AIDS-defining events among people living with HIV who have been under continuous antiretroviral therapy for more than one year, a German cohort study 1999-2018.

PURPOSE: This study examined the characteristics, incidence and prognostic factors of the first AIDS-defining condition developed after more than one year of continuous antiretroviral therapy (ART) among people living with HIV (PLHIV). METHODS: We used data from two multicentre observational cohorts of PLHIV in Germany between 1999 and 2018. Our outcome was the first AIDS-defining event that occurred during follow-up after more than one year of continuous ART. Descriptive analyses at ART initiation, at the time of the AIDS event and of the most frequently observed types of AIDS-defining illnesses were performed. We calculated the incidence rate (IR) per 1000 person-years (PY) and used a bootstrap stepwise selection procedure to identify predictors of the outcome. RESULTS: A total of 12,466 PLHIV were included in the analyses. 378 developed the outcome, constituting an overall IR of 5.6 (95% CI 5.1-6.2) AIDS events per 1000 PY. The majority of PLHIV was virally suppressed at the time of the event. Oesophageal candidiasis and wasting syndrome were the most frequently diagnosed AIDS-defining illnesses. We found a low CD4 count at ART initiation, a previous AIDS-defining condition and transmission through intravenous drug use to be meaningful prognostic factors of the outcome. CONCLUSION: The overall rate of AIDS-defining events among PLHIV under long-term ART was low, highlighting the importance of continuous treatment. PLHIV who started ART with indicators of impaired immune functioning were more susceptible to disease progression, suggesting that the public health response should continue to focus on early and sustained treatment for all PLHIV.

Dynamics of HIV PrEP use and coverage during and after COVID-19 in Germany.

BACKGROUND: Pre-exposure prophylaxis (PrEP) with oral emtricitabine/tenofovir disoproxil (FTC/TDF) proved highly efficient in preventing HIV. Since 09/2019, FTC/TDF-PrEP is covered by health insurances in Germany, if prescribed by licensed specialists. However, methods to longitudinally monitor progress in PrEP implementation in Germany are lacking. METHODS: Utilizing anonymous FTC/TDF prescription data from 2017-2021, we developed a mathematical model to disentangle HIV-treatment from PrEP prescriptions, as well as to translate PrEP prescriptions into number of PrEP users. We used the model to estimate past- and future PrEP uptake dynamics, to predict coverage of PrEP needs and to quantify the impact of COVID-19 on PrEP uptake on a national and regional level. RESULTS: We identified significant (p<0.01) decelerating effects of the first- and second COVID-19-lockdown on PrEP uptake in 04/2020 and 12/2020. We estimated 26,159 (CI: 25,751-26,571) PrEP users by 12/2021, corresponding to 33% PrEP coverage of people in need. We projected 64,794 (CI: 62,956-66,557) PrEP users by 12/2030, corresponding to 81% PrEP coverage. We identified profound regional differences, with high PrEP coverage and uptake in metropoles and low coverage in more rural regions. CONCLUSIONS: Our approach presents a comprehensive solution to monitor and forecast PrEP implementation from anonymous data and highlighted that the COVID-19 pandemic significantly decelerated PrEP uptake in Germany. Moreover, slow PrEP uptake in rural areas indicate that structural barriers in PrEP care, education or information exist that may hamper the goal of ending the AIDS epidemic by 2030.

AIDS in the era of antiretroviral therapy: Changes in incidence rates and predictors of AIDS among people living with HIV under clinical care in Germany, a cohort study 1999-2018.

OBJECTIVES: This study examined the incidence rates and predictive utility of established prognostic factors for the progression to AIDS among people living with HIV under clinical care. METHODS: We used data from two observational cohorts of people living with HIV in Germany between 1999 and 2018. The outcome measure was the first AIDS-defining event that occurred during follow-up. Incidence rates (IRs) per 1000 person-years (PY) were calculated by years of follow-up and calendar periods. We used Cox models in our prediction analyses, including CD4 count, viral load, and age at baseline to estimate the predictive performance. Additionally, we included transmission mode to examine its predictive utility. RESULTS: A total of 23 299 people living with HIV were included in the analyses. Of these, 1832 developed a first AIDS event during follow-up, constituting an overall rate of 14.6/1000 PY (95% confidence interval [CI] 13.9-15.2). IRs were highest in the first year of follow-up (45.6/1000 PY, 95% CI 42.6-48.8) and then declined continuously. IRs were highest among people living with HIV who enrolled between 1999 and 2003 (36.1/1000 PY, 95% CI 32.6-40.0). A low CD4 count, high viral load, and older age at baseline increased the likelihood of progressing to AIDS. Adding transmission mode to the models did not improve the predictive performance. CONCLUSIONS: The rates of a first AIDS event among people living with HIV have continuously declined in Germany. Health outcomes depend on a person's CD4 count, viral load, and age but not on transmission mode. To further reduce the number of AIDS cases, the focus should be on groups more likely to present in progressed stages of their HIV infection.

Low incidence of HIV infection and decreasing incidence of sexually transmitted infections among PrEP users in 2020 in Germany.

INTRODUCTION: Objectives of this study, as part of a nation-wide HIV pre-exposure prophylaxis (PrEP) evaluation project, were to determine the incidence of infections with HIV, chlamydia, gonorrhea, syphilis, hepatitis A/B/C in persons using PrEP, and to describe the health care funded PrEP use in Germany. Additionally, factors associated with chlamydia/gonorrhea and syphilis infections were assessed. METHODS: Anonymous data of PrEP users were collected at 47 HIV-specialty centers from 09/2019-12/2020. Incidence rates were calculated per 100 person years (py). Using longitudinal mixed models, we analyzed risk factors associated with sexually transmitted infections (STIs). RESULTS: 4620 PrEP users were included: 99.2% male, median age 38 years (IQR 32-45), 98.6% men who have sex with men (MSM). The median duration of PrEP exposure was 451 days (IQR 357-488), totaling 5132 py. Four HIV infections were diagnosed, incidence rate 0,078/100py (95% CI 0.029-0.208). For two, suboptimal adherence was reported and in the third case, suboptimal adherence and resistance to emtricitabine were observed. One infection was likely acquired before PrEP start. Incidence rates were 21.6/100py for chlamydia, 23.7/100py for gonorrhea, 10.1/100py for syphilis and 55.4/100py for any STI and decreased significantly during the observation period. 65.5% of syphilis, 55.6% of chlamydia and 50.1% of gonorrhea cases were detected by screening of asymptomatic individuals. In a multivariable analysis among MSM younger age, PrEP start before health insurance coverage and daily PrEP were associated with greater risk for chlamydia/gonorrhea. Symptom triggered testing and a history of STI were associated with a higher risk for chlamydia/gonorrhea and syphilis. A significantly lower risk for chlamydia/gonorrhea and syphilis was found for observations during the COVID-19 pandemic period. CONCLUSIONS: We found that HIV-PrEP is almost exclusively used by MSM in Germany. A very low incidence of HIV infection and decreasing incidence rates of STIs were found in this cohort of PrEP users. The results were influenced by the SARS-CoV-2 pandemic. Rollout of PrEP covered by health insurance should be continued to prevent HIV infections. Increased PrEP availability to people at risk of HIV infection through the elimination of barriers requires further attention. Investigation and monitoring with a longer follow-up would be of value.

[Evaluating the introduction of HIV pre-exposure prophylaxis as a benefit of statutory health insurance (EvE-PrEP) : Highly effective protection against HIV without an increase in sexually transmitted infections]. / Evaluation der Einführung der HIV-Präexpositionsprophylaxe als Leistung der gesetzlichen Krankenversicherung (EvE­PrEP) : Hocheffektiver Schutz vor HIV und keine Zunahme von sexuell übertragbaren Infektionen.

BACKGROUND: We investigated the impact of HIV pre-exposure prophylaxis (PrEP) as a new service of the statutory health insurance (SHI) on the incidence of HIV and other sexually transmitted infections (STIs) in Germany. In addition, PrEP needs and access barriers were analyzed. METHODS: The following data were evaluated as part of the evaluation project: HIV and syphilis notification data and extended surveillance by the Robert Koch Institute (RKI), pharmacy prescription data, SHI routine data, PrEP use in HIV-specialty care centers, Checkpoint, the BRAHMS and PrApp studies, as well as a community board. RESULTS: The majority of PrEP users were male (98-99%), primarily aged between 25-45 years, and predominantly of German nationality or origin (67-82%). The majority were men who have sex with men (99%). With regard to HIV infections, PrEP proved to be highly effective. There were only isolated cases of HIV infections (HIV incidence rate 0.08/100 person years); in most cases the suspected reason was low adherence. The incidences of chlamydia, gonorrhea, and syphilis did not increase but remained almost the same or even decreased. A need for information on PrEP for people in trans*/non-binary communities, sex workers, migrants, and drug users emerged. Needs-based services for target groups at increased risk of HIV are necessary. DISCUSSION: PrEP proved to be a very effective HIV prevention method. The partly feared indirect negative influences on STI rates were not confirmed in this study. Due to the temporal overlap with the containment measures during the COVID-19 pandemic, a longer observation period would be desirable for a conclusive assessment.

Decreasing prevalence and stagnating incidence of Hepatitis C-co-infection among a cohort of HIV-1-positive patients, with a majority of men who have sex with men, in Germany, 1996-2019.

Co-infection with Hepatitis C virus (HCV) among HIV-positive patients leads to accelerated progression of liver disease and AIDS. Due to increased HCV prevalence and incidence, co-infection requires monitoring trends among HIV-positive individuals. This will help target prevention strategies and support to reach the global goals of eliminating viral hepatitis as a public health threat. In this analysis HCV prevalence and incidence were determined for the years 1996-2019 from yearly blood samples and questionnaire details among HIV-1-positive patients, with a majority of men who have sex with men, belonging to a nationwide, multicentre observational, prospective cohort study. The results show that HCV prevalence for acute/chronic and resolved infection increased until 2014 to 12%. Since then, prevalence of acute/chronic HCV infection rapidly decreased and prevalence of resolved infections showed a steady increase. HCV incidence was highest in 2010 and lowest in 2017; however, no significant change in HCV incidence could be seen over the years. Therefore, the introduction of directly-acting antiviral agents for HCV treatment notably decreased prevalence and potentially incidence of acute/chronic HCV infection. Nevertheless, prevalence and incidence of HCV among these HIV-1-positive study participants remain high compared with the general population and justify the need for continuous HCV prevention and treatment efforts among HIV-positive individuals.

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/emtricitabine (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 consider the medical requirements for the treatment.

Everything counts - a method to determine viral suppression among people living with HIV using longitudinal data for the HIV care continuum - results of two large, German, multi-center real-life cohort studies over 20 years (1999-2018).

BACKGROUND: The aim of this study was to develop a standardized method to reconstruct persons' individual viral load (VL) courses to determine viral suppression and duration of viremia for the HIV care continuum in Germany using longitudinal cohort data. METHODS: We analyzed data from two large, multi-center German cohort studies under the direction of the Robert Koch Institute. We included data from 1999 to 2018 of all diagnosed people and of people who initiated antiretroviral treatment (ART). We developed a model generating virtual VL values and an individual VL course corresponding to real VL measurements with a maximum distance of 180 days, considering ART status and VL dynamics. If the distance between VL measurements was > 180 days, the time between was defined as gap time. Additionally, we considered blips, which we defined as a single detectable VL < 1000 copies/ml within 180 days. RESULTS: A total of 22,120 people (164,691 person-years, PY) after ART initiation were included in the analyses. The proportion of people with viral suppression (VL < 50 copies/ml) increased from 34% in 1999 to 93% in 2018. The proportion of people with VL < 200 copies/ml increased from 47% in 1999 to 96% in 2018. The proportion of people with viremia > 1000 copies/ml decreased from 37% in 1999 to 3% in 2018. The proportion of people with gap time fluctuated and ranged between 18 and 28%. An analysis of the first VL after gap time showed that 90% showed viral suppression, 5% VL between 50- < 1000 copies/ml and 5% VL > 1000 copies/ml. CONCLUSION: We provide a method for estimating viral suppression and duration of viremia using longitudinal VL data. We observed a continuous and remarkable increase of viral suppression. Furthermore, a notable proportion of those with viremia showed low-level viremia and were therefore unlikely to transmit HIV. Individual health risks and HIV drug resistance among those with low-level viremia are problematic, and viral suppression remains the goal. In 2018, 93 and 96% of people after ART initiation showed VL < 50 copies/ml and VL < 200 copies/ml, respectively. Therefore, using the threshold of VL < 200 copies/ml, Germany reached the UNAIDS 95 target of viral suppression since 2017.

[How do generic quotas work? An analysis using HIV infection as an example]. / Wie wirken Generikaquoten? Eine Analyse am Beispiel der HIV-Infektion.

BACKGROUND: Instruments controlling statutory healthcare medical supply have long been a topic of debate in health policy reform discussions. Over the years, a variety of tools have been developed, most of which are aimed at controlling drug expenditure. The instruments controlling regional prescriptions primarily focus on controlling behavioural patterns of the prescribing physicians. Important to note is the increased use of indication-directed quotas, primarily of drug leads and/or generics/biosimilars. These are now also available in the area of the human immunodeficiency virus (HIV), such as the generic quotas for HIV medications introduced in Bavaria and Berlin in 2020. OBJECTIVE: The aim of this article is to analyse the benefits and limitations of generic quota solutions in HIV care using statutory health insurance drug prescription data and to outline recommendations for action. RESULTS: It was observed that the quota potential for generics in the area of patent-free drugs in HIV care has already been largely exhausted. This can be explained by HIV prescribers supporting product exchange on the prescription. DISCUSSION: The best-case scenario in terms of regulation has almost been reached. This is due to a suitable set of instruments, including the framework agreement for medical supply as well as prescribing according to guidelines - in conjunction with the Pharmaceuticals Market Reorganisation Act (AMNOG) and reference prices for drugs. Conforming with guidelines and (existing) single-tablet regimens play an integral role in maintaining good quality of care.

Treatment modification after starting cART in people living with HIV: retrospective analysis of the German ClinSurv HIV Cohort 2005-2017.

OBJECTIVE: Combination antiretroviral therapy (cART) has markedly increased survival and quality of life in people living with HIV. With the advent of new treatment options, including single-tablet regimens, durability and efficacy of first-line cART regimens are evolving. METHODS: We analyzed data from the prospective multicenter German Clinical Surveillance of HIV Disease (ClinSurv) cohort of the Robert-Koch Institute. Kaplan-Meier and Cox proportional hazards models were run to examine the factors associated with treatment modification. Recovery after treatment initiation was analyzed comparing pre-cART viral load and CD4+ T-cell counts with follow-up data. RESULTS: We included 8788 patients who initiated cART between 2005 and 2017. The sample population was predominantly male (n = 7040; 80.1%), of whom 4470 (63.5%) were reporting sex with men as the transmission risk factor. Overall, 4210 (47.9%) patients modified their first-line cART after a median time of 63 months (IQR 59-66). Regimens containing integrase strand transfer inhibitors (INSTI) were associated with significantly lower rates of treatment modification (adjusted hazard ratio 0.44; 95% CI 0.39-0.50) compared to protease inhibitor (PI)-based regimens. We found a decreased durability of first-line cART significantly associated with being female, a low CD4+ T-cell count, cART initiation in the later period (2011-2017), being on a multi-tablet regimen (MTR). CONCLUSIONS: Drug class and MTRs are significantly associated with treatment modification. INSTI-based regimens showed to be superior compared to PI-based regimens in terms of durability.

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.

Antiretroviral treatment indications and adherence to the German-Austrian treatment initiation guidelines in the German ClinSurv HIV Cohort between 1999 and 2016.

PURPOSE: The aim of the study was to assess guideline adherence to combined antiretroviral therapy (ART) in the German ClinSurv HIV Cohort and the real-life impact of the Strategic Timing of Antiretroviral Therapy (START) study, to identify patients not treated as recommended by new guidelines. METHODS: We used data from the multicenter ClinSurv cohort of the Robert-Koch-Institute (RKI) between 1999 and 2016. Inclusion criteria were people living with HIV/AIDS, ≥ 18 years of age and cART naïve at the first visit (FV). Adherence was defined as starting cART within 6 months of crossing the CD4+ T cell threshold as suggested by the German-Austrian treatment guidelines. Logistic regression was used to identify factors associated with non-adherence. RESULTS: 11,817 patients met the inclusion criteria. We observed an overall adherence rate of 60%, in patients with treatment indication who started cART timely between 2002 and 2015. Adherence rate increased constantly, demonstrating a potential increase in patients, with treatment indication, starting cART within 6 months of presentation from 55% in 2008 to 94% in 2015. Patients reporting injection drug use (OR 2.18, 95% CI 1.70-2.95) and patients between 18 years and 39 years of age at the time of their first visit (OR 2.89, 95% CI 1.35-6.18) were identified as risk groups associated with non-adherence. CONCLUSION: The majority of patients below the CD4+ T cell count threshold of applicable guidelines initiated treatment within 6 months. We observed a slowly diminishing proportion of patients not starting cART timely. Delayed treatment was more frequent in patients reporting injection drug use.

Correction to: Antiretroviral treatment indications and adherence to the German-Austrian treatment initiation guidelines in the German ClinSurv HIV Cohort between 1999 and 2016.

In this article the cooperating partners of the ClinSurv HIV cohort were not listed in the acknowledgements. The correct paragraph appears below.

Cost-effectiveness and budget effect of pre-exposure prophylaxis for HIV-1 prevention in Germany from 2018 to 2058.

BackgroundPre-exposure prophylaxis (PrEP) is a highly effective HIV prevention strategy for men-who-have-sex-with-men (MSM). The high cost of PrEP has until recently been a primary barrier to its use. In 2017, generic PrEP became available, reducing the costs by 90%.AimOur objective was to assess cost-effectiveness and costs of introducing PrEP in Germany.MethodsWe calibrated a deterministic mathematical model to the human immunodeficiency virus (HIV) epidemic among MSM in Germany. PrEP was targeted to 30% of high-risk MSM. It was assumed that PrEP reduces the risk of HIV infection by 85%. Costs were calculated from a healthcare payer perspective using a 40-year time horizon starting in 2018.ResultsPrEP can avert 21,000 infections (interquartile range (IQR): 16,000-27,000) in the short run (after 2 years scale-up and 10 years full implementation). HIV care is predicted to cost EUR 36.2 billion (IQR: 32.4-40.4 billion) over the coming 40 years. PrEP can increase costs by at most EUR 150 million within the first decade after introduction. Ten years after introduction, PrEP can become cost-saving, accumulating to savings of HIV-related costs of EUR 5.1 billion (IQR: 3.5-6.9 billion) after 40 years. In a sensitivity analysis, PrEP remained cost-saving even at a 70% price reduction of antiretroviral drug treatment and a lower effectiveness of PrEP.ConclusionIntroduction of PrEP in Germany is predicted to result in substantial health benefits because of reductions in HIV infections. Short-term financial investments in providing PrEP will result in substantial cost-savings in the long term.

Real-world treatment for chronic hepatitis C infection in Germany: Analyses from drug prescription data, 2010-2015.

BACKGROUND & AIMS: Direct-acting antivirals (DAAs) for hepatitis C virus (HCV) have strongly improved treatment options since 2014, but it is unclear if treatment numbers have increased. We aimed to estimate the number of treatment regimens per month from 2010-2015 and the number of patients treated and cured with DAAs since 2014, as well as the associated costs. METHODS: Drug prescription data of hepatitis C virus (HCV) antivirals for patients with statutory health insurance in Germany (∼85% of population) from January 2010-December 2015 were evaluated. Standard 28-day prescriptions of pegylated interferon (PegIFN) and 1st/2nd generation DAAs were combined according to treatment guidelines and analysed. Drug costs were calculated from pharmacy sales prices. Mean treatment durations/regimen from real-world data were used to calculate drug costs/regimen and numbers of DAA-treated persons in 2014/15. RESULTS: From January 2010-December 2015 PegIFN/ribavirin-treatments/month decreased from ∼6500 to ∼650. Monthly HCV-prescriptions rose with the approval of 1st generation DAAs (2011), and decreased at the end of 2013. With the approval of 2nd generation DAAs, prescriptions/month increased (peak: ∼6600; March 2015), and subsequently decreased (∼4000; December 2015). In 2014, ∼7000 patients were treated with DAAs, and ∼20,100 in 2015. Treatment costs/month were stable at 12 million EUR (2010-2011), increased to ∼38 million EUR (March 2012), and peaked to 150 million EUR (March 2015). DAA-drug costs/year added up to ∼664million EUR (2014) and ∼1.3billion EUR (2015). CONCLUSIONS: Despite an increase in DAA prescriptions, in December 2015 less persons/month were under treatment compared to January 2010, even though access to DAAs is not limited. However, yearly treatment numbers increased from 2014-2015. Under observed conditions, ∼18,000 patients/year can be cured, making substantial reduction of the estimated 160,000 diagnosed patients realizable. Political commitment to achieve further reduce DAA-prices and increase treatment numbers is recommended. LAY SUMMARY: New treatment options with all-oral second generation direct-acting antivirals (DAAs) have resulted in the potential to cure chronic hepatitis C infection, but at high costs. Analyses from HCV drug prescription data of patients with statutory health insurance in Germany from 2010-2015, showed that DAAs replaced treatments with pegylated interferon and ribavirin, but accompanied by a disproportionate rise in costs. Although the monthly number of patients under treatment did not increase over time, the total number of patients yearly treated with DAAs increased from ∼7000 patients in 2014 to ∼20,100 in 2015, with a trend to shorter treatment regimens. Under observed conditions ∼18,000 patients can be cured yearly, making a substantial reduction of the estimated 160,000 diagnosed patients in Germany achievable.

Immunological recovery in tuberculosis/HIV co-infected patients on antiretroviral therapy: implication for tuberculosis preventive therapy.

BACKGROUND: Understanding the immune response to combination antiretroviral therapy (cART) is essential for a clear approach to tuberculosis (TB) preventive therapy. We investigated the immunological recovery in cART-treated HIV-infected patients developing TB compared to those who remained free of TB. METHODS: We extracted data of HIV-infected patients from a multicenter cohort for the HIV clinical surveillance in Germany. No patients included in our study had TB at the beginning of the observation. Using a longitudinal mixed model, we assessed the differences in the mean change of biomarkers (CD4+ cell count, CD8+ cell count, CD4:CD8 ratio and viral load) since cART initiation in patients who remained free of TB vs. those developing TB. To detect the best-fit trajectories of the immunological biomarkers, we applied a multivariable fractional polynomials model. RESULTS: We analyzed a total of 10,671 HIV-infected patients including 139 patients who developed TB during follow-up. The highest TB incidences were observed during the first two years since cART initiation (0.32 and 0.50 per 100 person-years). In an adjusted multivariable mixed model, we found that the average change in CD4+ cell count recovery was significantly greater by 33 cells/µl in patients who remained free of TB compared with those developing TB. After the initial three months of cART, 65.6% of patients who remaining free of TB achieved CD4+ count of ≥400 cells/µl, while only 11.3% of patients developing TB reached this immunological status after the three months of cART. We found no differences in the average change of CD8+ cell count, CD4:CD8 ratio or viral load between the two-patient groups. CONCLUSION: All HIV-infected patients responded to cART. However, patients developing TB showed reduced recovery in CD4+ cell count and this might partly explain the incident TB in HIV-infected patients receiving cART. These findings reinforce the importance of adjunctive TB preventive therapy for patients with reduced recovery in CD4+ cell count.

High variability of TB, HIV, hepatitis C treatment and opioid substitution therapy among prisoners in Germany.

BACKGROUND: In Germany, medical care of prisoners is completely separated from extramural health care. The extent and quality of medical care among prisoners in Germany are therefore largely unknown. We performed a secondary data analysis of pharmacy sales data for tuberculosis (TB), HIV, hepatitis C (HCV) and opioid substitution treatment (OST) delivered to prisons in 11 federal states (FS) in Germany between 01/2012 and 03/2013. The aims of this study were to assess (i) the treatment availability for the selected diseases and OST in German prisons, (ii) the proportion of prisoners treated per FS and overall for TB, HIV, HCV and OST during the study period. METHODS: Substances unique to or typically used for the treatment of each disease were defined as marker substances with defined daily doses (DDD). For each marker substance we assessed the cumulative number of DDD, the average daily number of DDD (DDDd) and average treatment prevalence per day in percent (adTP). Accordingly, the DDDd represents one person treated per day and the adTP means the proportion of prisoners treated per day. We compared the adTP of the diseases with previously measured prevalences. RESULTS: We obtained data from pharmacies supplying prisons in 11 of 16 German FS. Of the included prisons, 41% were supplied with medicines for TB, 71% for HIV and 58% for HCV and OST. Twice as many delivered marker substances for TB were indicated for the continuation phase and chemoprevention than the intensive phase. The HIV adTP ranged from 0.06% to 0.94%, HCV adTP ranged from 0.03% to 0.59% and OST adTP ranged from 0% to 7.90%. The overall adTP for the respective treatment was 0.39% for HIV, 0.12% for HCV and 2.18% for OST. CONCLUSIONS: According to our findings treatment rates for TB were consistent with the expected TB prevalence, at least in Berlin. HIV treatment seems to be offered to an adequate proportion of estimated infected prisoners. In contrast, the HCV treatment prevalence was low. High variation among FS in provision of all treatments, particularly of OST, point to inconsistent treatment practices, although nationwide extramural treatment guidelines for Germany exist.

CD4-cell counts and presence of AIDS in HIV-positive patients entering specialized care-a comparison of migrant groups in the German ClinSurv HIV Cohort Study, 1999-2013.

BACKGROUND: Although early presentation to HIV-care is essential to ensure timely initiation of antiretroviral therapy, recent studies have shown that especially migrants present to HIV-care at a later stage of HIV-infection. Currently, thirty percent of all newly diagnosed HIV cases in Germany originate from abroad. So far it is unknown, which specific migrant groups in Germany are particularly at risk for late presentation to HIV-care. METHODS: We used data from the Clinical Surveillance of HIV Disease (ClinSurv) cohort, a multi-centre observational cohort (01/01/1999 and 31/07/2013) and included treatment-naïve patients with valid information on country of origin and date of enrolment. Migrants were patients with country of origin outside Germany. We compared time trends for percentage of AIDS (CDC Stage C) and mean CD4-count at enrolment between migrants from Western Europe (WE), Central Europe (CE), Eastern Europe (EE), Sub-Saharan Africa (SSA), South East Asia (SEA) and non-migrants using multivariable regressions. Male non-migrants with mean age of 38-years constituted the reference group. RESULTS: In total, 10,211 patients fulfilled the inclusion criteria, of which 2784 were migrants (SSA: 42%, CE: 17%, WE: 11%, EE: 10%, SEA: 9%). The percentage of patients with AIDS at enrolment was higher in SSA (Odds Ratio (OR)SSA: 1.44, 95%-confidence interval (95%-CI):1.12-1.84) and SEA-migrants (ORSEA:2.16, 95%-CI:1.43-3.27). In addition, female SEA-migrants, were more likely to present with AIDS than their male counterparts (OR:2.22, 95%-CI:1.18-4.17). Mean CD4-count at enrolment was lower for SSA- (Mean CD4-count ratio (IRR):0.72; 95%-CI:0.64-0.82) and SEA-migrants (IRR:0.62, 95%-CI:0.49-0.78). Over time, it increased in non-migrants and CE-migrants (by 1 and 3%/year, respectively), whereas no increase was seen for SEA and SSA. CONCLUSIONS: SSA and SEA-migrants in Germany present to HIV-care at a later stage of HIV infection than non-migrants. Additionally, previous research found a higher risk for late HIV-testing for migrants. Collecting information about the arrival date of migrants in Germany in the HIV notification system would help to understand to which extent these problems could be tackled in Germany. Moreover, participatory approaches for HIV-testing and care as well as research regarding knowledge, behaviour and attitudes towards these topics for SSA and SEA migrants should be expanded.

From pills to patients: an evaluation of data sources to determine the number of people living with HIV who are receiving antiretroviral therapy in Germany.

BACKGROUND: This study aimed to determine the number of people living with HIV receiving antiretroviral therapy (ART) between 2006 and 2013 in Germany by using the available numbers of antiretroviral drug prescriptions and treatment data from the ClinSurv HIV cohort (CSH). METHODS: The CSH is a multi-centre, open, long-term observational cohort study with an average number of 10.400 patients in the study period 2006-2013. ART has been documented on average for 86% of those CSH patients and medication history is well documented in the CSH. RESULTS: The proportion of CSH patients receiving TCMs increased continuously over time (from 85% to 93%; 2006-2013). In contrast, treatment interruptions declined remarkably (from 11% to 2%; 2006-2013). The total number of HIV-infected people with ART experience in Germany increased from 31,500 (95% CI 31,000-32,000) individuals to 54,000 (95% CI 53,000-55,500) over the observation period (including 16.3% without SHI and persons who had interrupted ART). An average increase of approximately 2,900 persons receiving ART was observed annually in Germany. CONCLUSIONS: A substantial increase in the number of people receiving ART was observed from 2006 to 2013 in Germany.