[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.

Socio-demographic and psycho-social determinants of HIV late presentation in Germany - results from the FindHIV study.

Delayed HIV diagnosis at advanced stages of disease remains common (33%-64%). This analysis of the multi-center FindHIV study including newly diagnosed HIV-infected adults in Germany, focused on the potential role of socio-demographic and psychological factors on late diagnosis (formerly "late presentation", AIDS diagnosis or CD4 cells <350/µL). These data were collected from patient profiles, physician-patient interviews and questionnaires. Participating centers (n = 40) represented the diverse health care settings in HIV care and geographic regions. Of 706 newly diagnosed adults (92% male, median age 39 years) between 2019 and 2020, 55% (388/706) were diagnosed late with a median CD4 cell count of 147/µL; 20% (142/706) presented with AIDS. From the physicians' perspective, earlier diagnosis would have been possible in 45% of participants (late versus non-late presentation 58% versus 29%). The most common physician-perceived reason was an underestimated risk for HIV infection by the patient (37%). In multivariable logistic regression analysis, older age, sexual contacts with both sexes as possible route of HIV transmission, being married, and a poor level of knowledge about HIV treatment were found to be associated with a significantly elevated risk for late presentation. Education, employment status, sexual relations, migration background and personality traits were not.Trial registration: German Clinical Trials Register (DRKS00016351).

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.

Understanding and avoiding late presentation for HIV diagnosis - study protocol of a trial using mixed methods (FindHIV).

Many patients infected with HIV are diagnosed at an advanced stage of illness. These late presenters are individuals with a CD4 cell count of less than 350 cells/µL and/or an AIDS defining disease at initial HIV diagnosis. Purpose of FindHIV is to develop and distribute a questionnaire/scoring system aimed at a reduction in late presentation. FindHIV uses a mixed methods approach. In a first step, primary data of patients were collected. Inclusion criteria were: age ≥ 18 years, cognitive ability and language skills to participate in the study, initial HIV diagnosis within the past 6 months, and patient informed consent. Descriptive methods and regression models are used to identify: (1) patient characteristics associated with late presentation and (2) contacts to the healthcare system with indicator diseases that did not lead to HIV testing. Secondly, a questionnaire/scoring system is created by an expert panel. Afterwards the questionnaire/scoring system is to be disseminated. The greatest challenge was in reaching an adequate sample size. Another risk may be a recall bias. Nevertheless, FindHIV is devised as an in-depth study of the phenomenon of late presentation with potential to significantly improve HIV detection.

Cost of Human Immunodeficiency Virus (HIV) and Determinants of Healthcare Costs in HIV-Infected Treatment-Naive Patients Initiated on Antiretroviral Therapy in Germany: Experiences of the PROPHET Study.

OBJECTIVES: The purpose of the prospective clinical and pharmacoeconomic outcomes study of different first-line antiretroviral treatment strategies (PROPHET) was to examine the healthcare costs of human immunodeficiency virus (HIV)-infected persons in Germany treated with different antiretroviral therapy (ART) strategies and to identify variables associated with high costs. METHODS: The setting was a 24-month prospective multicenter observational cohort study in a German HIV-specialized care setting from 2014 to 2017. A microcosting approach was used for the estimation of healthcare costs. Data were obtained via electronic case report forms. The costs were calculated from both the societal and the statutory health insurance perspective. Regression models were performed that took into consideration the impact of several independent variables. RESULTS: Four hundred thirty-four patients from 24 centers throughout Germany were included. Average annual healthcare costs were €20 118 (standard deviation [SD] €6451) per patient from the societal perspective (n = 336) and €17 306 (SD €4106) from the statutory health insurance perspective (n = 292). Expenditures for the ART medication had the highest impact. Total costs declined in the second year of therapy. There was a significant association between the amount of total cost and clinical or therapeutic variables from both perspectives; a diagnosis of acquired immune deficiency syndrome (AIDS) led to higher costs as well as the chosen ART strategy. Age also increased cost from the statutory health insurance perspective. CONCLUSIONS: The main cost driver of the healthcare costs for HIV-positive patients was antiretroviral drug expenses. Further variables that influenced the costs were identified. The results provide a detailed overview of the resource use of patients in the PROPHET cohort.

Impact of three decades of antiretroviral therapy in a longitudinal population cohort study.

BACKGROUND: We have used a comprehensive HIV population to characterize antiretroviral therapy (ART), drug class selection, pill burden, drug costs and health outcomes over the entire span of the HIV epidemic. METHODS: Antiretroviral (ARV) use (drugs, classes, formulations) and both the laboratory and clinical outcomes (HIV-1 RNA, CD4+ T-cell count and mortality) were determined for all patients in Southern Alberta, Canada, at each year-end between 1986 and 2017. Pill burden, cumulative drug exposure and costs were calculated for each year. RESULTS: The number of ARV-treated patients increased from 29.6% (77/260) in 1989 to 93.4% (1,814/1,943) in 2017. Regimen selection showed continuous adjustments for toxicity, resistance, pill burden and adherence. Dramatic improvements in outcomes were seen. In 1997, 22.4% of treated patients had an undetectable viral load, this has been consistently around 90% since 2010 (92.7% in 2017). While HIV-related annual mortality rate declined from 11.0% in 1994 to 0.1% in 2017, all-cause mortality remained relatively stable from 1997 onwards. ART pill burden escalated in 1997 (12.4/day), then decreased to 2.1/day in 2016. Mean ART cost increased in 1997 (CAN$905/month/regimen in 1997, $1,223 in 2016). Mean cumulative lifetime exposure to protease inhibitors is 5.98 ±4.9 and to nucleoside reverse transcriptase inhibitors 8.8 ±6.2 years. CONCLUSIONS: Our findings demonstrate not only the immense burden that HIV has imposed on both patients and society, but also the substantial benefit of ART on patient outcomes. They show that research, patient engagement and programme support can with time minimize the harmful long-term effects of HIV-infection.

Identifying Risk of Viral Failure in Treated HIV-Infected Patients Using Different Measures of Adherence: The Antiretroviral Therapy Cohort Collaboration.

Adherence to antiretroviral therapy (ART) is critical for successful treatment of Human Immunodeficiency Virus (HIV), but comparisons across settings are difficult because adherence is measured in different ways. We examined utility of different adherence measures for identification of patients at risk of viral failure (VF). Eight cohorts in the ART Cohort Collaboration contributed data from pharmacy refills or self-report questionnaires collected between 1996 and 2013 (N = 11689). For pharmacy data (N = 7156), we examined associations of percentage adherence during the 1st year of ART with VF (>500 copies/mL) at 1 year. For self-report data (N = 4533), we examined 28-day adherence with VF based on closest viral load measure within 6 months after questionnaire date. Since adherence differed markedly by measurement type, we defined different cut-off points for pharmacy (lower <45%, medium 45⁻99%, higher 100%) and self-report (lower ≤95%, medium 96⁻99%, higher 100%) data. Adjusted odds ratios (ORs) for VF in lower and medium, compared to higher adherence groups, were 23.04 (95% CI: 18.44⁻28.78) and 3.84 (3.36⁻4.39) for pharmacy data. For self-report data, they were 3.19 (2.31⁻4.40) and 1.08 (0.80⁻1.46). Both types of measure were strongly associated with VF. Although adherence measurements over longer time-frames are preferable for prediction, they are less useful for intervention.

2016 PREP attitudes in Germany: high awareness and acceptance in MSM at risk of HIV.

PRUPOSE: To examine current risk behavior, awareness, experience, and attitudes towards pre-exposure-prophylaxis (PrEP), and to estimate a potential impact on the prevention of HIV transmission among HIV-negative MSM in Germany. PrEP was not officially licensed at the time of survey. METHODS: Web-based questionnaire from 03-06/2016. Potential participants were informed through social media, flyers, and advertisements. Risk contacts were defined as unprotected sexual intercourse under the influence of recreational drugs in the past 6 months. RESULTS: In total, 1208 subjects participated, 342 subjects were excluded for being HIV-infected or non-MSM, leaving 866 subjects to be evaluated in this analysis. Mean age was 37.0 ± 10.4 years. 593 participants (68.5%) were tested for HIV within the past 12 months. A total of 206 STDs in the past 6 months were reported by 144 (16.6%). Aware of PrEP was 748 (86.4%) respondents, while 65.1% reported willingness to use it. Risk behavior was significantly associated with higher PrEP acceptance (OR 2.90, 95% CI 2.14-3.90), as was a history of STDs (OR 1.85, 95% CI 1.17-2.91). The use of condoms would forgo 52.3% of subjects if taking PrEP. Sixty-five respondents (7.5%) reported PrEP use. Only 19 (29.2%) had accessed PrEP under medical supervision. PrEP use was reported by 14.8% with > 5 risk contacts in the past 6 months, compared to 6.3% with one risk contact (p < 0.001). CONCLUSION: We found a high PrEP awareness and acceptance, especially among subgroups of MSM at highest risk of HIV infection. Structured access and availability of PrEP to this population may have an important impact on the HIV epidemic in Germany.

High seroprevalence of antibodies against Kaposi's sarcoma-associated herpesvirus (KSHV) among HIV-1-infected children and adolescents in a non-endemic population.

Human herpesvirus-8 (HHV-8) is the etiological agent of Kaposi's sarcoma (KS), which primarily affects human immunodeficiency virus (HIV)-infected adults with advanced immunodeficiency. Currently, only limited prevalence data for HHV-8 infection in HIV-infected children living in non-endemic areas are available. This multicenter cross-sectional study was conducted in four university hospitals in Germany specializing in pediatric HIV care. Stored serum specimens obtained from 207 vertically HIV-1-infected children and adolescents were tested for antibodies against lytic and latent HHV-8 antigens. Logistic regression was used to assess independent risk factors associated with HHV-8 seropositivity. The overall HHV-8 seroprevalence was 24.6 % (n = 51/207) without significant differences related to sex, age, or ethnicity. In univariate analysis, HHV-8 seropositivity was significantly associated with a child having being born outside Germany, maternal origin from sub-Saharan Africa, a history of breastfeeding, CDC immunologic category 3, and deferred initiation of antiretroviral therapy (>24 months of age). In multivariate analysis, a child's birth outside Germany was the only significant risk factor for HHV-8 seropositivity (odds ratio 3.98; 95 % confidence interval 1.27-12.42). HHV-8-associated malignancies were uncommon; only one patient had a history of KS. Serum specimen of vertically HIV-infected children and adolescents living in Germany showed a high HHV-8 seroprevalence. These findings suggest that primary HHV-8 infection-a risk factor for KS and other HHV-8-associated malignancies-occurs early in life. Thus, management of perinatally HIV-infected children should include testing for HHV-8 coinfection and should consider future risks of HHV-8-associated malignancies.

Drug-Drug Interactions With Antiviral Agents in People Who Inject Drugs Requiring Substitution Therapy.

OBJECTIVE: To describe potential drug-drug interactions in the area of HIV/hepatitis C virus (HCV) coinfection and injection drug use, including those between antiretrovirals (ARVs), direct-acting antivirals (DAAs), and opioid-agonist therapy, and to supply a practical approach to their management. DATA SOURCES: We searched PubMed for relevant articles published up until February 2015 as well as conference reports and drug-drug-interaction Web sites. DATA SELECTION AND DATA EXTRACTION: We used the following search terms: pharmacokinetic and pharmacodynamic drug-drug interaction, opioid substitution, HIV, hepatitis and the individual names of the relevant agents of the following drug classes and the drug classes itself: reverse transcriptase inhibitors, nonnucleoside reverse transcriptase inhibitors, protease inhibitors, direct-acting antivirals, opioide, benzodiazepines, anticonvulsants, antidepressants and antipsychotics. Additional references were identified from a review of literature citations and drug-drug interaction Web sites. In our evaluation, we included German- and English-language studies and reports addressing drug-drug interactions between opioid agonist therapy and ARVs or DAAs. DATA SYNTHESIS: Pharmacokinetic data were available for all ARVs and DAAs except rilpivirine, indinavir, saquinavir, maraviroc, dolutegravir, and MK-8742 with buprenorphine as well as maraviroc with methadone Drug-drug interactions of potential clinical relevance are most likely to occur between opioid-replacement therapy and ARVs, particularly the nonnucleoside reverse transcriptase inhibitors, efavirenz and nevirapine, and HIV protease inhibitors. CONCLUSION: Integrase inhibitors may be safely coadministered with opioid-replacement therapy. With respect to HCV DAAs, most currently approved and late-stage investigational agents do not have clinically significant interactions with opioid-replacement therapy. ARV and DAAs may interact with other drug classes commonly used in the opioid-dependent population, including benzodiazepines, antidepressants, anticonvulsants, and antipsychotics.

Cost of HIV and determinants of health care costs in HIV-positive patients in Germany: results of the DAGNÄ K3A Study.

OBJECTIVES: The aims of this study were to estimate the expenditure for HIV-care in Germany and to identify variables associated with resource use. DESIGN/SETTING: We performed an 18-month prospective multi-center study in an HIV specialized ambulatory care setting from 2006 to 2009. SUBJECTS, PARTICIPANTS: Patients were eligible for study participation if they (1) were HIV-positive, (2) were ≥ 18 years of age, (3) provided written consent and (4) were not enrolled in another clinical study; 518 patients from 17 centers were included. MAIN OUTCOME MEASURES: Health care costs were estimated following a micro-costing approach from two perspectives: (1) costs incurred to society in general, and (2) costs incurred to statutory health insurance. Data were obtained using questionnaires. Several empirical models for identifying the relationship between health care costs and independent variables, including age, gender, route of transmission and CD4 cell count at baseline, were developed. RESULTS: Average annual health care costs were 23,298 per patient from the societal perspective and 19,103 from the statutory health insurance perspective. Most expenses are caused by antiretroviral medication (80 % of the total and 89 % of direct costs), while hospital costs represented 7 % of total expenditure. A statistically significant association was found between health care costs and clinical variables, with higher CD4 count and female gender generating lower costs, while increased antiretroviral experience and injection drug use led to higher expenditures (P < 0.05). CONCLUSIONS: Expenditures for HIV-infection are driven mainly by drug costs. We identified several clinical variables influencing the costs of HIV-treatment. This information could assist policymakers when allocating limited health care resources to HIV care.