Clinical characteristics of monkeypox virus infections among men with and without HIV: A large outbreak cohort in Germany.

BACKGROUND: Since May 2022, increasing numbers of monkeypox virus (MPXV) infections have been reported from across Europe and North America. Studies, mainly from Africa, have suggested a higher risk for severe MPXV cases in people living with HIV. METHODS: This was a retrospective study of all confirmed MPXV infections observed in the participating centres since 19 May 2022. We conducted a chart review to evaluate clinical characteristics, comorbidities, and coinfections, including HIV, viral hepatitis, and sexually transmitted infections (STIs). RESULTS: By 30 June 2022, a total of 546 MPXV infections were reported from 42 German centres. All patients were men who have sex with men (MSM), of whom 256 (46.9%) were living with HIV, mostly with a preserved immune system and with viral suppression. In total, 232 (42.5%) MSM were also taking HIV pre-exposure prophylaxis (PrEP) and 58 (10.6%) MSM had no known HIV infection or PrEP use. The median age was 39 years (range 20-67), and comorbidities were rare. However, 52.4% and 29.4% of all patients had been diagnosed with at least one STI within the last 6 months or within the last 4 weeks, respectively. The most frequent localizations of MPXV infection were genital (49.9%) and anal (47.9%), whereas fever (53.2%) and lymphadenopathy (42.6%) were the most frequent general symptoms. The hospitalization rate was low (4.0%), and no fatal course was observed. The clinical picture showed no apparent differences between MSM with or without HIV. CONCLUSIONS: In this preliminary cohort analysis from a current large outbreak among MSM in Germany, the clinical picture of MPXV infection did not differ between MSM with and without HIV infection. Severe courses were rare and hospitalization rates were low. However, most patients were relatively healthy, and only a few people living with HIV were viremic or severely immunosuppressed.

Genetic variation in IL28B and treatment-induced clearance of hepatitis C virus in HIV-positive patients with acute and chronic hepatitis C.

Recently, a IL28B (rs 12979860) gene polymorphism was identified as a predictor for response to hepatitis C virus-specific treatment in human immunodeficiency virus (HIV)-uninfected and -infected patients with chronic hepatitis C. In an analysis of HIV-infected patients with acute hepatitis C, we found that the IL28B genotype was associated with serum levels of hepatitis C virus RNA, g-GT, and CD4 cell count. In contrast to HIV-infected patients with chronic hepatitis C, the IL28B genotype was not significantly associated with treatment response rates in patients with acute hepatitis C. Thus, effects of the IL28B single-nucleotide polymorphism may differ in HIV-infected patients with chronic and acute hepatitis C.

Pegylated interferon-alpha for the treatment of sexually transmitted acute hepatitis C in HIV-infected individuals.

BACKGROUND: Sexually transmitted acute hepatitis C among HIV-positive homosexual men has been noted as an emerging epidemic. METHODS: Forty-seven patients with mainly sexually acquired, acute hepatitis C were enrolled in this prospective, multicentre trial, and 36 of these patients were treated within the acute phase of hepatitis C infection with pegylated interferon (peg-IFN) therapy. RESULTS: Early treatment resulted in sustained virological response in 61% of patients. Peg-IFN alone showed similar treatment response rates and lower incidence of anaemia compared with peg-IFN+ribavirin combination therapy. Higher treatment response rates were observed in patients treated over 48 weeks compared with 24 weeks. CONCLUSIONS: Treatment of hepatitis C in HIV-positive individuals in the acute phase of infection leads to high rates of sustained virological response. Optimal time and mode of therapy have yet to be defined.

Selection of hepatitis B virus polymerase mutations in HIV-coinfected patients treated with tenofovir.

BACKGROUND: Tenofovir (TDF) is an adenosine nucleotide analogue that has been approved for the treatment of HIV-1 infection. It also shows activity against hepatitis B virus (HBV) in patients with or without lamivudine (LAM)-associated mutations. Development of clinical or virological HBV breakthrough during TDF therapy has not been reported so far. The aim of this study was to analyse the HBV polymerase (pol) from HIV/HBV-coinfected patients with detectable serum levels of HBV DNA during treatment with TDF for longer than 6 months. METHODS: The HBV pol was sequenced from 43 patient's serum before and during TDF therapy. Phenotypic analyses were performed using HBV replication-competent plasmids carrying unique mutations selected under TDF therapy. RESULTS: Mean exposure to LAM was 35.3 +/- 27.5 months and to TDF 11.2 +/- 6.7 months. Genotypic analyses from 21 of the patients revealed LAM-associated mutations, and a further two patients developed a novel mutation, rtA194T, along with LAM-resistance-associated mutations. Phenotypic analyses revealed that constructs harbouring rtA194T combined with rtL180M and rtM204V displayed an over 10-fold increase in the IC50 for TDF compared with the wild type. CONCLUSION: The selection of HBV mutations in HBV/HIV-coinfected patients failing TDF therapy is an unlikely event within the first 12 months of treatment. However, HBV from two of the 43 patients treated with TDF for more than 12 months was found to contain one novel mutation located distal to the catalytic site of the HBV pol. In vitro, rtA194T conferred a reduced susceptibility to TDF in the presence of LAM-associated mutations.

Pilot study of interferon alpha high-dose induction therapy in combination with ribavirin for chronic hepatitis C in HIV-co-infected patients.

Twenty-three HIV/hepatitis C virus (HCV)-co-infected patients received dose-escalated IFN-alpha (5 MIU/day) induction therapy for 10 weeks, followed by 36 weeks of thrice-weekly IFN-alpha treatment (5 MIU), both in combinations with ribavirin. Sustained HCV clearance was observed in three patients. Nine patients discontinued the study aas a result of adverse reactions such as anaemia, pancreatitis and depression. In HIV/HCV-co-infected patients, the therapeutic benefit of high-dose IFN-alpha therefore seems to be limited by its poor tolerability.

Effect of the interleukin-6 C174G gene polymorphism on treatment of acute and chronic hepatitis C in human immunodeficiency virus coinfected patients.

UNLABELLED: Hepatitis C virus (HCV)/human immunodeficiency virus (HIV) coinfection poses a difficult therapeutic problem. Response to HCV-specific therapy is variable but might be influenced by host genetic factors, including polymorphisms of cytokine genes. Here, we studied whether interleukin-6 (IL-6) C174G gene polymorphism affects the response to antiviral treatment in HCV-infected HIV-positive subjects. We determined IL-6 genotypes in HIV-positive patients with acute (n = 52) and chronic (n = 60) hepatitis C treated with pegylated interferon-alpha. Two hundred ten HCV monoinfected, 197 HIV monoinfected, and 100 healthy individuals were studied as controls. Patients were classified into high and low producers according to IL-6 genotypes. Rates of sustained virological responses (SVRs) were compared between the IL-6 genotypes. Signal transducer and activator of transcription three phosphorylation was analyzed by Western blot in HCV core-transfected human hepatoma cell line (HUH7) cells. Distribution of IL-6 genotypes did not differ significantly between the study groups. SVR was achieved in 63% of HIV/HCV coinfected patients. Carriers of the IL-6 high producer (HP) genotype had significantly higher SVR rates than patients with an IL-6 low producer genotype (70.1% versus 52%; P < 0.002). This effect was seen in both HIV-positive patients with acute (74% versus 33%; P < 0.05) and chronic (66% versus 33%; P < 0.05) hepatitis C. Multivariate analysis confirmed IL-6 HP carriage as an independent positive predictor for SVR (Odd's ratio 6.1; P = 0.004). This effect corresponds to the in vitro observation that in HCV core-transfected HUH7 cells, IL-6 overcomes the HCV core-mediated inhibition of STAT3 activation. CONCLUSION: Response rates to HCV-specific treatment are higher in HCV/HIV-positive patients carrying the IL-6 HP genotype, which might be because of IL-6 mediated STAT3 activation.

Pegylated interferon alpha-2b plus ribavirin for the treatment of chronic hepatitis C in HIV-coinfected patients.

OBJECTIVES: HIV-coinfection accelerates the course of HCV-related liver disease. Since, highly active anti-retroviral therapy significantly improved survival of HIV-patients more coinfected patients develop end stage liver disease. Therefore, treatment options for chronic hepatitis C in HIV-coinfected patients need to be evaluated. METHODS: Efficacy and safety of pegylated interferon alpha-2b (peg IFN) plus ribavirin (RBV) was examined within this prospective, uncontrolled, multicentre trial. Patients received peg IFN (1.5 microg/kg) once weekly plus RBV 800 mg daily for 48 weeks for HCV genotypes (GT) 1/4 and 24 weeks for GT 2/3. RESULTS: One hundred and twenty-two patients were enrolled. Patients were predominantly male (68%) and former i.v. drug users (61%). Baseline characteristics (median) were as follows: age 39 years (range 23-58), CD4 count 494 cells/microl (range 150-1578/microl), HIV-RNA 2.3log copies/ml (range <1.7-5.4log copies/ml). 61% currently received anti-retroviral treatment. Fifty-six percent had HCV GT 1. EOT response was achieved by 52%. However, only 25% achieved sustained response (SR) due to a high relapse rate. SR rates were significantly higher among patients with GT 2/3 compared to those with GT 1/4 (44 vs. 18%). SR was observed in only one patient without early response (ER). Discontinuation rate was 30%, 21% discontinued due to adverse events. CONCLUSION: Peg IFN/RBV appears safe and effective in HIV/HCV-coinfected patients. GT 2/3 is associated with better SR. Lack of ER strongly predicts non-response. High relapse rates substantially reduce treatment success. In terms of toxicity neuro-psychiatric side effects frequently required treatment discontinuation.