous HIV and TB surveillance data sources. The identified level of HIV in TB patients approximates available surveillance data from neighbouring countries and indicates a non-negligible HIV/TB burden in Germany. Our estimation approach is valuable for epidemiological monitoring of HIV/TB within the current legal frameworks.
PLoS ONE 01/2012; 7(11):e49111. · 4.09 Impact Factor
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Matthias Stoll, Christian Kollan,
Frank Bergmann,
Johannes Bogner,
Gerd Faetkenheuer,
Carlos Fritzsche,
Kirsten Hoeper,
Heinz-August Horst,
Jan van Lunzen,
Andreas Plettenberg,
Stefan Reuter,
Jürgen Rockstroh,
Hans-Jürgen Stellbrink,
Osamah Hamouda,
Barbara Bartmeyer
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ABSTRACT: BACKGROUND/AIM OF THE STUDY: The study aimed to determine the cost impacts of antiretroviral drugs by analysing a long-term follow-up of direct costs for combined antiretroviral therapy, cART, -regimens in the nationwide long-term observational multi-centre German HIV ClinSurv Cohort. The second aim was to develop potential cost saving strategies by modelling different treatment scenarios.
Antiretroviral regimens (ART) from 10,190 HIV-infected patients from 11 participating ClinSurv study centres have been investigated since 1996. Biannual data cART-initiation, cART-changes, surrogate markers, clinical events and the Centre of Disease Control- (CDC)-stage of HIV disease are reported. Treatment duration was calculated on a daily basis via the documented dates for the beginning and end of each antiretroviral drug treatment. Prices were calculated for each individual regimen based on actual office sales prices of the branded pharmaceuticals distributed by the license holder including German taxes.
During the 13-year follow-up period, 21,387,427 treatment days were covered. Cumulative direct costs for antiretroviral drugs of €812,877,356 were determined according to an average of €42.08 per day (€7.52 to € 217.70). Since cART is widely used in Germany, the costs for an entire regimen increased by 13.5%. Regimens are more expensive in the advanced stages of HIV disease. The potential for cost savings was calculated using non-nucleotide-reverse-transcriptase-inhibitor, NNRTI, more frequently instead of ritonavir-boosted protease inhibitor, PI/r, in first line therapy. This calculation revealed cumulative savings of 10.9% to 19.8% of daily treatment costs (50% and 90% substitution of PI/r, respectively). Substituting certain branded drugs by generic drugs showed potential cost savings of between 1.6% and 31.8%.
Analysis of the data of this nationwide study reflects disease-specific health services research and will give insights into the cost impacts of antiretroviral therapy, and might allow a more rational allocation of resources within the German health care system.
PLoS ONE 01/2011; 6(9):e23946. · 4.09 Impact Factor
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ABSTRACT: The aim of this study is to analyse the prevalence of transmitted drug resistance, TDR, and the impact of TDR on treatment success in the German HIV-1 Seroconverter Cohort.
Genotypic resistance analysis was performed in treatment-naïve study patients whose sample was available 1,312/1,564 (83.9% October 2008). A genotypic resistance result was obtained for 1,276/1,312 (97.3%). The resistance associated mutations were identified according to the surveillance drug resistance mutations list recommended for drug-naïve patients. Treatment success was determined as viral suppression below 500 copies/ml.
Prevalence of TDR was stable at a high level between 1996 and 2007 in the German HIV-1 Seroconverter Cohort (N = 158/1,276; 12.4%; CI(wilson) 10.7-14.3; p(for trend) = 0.25). NRTI resistance was predominant (7.5%) but decreased significantly over time (CI(Wilson): 6.2-9.1, p(for trend) = 0.02). NNRTI resistance tended to increase over time (NNRTI: 3.5%; CI(Wilson): 2.6-4.6; p(for trend)= 0.07), whereas PI resistance remained stable (PI: 3.0%; CI(Wilson): 2.1-4.0; p(for trend) = 0.24). Resistance to all drug classes was frequently caused by singleton resistance mutations (NRTI 55.6%, PI 68.4%, NNRTI 99.1%). The majority of NRTI-resistant strains (79.8%) carried resistance-associated mutations selected by the thymidine analogues zidovudine and stavudine. Preferably 2NRTI/1PIr combinations were prescribed as first line regimen in patients with resistant HIV as well as in patients with susceptible strains (susceptible 45.3%; 173/382 vs. resistant 65.5%; 40/61). The majority of patients in both groups were treated successfully within the first year after ART-initiation (susceptible: 89.9%; 62/69; resistant: 7/9; 77.8%).
Overall prevalence of TDR remained stable at a high level but trends of resistance against drug classes differed over time. The significant decrease of NRTI-resistance in patients newly infected with HIV might be related to the introduction of novel antiretroviral drugs and a wider use of genotypic resistance analysis prior to treatment initiation.
PLoS ONE 01/2010; 5(10):e12718. · 4.09 Impact Factor
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ABSTRACT: AIDS-related lymphoma contributes to significant morbidity and mortality among human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART). We assessed the predictive role of cumulative HIV viremia and other risk factors in the development of AIDS-related non-Hodgkin lymphoma.
Data from the Clinical Surveillance of HIV Disease (ClinSurv) study, an ongoing, observational, open cohort study of HIV-infected patients from different urban areas in Germany, were analyzed using a Cox proportional hazards model.
In the Cox model, which comprised 6022 patients and 27,812 patient-years of follow-up while patients were receiving HAART from 1999 through 2006, cumulative HIV viremia was found to be independently associated with the risk of lymphoma (hazard ratio, [HR], 1.67 [95% confidence interval {CI}, 1.27-2.20]) (P < .001]). This association differed markedly between lymphoma subtypes. Although the association was more pronounced for Burkitt-type lymphoma (HR, 3.45 [95% CI, 1.52-7.85]) (P = .003), there was no association between cumulative HIV viremia and the incidence of primary central nervous system lymphoma (HR, 1.00 [95% CI, 0.39-2.57]) (P = .997). Other risk factors associated with an increased risk in a multivariable analysis included the latest CD4 T cell count as well as age per 10-year increment.
Cumulative HIV viremia is an independent and strong predictor of AIDS-related lymphoma among patients receiving HAART. The influence of cumulative HIV viremia may differ between lymphoma subtypes.
The Journal of Infectious Diseases 08/2009; 200(1):79-87. · 6.41 Impact Factor
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ABSTRACT: Measuring prevalence and incidence of sexually transmitted infections in hard to reach populations like men who have sex with men (MSM) is hampered by unknown size and regional distribution of this population. Community sample- and study-based measurements are often fraught with participation biases and do not allow generalization of the results for other regions or the whole population group of MSM.
We used the proportional regional distribution of participants of large internet-based surveys among MSM from Germany together with a general population survey-derived estimate of the MSM population to estimate regional population sizes. Based on transmission group category from surveillance data and regional MSM population size we calculated regional population-specific incidence rates of newly diagnosed HIV infection and syphilis. For HIV prevalence we compared estimates of prevalent HIV infections in MSM from a surveillance data-based model with a mixed model in which we used the proportional regional distribution of HIV positive participants from surveys and the estimated total number of prevalent HIV infections from the surveillance based model.
Assuming a similar regional distribution of survey participants and the MSM population as a whole, the regional proportion of MSM in the general population can be estimated. Regional incidence calculated with the estimated MSM population as denominator and national surveillance data as numerator results in regional peak incidence rates of 7-8 per 1,000 MSM for newly diagnosed HIV infection and syphilis. The gradient between metropolitan and rural areas narrows considerably compared with calculations which use the total (male) population as denominator. Regional HIV prevalence estimates are comparable in the two models.
Considering the difficulties to obtain regionally representative data by other sampling methods for MSM, in Western post-industrialized countries internet-based surveys may provide an easy and low cost tool to estimate regional population distributions. With national surveillance data, which categorize transmission groups, regional population-specific incidence rates for reportable sexually transmitted infections can be estimated. HIV prevalence estimates for regional MSM populations show differences related to the level of urbanization, MSM concentration, and starting points of the HIV epidemic in western and eastern Germany.
BMC Public Health 07/2009; 9:181. · 2.00 Impact Factor
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ABSTRACT: Zwischen dem Zeitpunkt der Infektion und dem Zeitpunkt der Diagnose der HIV-Infektion vergeht in aller Regel ein individuell unterschiedlich langer Zeitraum von oftmals mehreren Jahren. Die Meldedaten über HIV-Neudiagnosen erlauben daher keinen direkten Rückschluss auf den Infektionszeitpunkt. Die tatsächliche Zahl der HIV-Neuinfektionen (HIV-Inzidenz) und der zurückliegende Verlauf der HIV-Epidemie in Deutschland können bis zum Zeitraum der frühen 1990er-Jahre mit Hilfe von Rückrechnungsmodellen beschrieben werden. Zur Beschreibung des aktuellen Verlaufes der HIV-Epidemie muss man sich unter Berücksichtigung anderer Datenquellen überwiegend auf die Meldungen der HIV-Neudiagnosen stützen. Auf dieser Grundlage kann davon ausgegangen werden, dass die Zahl der jährlichen HIV-Neuinfektionen in Deutschland ihren Höhepunkt in den frühen 1980er-Jahren erreicht hat und seit Anfang der 1990er-Jahre relativ stabil zwischen 2000 und 2500 pro Jahr lag. Größte Betroffenengruppe sind nach wie vor Männer, die Sex mit Männern haben, gefolgt von heterosexuell Infizierten und Migranten aus Hochprävalenzregionen. I.v.-Drogengebraucher haben zahlenmäßig über die Jahre abgenommen und belegen den vierten Rang. Aktuell gibt es Anzeichen dafür, dass eine Zunahme von Risikoverhalten sowie die Zunahme anderer sexuell übertragbarer Infektionen in Verbindung mit Veränderungen in Bezug auf den Zeitpunkt des Therapiebeginns zu einem Anstieg der HIV-Neuinfektionen geführt haben. Zur frühzeitigen Erfassung einer Änderung des Risikoverhaltens wäre eine Verbesserung der epidemiologischen Erfassung weiterer sexuell übertragbarer Infektionen in Verbindung mit Erhebungen zum Verhalten im Sinne einer „Second Generation Surveillance“ wünschenswert. The course of the HIV epidemic in Germany can be modelled by back calculation until the beginning of the nineties. The recent course of the epidemic can only be derived from surveillance data of newly diagnosed HIV infections in conjunction with other data sources. Based on these surveillance data HIV incidence in Germany can be estimated to have been stable with 2000 to 2500 new infections per year since the early nineties, after having peaked in the early eighties. The most affected group are men who have sex with men followed by persons infected by heterosexual contact and migrants from high prevalence countries. The number of intravenous drug users has declined over the years and is now in fourth place. There are indications that increased risk behaviour and rising numbers of other sexually transmitted infections together with a change towards later initiation of antiretroviral therapy has led to an increase in new HIV infections in Germany in recent years. An improvement of the epidemiological surveillance for “indicator” STIs in combination with the assessment of risk behaviours in high risk groups would be desirable steps towards a second generation surveillance in Germany.
