Predictors of serofast state after treatment for early syphilis in HIV-infected patients.

OBJECTIVES: Non-treponemal serological tests are used to monitor treatment response during syphilis infection. Syphilis- and HIV-coinfected patients may experience incomplete resolution in non-treponemal titres, which is referred to as the serofast state. The goal of this study was to evaluate risk factors for serofast state in HIV-infected patients. METHODS: From November 2015 to June 2018, 1530 HIV-positive patients were tested for syphilis using a Treponema pallidum particle agglutination (TPPA) assay. Among TPPA-positive patients, medical records were reviewed for early syphilis infection. Serofast state was defined as a less than four-fold decrease in non-treponemal antibody titres during a 6-month follow-up period in the absence of symptoms of syphilis. Baseline characteristics were tested as predictive factors of serological response. RESULTS: In all, 515 patients (33.7%) tested positive in TPPA assays, and in 163 patients at least one previous syphilis infection was documented. A total of 61 out of 163 patients (37.4%) were in a serofast state. A history of previous syphilis infection (61 vs. 43%; P = 0.04) was more common in serofast patients than in patients with serological cure after 6 months. Non-treponemal titres ≥ 1:32 before therapy (47 vs. 25%; P = 0.005) and adjunctive corticosteroids to prevent the Jarisch-Herxheimer reaction (35% vs 15%; P = 0.006) were associated with serological cure after 6 months, but corticosteroid therapy had no influence at 12 months. The intensity of syphilis treatment did not affect serological cure. CONCLUSION: Corticosteroids for prevention of the Jarisch-Herxheimer reaction were associated with earlier serological cure. Although serological response is the accredited surrogate method to monitor syphilis treatment, the biological significance of the serofast state remains unclear.

To prescribe, or not to prescribe: decision making in HIV-1 post-exposure prophylaxis.

OBJECTIVES: We investigated the trend in usage of post-exposure prophylaxis (PEP) after HIV-1 risk exposure and evaluated PEP prescription decision making of physicians according to guidelines. METHODS: All PEP consultations from January 2014 to December 2016 in patients presenting at the University Hospital of Cologne (Germany) were retrospectively analysed. HIV risk contacts included sexual and occupational exposure. The European AIDS Clinical Society (EACS) Guidelines for HIV PEP (version 9.0, 2017) were used for assessment. RESULTS: A total of 649 patients presented at the emergency department (ED) or the clinic for infectious diseases (IDC) for PEP consultations. A continuous increase in the number of PEP requests was recorded: 189 in 2014, 208 in 2015 and 252 in 2016. PEP consultations in men who have sex with men (MSM) showed a remarkable increase in 2016 (2014, n = 96; 2015, n = 101; 2016, n = 152). Decisions taken by physicians with a specialization in infectious diseases (n = 547) included 61 (11%) guideline-discordant prescriptions [2014: 14% (n = 22); 2015: 9% (n = 16); 2016: 11% (n = 23)]. Among these, sexual exposure accounted for 45 (74%) cases, including 15 cases of nonconsensual sex, while occupational exposure accounted for 14 (23%) cases and other exposure two cases (3%). The main reason for guideline-discordant PEP prescriptions was emotional stress of the patient (n = 37/61). CONCLUSIONS: PEP prescriptions are increasing and decision making is influenced by patients' emotional stress, but PEP prescriptions should be strictly administered according to risk assessment.

Measles, mumps, rubella and VZV: importance of serological testing of vaccine-preventable diseases in young adults living with HIV in Germany.

Measles, mumps, rubella (MMR) and varicella zoster virus (VZV) infection can cause serious diseases and complications in the HIV-positive population. Due to successful vaccination programmes measles, mumps and congenital rubella syndrome has become neglected in Germany. However, recent outbreaks of measles have occurred from import-associated cases. In this cross-sectional study the serostatus for MMR and VZV in 2013 HIV-positive adults from three different university outpatient clinics in Bonn (n = 544), Cologne (n = 995) and Munich (n = 474) was analysed. Sera were tested for MMR- and VZV-specific immunglobulin G antibodies using commercial immunoassays. Seronegativity was found in 3% for measles, 26% for mumps, 11% for rubella and 2% for VZV. Regarding MMR, 35% of patients lacked seropositivity against at least one infectious agent. In multivariable analysis younger age was strongly associated with seronegativity against all four viruses, measles, mumps, rubella (P < 0·001, P < 0·001 and P = 0·001, respectively) and VZV (P = 0·001). In conclusion, there is high need for MMR and VZV vaccination in people living with HIV in Germany born in 1970 or later. Thus, systematic MMR and VZV antibody screening and vaccination should be implemented in the HIV-positive population to prevent serious disease and complications of vaccine-preventable diseases.

PEPDar: A randomized prospective noninferiority study of ritonavir-boosted darunavir for HIV post-exposure prophylaxis.

OBJECTIVES: PEPDar compared the tolerability and safety of ritonavir-boosted darunavir (DRV/r)-based post-exposure prophylaxis (PEP) with the tolerability and safety of standard of care (SOC). The primary endpoint was the early discontinuation rate among the per-protocol population. METHODS: PEPDar was an open-label, randomized, multicentre, prospective, noninferiority safety study. Subjects were stratified by type of event (occupational vs. nonoccupational, i.e. sexual) and were randomized to receive DRV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) or SOC PEP. Twenty-two private or university HIV clinics in Germany participated. Subjects were ≥ 18 years old and had documented or potential HIV exposure and indication for HIV PEP. They initiated PEP not later than 72 h after the event and were HIV negative. RESULTS: A total of 324 subjects were screened, the per-protocol population was 305, and 273 subjects completed the study. One hundred and fifty-five subjects received DRV/r-based PEP and 150 subjects received ritonavir-boosted lopinavir (LPV/r)-based PEP for 28-30 days; 298 subjects also received tenofovir/emtricitabine. The early discontinuation rate in the DRV/r arm was 6.5% compared with 10.0% in the SOC arm (P = 0.243). Adverse drug reactions (ADRs) were reported in 68% of DRV/r subjects and 75% of SOC subjects (P = 0.169). Fewer DRV/r subjects (16.1%) had at least one grade 2 or 3 ADR compared with SOC subjects (29.3%) (P = 0.006). All grades of diarrhoea, nausea, and sleep disorders were significantly less frequent with DRV/r, while headache was significantly more frequent. No HIV seroconversion was reported during follow-up. CONCLUSIONS: Noninferiority of DRV/r to SOC was demonstrated. DRV/r should be included as a standard component of recommended regimens in PEP guidelines.

Clinical and epidemiological characteristics of patients with early syphilis from three academic centres in Poland, Germany and Ireland: initial findings from the POETS study.

OBJECTIVES: Syphilis recognition in HIV-positive patients has important implications. Initial data from this study, established in June 2012 to better understand the natural history of syphilis and treatment response, examine the characteristics of patients including sexual behaviour, rates of concurrent sexually transmitted infections (STI) and type of treatment given. METHODS: Patients were recruited from Ireland, Poland and Germany. Data gathered included demographics, method of syphilis acquisition, stage of syphilis infection, HIV status, nadir and current CD4 counts and HIV viral suppression rates. Data were then subanalysed into HIV-positive and HIV-negative groups. RESULTS: Of 175 patients recruited, 68% were HIV-positive and 86.3% were men who have sex with men. Most HIV-positive patients presented with secondary syphilis (55.7% vs 13.2%) (p=0.0001) while the majority of HIV-negative patients had primary syphilis noted at the time of recruitment (47.2% vs18.9%, p=0.0002). Approximately half of all patients had a HIV RNA viral load <40 copies/mL (55%). Previous syphilis infection occurred more frequently in HIV-positive than HIV-negative patients (p=0.0001). Concurrent STIs at the time of syphilis diagnosis were found in 26.8%, of whom 31 (25.4%) were HIV-positive (p=0.64). HIV-positive patients received doxycycline more frequently than their HIV-negative counterparts (33.6% vs 1.9%, p=0.0001) while HIV-negative patients were treated with long-acting penicillin in 88.7% of cases vs 58% of HIV-positive patients (p=0.0002). CONCLUSIONS: A 40% rate of unsuppressed viraemia, high levels of STIs and varying treatment regimens represent a public health risk for Europe, suggesting the model of sexual healthcare delivery in HIV-positive patients requires further evaluation.

Clinical course and quality of care in ART-naïve patients newly presenting in a HIV outpatient clinic.

OBJECTIVES: Little data exist about the quality of care for HIV-infected subjects in Germany. We investigated the clinical course of HIV-infected subjects newly presenting in our HIV outpatient clinic. METHODS: Antiretroviral therapy (ART)-naïve HIV-infected subjects presenting between 2007 and 2008 were followed until June 2012. Clinical data and laboratory parameters were collected prospectively and analysed retrospectively. RESULTS: From 281 subjects included, 34 patients (12%) were lost to follow-up. 247 subjects remained, and 171 patients were followed for 1,497 days [1,121/1,726] (all data: median [interquartile range]). ART was started in 199 patients (81%) 182 days [44/849] after HIV diagnosis, and all patients were treated according to European guidelines or within clinical trials. The CD4 cell count at first presentation was 320/µL [160/500] and declined to 210/µL [100/300] at ART start. 12 months thereafter, the CD4 cell count increased to 410/µL [230/545]. The HIV RNA was suppressed below 50 copies/mL after 108 days [63/173] in 182 patients (91%). Initial ART was changed in 71 patients (36%) after 281 days [99/718], in five patients (7%) due to virological failure, in 66 patients (93%) due to other reasons, e.g. side effects or patient's request. CONCLUSION: Two-thirds of the included patients were followed for more than 3 years, and ART was initiated in 81% of the patients leading to complete virological suppression in most patients. Compliance of physicians with treatment guidelines was high. Late presentation with a severely compromised immune function remains a problem and impairs the otherwise good prognosis of HIV infection.

Echocardiographic screening for pulmonary arterial hypertension in HIV-positive patients.

Human immunodeficiency virus (HIV) infection is associated with an increased risk for pulmonary arterial hypertension (PAH). Upon the screening of 220 asymptomatic HIV-positive individuals by echocardiography, we detected and confirmed HIV-associated PAH in 0.45 % of cases. Mild elevations of systolic pulmonary arterial pressure most probably owing to left ventricular diastolic dysfunction were found in 7.7 % of cases, without progress after 2 years. We suggest that the screening of asymptomatic HIV-positive patients for PAH should not be performed.

Causes of death in HIV-infected patients from the Cologne-Bonn cohort.

PURPOSE: Causes of death in human immunodeficiency virus (HIV)-infected subjects have changed in countries with high resources over the last several years. Acquired immunodeficiency syndrome (AIDS)-related diseases have become less prevalent, whereas deaths due to non-AIDS causes are increasing. The aim of the present study was to analyse causes of death in the Cologne-Bonn cohort. METHODS: Causes of death from the Cologne-Bonn cohort between 2004 and 2010 were systematically recorded using the CoDe algorithm (The Coding Causes of Death in HIV Project). RESULTS: In 3,165 patients followed from 2004 to 2010, 182 deaths occurred (5.7 %, 153 males, 29 females). The median age at the time of death was 47 years (range 24-85 years). The most frequent causes of death were AIDS-defining events (n = 60, 33 %), with non-Hodgkin lymphoma (NHL) (n = 29, 16 %) and infections (n = 20, 11 %) being the leading entities in this category. Non-AIDS malignancies accounted for 16 % (n = 29), non-HIV-related infections for 10 % (n = 18), cardiovascular diseases for 7 % (n = 14), suicide or accident for 4 % (n = 7) and liver diseases for 3 % (n = 5) of deaths (unknown n = 47, 26 %). Although the majority of patients (92.5 %) was on antiretroviral therapy (ART), only 50 % were virologically suppressed (HIV-RNA <50 copies/mL) and 44 % had a decreased CD4+ count (<200/µL) at their last visit before death. CONCLUSION: One-third of the causes of death in our cohort between 2004 and 2010 was AIDS-related. Since most of these deaths occur with severe immune suppression, they can possibly be prevented by the early diagnosis and treatment of HIV infection. Care providers must be aware of an increased risk for a broad range of diseases in HIV-infected patients and should apply appropriate preventive measures.

Liver involvement in HIV-infected patients diagnosed with syphilis.

PURPOSE: Liver involvement in syphilis has been studied in cohorts of human immunodeficiency virus (HIV)-negative individuals despite the scarcity of data on such HIV-infected patients. Th aim of this study was to assess hepatic involvement of HIV-infected patients diagnosed with syphilis. METHODS: Patients with syphilis and liver involvement, including all stages of syphilis, were systematically identified in our HIV cohort between 2004 and 2008. RESULTS: Of the 1,599 HIV-infected patients identified during the study period, 100 were diagnosed with acute syphilis, all of whom were male. Of these 100 patients, 84% were men who have sex with men. Laboratory parameters of liver involvement were present in 19 of the 100 HIV-infected patients with syphilis; these resolved after successful antibiotic treatment. Among these 19 patients, six were diagnosed to be in the latent stage, with elevated liver enzymes and parameters of inflammation representing the only distinctive feature. CONCLUSIONS: Based on our results, syphilis should be included in the differential diagnosis of increased liver enzymes in HIV-infected patients.

[Vaccination against rabies: how and when?]. / Tollwut-Impfung: wann und wie?

Each year, more than 55,000 people die from rabies. Rabies virus (RABV) is transmitted via bites from infected animals. Dogs represent the most important source of infections worldwide. In Germany, the last case of terrestrial rabies was reported in 2006. Therefore, the country has been considered rabies-free since September 2008 (as defined by World Organization of Animal Health, OIE). Bat rabies, however, is still endemic and mostly occurs in northern Germany. It is caused by the European Bat Lyssa Virus (EBLV), which is closely related to RABV. Cases of rabies in humans are almost 100 % lethal, therefore, the correct choice of prophylactic measures is essential. Pre-exposition vaccination is recommended for individuals at risk of contact to Rabies Virus. If used together with post-exposure measures, it confers high-grade protection against disease manifestation. Even non-vaccinated individuals exposed to Rabies Virus can be protected from overt disease in almost all cases with timely and accurate application of post-exposure vaccination. The mode and intensity of exposure determine the choice of regimen (wound treatment, active and passive vaccination).

Acceptance and tolerability of an adjuvanted nH1N1 vaccine in HIV-infected patients in the Cologne-Bonn cohort.

OBJECTIVE: To evaluate the acceptance and tolerability of the nH1N1 2009 vaccine in HIV-positive individuals. METHOD: 758 patients were included in this prospective study. Different study populations were formed: The Tolerability Study Group consists of HIV-infected patients who visited three outpatient clinics (Cologne, Bonn, Freiburg) during a predefined time period. Patients were offered nH1N1 vaccination. Those accepting were administered a standard dose AS03 adjuvant nH1N1 vaccine. Questionnaires to report side effects occurring within 7 days after immunization were handed out. In a substudy conducted during the same time period, acceptance towards immunization was recorded. This Acceptance Study Group consists of all HIV-infected patients visiting the Cologne clinic. They were offered vaccination. In case of refusal, motivation was recorded. RESULTS: In the Tolerability Study Group, a total of 475 patient diaries returned in the three study centres could be evaluated, 119 of those (25%) reported no side effects. Distribution of symptoms was as follows: Pain 285/475 patients (60%), swelling 96 (20%), redness 54 (11%), fever 48/475 (10%), muscle/joint ache 173 (36%), headache 127 (27%), and fatigue 210 (44%). Association of side effects with clinical data was calculated for patients in Cologne and Bonn. Incidence of side effects was significantly associated with CDC stages A, B compared to C, and with a detectable viral load (>50 copies/mL). No correlation was noted for CD4 cell count, age, gender or ethnicity. - In the Acceptance Study Group, 538 HIV-infected patients were offered vaccination, 402 (75%) accepted, while 136 (25%) rejected. Main reasons for rejection were: Negative media coverage (35%), indecisiveness with preference to wait until a later date (23%), influenza not seen as personal threat (19%) and scepticism towards immunization in general (10%). CONCLUSION: A total of 622 HIV-infected patients were vaccinated against nH1N1-influenza in the three study centres. No severe adverse events were reported. The tolerability was in most parts comparable to general population. Acceptance rate towards influenza vaccination was high (75%). Those refusing the immunization mentioned negative media coverage as the major influence on their decision.

[Value of p53, urokinase plasminogen activator, PAI-1 and Ki-67 in vulvar carcinoma]. / Untersuchungen zu p53, UPA, PAI-1 und Ki-67 beim Vulvakarzinom.

OBJECTIVE: The present study was to measure new prognostic factors including the plasminogen activator urokinase and the plasminogen inhibitor PAI-1, as well as p53 and Ki-67, a marker of proliferation and to compare the clinical value of these in relation to the classic histopathological prognostic factors. MATERIAL AND METHODS: The patient collective included 45 patients with vulvar carcinoma, both primary tumors and recurrences. RESULTS: Highly significant correlations were found for tumor diameter and thickness. According to Kaplan-Meier estimations, the influence of thickness on the prognosis had a p-value of 0.048, while the influence of diameter had a p-value of 0.029. The variable grading was also significantly associated to the probability of survival (p = 0.01). There was no statistically significant correlation between p53 and the parameters grading, degree of keratinization and Ki-67 color index. The correlation between p53 and PAI-1 as well as between UPA and PAI-1 was highly significant. According to the Kaplan-Meier estimations, Ki-67, UPA and PAI-1 had no influence on survival in our group of patients. CONCLUSIONS: For p53, the median value could be used as a divider with the median survival of patients with a p53 below 122 pg/mg protein being 151 months and with a p53 above 122 pg/mg being only 61 months. The corresponding p-value was significant at 0.0201.