Hepatitis: Gazzard B

Gazzard B, Anonymous00323. · Chelsea and Westimnster Hospital, London, UK. · HIV Med. · Pubmed #16011536 No free full text.

This publication has no abstract.

Justin S, Gazzard B. · No affiliation provided · Int J Clin Pract. · Pubmed #14529053 No free full text.

This publication has no abstract.

Nelson M, Portsmouth S, Stebbing J, Atkins M, Barr A, Matthews G, Pillay D, Fisher M, Bower M, Gazzard B. · Chelsea and Westminster Hospital, London, UK. · AIDS. · Pubmed #12478090 No free full text.

Abstract: BACKGROUND: Tenofovir is a novel nucleotide analogue recommended for use in HIV-1 infected treatment-experienced patients. Recent data suggest an effect on Hepatitis B virus (HBV) replication. We therefore investigated the use of tenofovir in HIV-1 and HBV co-infected individuals. METHODS: Twenty HIV-1/HBV co-infected patients with a median of 108 weeks lamivudine experience (range, 0-270 weeks) received tenofovir 245 mg daily in addition to or as part of their combination antiretroviral therapy. Their immunologic parameters and HIV-1 RNA and HBV DNA viral loads were followed over a period of 52 weeks. In addition, their HBV DNA polymerase was sequenced at baseline to measure the frequency of YMDD mutations that are associated with lamivudine resistance. FINDINGS: A significant decrease in HBV DNA viral load (4 x log ) and alanine aminotransferase levels was observed. There were no significant overall differences between the lamivudine-experienced (n = 15) and -naive (n = 5) individuals and tenofovir was well tolerated. Five patients (25%) underwent HBe antigen seroconversion during the study period. Out of the 15 lamivudine-experienced individuals, 10 had YMDD mutations and one had YIDD mutations in HBV DNA. INTERPRETATION: These results indicate that 52 weeks of tenofovir in addition to antiretroviral therapy is active against HBV, and it appears to overcome lamivudine resistance.

Pessôa MG, Gazzard B, Huang AK, Brandão-Mello CE, Cassetti I, Mendes-Corrêa MC, Soriano V, Phiri P, Hall A, Brett-Smith H. · Instituto de Infectologia Emilio Ribas, São Paulo, Brazil bChelsea and Westminster Hospital, London, UK. · AIDS. · Pubmed #18753861 No free full text.

Abstract: BACKGROUND: Prolonged use of lamivudine in patients coinfected with HIV and hepatitis B virus (HBV) leads to an increasing risk of lamivudine resistance in both diseases. We investigated the addition of entecavir, a potent inhibitor of HBV polymerase, to lamivudine-containing highly active antiretroviral therapy (HAART) in patients who experienced rebound in HBV viremia while maintaining suppression of plasma HIV RNA less than 400 copies/ml. METHODS: Sixty-eight patients were randomized to entecavir 1 mg (n = 51) or placebo (n = 17) once daily for 24 weeks; 65 patients continued the study with entecavir for an additional 24 weeks. Lamivudine-containing HAART was continued throughout. RESULTS: At week 24, the mean HBV DNA in entecavir-treated patients was 5.52 log10 copies/ml versus 9.27 log10 copies/ml for placebo, and at week 48, it was 4.79 log10 copies/ml versus 5.63 log10 copies/ml, respectively. The mean HBV DNA change from baseline for entecavir was -3.65 log10 copies/ml (versus + 0.11 for placebo, P < 0.0001) and alanine aminotransferase normalization in 34% of patients (versus 8% for placebo, P = 0.08). At 48 weeks, mean change in HBV DNA reached -4.20 log10 copies/ml in patients who received entecavir for the entire 48 weeks. The frequency of adverse events with entecavir and placebo was comparable. Through 48 weeks, no clinically relevant changes in HIV viremia or CD4 cell counts were identified. CONCLUSION: In this study, entecavir was associated with rapid, clinically significant reductions in HBV DNA, with maintenance of HIV viremia suppression, in HIV/HBV coinfected patients with HBV viremia while on lamivudine treatment.

Stebbing J, Waters L, Mandalia S, Bower M, Nelson M, Gazzard B. · Department of HIV Medicine, Chelsea and Westminster Hospital, London, United Kingdom. · Clin Infect Dis. · Pubmed #16107994 No free full text.

Abstract: Human immunodeficiency virus type 1 (HIV-1) appears to adversely affect hepatitis C, but whether hepatitis C virus (HCV) has a reciprocal effect on HIV-1 infection remains a point of controversy. In a multivariate analysis of a cohort of 5832 individuals, we found that individuals coinfected with HCV and HIV-1 (prevalence of coinfection, 5.8%) had a CD4+ cell count that decreased at a rate similar to that for individuals infected with HIV-1 alone. However, coinfection was associated with a statistically significant increased likelihood of onset of an acquired immunodeficiency syndromedefining illness or developing a CD4+ cell count of <200 cells/mm3, compared with infection with HIV-1 alone (hazard ratio, 1.52; 95% confidence interval, 1.072.17). Patients who were naive to highly active antiretroviral therapy were significantly less likely to progress to either end point, because of their higher CD4+ cell counts. In conclusion, there was an increased number of adverse events in coinfected individuals, compared with individuals infected with HIV-1 alone.

Waters L, Stebbing J, Mandalia S, Young AM, Nelson M, Gazzard B, Bower M. · Department of HIV Medicine, The Chelsea and Westminster Hospital, London, United Kingdom. · Int J Cancer. · Pubmed #15756687 No free full text.

Abstract: Immunosuppression induced by the human immunodeficiency virus (HIV) increases the risk of developing non-Hodgkin's lymphoma (NHL). As the hepatitis C virus (HCV) has been implicated in the development of B cell lymphomas, we compared the incidence of systemic NHL during HIV infection compared to HIV and HCV co-infection. Of 5,832 individuals studied during the era of highly active anti-retroviral therapy (HAART), 102 patients were diagnosed with systemic NHL. The incidence of systemic NHL was 6.9 of 10(4) patient years during HIV infection compared to 7.1 of 10(4) patient years during HIV alone (p = 0.9). In this immunocompromised patient population, there was no association between HCV infection and an increased risk of lymphoma.

Stebbing J, Patterson S, Portsmouth S, Thomas C, Glassman R, Wildfire A, Gotch F, Bower M, Nelson M, Gazzard B. · The Department of Immunology, Division of Investigative Science, Faculty of Medicine, Imperial College of Science, Technology and Medicine, The Chelsea and Westminster Hospital, 369 Fulham Road, London SW10 9NH,UK. · Cell Res. · Pubmed #15225419 links to  free full text

Abstract: There is increasing recognition of the potential morbidity and mortality associated with HIV-1 and hepatitis C (HCV) co-infection. HIV appears to adversely affect HCV disease while the reciprocal effect of HCV on HIV remains controversial. We therefore studied the effect of co-infection on dendritic cell function versus HIV infection alone, as previous work has shown that HCV impairs dendritic cell (DC) function. HIV-1 positive individuals with HCV were matched for CD4 count, HIV-1 RNA viral load and therapy, to HIV-1 positive patients without HCV. Monocyte-derived DC were generated and mixed leukocyte reactions were performed. We assessed allostimulatory capacity with and without administration of exogenous Th1 cytokines, using thymidine uptake and cell division analyses with the vital dye CFSE. We found that monocyte-derived DC from co-infected individuals showed no significant differences in allostimulatory capacity to ex vivo generated DC from HIV-1 infected individuals without HCV. Unlike the situation with HCV infection alone, this impairment was not reversed by increasing concentrations of either interleukin-2 or -12. Monocyte-derived DC from HIV-1 and HCV co-infected individuals have a similar allostimulatory capacity to DC from matched patients with HIV-1 alone. These findings are compatible with results of prior clinical studies that found no evidence that HCV co-infection altered HIV disease progression and has implications for immunotherapeutic approaches in co-infected individuals.

Matthews GV, Pillay D, Cane P, Ratcliffe D, Gazzard B, Nelson M. · Department of HIV Medicine, Chelsea & Westminster Hospital, SW10 9NH London, United Kingdom. · Clin Infect Dis. · Pubmed #11698987 No free full text.

Abstract: Individuals coinfected with human immunodeficiency virus 1 (HIV-1) and hepatitis B virus (HBV) often receive treatment with an antiretroviral regimen including lamivudine. Lamivudine monotherapy for HBV may lead to drug-resistant mutations in a significant number of patients. The virological and biochemical responses of 8 patients coinfected with HBV/HIV-1 treated with both lamivudine and famciclovir were studied. Patients exhibiting HBV viral rebound at 1 year were analyzed for the emergence of HBV polymerase mutations. Only 1 patient had no prior exposure to lamivudine. Addition of famciclovir to the treatment regimen resulted in a median fall in HBV DNA level of 0.33 log(10) at 3 months and an overall rise in HBV DNA level of 3 log(10) at 12 months. The only patient in whom durable viral suppression and HBV e antigen seroconversion were noted began receiving lamivudine and famciclovir simultaneously. HBV polymerase gene sequencing identified resistance-associated mutations in 6 of 7 patients with viral rebound. Sequential nucleoside analogue therapy is unlikely to be successful in achieving long-term suppression of HBV replication, and combination therapy should be considered at treatment initiation.

Panos G, Holmes P, Valero S, Anderson M, Gazzard B, Nelson M. · No affiliation provided · Hepatology. · Pubmed #18508302 No free full text.

This publication has no abstract.

Browne R, Asboe D, Gilleece Y, Atkins M, Mandalia S, Gazzard B, Nelson M. · No affiliation provided · Sex Transm Infect. · Pubmed #15295139 links to  free full text

This publication has no abstract.

Stebbing J, Atkins M, Nelson M, Rajpopat S, Newsom-Davis T, Gazzard B, Bower M. · No affiliation provided · Blood. · Pubmed #14998920 links to  free full text

This publication has no abstract.