Still trouble with bleeding: Risk factors for HCV transmission in men who have sex with men and behavioural trajectories from 2019 to 2021.

OBJECTIVES: To identify sexual/sex-associated risk factors for hepatitis C transmission among men who have sex with men (MSM) and visualise behavioural trajectories from 2019 to 2021. METHODS: We linked a behavioural survey to a hepatitis C cohort study (NoCo), established in 2019 across six German HIV/hepatitis C virus (HCV) treatment centres, and performed a case-control analysis. Cases were MSM with recent HCV infection, and controls were matched for HIV status (model 1) or proportions of sexual partners with HIV (model 2). We conducted conditional univariable and multivariable regression analyses. RESULTS: In all, 197 cases and 314 controls completed the baseline questionnaire and could be matched with clinical data. For regression models, we restricted cases to those with HCV diagnosed since 2018 (N = 100). Factors independently associated with case status included sex-associated rectal bleeding, shared fisting lubricant, anal douching, chemsex, intravenous and intracavernosal injections, with population-attributable fractions of 88% (model 1) and 85% (model 2). These factors remained stable over time among cases, while sexual partner numbers and group sex decreased during COVID-19 measures. CONCLUSIONS: Sexual/sex-associated practices leading to blood exposure are key factors in HCV transmission in MSM. Public health interventions should emphasize the importance of blood safety in sexual encounters. Micro-elimination efforts were temporarily aided by reduced opportunities for sexual encounters during the COVID-19 pandemic.

Recently acquired HCV infection in men who have sex with men in Germany in the direct-acting antivirals era and during the COVID-19 pandemic.

INTRODUCTION: Direct-acting antivirals (DAAs) are key to eliminating hepatitis C virus (HCV). In men who have sex with men (MSM) with HIV co-infection, recently acquired HCV infection is common. Sexual practices and reinfection rates may hamper micro-elimination despite high treatment rates. METHODS: The cohort included MSM with recently acquired HCV infection from 2014 to 2021. The patients' demographic, clinical, behavioural, and laboratory data and treatment and reinfection outcomes were documented. RESULTS: A total of 237 men with recently acquired HCV infection were included: 216 (91%) had HIV. The median age was 46 years (interquartile range [IQR] 39-52), and the median CD4 count was 660/mm3 (IQR 527-835). The annual incidence of recently acquired HCV remained between 0.28% and 0.43% but dropped to 0.02% in 2021 during the COVID pandemic, almost reaching micro-elimination. The reinfection incidence was 15.5 per 100 patient-years (95% confidence interval 12.6-18.8), and reinfection was associated with the use of crystal methamphetamine (p = 0.032) and ketamine (p = 0.042). In total, 31.3% had multiple reinfections, and four reinfections occurred in users of pre-exposure prophylaxis. CONCLUSIONS: High treatment and cure rates did not lead to HCV elimination. A change in sexual behaviour, potentially imposed by COVID-19 restrictions, led to micro-elimination in the NoCo cohort. As recently acquired HCV is prevalent in MSM with and without HIV, surveillance is necessary to consolidate elimination goals.

Is doxycycline post-exposure prophylaxis being utilised in Germany? Insights from an online survey among German men who have sex with men.

PURPOSE: Doxycycline post-exposure prophylaxis (Doxy-PEP) reduces the likelihood of Chlamydia and early syphilis by approximately two-thirds. Currently, data on the frequency of Doxy-PEP use in men who have sex with men (MSM) are limited. This study aimed to assess knowledge, attitude towards, and frequency of Doxy-PEP use among MSM in Germany. METHODS: We conducted a national online survey in Germany from summer to fall 2023, recruiting MSM and transgender women. Participants were invited to complete the online survey through social media, online dating platforms, and print media advertisements with active recruitment and poster advertising in private practices, tertiary outpatient clinics, and MSM community events in Germany. RESULTS: In total, 438 participants completed the survey and were included in the analysis, and 285 (65.1%) were living with the human immunodeficiency virus (HIV) or taking HIV-pre-exposure prophylaxis (PrEP). Overall, 170 participants (38.8%) had heard of Doxy-PEP, and 275 (62.8%) would consider taking it, but only 32 (7.3%) reported having ever taken Doxy-PEP. The most common reason for a negative attitude towards Doxy-PEP were apprehension about insufficient detailed information, and concerns about antibiotic resistance. Doxy-PEP users were more likely to be on HIV-PrEP, had a higher self-reported risk of bacterial sexually transmitted infections (STIs), and often had a history of bacterial STIs. CONCLUSION: The study demonstrated high awareness and strong interest in Doxy-PEP among MSM in Germany, most of whom were living with HIV or taking HIV-PrEP; however, the actual usage of Doxy-PEP remains low in the summer and fall of 2023.

A seroprevalence study indicates a high proportion of clinically undiagnosed MPXV infections in men who have sex with men in Berlin, Germany.

INTRODUCTION: During the mpox outbreak in 2022, the highest number of cases in Germany were registered in Berlin, almost all of them in men who have sex with men (MSM). However, the frequency of clinically undiagnosed infections is unknown. METHODS: A cross-sectional study was conducted among MSM in Berlin, Germany. Participants were recruited from private practices and community-based checkpoints specialised in HIV and STI care for MSM. They were asked to complete an online questionnaire on socio-demographic data, mpox diagnosis, vaccination history and sexual behaviour, and to provide a blood sample for serological analysis. The samples were tested for antibodies against a range of antigens to distinguish between antibodies induced by mpox infection and MVA vaccination, with pre-immune sera from childhood smallpox vaccination as a confounding factor. Associations of behavioural variables with reported and suspected mpox diagnosis as the outcome were tested using univariable and multivariable logistic regression models. RESULTS: Between the 11th April and 1st July 2023, 1,119 participants were recruited in eight private practices and two community-based checkpoints in Berlin. All participants provided a blood sample for serological testing. Information for the online questionnaire was provided by 728 participants; core data on age and mpox history for participants who did not provide questionnaire data were provided by the practices for an additional 218 participants. A previous diagnosis of mpox was reported for/by 70 participants (7.4%). Using a conservative and strict case definition, we serologically identified an additional 91 individuals with suspected undiagnosed mpox infection. Individuals with reported or suspected mpox infections reported more condomless anal sex partners in the past 3 months (OR = 5.93; 95% CI 2.10-18.35 for 5-10 partners; OR = 9.53; 95% CI 2.72-37.54 for > 10 partners) and were more likely to report sexual contact with partners diagnosed with mpox (OR = 2.87; 95% CI 1.39-5.84). CONCLUSION: A substantial proportion of mpox infections were clinically undiagnosed. The number of condomless anal sex partners was strongly associated with both confirmed and suspected undiagnosed mpox infection. Therefore, mpox control measures based on clinical diagnosis of mpox are likely to have limited effectiveness in preventing mpox transmission in outbreak situations because many infections remain unrecognised and undiagnosed.

Long-Acting Cabotegravir and Rilpivirine for Maintenance of HIV-1 Suppression.

BACKGROUND: Simplified regimens for the treatment of human immunodeficiency virus type 1 (HIV-1) infection may increase patient satisfaction and facilitate adherence. METHODS: In this phase 3, open-label, multicenter, noninferiority trial involving patients who had had plasma HIV-1 RNA levels of less than 50 copies per milliliter for at least 6 months while taking standard oral antiretroviral therapy, we randomly assigned participants (1:1) to either continue their oral therapy or switch to monthly intramuscular injections of long-acting cabotegravir, an HIV-1 integrase strand-transfer inhibitor, and long-acting rilpivirine, a nonnucleoside reverse-transcriptase inhibitor. The primary end point was the percentage of participants with an HIV-1 RNA level of 50 copies per milliliter or higher at week 48, determined with the use of the Food and Drug Administration snapshot algorithm. RESULTS: Treatment was initiated in 308 participants per group. At week 48, HIV-1 RNA levels of 50 copies per milliliter or higher were found in 5 participants (1.6%) receiving long-acting therapy and in 3 (1.0%) receiving oral therapy (adjusted difference, 0.6 percentage points; 95% confidence interval [CI], -1.2 to 2.5), a result that met the criterion for noninferiority for the primary end point (noninferiority margin, 6 percentage points). An HIV-1 RNA level of less than 50 copies per milliliter at week 48 was found in 92.5% of participants receiving long-acting therapy and in 95.5% of those receiving oral therapy (adjusted difference, -3.0 percentage points; 95% CI, -6.7 to 0.7), a result that met the criterion for noninferiority for this end point (noninferiority margin, -10 percentage points). Virologic failure was confirmed in 3 participants who received long-acting therapy and 4 participants who received oral therapy. Adverse events were more common in the long-acting-therapy group and included injection-site pain, which occurred in 231 recipients (75%) of long-acting therapy and was mild or moderate in most cases; 1% withdrew because of this event. Serious adverse events were reported in no more than 5% of participants in each group. CONCLUSIONS: Monthly injections of long-acting cabotegravir and rilpivirine were noninferior to standard oral therapy for maintaining HIV-1 suppression. Injection-related adverse events were common but only infrequently led to medication withdrawal. (Funded by ViiV Healthcare and Janssen; ATLAS ClinicalTrials.gov number, NCT02951052.).

Screening HIV Patients at Risk for NAFLD Using MRI-PDFF and Transient Elastography: A European Multicenter Prospective Study.

BACKGROUND & AIMS: Nonalcoholic fatty liver disease (NAFLD) is a growing concern in the aging population with human immunodeficiency virus (HIV). Screening for NAFLD is recommended in patients with metabolic risk factors or unexplained transaminitis. This study aimed to prospectively assess the prevalence and associated factors of liver steatosis and advanced fibrosis (AF) in HIV-monoinfected patients at risk of NAFLD. METHODS: We conducted a multicenter study in HIV-monoinfected patients, nonexcessive drinkers with metabolic syndrome, and/or persistently elevated liver enzymes, and/or clinical lipodystrophy. All participants had magnetic resonance imaging proton density fat fraction (MRI-PDFF), Fibroscan/controlled attenuation parameter (CAP), and cytokine and genetic analysis. RESULTS: From March 2014 to November 2015, we enrolled 442 participants and analyzed 402: male (85%); median age, 55 years (interquartile range [IQR], 50-61 years); body mass index, 27.0 kg/m2 (IQR, 23.6-28.7 kg/m2); metabolic syndrome (67%); and CD4 cell count, 630/mm3 (IQR, 510-832/mm3). Overall 257 of 402 (64%) had NAFLD (MRI-PDFF ≥5%). Among them, 11.3% had a liver stiffness ≥9.6 kPa, suggestive of AF. Multivariable analysis identified 7 factors of steatosis: high CD4-cell count (odds ratio [OR], 4.04; 95% confidence interval [CI], 1.92-8.51), high leptin level (OR, 2.12; 95% CI, 1.14-3.93), non-CC PNPLA3s738409 genetic polymorphism (OR, 1.92; 95% CI, 1.11-3.33), low high-density lipoprotein (OR, 1.83; 95% CI, 1.03-3.27), high triglycerides (OR, 1.48; 95% CI, 1.18-1.84), elevated alanine transaminase (OR, 1.23; 95% CI, 1.16-1.31), and hyper ferritinemia (OR, 1.05; 95% CI, 1.03-1.07). Two factors were associated with AF: high body mass index (OR, 1.23 ; 95% CI, 1.07-1.42 ; P = .005, and elevated aspartate aminotransferase (OR, 1.03; 95% CI, 1.01-1.05; P = .001). Using MRI-PDFF as a reference, CAP (best cutoff, 280 dB/m) had good accuracy (area under the receiver operating characteristic curve = 0.86; 95% CI, 0.82-0.90) for the diagnosis of moderate to severe steatosis. CONCLUSIONS: In a large cohort of HIV-moninfected patients at risk of NAFLD, steatosis is present in two-thirds of cases, and around 10% have AF. The CAP technique is accurate for screening steatosis in this population.

Transmitted drug resistance and subtype patterns of viruses from reported new HIV diagnoses in Germany, 2017-2020.

BACKGROUND: The transmission of resistant HIV variants jeopardizes the effective use of antiretrovirals for therapy and prophylaxis. Molecular surveillance of new HIV diagnoses with a focus on prevalence and type of resistance associated mutations and the subtype of circulating viruses is mandatory. METHOD: From 2017 to 2020, 11,527 new HIV diagnoses were reported in Germany to the Robert Koch Institute (RKI). Protease (PR) and reverse-transcriptase (RT) sequences were obtained from 4559 (39.6%) cases, and PR, RT and integrase (IN) sequences were obtained from 3097 (26.9%) cases. The sequences were analyzed with data from the national HIV reports. RESULTS: Among all cases in the analysis, the proportion of primary resistance was 4.3% for nucleoside reverse-transcriptase inhibitors (NRTIs), 9.2% for non-NRTI (NNRTIs), 3.3% for protease inhibitors (PIs) and 1.4% for integrase inhibitors (INIs). Dual-class resistance was highest for NRTIs/NNRTIs with 1.2%. There was no trend in the proportion of viruses resistant to drug classes. Most individual key mutations associated with relevant resistance had a prevalence below 1% including K65R (0.1%) and M184V (0.6%). A notable exception was K103NS, with a prevalence of 2.9% and a significant increase (pTrend=0.024) during 2017-2020. In this period, diagnoses of infections with HIV-1 subtype B were the most common at 58.7%, but its prevalence was declining (pTrend=0.049) while the frequency of minority subtypes (each < 1%) increased (pTrend=0.007). Subtype B was highest (75.6%) in men who have sex with men (MSM) and lowest in reported heterosexual transmissions (HETs, 22.6%). CONCLUSION: The percentage of primary resistance was high but at a stable level. A genotypic determination of resistance is therefore still required before the start of therapy. The subtype diversity of circulating HIV-1 is increasing.

[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.

Reinfection With the Hepatitis C Virus in Men Who Have Sex With Men After Successful Treatment With Direct-acting Antivirals in Germany: Current Incidence Rates, Compared With Rates During the Interferon Era.

BACKGROUND: Micro-elimination of the hepatitis C virus (HCV) includes treatment in populations at risk of ongoing HCV transmission, such as men who have sex with men (MSM) or people who inject drugs (PWID). We analyzed the HCV reinfection incidence rates of participants in the German hepatitis C cohort (GECCO) and compared our data to previous findings from the interferon era. METHODS: Patients with HCV reinfections in the multi-centric GECCO cohort were compared to patients in whom no reinfection occurred. The HCV reinfection incidence rate in MSM was also compared to the incidence rate in the interferon era (using data from the European Acquired Immunodeficiency Syndrome Treatment Network [NEAT]). RESULTS: Between January 2014 and April 2018, 48 HCV reinfections occurred in 2298 individuals (2%), with 2346 cured HCV episodes. The median time to reinfection was 500 days (range 16-1160) and the overall HCV reinfection incidence rate was 1.89 per 100 person-years (py; 95% confidence interval [CI], 1.41-2.48). In a multivariate analysis, the transmission risk in MSM was the only independent risk factor of HCV reinfection (odds ratio, 39.3; 95% CI, 4.57-334.40; P = .001). The incidence rate in MSM was 9.02 (95% CI, 6.48-12.26) per 100 py, compared to 1.14 per 100 py in PWID (95% CI, .56-2.09). The incidence rate for a first HCV reinfection in MSM was similar in the direct-acting antiviral era, compared to the interferon era, with a hazard ratio of 1.05 (95% CI, .64-1.74; P = .831). CONCLUSIONS: HCV reinfection remains a frequent finding among MSM in Germany. In addition to behavioral interventions, early HCV treatment and retreatment should be implemented for this subgroup to prevent HCV transmission.

Has Increased Rollout of Direct Acting Antiviral Therapy Decreased the Burden of Late Presentation and Advanced Liver Disease in Patients Starting Hepatitis C Virus Therapy in Germany?

GOALS AND BACKGROUND: International guidelines recommend prioritized treatment initiation in hepatitis C virus (HCV)-infected patients with advanced liver disease. We aimed to evaluate whether the widespread usage of direct acting antivirals (DAAs) has led to a decrease in late presentation for care. STUDY: Data derived from the multicenter German Hepatitis C Cohort (GECCO) was analyzed. Treatment naive HCV-infected patients initiating DAA-based treatment between January 2014 and September 2017 were included. Advanced liver disease was defined by aspartate aminotransferase to platelet ratio index score ≥1.5, METAVIR≥F3, or FibroScan ≥9.5 kPa. Period prevalence and risk factors for late presentation were evaluated. RESULTS: Six hundred fifty-three HCV-monoinfected and 210 HIV/HCV-coinfected patients (mean age, 48.6±12.7 y; 65.5% male) were included. Overall 32.5% of patients had advanced liver disease. In 2014 39.4% of patients presented with advanced liver disease, decreasing to 30.1%, 34.4%, and 26.4% in the years 2015, 2016, and 2017 (P=0.057), respectively. Patients with and without advanced liver disease differed in age (P<0.0001), CD4 ≤350/µL (P=0.027), genotype (P=0.005), transmission route (P=0.047), body mass index (P<0.001), and time since diagnosis (P=0.007). In the multivariable binary logistic regression analysis GT3, age above 45 years and being diagnosed >2 years ago were positively and HCV transmission through men who have sex with men was negatively associated with advanced liver disease. CONCLUSIONS: Overall 32.5% of patients presented with advanced liver disease. We observed a trend toward a lower proportion of patients starting treatment late.GT3, age, years since HCV diagnosis and HCV transmission route were identified as risk factors for presentation with advanced liver disease.

High effectiveness of recommended first-line antiretroviral therapies in Germany: a nationwide, prospective cohort study.

PURPOSE: Current German/Austrian antiretroviral treatment guidelines recommend more than 20 combination regimens for first-line therapy, without a preference. Regimens include two nucleoside reverse transcriptase inhibitors (NRTIs) plus either an integrase strand transfer inhibitor (INSTI), a non-NRTI (NNRTI) or a boosted protease inhibitor (PI). The objective was to examine the outcomes of recommended first-line ART in Germany. METHODS: This nationwide observational study included treatment-naïve chronically HIV-1 infected patients receiving one of the recommended first-line regimens. Patients were allocated to three arms (INSTI, NNRTI, PI) and were prospectively followed for 24 months. Delayed treatment initiation was defined by a baseline CD4 T-cell count of < 350/µl or CDC clinical stage C. RESULTS: Among a total of 434 patients enrolled, virologic failure was rare and occurred in 4.3% (6/141) in the PI arm, in 3.3% (4/122) in the NNRTI arm and in 0.6% (1/171) in the INSTI arm (p = 0.10). De novo drug resistance mutations developed in only two patients in the NNRTI arm. Nonetheless, treatment modifications were frequent (51%) and mostly performed for strategic reasons. Retention on all initial compounds at month 24 was 64%, 49%, and 22% in the INSTI, NNRTI and PI arms respectively. Delayed treatment initiation was common (47%) and more frequently observed in patients in the PI arm. It was not associated with virological failure. CONCLUSION: High efficacy and low virological failure rates were observed with recommended first-line regimens independent of delayed treatment initiation, chosen regimen and subsequent treatment modifications, demonstrating the validity of the current treatment guidelines.

[Prevalence of patients with HIV receiving outpatient medical care in Germany-an analysis based on secondary data]. / Häufigkeiten von Patienten mit HIV in der ambulanten Versorgung in Deutschland ­ Eine Analyse auf Basis von Sekundärdaten.

BACKGROUND: The Robert Koch Institute (RKI) annually publishes an estimate of the number of new HIV diagnoses and the total number of people diagnosed with HIV in Germany. So far, only medication prescription data have served as secondary data as a basis for such estimates. OBJECTIVES: In this study, we used billing data from the outpatient sector to estimate the number of patients with newly diagnosed HIV, the overall number of patients with HIV, and the HIV test rates in those with statutory health insurance in Germany. MATERIALS AND METHODS: We analyzed billing data from the outpatient sector for all persons covered by statutory health insurance between 2009 and 2018. We designed annual cohorts of patient for the years 2011 to 2017 and analyzed the number of HIV diagnoses, the number of HIV-related care services, and HIV testing rates. RESULTS: Every year, about 6000 new patients with HIV are treated in outpatient care. The total number of patients with HIV in 2011 was about 59,300 (0.106%), which increased to 80,800 (0.141%) in 2017. The average increase in the total number of patients per year of about 3600 was significantly below the estimated number of newly treated patients for each year. CONCLUSION: The results may provide an indication of patients receiving HIV care in the outpatient sector. The secondary data provide the possibility of developing another epidemiological data source for population-based representation of the administrative prevalence of HIV. To clarify over-representation, there is a need for further research on patients who are using outpatient care for the first time.

Eliminating Hepatitis C Virus Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men in Berlin: A Modeling Analysis.

BACKGROUND: Despite high hepatitis C virus (HCV) treatment rates, HCV incidence among human immunodeficiency virus (HIV)-infected men who have sex with men (HIV-infected MSM) in Germany rose before HCV direct-acting antivirals (DAAs). We model what intervention can achieve the World Health Organization (WHO) elimination target of an 80% reduction in HCV incidence by 2030 among HIV-infected MSM in Berlin. METHODS: An HCV transmission model among HIV-diagnosed MSM was calibrated to Berlin (rising HCV incidence and high rates of HCV testing and treatment). We modeled the HCV incidence among HIV-diagnosed MSM in Berlin until 2030 (relative to 2015 WHO baseline) under scenarios of DAA scale-up with or without behavior change (among HIV-diagnosed MSM and/or all MSM). RESULTS: Continuing current treatment rates will marginally reduce the HCV incidence among HIV-diagnosed MSM in Berlin by 2030. Scaling up DAA treatment rates, beginning in 2018, to 100% of newly diagnosed HCV infections within 3 months of diagnosis and 25% each year of previously diagnosed and untreated HCV infections could reduce the HCV incidence by 61% (95% confidence interval, 55.4%-66.7%) by 2030. The WHO target would likely be achieved by combining DAA scale-up with a 40% reduction in HCV transmission among HIV-diagnosed MSM and a 20% reduction among HIV-undiagnosed or HIV-uninfected MSM. DISCUSSION: HCV elimination among HIV-infected MSM in Berlin likely requires combining DAA scale-up with moderately effective behavioral interventions to reduce risk among all MSM.

Real-world effectiveness of sofosbuvir-based treatment regimens for chronic hepatitis C genotype 3 infection: Results from the multicenter German hepatitis C cohort (GECCO-03).

There are limited data regarding the real world effectiveness of direct acting antivirals (DAA) for the therapy of chronic genotype 3 hepatitis C virus (HCV) infection. All HCV genotype 3 infected patients from the German hepatitis C cohort (GECCO), which is a prospective database of nine German hepatitis C treatment centers, were included in the study. Three hundred forty-two chronically infected HCV genotype 3 patients were analyzed (253 males [74.0%], mean age 47.3 years, 127 cirrhotic patients [37.1%] mostly with Child A cirrhosis, 113 treatment experienced patients [37.1%], 38 HCV/HIV co-infected patients [11.1%]). SVR12 rates in the "intention-to-treat" analysis were as follows: sofosbuvir/ribavirin 69.4% (75/108), sofosbuvir/peginterferon/ribavirin 80.6% (58/72), sofosbuvir/daclatasvir ± ribavirin for 12 weeks 88.3% (53/63), sofosbuvir/daclatasvir ± ribavirin for 24 weeks 79.3% (23/29), sofosbuvir/ledipasvir ± ribavirin for 12 weeks 71.4% (10/14), and sofosbuvir/ledipasvir ± ribavirin for 24 weeks 86.7% (26/30). Forty patients were lost to follow-up, 23 patients had a relapse, 4 patients stopped treatment prematurely and 1 patient died. Female sex (P = 0.038) and treatment with two different DAAs (P = 0.05) were predictors for SVR12 in the multivariate analysis. In conclusion, sofosbuvir/daclatasvir ± ribavirin for 12 weeks and sofosbuvir/ledipasvir ± ribavirin for 24 weeks are effective for the treatment of HCV genotype 3 infected patients including cirrhotic, treatment-experienced or HIV/HCV co-infected patients.

Anxiety, depression, and health-related quality of life in aging people living with HIV compared to diabetes patients and patients with minor health conditions: a longitudinal study.

HIV infection has evolved from a fatal to a treatable condition, leading to an increase in the rate of elderly People Living with HIV (PLWH). However, little is known about the psychosocial burden of elderly PLWH. Thus, the aim of this longitudinal multi-center cohort study was to investigate whether elderly PLWH experience more anxiety and depression and reduced health related quality of life (HRQOL) compared to elderly patients with other chronic conditions. PLWH were compared to diabetes patients (DM) and patients with minor health conditions (MHC), e.g. patients with hypertension or allergic conditions. All patients were over 50 years old. Anxiety and depression (HADS) as well as HRQOL (SF-36) were assessed at baseline and after 12 months. 218 PLWH, 249 DM and 254 MHC were included. At baseline, the study groups did not differ in anxiety, depression, and physical HRQOL. However, PLWH indicated lower mental HRQOL than DM and MHC patients (p = 0.001). We did not obtain any moderating effects showing a differential effect of patient characteristics on anxiety, depression, and HRQOL in the three patient groups. At follow-up, the level of anxiety, depression, and HRQOL did not change significantly. The prevalence of anxiety ranged between 27 and 35%, and that of depression between 17 and 28%. Thus, the results of our investigation tentatively suggest that the psychosocial adaptation to HIV among elderly PLWH resembles those of other chronic diseases. There may be some subtle impairments, though, as PLWH experienced lower mental HRQOL.

HCV reinfection incidence and spontaneous clearance rates in HIV-positive men who have sex with men in Western Europe.

BACKGROUND & AIMS: Moderate cure rates of acute hepatitis C virus (HCV) infections with pegylated interferon and ribavirin have been described in the last decade in men who have sex with men (MSM), who are also coinfected with the human immunodeficiency virus (HIV). However, a subsequent high incidence of HCV reinfections has been reported regionally in men who both clear the infection spontaneously or who respond to treatment. METHODS: Retrospective analysis of reinfections in HIV infected MSM in eight centers from Austria, France, Germany, and the UK within the NEAT network between May 2002 and June 2014. RESULTS: Of 606 individuals who cleared HCV spontaneously or were successfully treated, 149 (24.6%) presented with a subsequent HCV reinfection. Thirty out of 70 (43%) who cleared again or were successfully treated, presented with a second reinfection, 5 with a third, and one with a fourth reinfection. The reinfection incidence was 7.3/100 person-years (95% CI 6.2-8.6). We found a trend for lower incidence among individuals who had spontaneously cleared their incident infection than among individuals who were treated (Hazard ratio 0.62, 95% CI 0.38-1.02, p=0.06). Spontaneous clearance of reinfection was associated with ALT levels >1000IU/ml and spontaneous clearance of a prior infection. CONCLUSIONS: HCV reinfection is an issue of major concern in HIV-positive MSM. Prevention strategies are needed for high risk groups to reduce morbidity and treatment costs. HIV-positive MSM with a prior HCV infection should be tested every 3 to 6months for reinfection. Those who had achieved a reinfection should be tested every 3months. LAY SUMMARY: We evaluated the occurrence of HCV reinfection in HIV-positive men who have sex with men. We found an alarming incidence of 7.3/100 person-years. Prevention measures need to address this specific subgroup of patients at high risk for HCV.

Favourable outcomes of poor prognosis diffuse large B-cell lymphoma patients treated with dose-dense Rituximab, high-dose Methotrexate and six cycles of CHOP-14 compared to first-line autologous transplantation.

The optimal therapeutic approach for young diffuse large B-cell lymphoma (DLBCL) patients with high-intermediate and high-risk age-adjusted international prognostic index (aaIPI) remains unknown. Hereby we report a 10-year single-centre study of 63 consecutively treated patients. To optimize outcome, two approaches were carried out: Cohort 1 patients received four cycles R-CHOP-21 (rituximab, cyclophosphamide, daunorubicin, vincristine, prednisolone over 21 days) followed by first-line high-dose chemotherapy with autologous stem-cell support (HDCT-ASCT), resulting in 2-year progression-free (PFS) and overall survival (OS) of 60·6% and 67·9%. 39·4% of those patients were not transplanted upfront, mainly due to early progressive disease (24·2%). Cohort 2 patients received an early intensified protocol of six cycles of CHOP-14 (cyclophosphamide, daunorubicin, vincristine, prednisolone over 14 days) with dose-dense rituximab and high-dose methotrexate resulting in promising overall response- (93·3%) and complete remission (90%) rates and sustained survival (2-year PFS and OS: 93·3%). In an intention-to-treat analysis, 2-year PFS (60·6% vs. 93·3%, hazard ratio [HR] 7·2, P = 0·009) and OS (69·7% vs. 93·3%, HR 4·95, P = 0·038) differed significantly, in favour of the early intensified protocol (Cohort 2). In a multivariate Cox-regression model, PFS (HR 8·12, 95% confidence interval [CI] 1·83-35·9, P = 0·006) and OS (HR 5·86, 95% CI 1·28-26·8, P = 0·02) remained superior for Cohort 2 when adjusted for aaIPI3 as the most important prognostic factor. Survival of young poor-prognosis DLBCL patients appears superior after early therapy intensification.

Sofosbuvir and Ledipasvir for 8 Weeks for the Treatment of Chronic Hepatitis C Virus (HCV) Infection in HCV-Monoinfected and HIV-HCV-Coinfected Individuals: Results From the German Hepatitis C Cohort (GECCO-01).

BACKGROUND: Shortening the duration of treatment with HCV direct-acting antivirals (DAAs) leads to substantial cost reductions. According to the label, sofosbuvir and ledipasvir can be prescribed for 8 weeks (SL8) in noncirrhotic women or men with HCV genotype 1 and low viral loads. However, real-world data about the efficacy and safety of SL8 are largely missing. METHODS: Interim results from an ongoing prospective, multicenter cohort of 9 treatment centers in Germany (GECCO). All patients started on treatment with HCV DAAs since January 2014 were included. This report describes safety and efficacy outcomes in 210 patients with HCV monoinfection and 35 with human immunodeficiency virus (HIV)-HCV coinfection given SL8 in a real-world setting. RESULTS: Of 1353 patients included into the GECCO cohort until December 2015, a total of 1287 had complete data sets for this analysis; 337 (26.2%) fulfilled the criteria for SL8 according to the package insert, but only 193 (57.2%) were eventually treated for 8 weeks. Another 52 patients did not fulfill the criteria but were treated for 8 weeks. SL8 was generally well tolerated. The overall sustained virologic response rate 12 weeks after the end of treatment was 93.5% (186 of 199). The on-treatment response rate was 99.4% (159 of 160) in HCV-monoinfected and 96.4% (27 of 28) in HIV-HCV-coinfected patients. Ten patients were lost to follow-up. CONCLUSIONS: SL8 seems highly effective and safe in well-selected HCV-monoinfected and HIV-HCV-coinfected patients in a real-world setting.

Dual treatment of acute HCV infection in HIV co-infection: influence of HCV genotype upon treatment outcome.

PURPOSE: With DAAs still only being licensed for chronic HCV infection, the ongoing epidemic of acute hepatitis C (AHC) infection among MSM highlights the need to identify factors allowing for optimal HCV treatment outcome. METHODS: 303 HIV-infected patients from 4 European countries with diagnosed acute HCV infection were treated early with pegylated interferon (pegIFN) and ribavirin (RBV) (n = 273) or pegylated interferon alone (n = 30). RESULTS: All patients were male, median age was 39 years. Main routes of transmission were MSM (95%) and IVDU (3%). 69% of patients were infected with HCV GT 1, 4.3% with GT 2, 10.6% with GT 3, 16.1% with GT 4. Overall SVR rate was 69.3% (210/303). RVR (p ≤ 0.001), 48-w treatment duration (p ≤ 0.001) and GT 2/3 (p = 0.024) were significantly associated with SVR. SVR rates were significantly higher in HCV GT 2/3 receiving pegIFN and RBV (33/35) when compared with pegIFN mono-therapy (6/10) (94% vs. 60 % respectively; p = 0.016). In multivariate analysis, pegIFN/RBV combination therapy (p = 0.017) and rapid virological response (RVR) (p = 0.022) were significantly associated with SVR in HCV GT 2/3. In HCV GT 1/4, RVR (p ≤ 0.001) and 48-w treatment duration (p ≤ 0.001) were significantly associated with SVR. CONCLUSIONS: Treatment of AHC GT 2 and 3 infections with pegIFN/RBV is associated with higher SVR rates suggesting different cure rates depending on HCV genotype similar to the genotype effects seen previously in chronic HCV under pegIFN/RBV. With pegIFN/RBV still being the gold standard of AHC treatment and in light of cost issues around DAAs and very limited licensed interferon-free DAA treatment options for chronic HCV GT 3 infection AHC GT 3 patients might benefit most from early interferon-containing treatment.