Hepatitis: Masur H

Kaplan JE, Benson C, Holmes KH, Brooks JT, Pau A, Masur H, Anonymous00080, Anonymous00081, Anonymous00082. · CDC, Atlanta, Georgia, USA. · MMWR Recomm Rep. · Pubmed #19357635 links to  free full text

Abstract: This report updates and combines earlier versions of guidelines for the prevention and treatment of opportunistic infections (OIs) in HIV-infected adults (i.e., persons aged >/=18 years) and adolescents (i.e., persons aged 13--17 years), last published in 2002 and 2004, respectively. It has been prepared by the Centers for Disease Control and Prevention (CDC), the National Institutes of Health (NIH), and the HIV Medicine Association (HIVMA) of the Infectious Diseases Society of America (IDSA). The guidelines are intended for use by clinicians and other health-care providers, HIV-infected patients, and policy makers in the United States. These guidelines address several OIs that occur in the United States and five OIs that might be acquired during international travel. Topic areas covered for each OI include epidemiology, clinical manifestations, diagnosis, prevention of exposure; prevention of disease by chemoprophylaxis and vaccination; discontinuation of primary prophylaxis after immune reconstitution; treatment of disease; monitoring for adverse effects during treatment; management of treatment failure; prevention of disease recurrence; discontinuation of secondary prophylaxis after immune reconstitution; and special considerations during pregnancy. These guidelines were developed by a panel of specialists from the United States government and academic institutions. For each OI, a small group of specialists with content-matter expertise reviewed the literature for new information since the guidelines were last published; they then proposed revised recommendations at a meeting held at NIH in June 2007. After these presentations and discussion, the revised guidelines were further reviewed by the co-editors; by the Office of AIDS Research, NIH; by specialists at CDC; and by HIVMA of IDSA before final approval and publication. The recommendations are rated by a letter that indicates the strength of the recommendation and a Roman numeral that indicates the quality of evidence supporting the recommendation, so that readers can ascertain how best to apply the recommendations in their practice environments. Major changes in the guidelines include 1) greater emphasis on the importance of antiretroviral therapy for the prevention and treatment of OIs, especially those OIs for which no specific therapy exists; 2) information regarding the diagnosis and management of immune reconstitution inflammatory syndromes; 3) information regarding the use of interferon-gamma release assays for the diagnosis of latent Mycobacterium tuberculosis (TB) infection; 4) updated information concerning drug interactions that affect the use of rifamycin drugs for prevention and treatment of TB; 5) the addition of a section on hepatitis B virus infection; and 6) the addition of malaria to the list of OIs that might be acquired during international travel. This report includes eleven tables pertinent to the prevention and treatment of OIs, a figure that pertains to the diagnois of tuberculosis, a figure that describes immunization recommendations, and an appendix that summarizes recommendations for prevention of exposure to opportunistic pathogens.

Masur H, Kaplan JE, Holmes KK, Anonymous00122, Anonymous00123. · National Institutes of Health, Bethesda, Maryland, USA. · Ann Intern Med. · Pubmed #12617574 No free full text.

Abstract: In 1995, the U.S. Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA) developed guidelines for preventing opportunistic infections (OIs) among persons infected with human immunodeficiency virus (HIV); these guidelines were updated in 1997 and 1999. This fourth edition of the guidelines, made available on the Internet in 2001, is intended for clinicians and other health-care providers who care for HIV-infected persons. The goal of these guidelines is to provide evidence-based guidelines for preventing OIs among HIV-infected adults and adolescents, including pregnant women, and HIV-exposed or infected children. Nineteen OIs, or groups of OIs, are addressed, and recommendations are included for preventing exposure to opportunistic pathogens, preventing first episodes of disease by chemoprophylaxis or vaccination (primary prophylaxis), and preventing disease recurrence (secondary prophylaxis). Major changes since the last edition of the guidelines include 1) updated recommendations for discontinuing primary and secondary OI prophylaxis among persons whose CD4+ T lymphocyte counts have increased in response to antiretroviral therapy; 2) emphasis on screening all HIV-infected persons for infection with hepatitis C virus; 3) new information regarding transmission of human herpesvirus 8 infection; 4) new information regarding drug interactions, chiefly related to rifamycins and antiretroviral drugs; and 5) revised recommendations for immunizing HIV-infected adults and adolescents and HIV-exposed or infected children.

Kaplan JE, Masur H, Holmes KK, Anonymous00119, Anonymous00120. · Division of AIDS, STD, and TB Laboratory Research, National Center for Infectious Diseases, USA. · MMWR Recomm Rep. · Pubmed #12081007 links to  free full text

Abstract: In 1995, the U.S. Public Health Service (USPHS) and the Infectious Diseases Society of America (IDSA) developed guidelines for preventing opportunistic infections (OIs) among persons infected with human immunodeficiency virus (HIV); these guidelines were updated in 1997 and 1999. This fourth edition of the guidelines, made available on the Internet in 2001, is intended for clinicians and other health-care providers who care for HIV-infected persons. The goal of these guidelines is to provide evidence-based guidelines for preventing OIs among HIV-infected adults and adolescents, including pregnant women, and HIV-exposed or infected children. Nineteen OIs, or groups of OIs, are addressed, and recommendations are included for preventing exposure to opportunistic pathogens, preventing first episodes of disease by chemoprophylaxis or vaccination (primary prophylaxis), and preventing disease recurrence (secondary prophylaxis). Major changes since the last edition of the guidelines include 1) updated recommendations for discontinuing primary and secondary OI prophylaxis among persons whose CD4+ T lymphocyte counts have increased in response to antiretroviral therapy; 2) emphasis on screening all HIV-infected persons for infection with hepatitis C virus; 3) new information regarding transmission of human herpesvirus 8 infection; 4) new information regarding drug interactions, chiefly related to rifamycins and antiretroviral drugs; and 5) revised recommendations for immunizing HIV-infected adults and adolescents and HIV-exposed or infected children.

Brooks JT, Kaplan JE, Holmes KK, Benson C, Pau A, Masur H. · Centers for Disease Control and Prevention, National Centers for HIV, Hepatitis, Tuberculosis and STD Prevention, Division of HIV/AIDS Prevention, Atlanta, GA 30333, USA. · Clin Infect Dis. · Pubmed #19191648 No free full text.

This publication has no abstract.

Wu L, Kottilil S, Lempicki R, Yang J, McLaughlin M, Hu Z, Koratich C, Reitano KN, Rehm CA, Masur H, Wood B, Kleiner DE, Polis MA. · Laboratory of Immunoregulation, NIAID, NIH, DHHS, Bethesda, Maryland, USA. · AIDS Res Hum Retroviruses. · Pubmed #17147494 No free full text.

Abstract: Most HIV/HCV-coinfected patients fail to achieve a sustained virologic response (SVR) to peginterferon-ribavirin therapy. We examined the hepatic histologic response (HR), defined as an improvement in hepatic inflammation scores of two points or more, to combination therapy among HIV/HCV-coinfected subjects. An open label prospective trial treated 32 HIV/HCV-coinfected patients with peginterferon alpha-2b and ribavirin for 48 weeks. Liver biopsies, scored by a single pathologist using the Histology Activity Index (HAI, range 0-18) and Ishak fibrosis scores (range 0-6), were performed before and after treatment. Gene expression profiles of PBMCs were performed using Affymetrix U133A gene chips. A total of 87% of SVR subjects and 88% of nonresponders (NR) had an HR, but no significant change in the liver fibrosis scores was observed (p > 0.05). For genotype 1 patients, a baseline fibrosis score </=2 was related to a higher likelihood of SVR than those with a score >2 (p = 0.012). Combination therapy for HCV among HIV-coinfected subjects resulted in a modest SVR rate. Persons with mild liver disease had a better SVR rate, suggesting early treatment may be beneficial. Combination therapy resulted in an HR for most of the patients, however, further follow-up of these patients will determine the durability of such an HR.

Kottilil S, Jagannatha S, Lu A, Liu S, McLaughlin M, Metcalf JA, Dewar R, Campbell C, Koratich C, Maldarelli F, Masur H, Polis MA. · Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA. · HIV Clin Trials. · Pubmed #15002084 links to  free full text

Abstract: BACKGROUND: HIV seropositive individuals co-infected with hepatitis C virus (HCV) have an increased risk for liver cirrhosis. We examined the long-term effect of controlling HIV infection with highly active antiretroviral therapy (HAART) on HCV viremia among co-infected patients. METHOD: HIV/HCV co-infected patients who initiated HAART and were able to control HIV viremia to <500 copies/mL were evaluated. HIV and HCV viremia were measured at each time point from frozen plasma samples by using bDNA methodology. Liver function tests and CD4+ and CD8+ T cell counts of all patients were obtained at each time point. RESULTS: Seventeen co-infected patients met criteria for study from a cohort of 156 patients. Median time to achieve an HIV viral load (VL) <500 copies/mL after initiation of HAART was 28 weeks (range, 5-225 weeks). Thirteen of 17 patients had increases in HCV VL. Slope analysis of HCV VL vs. HIV VL was -0.14 (p=.0496), demonstrating a 0.14 log increase in HCV VL concomitant with control of HIV viremia. HCV viremia returned toward baseline levels in the 16 patients who maintained HIV suppression for 6 months. None cleared HCV after initiation of HAART during this time. Alkaline phosphatase, ALT, and AST levels were not significantly changed from baseline nor correlated with change in HCV VL (p>.05). CONCLUSION: Control of HIV viremia may result in an early increase in HCV viremia. In this study, for every 1 log decrease of HIV VL there was a 0.14 log increase of HCV VL. The exact mechanism of this flare seen with control of HIV viremia is unknown. However, HAART alone was not able to eliminate or significantly reduce the HCV viremia in this cohort of co-infected patients.

Osinusi A, Kleiner D, Wood B, Polis M, Masur H, Kottilil S. · Department of Infectious Diseases, University of Maryland , Baltimore, Maryland, USA. · AIDS Patient Care STDS. · Pubmed #19519227 No free full text.

Abstract: We report the first reported case of a 61-year-old MSM who was diagnosed with syphilis, primary HIV infection, and acute hepatitis C (HCV) within the same time period who rapidly developed significant liver fibrosis within 6 months of acquisition of both infections. It has been well described that individuals with primary HIV infection have an increase in activated CD8+ T cells, which causes a state of immune activation as was evident in this patient. Acquisition of HCV during this time could have further skewed this response resulting in massive hepatocyte destruction, inflammation, and subsequent liver fibrosis. Recent literature suggest that MSM with primary HIV infection have higher rates of acquisition of HCV than other HIV-positive cohorts and HCV acquisition can occur very soon after acquiring HIV. This case of rapid hepatic fibrosis progression coupled with the increasing incidence of HCV in individuals with primary HIV infection demonstrates a need for this phenomenon to be studied more extensively.

Suzman DL, McLaughlin M, Hu Z, Kleiner DE, Wood B, Lempicki RA, Mican JM, Suffredini A, Masur H, Polis MA, Kottilil S. · Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA. · AIDS. · Pubmed #18614866 links to  free full text

Abstract: OBJECTIVE: The degree of liver fibrosis is a determinant for initiation of therapy for hepatitis C virus. Liver biopsy is invasive, risky and costly, but is required to assess fibrosis. This study intended to identify novel noninvasive markers to accurately assess fibrosis in HIV/hepatitis C virus coinfection. METHODS: Using 100 biopsies from 68 HIV/hepatitis C virus coinfected patients, we developed a predictive model consisting of six serum markers along with age and antiretroviral therapy experience. DNA microarray analysis of peripheral blood mononuclear cells associated with a subset of 51 biopsies obtained from 28 patients was performed and incorporated into a second model. RESULTS: The eight-marker model yielded an area under the receiver operating characteristic curve of 0.904. Combined analysis of clinical and DNA microarray data in the 51-biopsy subset identified two genes (alanine amino peptidase-N and mitogen-activated protein kinase kinase-3) that predicted fibrosis with high significance. The four-marker model that included the two genes and two serum markers had an area under the receiver operating characteristic curve of 0.852, which did not differ significantly from the eight-marker model on this subset (area under the receiver operating characteristic curve = 0.856, P = 0.96). CONCLUSION: Both models accurately predicted fibrosis with an accuracy of 87.9%, thereby sparing 83% of patients from obtaining a biopsy. DNA microarray analysis can be invaluable in identifying novel biomarkers of liver fibrosis.

Nussenblatt V, McLaughlin M, Rehm CA, Lempicki RA, Brann T, Yang J, Proschan M, Highbarger HC, Dewar RL, Imamichi T, Koratich C, Neumann AU, Masur H, Polis MA, Kottilil S. · Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland 20892, USA. · AIDS Res Hum Retroviruses. · Pubmed #18184077 No free full text.

Abstract: Viral breakthroughs (VB), defined as having detectable HCV VL while on anti-HCV therapy after achieving maximal suppression, have not yet been characterized with the use of PEG-IFN in HIV/HCV-coinfected patients. We evaluated possible mechanisms for VB among HIV/HCV-coinfected patients receiving PEG-IFN/RBV. Thirty HIV/HCV coinfected patients were treated with PEG-IFN (1.5 mug/kg sc qwk) and RBV (1-1.2 g daily) for 48 weeks. Liver chemistry, HCV VL, genotyping, DNA microarray, and sequencing of HCV E-2 envelope were performed before and during treatment. VB had lower baseline HCV VL but higher ALT and AST than relapsers (ETR) (p < 0.05) and lower CD4+ T lymphocytes (%) than patients with sustained virological responses (SVR), but similar first and second phase HCV viral kinetics (vs. ETR and SVR; p > 0.05). HCV genotypes and envelope sequences were similar for patients with VB pretreatment and at break-through. VB had higher levels of interferon-induced gene (IFIG) expression pretreatment than patients with ETR (p < 0.01). HIV/HCV-coinfected patients have a high rate of VB on PEG-IFN/RBV therapy characterized by higher levels of IFIG expression, immunodeficiency, and hepatic inflammation. Novel strategies are required for the treatment of persons with VB.

Neumann A, Polis M, Rozenberg L, Jackson J, Reitano K, McLaughlin M, Koratich C, Dewar R, Masur H, Haagmans B, Kottilil S. · Faculty of Life Sciences, Bar-Ilan University, Ramat-Gan 52900, Israel. · AIDS. · Pubmed #17721093 No free full text.

Abstract: OBJECTIVE: The major antiviral effect of interferon (IFN)-alpha on hepatitis C virus (HCV) is blocking of virion production from infected cells. We now investigate the previously unknown mechanism of action of IFN-alpha against HIV. METHODS: HIV kinetics in parallel to HCV kinetics and IFN pharmacokinetics during pegylated-IFN-alpha-2b (1.5 microg/Kg q.w., PEG-IFN) and ribavirin (1-1.2 g daily) treatment in nine HIV patients co-infected with HCV genotype 1 were analyzed. In vivo modeling predictions of suppression of HIV replication by PEG-IFN in CD8-depleted peripheral blood mononuclear cells were verified by in vitro experiments. RESULTS: HCV and HIV show different viral decline patterns after administration of PEG-IFN. Unlike the bi-phasic decline shown by HCV, HIV shows a slow continuous decline during the first week, with no rebound when PEG-IFN levels decline. Fitting of HIV kinetics with known half-lives of free virus and infected cells indicates that the major effect of IFN on HIV is to block de novo infection rather than to block virion production. The magnitude of the antiviral effect is similar (mean 1.1 log10 decline at 7 days) to those of direct anti-HIV drugs, but shows an inverse correlation with baseline viremia. In vitro studies show that preincubation with IFN renders a suppression of HIV replication superior to that of treatment postinfection, thus corroborating the mathematical analysis in vivo. CONCLUSION: The complimentary antiviral properties of IFN-alpha and antiretroviral therapy suggest a role for pharmacokinetically improved formulations of IFN as part of salvage therapy for HIV-infected individuals.

Lempicki RA, Polis MA, Yang J, McLaughlin M, Koratich C, Huang DW, Fullmer B, Wu L, Rehm CA, Masur H, Lane HC, Sherman KE, Fauci AS, Kottilil S. · Science Applications International Program (SAIC)-Frederick, Inc., National Cancer Institute-Frederick, National Institutes of Health, Frederick, Maryland, USA. · J Infect Dis. · Pubmed #16544259 No free full text.

Abstract: Therapy for hepatitis C virus (HCV) infection in human immunodeficiency virus (HIV)-infected patients results in modest cure rates. Gene expression patterns in peripheral blood mononuclear cells from 29 patients coinfected with HIV and HCV were used to predict virological response to therapy for HCV infection. Prediction analysis using pretherapy samples identified 79 genes that correctly classified all 10 patients who did not respond to therapy, 8 of 10 patients with a response at the end of treatment, and 7 of 9 patients with sustained virological response (86% overall). Analysis of 17 posttreatment samples identified 105 genes that correctly classified all 9 patients with response at the end of treatment and 7 of 8 patients with sustained virological response (94% overall). Failure of anti-HCV therapy was associated with elevated expression of interferon-stimulated genes. Gene expression patterns may provide a tool to predict anti-HCV therapeutic response.

Farel C, Suzman DL, McLaughlin M, Campbell C, Koratich C, Masur H, Metcalf JA, Robinson MR, Polis MA, Kottilil S. · Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, Bethesda, Maryland, USA. · AIDS. · Pubmed #15316341 No free full text.

Abstract: OBJECTIVE: To characterize the ocular changes associated with peginterferon alpha 2b (peg-IFN alpha-2b) and ribavirin therapy for chronic hepatitis C infection in HIV co-infected individuals. METHODS: A prospective, open-label trial treating HIV/hepatitis C (HCV) co-infected individuals with peg-IFN alpha-2b and ribavirin at the Warren Grant Magnusson Clinical Center, National Institutes of Health, Bethesda, Maryland, USA. Twenty-three patients with a high mean CD4+ T-cell count were treated with peg-IFN alpha-2b and ribavirin and followed for 40 to 88 weeks. Ophthalmologic evaluations including visual acuity, visual field testing, color vision examination and indirect ophthalmoscopy were performed at baseline and every 3 months. RESULTS: Eight of the 23 patients (35%) developed ophthalmologic pathology, including cotton wool spots, cataracts, and two patients developed decreased color vision. These two patients regained their color vision, one after cessation of anti-HCV therapy. CONCLUSIONS: Although retinal pathologies have been reported in patients treated with interferon-alpha, they have not been reported during peg-IFN alpha-2b therapy nor in HIV/HCV co-infected patients. The incidence of serious ocular pathology associated with anti-HCV therapy may be very high and is probably associated with peg-IFN alpha-2b. Increased monitoring of patients treated with peg-IFN alpha-2b for retinal and visual changes is warranted.

Kaplan JE, Sepkowitz K, Masur H, Sirisanthana T, Russo M, Chapman L. · Centers for Disease Control and Prevention, Atlanta, Georgia 30333, USA. · Emerg Infect Dis. · Pubmed #11485658 links to  free full text

This publication has no abstract.