The use and impact of European Testing Week regional awareness campaigns to increase HIV and viral hepatitis testing coverage.

INTRODUCTION: Since 2013, the European Testing Week (ETW) awareness campaign has become a key regional event influencing testing efforts for HIV, viral hepatitis, and sexually transmitted infections (STIs) through participation of 720 organizations. Here, we report on a survey from May to June 2022 aimed at assessing the participant-reported impact of the campaign. METHODS: All past and current participating organizations were asked to complete an online questionnaire between 12 May and 17 June 2022. Multiple choice and open-text questions included organization information, usage of ETW to engage in local testing-related activities, and the effect of a regional campaign to reach a wider audience and generate impact. RESULTS: Of the 52 respondents, 34 (65%) stated first participating in ETW 5-10 years ago. ETW was used for awareness raising by 40 respondents (83%), new testing activities by 37 (77%), advocacy initiatives by 15 (31%), and training/capacity building by 18 (38%). For awareness raising, 95% used ETW to highlight the importance of and to encourage testing; for new testing activities, 74% used ETW to reach new groups. In total, 44 (85%) reported added benefits of a Europe-wide campaign compared with national/local campaigns, particularly the increased visibility and collaboration opportunities. Impact at the local level was observed by 24 (51%), and impact at a national level was observed by 20 (43%). A total of 28 (79%) reported increases in the number of tests performed and 25 (75%) reported increases in clients accessing services. CONCLUSIONS: Regional awareness campaigns reach wider audiences, boost local and national efforts to increase testing, and sensitize key populations about the critical value of testing compared with local/national campaigns.

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.

Rabies post-exposure prophylaxis in Germany - What are the challenges?

Rabies post-exposure prophylaxis (R-PEP) including wound treatment, vaccination and application of rabies immunoglobulin (RIG) is essential in preventing rabies mortality. Today, Germany is officially declared free from terrestrial rabies and rabies is only found in bats. However, physicians in A&E Departments are frequently consulted on the need for R-PEP. We retrospectively analysed patients who received R-PEP at the A&E Department of the University Hospital Bonn between 01.01.2013 and 30.06.2019. Demographic data, travel history, clinical and laboratory findings, previous rabies vaccinations and R-PEP vaccination regimen were recorded. During the study period, 90 patients received R-PEP at the University Hospital Bonn, in 10 cases without indication for R-PEP. Altogether, we found deviations from R-PEP guidelines in 51% (n = 41/80). Infiltration of RIG was missed in 12 patients and incorrectly administrated in 24 patients. Furthermore, vaccination scheme was incorrect in 11 patients. Correct wound washing and documentation of tetanus status was missing in 14% and 63% of patients, respectively. Despite rabies elimination in Germany patients frequently seek advice for R-PEP, the majority returning from foreign travel. Our data show that there is a high need for education on indication for R-PEP before and after travel and for implementation of precise R-PEP guidelines in daily clinical practice.

COVID-19 research: an opinion piece.

The unprecedented global scale of COVID-19 globally has triggered a race to discover interventions to reduce associated morbidity and mortality and rapid release of research findings prior to any degree of critical review. As with previous novel infection outbreaks, antiretrovirals are just one drug class that has been held up as a potential strategy for prophylaxis and treatment with scant evidence and risk of harm. Here we summarize the evidence for antiretrovirals to treat COVID-19 and, as a drug that has also been studied in HIV, hydroxychloroquine, and flag some of the pitfalls of using therapies that have not been evaluated robustly.

Switching tenofovir disoproxil fumarate to tenofovir alafenamide in a real life setting: what are the implications?

OBJECTIVES: Development of novel antiretrovirals aims at reducing long-term toxicities. Tenofovir disoproxil fumarate (TDF) has been associated with potential nephrotoxicity. The aim of our study was to assess the impact of switching from TDF to tenofovir alafenamide (TAF) on functional nephropathy and lipid parameters in a real-life setting. METHODS: We retrospectively analysed data from 347 HIV-infected patients switching from a TDF- to a TAF-containing regimen between April and December 2016. Sociodemographic, clinical and laboratory data were collected at TDF-to-TAF switch, and at 3 and 6 months thereafter. Proteinuria and albuminuria were classified according to Kidney Diseases Improving Global Outcomes (KDIGO) guidelines. RESULTS: At time of switch, moderately and severely increased proteinuria was detected in 32% and 8% of patients, respectively; however, urine dipstick analysis was negative in 84% and 42%, respectively. Moderately and severely increased albuminuria was found in 17% and 3% of patients, respectively. In patients with a urinary protein-to-creatinine ratio (UPCR) ≥ 150 mg/g, the mean value declined from 416 mg/g at baseline to 272 mg/g (P < 0.001) and 242 mg/g (P < 0.001) after 3 and 6 months, respectively. Patients with an albumin-to-creatinine ratio (UACR) ≥ 30 mg/g showed no significant decrease of albuminuria. Mean total cholesterol increased from 187 mg/dL at baseline to 202 (P < 0.001) and 208 mg/dL (P < 0.001) at 3 and 6 months, respectively, and mean low-density lipoprotein (LDL) cholesterol increased from 114 mg/dL at baseline to 124 (P < 0.001) and 128 mg/dL (P < 0.001), respectively. As mean high-density lipoprotein (HDL) cholesterol increased from 50 mg/dL at baseline to 54 (P < 0.001) and 57 mg/dL (P < 0.001) at 3 and 6 months, respectively, the LDL:HDL ratio remained stable. CONCLUSIONS: In an aging HIV-infected cohort, proteinuria and albuminuria were common findings and were underdiagnosed via urine dipstick. Our real-life data suggest that laboratory markers of moderately/severely increased proteinuria improved after TDF-to-TAF-switch. Lipid profiles were not aggravated. Long-term follow-up is needed to determine the clinical benefit of the TDF-to-TAF switch.

The EuroSIDA study: 25 years of scientific achievements.

The EuroSIDA study was initiated in 1994 and follows adult people living with HIV (PLHIV) in 100 collaborating clinics across 35 countries covering all European regions, Israel and Argentina. The study aims to study the long-term virological, immunological and clinical outcomes of PLHIV and to monitor temporal changes and regional differences in outcomes across Europe. Annually collected data include basic demographic characteristics, information on AIDS- and non-AIDS-related clinical events, and details about antiretroviral therapy (ART), hepatitis C treatment and other medications, in addition to a range of laboratory values. The summer 2016 data set held data from a total of 23 071 individuals contributing 174 481 person-years of follow-up, while EuroSIDA's unique plasma repository held over 160 000 samples. Over the past 25 years, close to 300 articles have been published in peer-reviewed journals (h-index 52), covering a range of scientific focus areas, including monitoring of clinical and virological outcomes, ART uptake, efficacy and adverse events, the influence of hepatitis virus coinfection, variation in the quality of HIV care and management across settings and regions, and biomarker research. Recognizing that there remain unresolved issues in the clinical care and management of PLHIV in Europe, EuroSIDA was one of the cohorts to found The International Cohort Consortium of Infectious Disease (RESPOND) cohort consortium on infectious diseases in 2017. In celebration of the EuroSIDA study's 25th anniversary, this article aims to summarize key scientific findings and outline current and future scientific focus areas.

Liver stiffness regression after successful Hepatitis C treatment is independent of HIV coinfection.

OBJECTIVES: The aim of the study was to assess the regression of liver stiffness after successful direct-acting antiviral (DAA) treatment in patients with hepatitis C virus (HCV) monoinfection and HCV/-HIV coinfection. In addition, we aimed to identify factors associated with liver stiffness regression. METHODS: We studied patients treated with interferon-free DAA regimens with a sustained virological response at week 12 (SVR12 ) or 24 (SVR24 ) post-treatment. Liver stiffness was assessed by transient elastography (TE) before the initiation and after the end of treatment (median 12 weeks). RESULTS: Of 214 enrolled patients, 85 (40%) were HCV monoinfected and 129 (60%) HCV/HIV coinfected. Baseline median TE values were 7.8 kPa [interquartile range (IQR) 5.9-12.0 kPa] in mono-infected patients and 10.7 kPa (IQR 7.8-17.0 kPa) in coinfected patients. Overall, the median TE value decreased from 10.1 to 6.8 kPa (n = 214; P < 0.0001). There was no difference between mono- and coinfected patients (-2.2 versus -3.3 kPa, respectively; P = 0.88), which was verified by an analysis of covariance (ANCOVA) adjusting for baseline TE values. Significant (≥ 30%) regression of liver stiffness was achieved by 45% of patients (54% with baseline TE ≥ 7.1 kPa). In multivariate analysis, a prior HCV treatment was a negative predictor of liver stiffness regression [odds ratio (OR) 0.31; P = 0.001]. A higher baseline TE value was positively associated with achieving a significant regression (OR 1.06; P = 0.02). HIV coinfection status, HCV genotype, age, sex, treatment duration, controlled attenuation parameter value, bilirubin concentration, platelet count and aspartate aminotransferase concentration were not associated with liver stiffness regression. CONCLUSIONS: Regression of liver stiffness after successful DAA treatment did not differ in patients with HCV monoinfection and those with HCV/HIV coinfection. Half of all patients achieved a significant (≥ 30%) regression. Prior treatment for HCV was a negative predictor for this endpoint, while a higher baseline TE value was positively associated with regression.

Establishing a hepatitis C continuum of care among HIV/hepatitis C virus-coinfected individuals in EuroSIDA.

OBJECTIVES: The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy. METHODS: Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment. RESULTS: Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n = 5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n = 3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow-up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P < 0.0001). CONCLUSIONS: In the proposed HCV continuum of care for HIV/HCV-coinfected individuals, we found major gaps at all stages, with almost 20% of anti-HCV-positive individuals having no documented HCV RNA test and a low proportion achieving SVR, in the pre-DAA era.

HIV testing for key populations in Europe: A decade of technological innovation and patient empowerment complement the role of health care professionals.

OBJECTIVES: With persisting high numbers of new HIV diagnoses in Europe, HIV testing remains an important aspect of HIV prevention. The traditional centralized and medicalized HIV testing approach has been complemented with newly developed and evaluated non-traditional approaches. Two important factors guided this process: technological innovation and empowerment of the patient. METHODS: We present a matrix to develop an HIV testing approach, and elaborate on three commonly used ones: community based testing, self-testing, and self-sampling. Despite non-traditional HIV testing approaches, barriers for testing remain. A potential disadvantage for users is the risk for false-reactive test results. As users receive an orientation test result, a reactive result should be confirmed. Another issue is the window phase, which is longer for some orientation tests compared to a traditional, laboratory-based test. RESULTS: Future implementation of non-traditional HIV testing approaches will depend on legal frameworks throughout Europe. Community testing centers may additionally improve empowerment of key populations by expanding their portfolio to testing and treatment for sexually transmitted infections. Community engagement and ownership may imply a shrinking role for health care providers, but they remain crucial actors for personalized information, counselling and referral to specialized HIV-care for many people. CONCLUSIONS: A highly effective HIV testing strategy to reduce undiagnosed people living with HIV in Europe is needed. Any approach, chosen according to the principles outlined in this paper, should reach the right people, diagnose them in the most accurate way, and optimize linkage to care.

The HepHIV 2017 Conference in Malta: joining forces for the earlier diagnosis of HIV and viral hepatitis.

OBJECTIVES: The objective of the article is to provide an overview of the results of the HepHIV 2017 Conference organized by the HIV in Europe initiative under the Maltese EU Presidency in January 2017. METHODS: A thourough review of all conference presentations (oral and poster presentations) was performed to retrieve the key outcomes of the conference. RESULTS: The key result from the conference was a call to action summarising key priorities in HIV and viral hepatitis testing and linkage to care. This included improving monitoring of viral hepatitis and HIV, mixing testing strategies and ensuring policy support. The important contribution and outcomes of EU funded projects OptTEST and EuroHIVEdat was highlighted. CONCLUSION: An integrated approach to earlier testing and linkage to care across diseases is needed in Europe and the HepHIV conferences create an important forum to reach this aim.

Rates of sustained virological response 12 weeks after the scheduled end of direct-acting antiviral (DAA)-based hepatitis C virus (HCV) therapy from the National German HCV registry: does HIV coinfection impair the response to DAA combination therapy?

OBJECTIVES: The European Association for the Study of the Liver (EASL) treatment recommendations for hepatitis C no longer discriminate between HIV/hepatitis C virus (HCV)-coinfected and HCV-monoinfected patients. However, recent data from Spain are questioning these recommendations on the basis of the findings of higher relapse rates and lower cure rates in HIV/HCV-infected subjects. The aim of our study was to compare HCV cure rates in monoinfected and coinfected patients from Germany. METHODS: Data acquired from the Deutsches Hepatitis C-Registry were analysed. A total of 5657 HCV-monoinfected subjects and 488 HIV/HCV-coinfected patients were included in the study. Rates of sustained virological response 12 weeks after the scheduled end of therapy (SVR12) were collected in both subgroups and in cirrhotic and noncirrhotic patients. RESULTS: HIV/HCV-coinfected patients were more frequently male (84.6% vs. 56.4%, respectively; P < 0.001) and younger than HCV-monoinfected subjects (46.5 ± 9 vs. 53.8 ± 12.5 years, respectively; P < 0.001). The CD4 blood cell count was > 350 cells/µL in 63.1% of HIV-positive subjects and 88.7% were on antiretroviral therapy. SVR12 rates were 90.3% (5111 of 5657) in our HCV-monoinfected cohort and 91.2% (445 of 488) in our coinfected patients. Liver cirrhosis was confirmed in 1667 of 5657 (29.5%) monoinfected patients and 84 of 488 (17.2%; P < 0.001) coinfected patients. SVR12 rates did not differ between HCV-monoinfected and HIV/HCV-coinfected patients with liver cirrhosis (87.8% vs. 89.3%, respectively; P = 0.864). A treatment duration of 8 weeks did not reduce the percentage of patients with SVR12 in either subgroup (93.7% in both groups). CONCLUSIONS: We found high SVR12 rates in monoinfected as well as coinfected individuals. No differences were detected between the two subgroups regardless of whether there was accompanying liver cirrhosis or a shortened treatment duration.

Week 96 results of the randomized, multicentre Maraviroc Switch (MARCH) study.

OBJECTIVES: The Maraviroc Switch (MARCH) study week 48 data demonstrated that maraviroc, a chemokine receptor-5 (CCR5) inhibitor, was a safe and effective switch for the ritonavir-boosted protease inhibitor (PI/r) component of a two nucleos(t)ide reverse transcriptase inhibitor [N(t)RTI] plus PI/r-based antiretroviral regimen in patients with R5-tropic virus. Here we report the durability of this finding. METHODS: MARCH, an international, multicentre, randomized, 96-week open-label switch study, enrolled HIV-1-infected adults with R5-tropic virus who were stable (> 24 weeks) and virologically suppressed [plasma viral load (pVL) < 50 HIV-1 RNA copies/mL]. Participants were randomized to continue their current PI/r-based regimen (PI/r) or to switch to MVC plus two N(t)RTIs (MVC) (1:2 randomization). The primary endpoint was the difference in the proportion with pVL < 200 copies/mL at 96 weeks. The switch arm was defined as noninferior if the lower limit of the 95% confidence interval (CI) for the difference was < -12% in the intention-to-treat (ITT) population. Safety endpoints (the difference in the mean change from baseline or a comparison of proportions) were analysed as key secondary endpoints. RESULTS: Eighty-two (PI/r) and 156 (MVC) participants were randomized and included in the ITT analysis; 71 (87%) and 130 (83%) were in follow-up and on therapy at week 96. At week 96, 89.0% and 90.4% in the PI/r and MVC arms, respectively, had pVL < 50 copies/mL (95% CI -6.6, 10.2). Moreover, in those switching away from PI/r, there were significant reductions in mean total cholesterol (differences 0.31 mmol/L; P = 0.02) and triglycerides (difference 0.44 mmol/L; P < 0.001). Changes in CD4 T-cell count, renal function, and serious and nonserious adverse events were similar in the two arms. CONCLUSIONS: MVC as a switch for a PI/r is safe and effective at maintaining virological suppression while having significant lipid benefits over 96 weeks.

Hepatitis C virus (HCV) RNA profiles among chronic HIV/HCV-coinfected individuals in ESPRIT; spontaneous HCV RNA clearance observed in nine individuals.

OBJECTIVES: Studies have shown that hepatitis C virus (HCV) RNA levels remain stable over time in HIV/HCV-coinfected individuals taking combination antiretroviral therapy (cART), while spontaneous clearance of HCV RNA during the persistent infection phase has been documented only rarely among those with the CC interleukin (IL)-28B genotype. This study describes HCV RNA profiles and factors associated with changes over time in HCV RNA levels in the ESPRIT study. METHODS: HIV/HCV-coinfected individuals positive for HCV RNA were included in the study. Follow-up was counted from the first HCV RNA positive test and censored at the initiation of interferon-based treatment. HCV RNA and IL-28B measurements were performed in the same reference laboratory. Random effects mixed models were used to analyse changes over time in HCV RNA. RESULTS: A total of 312 ESPRIT patients were included in the study (151 in the arm receiving subcutaneous recombinant IL-2 and 161 in the control arm). Most of the patients were white (89%) and male (76%), and they had a median of 5 HCV RNA measurements per person [interquartile range (IQR) 3-6; range 1-9]. Median follow-up was 5 years (IQR: 2-6 years). At baseline, 96% of patients were taking cART and 93% had undetectable HIV RNA. Mean HCV RNA levels decreased by 13% per year over the study period [95% confidence interval (CI) 8-18%; P < 0.0001]. Baseline HCV RNA levels and the change over time in HCV RNA did not differ by randomization arm (P = 0.16 and P = 0.56, respectively). Nine individuals spontaneously cleared HCV RNA during follow-up [IL-28B genotypes: CC, five patients (56%); CT, four patients (44%)]. CONCLUSIONS: HCV RNA levels decreased over time in this population with well-controlled HIV infection. Spontaneous clearance of HCV RNA was documented in five individuals with IL-28B genotype CC and four with the CT genotype.

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.

[Strategies for the Treatment of Community-Acquired Pneumonia in HIV-Positive Patients]. / Strategien zur Behandlung von ambulant erworbener Pneumonie bei HIV-positiven Patienten.

Study purpose According to the Robert Koch Institute, 84,700 people in Germany suffer from HIV infection. One-third of the affected persons is over 50 years old. In Germany, community-acquired pneumonia (CAP) is a widespread disease with more than 250,000 cases per year. Incidence and mortality increase with the age of the affected individuals. For this reason, diagnostic and therapeutic strategies are needed to guide medical care of HIV-infected patients presenting with CAP. Methodology HIV therapists were interviewed about their diagnostic approach, risk stratification strategy and therapeutic approach to HIV-associated community-acquired pneumonia (HIV +/CAP) using a questionnaire. 56 completed questionnaires were analysed. Results Half of the respondents reported that CAP occurred in 1 to 5 % of HIV-infected individuals per year. This indicates an estimated number of up to 4200 HIV +/CAP cases per year in Germany - a much higher number than expected from the literature. 58.9 % of respondents considered that the pathogenic spectrum did not differ in HIV +/CAP from non-HIV/CAP. 80.3 % of respondents applied the same antibiotic regimens in HIV +/CAP as used in patients with non-HIV/CAP. Conclusion Even though over 40 % of HIV therapists agree that the pathogenic spectrum of HIV +/CAP differs from that of non-HIV/CAP, over 80 % of therapists managed these patients in accordance with the S3-guidelines for non-immunocompromised CAP-patients, because specific guidelines for the treatment of HIV +/CAP are lacking. Since specific data on the aetiology and the clinical course of HIV +/CAP depending, for instance, on CD4-count and antiretroviral therapy are missing, we feel that the clinical course of HIV +/CAP should be further analysed in the context of prospective cohort studies.

Liver Retransplantation in Patients With HIV-1 Infection: An International Multicenter Cohort Study.

Liver retransplantation is performed in HIV-infected patients, although its outcome is not well known. In an international cohort study (eight countries), 37 (6%; 32 coinfected with hepatitis C virus [HCV] and five with hepatitis B virus [HBV]) of 600 HIV-infected patients who had undergone liver transplant were retransplanted. The main indications for retransplantation were vascular complications (35%), primary graft nonfunction (22%), rejection (19%), and HCV recurrence (13%). Overall, 19 patients (51%) died after retransplantation. Survival at 1, 3, and 5 years was 56%, 51%, and 51%, respectively. Among patients with HCV coinfection, HCV RNA replication status at retransplantation was the only significant prognostic factor. Patients with undetectable versus detectable HCV RNA had a survival probability of 80% versus 39% at 1 year and 80% versus 30% at 3 and 5 years (p = 0.025). Recurrence of hepatitis C was the main cause of death in the latter. Patients with HBV coinfection had survival of 80% at 1, 3, and 5 years after retransplantation. HIV infection was adequately controlled with antiretroviral therapy. In conclusion, liver retransplantation is an acceptable option for HIV-infected patients with HBV or HCV coinfection but undetectable HCV RNA. Retransplantation in patients with HCV replication should be reassessed prospectively in the era of new direct antiviral agents.

Infection-related and -unrelated malignancies, HIV and the aging population.

OBJECTIVES: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. METHODS: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. RESULTS: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/µL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/µL], independent of age, while a CD4 count < 200 cells/µL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40-4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5-5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2-7.2) per 1000 person-years over the same period. CONCLUSIONS: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost-benefit of screening for IURMs in HIV-infected populations.

Host and disease factors are associated with cognitive function in European HIV-infected adults prior to initiation of antiretroviral therapy.

OBJECTIVES: Deficits in cognitive function remain prevalent in HIV-infected individuals. The aim of this European multicentre study was to assess factors associated with cognitive function in antiretroviral therapy (ART)-naïve HIV-infected subjects at the time of enrolment in the NEAT 001/Agence Nationale de Recherche sur le SIDA (ANRS) 143 study. METHODS: Prior to starting ART, seven cognitive tests exploring domains including episodic memory, verbal fluency, executive function and psychomotor speed were administered with scores standardized to z-score using the study population sample mean and standard deviation. The primary measure was overall z-score average (NPZ). We assessed associations between baseline factors and test results using multivariable regression models. RESULTS: Of 283 subjects with baseline cognitive assessments, 90% were male and 12% of black ethnicity. Median (interquartile range) age, years of education, years of known HIV infection, baseline CD4 count and baseline HIV RNA were 39 (31, 47) years, 13 (11, 17) years, 1 (0, 4) years, 344 (279, 410) cells/µL and 4.74 (4.28, 5.14) log10 HIV-1 RNA copies/mL, respectively. Forty per cent were current smokers. Factors significantly associated with poorer overall cognitive performance in multivariable models included older age, shorter duration of education, black ethnicity, lower height, and lower plasma HIV RNA. CONCLUSIONS: In this large, European-wide, ART-naïve population with relatively preserved immunity and early HIV infection, cognitive function scores at the time of ART initiation were associated with demographic and HIV-disease factors.

Essentials from the 2015 European AIDS Clinical Society (EACS) guidelines for the treatment of adult HIV-positive persons.

BACKGROUND: The European AIDS Clinical Society (EACS) guidelines are intended for all clinicians involved in the care of HIV-positive persons, and are available in print, online, and as a free App for download for iPhone and Android. GUIDELINE HIGHLIGHTS: The 2015 version of the EACS guidelines contains major revisions in all sections; antiretroviral treatment (ART), comorbidities, coinfections and opportunistic diseases. Among the key revisions is the recommendation of ART for all HIV-positive persons, irrespectively of CD4 count, based on the Strategic Timing of AntiRetroviral Treatment (START) study results. The recommendations for the preferred and the alternative ART options have also been revised, and a new section on the use of pre-exposure prophylaxis (PrEP) has been added. A number of new antiretroviral drugs/drug combinations have been added to the updated tables on drug-drug interactions, adverse drug effects, dose adjustment for renal/liver insufficiency and for ART administration in persons with swallowing difficulties. The revisions of the coinfection section reflect the major advances in anti-hepatitis C virus (HCV) treatment with direct-acting antivirals with earlier start of treatment in individuals at increased risk of liver disease progression, and a phasing out of interferon-containing treatment regimens. The section on opportunistic diseases has been restructured according to individual pathogens/diseases and a new overview table has been added on CD4 count thresholds for different primary prophylaxes. CONCLUSIONS: The diagnosis and management of HIV infection and related coinfections, opportunistic diseases and comorbidities continue to require a multidisciplinary effort for which the 2015 version of the EACS guidelines provides an easily accessable and updated overview.

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.