Risk Factors and Outcomes for Late Presentation for HIV-Positive Persons in Europe: Results from the Collaboration of Observational HIV Epidemiological Research Europe Study (COHERE)

Background: Few studies have monitored late presentation (LP) of HIV infection over the European continent, including Eastern Europe. Study objectives were to explore the impact of LP on AIDS and mortality. Methods and Findings: LP was defined in Collaboration of Observational HIV Epidemiological Research Europe (COHERE) as HIV diagnosis with a CD4 count <350/mm3 or an AIDS diagnosis within 6 months of HIV diagnosis among persons presenting for care between 1 January 2000 and 30 June 2011. Logistic regression was used to identify factors associated with LP and Poisson regression to explore the impact on AIDS/death. 84,524 individuals from 23 cohorts in 35 countries contributed data; 45,488 were LP (53.8%). LP was highest in heterosexual males (66.1%), Southern European countries (57.0%), and persons originating from Africa (65.1%). LP decreased from 57.3% in 2000 to 51.7% in 2010/2011 (adjusted odds ratio [aOR] 0.96; 95% CI 0.95-0.97). LP decreased over time in both Central and Northern Europe among homosexual men, and male and female heterosexuals, but increased over time for female heterosexuals and male intravenous drug users (IDUs) from Southern Europe and in male and female IDUs from Eastern Europe. 8,187 AIDS/deaths occurred during 327,003 person-years of follow-up. In the first year after HIV diagnosis, LP was associated with over a 13-fold increased incidence of AIDS/death in Southern Europe (adjusted incidence rate ratio [aIRR] 13.02; 95% CI 8.19-20.70) and over a 6-fold increased rate in Eastern Europe (aIRR 6.64; 95% CI 3.55-12.43). Conclusions: LP has decreased over time across Europe, but remains a significant issue in the region in all HIV exposure groups. LP increased in male IDUs and female heterosexuals from Southern Europe and IDUs in Eastern Europe. LP was associated with an increased rate of AIDS/deaths, particularly in the first year after HIV diagnosis, with significant variation across Europe. Earlier and more widespread testing, timely referrals after testing positive, and improved retention in care strategies are required to further reduce the incidence of LP

Cytochrome P450 2B6 (CYP2B6) and constitutive androstane receptor (CAR) polymorphisms are associated with early discontinuation of efavirenz-containing regimens

Objectives Cytochrome P450 2B6 (CYP2B6) is responsible for the metabolic clearance of efavirenz and single nucleotide polymorphisms (SNPs) in the CYP2B6 gene are associated with efavirenz pharmacokinetics. Since the constitutive androstane receptor (CAR) and the pregnane X receptor (PXR) correlate with CYP2B6 in liver, and a CAR polymorphism (rs2307424) and smoking correlate with efavirenz plasma concentrations, we investigated their association with early (<3 months) discontinuation of efavirenz therapy. Methods Three hundred and seventy-three patients initiating therapy with an efavirenz-based regimen were included (278 white patients and 95 black patients; 293 male). DNA was extracted from whole blood and genotyping for CYP2B6 (516G → T, rs3745274), CAR (540C → T, rs2307424) and PXR (44477T → C, rs1523130; 63396C → T, rs2472677; and 69789A → G, rs763645) was conducted. Binary logistic regression using the backwards method was employed to assess the influence of SNPs and demographics on early discontinuation. Results Of the 373 patients, 131 withdrew from therapy within the first 3 months. Black ethnicity [odds ratio (OR) = 0.27; P = 0.0001], CYP2B6 516TT (OR = 2.81; P = 0.006), CAR rs2307424 CC (OR = 1.92; P = 0.007) and smoking status (OR = 0.45; P = 0.002) were associated with discontinuation within 3 months. Conclusions These data indicate that genetic variability in CYP2B6 and CAR contributes to early treatment discontinuation for efavirenz-based antiretroviral regimens. Further studies are now required to define the clinical utility of these association

Long-term Mortality in HIV-Positive Individuals Virally Suppressed for >3 Years With Incomplete CD4 Recovery

Virally suppressed HIV-positive individuals on combination antiretroviral therapy who do not achieve a CD4 count >200 cells/µL have substantially increased long-term mortality. The increased mortality was seen across different patient groups and for all causes of deat

The Competence Network for HIV/AIDS. Data, Samples, Facts

With funding for the Competence Networks in Medicine from the Federal Ministry of Education and Research, the Competence Network for HIV/AIDS (KompNet HIV/AIDS) was established as an interdisciplinary research association. Essential working groups were incorporated all over Germany, which are active in clinical and basic HIV/AIDS research. After successful establishment, providing research infrastructure for national and international cooperation in the field of HIV/AIDS was the focus of the network. By bringing together research activities, preconditions are created for improving HIV infection treatment and increasing life expectancy of HIV-infected patients. The members of KompNet HIV/AIDS are HIV experts from university clinics, HIV physicians, patient representatives, as well as national reference centers. As a scientific research basis, the network established an HIV patient cohort. Clinical and sociodemographic data of HIV patients were documented biannually and complemented by serum and DNA-samples collected twice per year. Furthermore, a child cohort was set up. Within the KompNet HIV/AIDS, a research infrastructure for HIV was established for internal, external as well international scientists. Within the HIV cohort a total of 16,500 patients are documented. The associated biobank comprises similar to 56,000 serum samples and similar to 16,000 DNA samples. The child cohort consists of 647 HIV-exposed and 230 infected children. The KompNet HIV/AIDS cohorts became an important partner in several international collaborations. Nevertheless, the maintenance of such infrastructures without public funding is a challenge

HIV-Präexpositionsprophylaxe-Versorgung in intersektoraler Zusammenarbeit

$\it Hintergrund$ Zur HIV("human immunodeficiency virus")-Präexpositionsprophylaxe (PrEP) wird am WIR – Walk In Ruhr – Zentrum für Sexuelle Gesundheit und Medizin ein innovatives Modellprojekt zur intersektoralen PrEP-Versorgung durchgeführt. $\it Forschungsziele$ Die vorliegende Studie beschreibt, wer mit der PrEP versorgt wurde und wie sich im Verlauf der PrEP-Einnahme das sexuelle Risikoverhalten änderte sowie welche sexuell übertragbaren Infektionen (STI) und unerwünschte Arzneimittelwirkungen auftraten. $\it Methoden$ In die Studie wurden bisher $\it N$ = 139 Probanden eingeschlossen, die zwischen 10/2017 und 12/2018 mit einer PrEP begonnen haben. Alle PrEP-Nutzer erhielten Fragebögen, zudem wurden Nebenwirkungen, HIV und andere STI mittels klinischer Laborwerte über einen Zeitraum von 13 Monaten erfasst. $\it Ergebnisse$ Die PrEP-Nutzer hatten ein durchschnittliches Alter von 38 Jahren, waren zu 98,6 % Männer, die Sex mit Männern (MSM) hatten, und zeichneten sich durch einen hohen Bildungsstatus und geringe Arbeitslosigkeit aus. Die durchschnittliche Partneranzahl pro Proband innerhalb der letzten 6 Monate stieg im Verlauf signifikant an, während die Kondomnutzung signifikant zurückging. Innerhalb der ersten 4 Monate nach PrEP-Beginn traten 44 STI bei 34 Patienten auf. Es wurde keine HIV-Infektion festgestellt. In den ersten 4 Wochen nach PrEP-Beginn zeigten sich bei 38,8 % der Probanden unerwünschte Arzneimittelwirkungen, hauptsächlich Symptome des Magen-Darm-Trakts. $\it Schlussfolgerung$ Die PrEP-Nutzer hatten einen guten Bildungsstatus und einen festen Arbeitsplatz bzw. eine Ausbildungsstelle. Das sexuelle Risikoverhalten nahm im Verlauf zu, verbunden mit einem gehäuften Auftreten von STI. Unerwünschte Arzneimittelwirkungen zeigten sich insbesondere zu Anfang der PrEP-Einnahme.$\it Background$ HIV pre-exposure prophylaxis (PrEP), a further opportunity to prevent HIV, is available at the WIR—Walk In Ruhr, Centre for Sexual Health and Medicine, as part of an innovative model project for intersectoral PrEP care. $\textit {Research objectives}$ The present study describes the collective of persons provided with PrEP and how PrEP use influences sexual risk behaviour, the incidence of sexually transmitted diseases (STD) and adverse drug reactions. $\it Methods$ A total of 139 men who started PrEP between 10/2017 and 12/2018 have been included in the study. During a period of 13 months of PrEP treatment, all PrEP users received questionnaires; side effects, HIV and other STI were also monitored via clinical laboratory examinations. $\it Results$ The participants’ average age was 38 years and 98.6% of them were men who had sex with men (MSM). Most of them had a high educational background; the unemployment rate was low. The average number of sexual partners within the last 6 months increased significantly, while the use of condoms decreased. In all, 44 STI were found in 34 participants within the first 4 months. No one was infected with HIV. Within the first 4 weeks of PrEP, 38.8% of the participants suffered from side effects, mainly gastrointestinal symptoms. $\it Conclusion$ Most of the participants were working in a job or a vocational training. The sexual risk behaviour increased in the course of using PrEP resulting in a high incidence of STD. Side effects appeared most frequently in the first few weeks after starting PrEP

Serological evidence of increased susceptibility to varicella-zoster virus reactivation or reinfection in natalizumab-treated patients with multiple sclerosis

Background: Serious adverse drug reactions of disease-modifying drugs in multiple sclerosis (MS) therapy may include enhanced susceptibility to reactivation of neurotropic herpes viruses like varicella-zoster virus (VZV) and the John Cunningham (JC) polyomavirus. Objective: Because symptomatic reactivation of these viruses are rare events, we determined the incidence of rises in anti-VZV IgG antibody levels as a potential marker for enhanced susceptibility to subclinical and symptomatic reactivation of neurotropic viruses. Methods: Anti-VZV IgG levels were measured in paired serum samples taken 6–8 months apart from natalizumab-treated MS patients, healthy blood donors and human immunodeficiency virus (HIV) infected patients. Results: The incidence of significant rises in anti-VZV IgG levels in natalizumab-treated MS patients was 4.26 per 100 person-years, which was significantly higher than in healthy blood donors. Retrospective evaluation of the available medical records of patients with rises of anti-VZV IgG levels did not reveal herpes zoster (i.e. shingles) manifestations. Conclusions: The increased incidence of significant rises of anti-VZV IgG levels in natalizumab-treated MS patients might indicate an association of natalizumab treatment of MS with an elevated risk of a subclinical VZV reactivation and/or reinfection events. Whether this is predictive of an increased risk of herpes zoster or even symptomatic reactivation of other neurotropic viruses remains to be determined in larger prospective studies