The denominator problem: Estimating MSM-specific incidence of sexually transmitted infections and prevalence of HIV using population sizes of MSM derived from Internet surveys

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Cost-savings and potential cost-savings through the distribution of generic antiretroviral drugs within the statutory health insurance market of Germany between January 2017 and June 2019

Background: Recent patent losses for antiretroviral drugs (ARV) have led to the debate of cost-saving through the replacement of patented drugs with generic drugs. The split of recommended single-tablet regimens (STR) into their single substance partners is one of the considerations mentioned in said debate. Particularly, generic tenofovir disoproxil/emtricitabine (TDF/FTC) is expected to hold untapped cost-saving potential, which may curb increasing overall expenditures for combined antiretroviral therapy (cART) within the statutory health insurance (SHI) of Germany. Methods: Data of ARV reimbursed by the SHI were used to describe the trends of defined daily doses (DDD) as well as the revenue within the German ARV market. They were also used to determine the cost-savings of moving to generic drugs. The time period observed was between January 2017 and June 2019. The potential cost-savings were determined with following assumption in mind: the maximum possible use of generic ARV, including 1) the split of STR and replacing all substance partners with generic ones, and 2) replacing patented tenofovir alafenamide/emtricit- abine (TAF/FTC) with generic TDF/FTC. Results: Throughout the observation period, the DDD of generic ARV increased nearly five-fold while their revenue increased more than four-fold. Total cost-saving showed a sharp increase over the same period, with generic TDF/FTC accounting for a share of around 70%. The largest potential cost-saving could have been achieved through replacing patented TAF/FTC with generic TDF/FTC, peaking at nearly 10% of total revenue, but showing decreasing trends in general. Conclusion: The progressive distribution of generic ARV ensured increasing cost-savings, but consequently curbed the potential cost-savings. Unique price reductions of generic TDF/FTC have played a pivotal role for these effects. In any case, substituting with generic ARV should not fail to adhere to the treatment guidelines and continue to con- sider the medical requirements for the treatment.Peer Reviewe

Wie steht es um Long Acting-Therapie in Deutschland? – Zahlen zu Verordnungen von Cabotegravir in Deutschland

In Europa ist Cabotegravir (CAB) in Kombination mit Rilpivirin (RPV) seit Dezember 2020 zur dualen Injektionstherapie für die Behandlung von HIV-1-Infektionen bei Erwachsenen zugelassen. Zwei Anwendungsszenarien stehen zur Verfügung: Das einmonatliche Dosierschema mit 400 mg CAB und 600 mg RPV sowie das zweimonatliche Dosierschema mit 600 mg CAB und 900 mg RPV. Diese Therapieform wird auch als „Long Acting“ (LA) bezeichnet. Die Anwendung von langwirksamen HIV-Medikamenten birgt Vorteile im Bereich der HIV-Therapie und -Prävention. Es gibt aber auch Herausforderungen u. a. in Fragen zu Handhabbarkeit, Arzneimittelsicherheit, möglicher Resistenzentwicklung, Lagerbarkeit, Distributionswegen und Kostenabwägungen. Ziel der Untersuchung war es, die Anzahl der in Deutschland monatlich mit CAB-LA/RPV-LA behandelten Menschen mit HIV nach über zwei Jahren Marktverfügbarkeit zu ermitteln.Peer Reviewe

Increasing hepatitis B vaccination coverage and decreasing hepatitis B co-infection prevalence among people with HIV-1 in Germany, 1996–2019. Results from a cohort study primarily in men who have sex with men

Objectives Viral hepatitis co-infection among people living with HIV is known to accelerate the progression of liver disease and AIDS. An increased prevalence and incidence of hepatitis B virus (HBV) infection among people living with HIV demands continuous monitoring to adapt targeted prevention strategies to reach the global goals of eliminating viral hepatitis as a public health threat. Methods We determined the prevalence and incidence of HBV for the years 1996–2019 from yearly blood sample testing and questionnaire reports among people living with HIV belonging to a nationwide, multicentre observational, prospective cohort study. Results Among this study population of 3479 participants, the majority (87%) indicated that being men who have sex with men (MSM) was their likely HIV transmission route; 51% were recruited from Berlin. HBV prevalence for acute/chronic and resolved infections decreased from 4.1% and 45% in 1996–1999 to 1.3% and 16% in 2019, respectively. Simultaneously, participants with a serological status indicating HBV vaccination increased from 25% in 1996–1999 to 69% in 2019. Among vaccinated participants with relevant information (n = 1135), 38% received their first HBV vaccination after HIV infection. The HBV incidence rate in 565 eligible participants decreased from 6.9/100 person-years in 2004–2007 to 0.45/100 person-years in 2015. Conclusion Increasing vaccination coverage because of a general HBV vaccination recommendation and catch-up vaccination efforts among risk groups decreased HBV infection prevalence over time among this study population of people living with HIV, primarily MSM and from Berlin. Despite this success, the prevalence and incidence of HBV remains higher than in the general population in Germany. This emphasizes the need for continued HBV prevention by promoting HBV vaccination and HBV screening at regular intervals based on the individual risk behaviour.Peer Reviewe

Increasing Number of Individuals Receiving Hepatitis B nucleos(t)ide Analogs Therapy in Germany, 2008–2019

Background: Germany is a low prevalence country for hepatitis B virus (HBV) infection with higher prevalence in vulnerable groups. The number of treated chronic hepatitis B (CHB) patients is unknown. We aimed to determine the number of CHB patients treated with nucleos(t)ide analogs (NUCs), the treatment costs within the statutory health insurance (SHI) in Germany and per patient per month. Methods: Data on pharmacy bills of NUCs to patients with SHI between 2008 and 2019 were purchased from Insight Health™ and described. Negative binomial regression was used for trend analysis. Results: Number of patients increased between 2008 and 2019 (4.9% per year) with little changes in treatment options. Overall prescription costs were increasing (6.7% per year on average) until the introduction of tenofovir and entecavir generics in 2017 after which costs decreased by 31% in 2019. Average therapy costs peaked at 498 Euro per patient per month in 2016 and decreased to 214 Euro in 2019. Prescriptions changed from 30 to 90 pills per pack over time. HBV therapy was prescribed to 97% by three medical specialist groups, mainly specialists in internal medicine (63%), followed by hospital-based outpatient clinics (20%) and general practitioners (15%). Contrary to guideline recommendation, adefovir was still prescribed after 2011 for 1–5% of patients albeit with decreasing tendency. Prescriptions per 100,000 inhabitants were highest in Berlin and Hamburg. Conclusion: Our data shows, that the number of treated CHB patients increased steadily, while NUC therapy costs decreased. We recommend continued testing and treatment for those eligible to prevent advanced liver disease and possibly decrease further transmission of HBV.Peer Reviewe

Gemeldete HIV-Erstdiagnosen 2021 – 2022

Gemäß § 7 Abs. 3 Infektionsschutzgesetz (IfSG) ist der direkte oder indirekte Nachweis einer Infektion mit dem Humanen Immundefizienz-Virus (HIV) nichtnamentlich unmittelbar an das Robert Koch-Institut (RKI) zu melden. Dem RKI wurden für das Jahr 2021 insgesamt 2.258 gesicherte HIV-Neudiagnosen gemeldet und bis zum 1.5.2023 für das Jahr 2022 insgesamt 3.239 gesicherte HIV-Neudiagnosen. Im Vergleich dazu wurden dem RKI 2.468 gesicherte HIV-Neudiagnosen für das Jahr 2020 gemeldet. Dies entspricht einem Rückgang um 9 % von 2020 auf 2021 und einer Zunahme um 43% von 2021 auf 2022. Für das Meldejahr 2022 ist zu berücksichtigen, dass nach Februar 2022 in erheblichem Umfang HIV-Meldungen von aus der Ukraine nach Deutschland geflüchteten Personen erfolgten. Bei den meisten dieser Geflüchteten erfolgten die HIV-Diagnosen und der Behandlungsbeginn bereits in der Ukraine. Deshalb handelt es sich bei den meisten dieser Fälle nicht um tatsächliche Neudiagnosen einer HIV-Infektion, sondern um einen erstmaligen Nachweis in Deutschland. Von den 3.239 Neudiagnosen im Jahr 2022 entfal¬len 724 auf Menschen aus der Ukraine.Peer Reviewe

Completeness of tuberculosis case notifications in Germany in 2013–2017: first results of an inventory study

Background Evaluating the completeness of tuberculosis (TB) notification data is important for monitoring of TB surveillance systems. We conducted an inventory study to calculate TB underreporting in Germany in 2013–2017. Methods Acquisition of two pseudonymized case-based data sources (national TB notification data and antibiotic resistance surveillance data) was followed by two-source Capture-recapture (CRC) analysis, as case-based data from a third source was unavailable. Aggregated data on consumption of a key anti-TB drug (pyrazinamide [PZA]) was compared to an estimated need for PZA based on TB notification data to obtain an independent underreporting estimation. Additionally, notified TB incidence was compared to TB rate in an aggregated health insurance fund dataset. Results CRC and PZA-based approaches indicated that between 93 and 97% (CRC) and between 91 and 95% (PZA) of estimated cases were captured in the national TB notification data in the years 2013–2017. Insurance fund dataset did not indicate TB underreporting on the national level in 2017. Conclusions Our results suggest that more than 90% of estimated TB cases are captured within the German TB surveillance system, and accordingly the TB notification rate is likely a good proxy of the diagnosed TB incidence rate. An increase in underreporting and discrepancies however should be further investigated.Peer Reviewe

Zur Situation bei wichtigen Infektionskrankheiten in Deutschland – Virushepatitis C im Jahr 2020

Die Anzahl übermittelter HCV-Infektionen im Jahr 2020 ist im Vergleich zu den Vorjahren 2018 und 2019 deutlich abgefallen. Die Meldedaten von 2020 sind nach den grundsätzlichen Änderungen des Surveillancesystems und der Meldepflicht nur bedingt mit den Vorjahren vergleichbar und der beobachtete deutliche Rückgang der Infektionen kann durch mehrere Faktoren beeinflusst worden sein. Die COVID-19-Pandemie hat durch die Belastung des Öffentlichen Gesundheitsdienstes auch erhebliche Auswirkungen auf die Erfassung, Meldung und Übermittlung von anderen meldepflichtigen Infektionskrankheiten. Ob es sich daher um einen tatsächlichen Abfall der Hepatitis-C-Neudiagnosen handelt oder ob dieser artifiziell bedingt ist durch Untererfassung und Rückgang der Diagnostik, lässt sich erst im Laufe der nächsten Jahre bewerten. Der Jahresbericht zur Virushepatitis C anlässlich des diesjährigen Welt-Hepatitis-Tages gibt einen Überblick u. a. über die epidemiologische Situation weltweit, in Europa und in Deutschland sowie die Therapie der Hepatitis C in den Jahren 2018-2020.Peer Reviewe

Estimating Trends in the Proportion of Transmitted and Acquired HIV Drug Resistance in a Long Term Observational Cohort in Germany

Objective: We assessed trends in the proportion of transmitted (TDR) and acquired (ADR) HIV drug resistance and associated mutations between 2001 and 2011 in the German ClinSurv-HIV Drug Resistance Study. Method: The German ClinSurv-HIV Drug Resistance Study is a subset of the German ClinSurv-HIV Cohort. For the ClinSurv-HIV Drug Resistance Study all available sequences isolated from patients in five study centres of the long term observational ClinSurv-HIV Cohort were included. TDR was estimated using the first viral sequence of antiretroviral treatment (ART) naive patients. One HIV sequence/patient/year of ART experienced patients was considered to estimate the proportion of ADR. Trends in the proportion of HIV drug resistance were calculated by logistic regression. Results: 9,528 patients were included into the analysis. HIV-sequences of antiretroviral naive and treatment experienced patients were available from 34% (3,267/9,528) of patients. The proportion of TDR over time was stable at 10.4% (95% CI 9.1-11.8; p (for trend)=0.6; 2001-2011). The proportion of ADR among all treated patients was 16%, whereas it was high among those with available HIV genotypic resistance test (64%; 1,310/2,049 sequences; 95% CI 62-66) but declined significantly over time (OR 0.8; 95% CI 0.77-0.83; p (for trend)<0.001; 2001-2011). Viral load monitoring subsequent to resistance testing was performed in the majority of treated patients (96%) and most of them (67%) were treated successfully. Conclusions: The proportion of TDR was stable in this study population. ADR declined significantly over time. This decline might have been influenced by broader resistance testing, resistance test guided therapy and the availability of more therapeutic options and not by a decline in the proportion of TDR within the study population

Schätzung der Anzahl von HIV-Neuinfektionen im Jahr 2021 und der Gesamtzahl von Menschen, die Ende 2021 mit HIV in Deutschland leben

Die Anzahl der HIV-Neuinfektionen in Deutschland sowie bei Menschen deutscher Herkunft, die sich im Ausland mit HIV infiziert haben, wird für das Jahr 2021 auf 1.800 ge¬schätzt und liegt damit in gleicher Höhe wie 2020 (nach aktualisierter Schätzung ebenfalls etwa 1.800 Neuinfektionen). Der Anteil der diagnostizierten HIV-Infektionen liegt wie im Vorjahr bei etwa 90 %. Der Anteil der antiretroviral therapierten HIV-Infektionen liegt bei 96 %, von denen ebenfalls etwa 96 % als erfolgreich therapiert gelten. Somit sind zumindest zwei der drei Zielwerte des von UNAIDS formulierten „95-95-95-Ziels“ erreicht. Wie das Epidemiologische Bulletin 47/2022 ausführt, bedarf es jedoch weiterer Anstrengungen, um den Rückgang der HIV-Neuinfektionen zu verstetigen: Neben einer Reduktion der HIV-Neuinfektionen muss auch die Anzahl der nicht diagnostizierten Infektionen verringert und eine Therapie für alle in Deutschland lebenden Menschen mit HIV zugänglich gemacht werden.Peer Reviewe