We investigated the relationship between hepatitis B virus surface antigen (HBsAg) serum level decline and posttreatment response in patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B from a large multinational study of pegylated interferon alfa-2a (peginterferon alfa-2a), with or without lamivudine, versus lamivudine alone. Serum HBsAg was quantified using the Architect assay (Abbott Diagnostics) at pretreatment, end of treatment (week 48), and 6 months after the end of treatment (week 72) in sera from 386 of the 537 patients who participated in the multinational study (peginterferon alfa-2a, 127; peginterferon alfa-2a plus lamivudine, 137; lamivudine monotherapy, 122). Pretreatment HBsAg levels varied according to genotype, with the highest levels present in patients infected with genotypes A (median, 4.11 log 10 IU/mL) and D (median, 3.85 log 10 IU/mL). Significant on-treatment decline in HBsAg was observed during treatment with peginterferon alfa-2a (alone or combined with lamivudine; mean decline at week 48, ؊0.71 and ؊0.67 log 10 IU/mL, respectively, P < 0.001), but not during treatment with lamivudine alone (؊0.02 log 10 IU/mL). Significantly more patients treated with peginterferon alfa-2a (21%) or peginterferon alfa-2a plus lamivudine (17%) achieved HBsAg levels <100 IU/mL at the end of treatment compared with lamivudine (1%) (both P < 0.001 versus lamivudine). End-of-treatment HBsAg level correlated strongly with HBV DNA suppression to <400 copies/mL 6 months posttreatment. An HBsAg level <10 IU/mL at week 48 and on-treatment decline >1 log 10 IU/mL were significantly associated with sustained HBsAg clearance 3 years after treatment (both P < 0.0001). Conclusion: On-treatment quantification of HBsAg in patients with HBeAg-negative chronic hepatitis B treated with peginterferon alfa-2a may help identify those likely to be cured by this therapy and optimize treatment strategies. C hronic hepatitis B is a global health problem accounting for 1 million deaths each year. 1 Ageadjusted death rates are 3 to 3.6 times higher in carriers of hepatitis B virus (HBV) surface antigen (HBsAg) than in persons without HBV infection. 2 The aim of treatment for patients with chronic hepatitis B (CHB) is to decrease progression of liver disease to cirrhosis and hepatocellular carcinoma, with the ultimate aim of improving survival. This can be pursued by maintaining constant inhibition of viral replication through a longterm treatment with nucleos(t)ide analogs or by inducing, through the combined antiviral and immunomodulatory Abbreviations: ALT, alanine aminotransferase; CART, classification and regression tree; CHB, chronic hepatitis B; HBeAg, hepatitis B e antigen; HBsAg, hepatitis B virus surface antigen; HBV, hepatitis B virus;

Objectives Dolutegravir (DTG), a second-generation integrase strand transfer inhibitor (INSTI), is now among the most frequently used antiretroviral agents. However, recent reports have raised concerns about potential neurotoxicity. MethodsWe performed a retrospective analysis of a cohort of HIV-infected patients who had initiated an INSTI in two large German out-patient clinics between 2007 and 2016. We compared discontinuation rates because of adverse events (AEs) within 2 years of starting treatment with dolutegravir, raltegravir or elvitegravir/cobicistat. We also evaluated factors associated with dolutegravir discontinuation. ResultsA total of 1950 INSTI-based therapies were initiated in 1704 patients eligible for analysis within the observation period. The estimated rates of any AE and of neuropsychiatric AEs leading to discontinuation within 12 months were 7.6% and 5.6%, respectively, for dolutegravir (n = 985), 7.6% and 0.7%, respectively, for elvitegravir (n = 287), and 3.3% and 1.9%, respectively, for raltegravir (n = 678). Neuropsychiatric AEs leading to dolutegravir discontinuation were observed more frequently in women [hazard ratio (HR) 2.64; 95% confidence interval (CI) 1.23-5.65; P = 0.012], in patients older than 60 years (HR: 2.86; 95% CI: 1.42-5.77; P = 0.003) and in human leucocyte antigen (HLA)-B*5701-negative patients who initiated abacavir at the same time (HR: 2.42; 95% CI: 1.38-4.24; P = 0.002). ConclusionsIn this large cohort, the rate of discontinuation of dolutegravir because of neuropsychiatric adverse events was significantly higher than for other INSTIs, at almost 6% within 12 months. Despite the limitations of this retrospective study, the almost three-fold higher discontinuation rates observed amongst women and older patients underscore the need for further investigation, especially in patient populations usually underrepresented in clinical trials.

Summary. HLA-DR and MT1, MT2, MT3 genotypes have been investigated in 123 Type 1 (insulin-dependent) diabetic subjects and their families. Ninety-eight percent of probands possessed either DR3 (relative risk = 5.0), or DR4 (relative risk = 6.8) or both antigens (relative risk = 14.3), emphasizing the strong association of the disease with these two antigens. Almost 51% of the probands were DR3, DR4 heterozygotes. The DR antigen combinations of the parents leading to DR3, DR4 heterozygous and to DR3 and DR4 homozygous offspring were analysed. There was a marked increase in DR3, DR4 heterozygosity, but no increase in homozygosity for these antigens compared with the expected frequencies. These results are compatible with the existence of two susceptibility genes operating at a locus or at loci closely linked to that of HLA-DR. There was a striking reduction of DR7 (relative risk = 0A) and only five probands possessed DR2 (relative risk = 0.1). In each case, the other inherited allele was DR3 or DR4. Linkage disequilibrium between B7 and DR2 was much lower in the haplotypes of the probands than in the 'non-diabetic' parental haplotype. In contrast, the association of BW62 with DR4 was more pronounced in the haplotypes of the probands. There was no increase in recombination frequency in these families and no strong effect of HLA-DR on age of onset could be demonstrated. There was a significant shift towards DR identity compared with identity for the whole HLA haplotype (A, B, C and DR) in both healthy and diabetic siblings (p < 0.025).

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Efficacy of HAART was independently associated with prolonged survival in this large cohort of patients with ARL. Information on patient's response to HAART is crucial for the evaluation of future treatment strategies.

In this cohort of HBV/HIV-coinfected individuals, full HBV DNA suppression was achieved in the majority of patients independent of treatment allocation. Loss of HBe- and HBs-antigen was not different between the two study arms. Over a median treatment period of 116 weeks tenofovir was as effective as tenofovir plus lamivudine. Longer treatment periods may be needed to evaluate potential benefits of first-line combination therapy for chronic hepatitis B.

Purpose To evaluate the association between the percentages of older age groups among confirmed SARS-CoV-2 infections and the country-specific case fatality rate (CFR). Methods This ecological study analyzed data from the 20 most severely affected European countries, USA and Canada, in which national health authorities provided data on age distribution and gender among confirmed SARS-CoV-2 cases and deaths. Results The proportion of individuals older than 70 years among confirmed SARS-CoV-2 cases differed markedly between the countries, ranging from 4.9 to 40.4%. There was a strong linear association between the proportion of individuals older than 75 years and the country-specific CFRs (R2 = 0.803 for all countries, R2 = 0.961 after exclusion of three countries with incongruent data). Each 5% point increase of this older age group among confirmed SARS-CoV-2 cases was associated with an increase in CFR of 2.5% points (95% CI 1.9–3.1). Conclusion Data from 20 European countries and the USA and Canada showed that the variance of crude CFR of COVID-19 is predominantly (80–96%) determined by the proportion of older individuals who are diagnosed with SARS-CoV-2. The age distribution of SARS-CoV-2 infections is still far from being homogeneous. Detailed demographic data have to be taken into account in all the analyses on COVID-19-associated mortality. We urgently call for standardized data collection by national health authorities.

Data from this cohort indicate that immune recovery induced by HAART leads to dramatic improvement in survival of patients with AIDS-associated PCNSL. These findings may have important implications for future treatment strategies.