Antiretroviral therapy in coinfected patients: viral hepatitis and tuberculosis.

Purpose Of Review: Highly active antiretroviral therapy in coinfected patients is complicated by a potentially increased risk for hepatotoxicity. Therefore, treatment strategies are urgently needed.

Recent Findings: In HIV/hepatitis B virus coinfected patients with an indication for therapy for both HIV and hepatitis B, tenofovir plus lamivudine or emtricitabine containing highly active antiretroviral therapy regimens are the favored first-line treatment as they include medications which are dually active.

Primary HIV drug resistance and efficacy of first-line antiretroviral therapy guided by resistance testing.

Background: Primary HIV drug resistance has been associated with poor treatment outcome of first-line highly active antiretroviral therapy (HAART) in several trials. The aim of the study was to assess the efficacy of first-line HAART guided by resistance testing.

Methods: In a prospective multicenter study in the state of Nordrhein-Westfalen, Germany, chronically HIV-infected patients underwent genotypic resistance testing and were monitored for 48 weeks after initiation of HAART.

Variant of hepatitis B virus with primary resistance to adefovir.

The reverse-transcriptase inhibitor lamivudine (Zeffix, GlaxoSmithKline) is often used to treat chronic infection with hepatitis B virus (HBV) until resistance develops. Treatment may then be switched to the reverse-transcriptase inhibitor adefovir (Hepsera, Gilead), which has a lower frequency of resistance. Here, we describe three cases of primary adefovir resistance that were sensitive to tenofovir (Viread, Gilead).

Distribution and effects of polymorphic RANTES gene alleles in HIV/HCV coinfection -- a prospective cross-sectional study.

Aim: Chemokines and their receptors are crucial for immune responses in HCV and HIV infection. RANTES gene polymorphisms lead to altered gene expression and influence the natural course of HIV infection. Therefore, these mutations may also affect the course of HIV/HCV coinfection.

Management of hepatitis C/HIV coinfection.

Purpose Of Review: One third of HIV-infected individuals in Europe and the USA have a hepatitis C coinfection. With the introduction of highly active antiretroviral therapy for treatment of HIV, liver disease caused by chronic hepatitis C virus infection has now become an increasingly important cause of morbidity and mortality among HIV-infected patients. Therefore, treatment strategies for management of hepatitis C coinfection in HIV-infected individuals are urgently needed.

Therapeutic management of hepatitis and HIV infection in co-infected patients: results of a survey performed before the 2005 Consensus Conference.

The First European Consensus Conference on the Treatment of Chronic Hepatitis B and C in HIV Co-infected Patients aimed to produce recommendations that could be applied across Europe. However, some important differences exist around Europe, in terms of access to treatment and tests for monitoring. This short survey of 24 European countries showed that access to anti-HCV treatment is low (approximately 10%) in patients with HCV/HIV co-infection--generally access is higher in Western Europe than in Eastern or Northern Europe.

Hepatitis C-associated autoimmunity in patients coinfected with HIV.

Background: Hepatitis C virus (HCV) infection is associated with multiple extrahepatic manifestations. It is unclear to what extent extrahepatic manifestations occur in HIV/HCV coinfection.

Methods: We prospectively assessed cross-sectional frequencies of autoimmune manifestations in HIV/HCV-coinfected patients (n=98), HIV-mono-infected (n=45) and HCV-mono-infected patients (n=78).

Influence of viral hepatitis on HIV infection.

The natural history of HBV is known to be complicated by HIV-co-infection. In contrast, the effect of HBV on the outcome of patients infected with HIV-1 is controversial. Some cohort studies from the pre-HAART era described a more rapid progression to AIDS in patients carrying antibodies to the core-antigen or having chronic HBV infection, but post-HAART studies did not detect any impact of HBV co-infection on HIV-disease progression.

Orthotopic liver transplantation in human immunodeficiency virus (HIV)-positive patients: outcome of 7 patients from the Bonn cohort.

The outcome and clinical features of 7 HIV-positive patients who were liver transplanted at Bonn University in the era of highly active antiretroviral therapy (HAART) between 1997 and 2004, analyzed by retrospective chart review, are reported. Reasons for orthotopic liver transplantation (OLT) were end-stage liver disease due to chronic hepatitis C (n = 4) or hepatitis B (n = 1) or acute liver failure due to fulminant hepatitis B (n = 2). Immunosuppression was based on cyclosporine A and prednisone.

Selective escape from CD8+ T-cell responses represents a major driving force of human immunodeficiency virus type 1 (HIV-1) sequence diversity and reveals constraints on HIV-1 evolution.

The sequence diversity of human immunodeficiency virus type 1 (HIV-1) represents a major obstacle to the development of an effective vaccine, yet the forces impacting the evolution of this pathogen remain unclear. To address this issue we assessed the relationship between genome-wide viral evolution and adaptive CD8+ T-cell responses in four clade B virus-infected patients studied longitudinally for as long as 5 years after acute infection. Of the 98 amino acid mutations identified in nonenvelope antigens, 53% were associated with detectable CD8+ T-cell responses, indicative of positive selective immune pressures.

Efficacy of short-term monotherapy with maraviroc, a new CCR5 antagonist, in patients infected with HIV-1.

We assessed the efficacy and safety of 10-d monotherapy with the orally administered CCR5 antagonist maraviroc in 63 HIV-1-positive individuals prescreened for the absence of CXCR4-using virus. Maximum reduction in viral load occurred at a median of 10-15 d, with a mean reduction of >or=1.6 log(10) copies/ml at all twice daily doses >or=100 mg.

Evolution of HIV resistance during treatment interruption in experienced patients and after restarting a new therapy.

Background: To analyse the evolution of resistance patterns in patients undergoing treatment interruption (TI) and re-initiating highly active anti-retroviral therapy (HAART).

Methods: HIV-RT and -PR gene-sequences were analysed in 14 patients (>5 failing prior drugs) before and during TI and under a new HAART. Genotypes were interpreted using two bioinformatics systems.

Influence of hepatitis C virus infection on HIV-1 disease progression and response to highly active antiretroviral therapy.

Objective: To assess hepatitis C virus (HCV) antibody prevalence in the EuroSIDA cohort, along with survival, human immunodeficiency virus (HIV)-1 disease progression, virologic response (plasma HIV-1 RNA load of < 500 copies/mL), and CD4 cell count recovery by HCV serostatus in patients initiating highly active antiretroviral therapy (HAART).

Results: HCV serostatus at or before enrollment was available for 5957 patients; 1960 (33%) and 3997 (67%) were HCV seropositive and seronegative, respectively. No association between an increased incidence of acquired immunodeficiency syndrome-defining illnesses or death and HCV serostatus was seen after adjustment for other prognostic risk factors known at baseline (adjusted incidence rate ratio [IRR], 0.

Comparison of GB virus C, HIV, and HCV infection markers in hemophiliacs exposed to non-inactivated or inactivated factor concentrates.

Background: Until the mandatory introduction of viral inactivation techniques of blood plasma products in the early 1980s many recipients of these products were infected with various viral pathogens.

Objectives: To determine the rate of transmission of GB virus C/hepatitis G virus (GBV-C/HGV) HCV, and HIV through non-virus-inactivated clotting factor concentrates in hemophiliacs, as well as the relation between amount of administered clotting factor and risk for GBV-C/HGV infection.

Study Design: In this cross-sectional study, we determined retrospectively the rates of infection markers for GBV-C/HGV, HCV, and HIV in a German cohort of hemophiliacs treated with documented amounts of non-virus-inactivated clotting factor concentrates (group A) and in a second group of hemophiliacs who were treated exclusively with virus-inactivated clotting factor (group B).

Safety of lopinavir/ritonavir for the treatment of HIV-infection.

Kaletra, a fixed-dose co-formulation of lopinavir/ritonavir, was the first boosted protease inhibitor developed for the treatment of HIV-infection. In September 2000, the US FDA granted Kaletra fast-track approval as data showed a higher efficacy in the treatment of HIV-infection than standard protease inhibitors of that time. Although potency was of major concern in the early years of highly active antiretroviral therapy (HAART), presently, with the perspective of HIV-infection becoming a chronic but well controllable disease, other issues begin to draw increased attention in the long-term management of HIV-infected patients.

Liver histopathology in human immunodeficiency virus-hepatitis C virus co-infected patients with fatal liver disease.

Background: Liver failure is an increasing cause of death in human immunodeficiency virus-hepatitis C virus (HIV-HCV) co-infected patients. Here, histopathological features of fatal liver disease in HIV-HCV co-infected patients were comparatively assessed.

Methods: Liver biopsies of seven HIV-HCV co-infected patients with clinically imminent liver death and advanced immune deficiency were studied.

Successful therapy of hepatitis B with tenofovir in HIV-infected patients failing previous adefovir and lamivudine treatment.

Three HIV-infected patients with chronic hepatitis B (genotype A) were switched to adefovir therapy after unsuccessful lamivudine treatment. Surprisingly, adefovir therapy failed, although none of the virus isolates displayed mutations known to be associated with adefovir resistance (A181V, N236T). In two isolates we identified hepatitis B virus DNA polymerase mutation L217R, in one case we found multiple frameshifts in the same region.

Rapid determination of the Delta32 deletion in the human CC-chemokine receptor 5 (CCR5) gene without DNA extraction by lightcycler real-time polymerase chain reaction.

CCR5 is a major coreceptor for cellular entry of macrophage-tropic isolates of the human immunodeficiency virus (HIV). A 32-base pair deletion of the CCR5 gene (CCR5Delta32) protects against HIV infection because the frame shift leads to a truncated protein not expressed on the cell surface. CCR5Delta32 also delays progression in heterozygous HIV-infected patients and improves responses to antiretroviral therapy.

Peginterferon Alfa-2a plus ribavirin for chronic hepatitis C virus infection in HIV-infected patients.

Background: Hepatitis C virus (HCV) infection is highly prevalent and is associated with substantial morbidity and mortality among persons infected with the human immunodeficiency virus (HIV). We compared the efficacy and safety of pegylated interferon alfa-2a (peginterferon alfa-2a) plus either ribavirin or placebo with those of interferon alfa-2a plus ribavirin for the treatment of chronic HCV infection in patients who were also infected with HIV.

Methods: A total of 868 persons who were infected with both HIV and HCV and who had not previously been treated with interferon or ribavirin were randomly assigned to receive one of three regimens: peginterferon alfa-2a (180 microg per week) plus ribavirin (800 mg per day), peginterferon alfa-2a plus placebo, or interferon alfa-2a (3 million IU three times a week) plus ribavirin.

Management of drug-to-drug interactions between cyclosporine A and the protease-inhibitor lopinavir/ritonavir in liver-transplanted HIV-infected patients.

Highly active antiretroviral therapy (HAART) has improved the life expectancy of HIV-infected patients, allowing orthotopic liver transplantation as a reasonable treatment option for selected patients with terminal liver disease. Both non-nucleoside reverse transcriptase inhibitors and protease inhibitors, key elements of HAART, give rise to substantial drug-to-drug interactions with immunosuppressive drugs such as tacrolimus and cyclosporine A. After studying 12-hour pharmacokinetic profiles in 3 HIV-positive patients after liver transplantation, we describe how dosing of cyclosporine A can be adjusted to maintain effective immunosuppressive drug levels on a daily dosing schedule when ritonavir-boosted indinavir or lopinavir-based antiretroviral therapy is given.

HIV and hepatitis C virus co-infection.

Since the decline in HIV-related morbidity and mortality after introduction of highly active antiretroviral therapy (HAART) in 1996, liver disease caused by chronic infection with hepatitis C virus (HCV) has become an increasingly important cause of morbidity and mortality among HIV-infected patients infected parenterally with HCV in more developed countries. A third of HIV-infected individuals in Europe and the USA have HCV co-infection. HIV accelerates HCV liver disease especially when HIV-associated immunodeficiency progresses.

Chemokine mRNA levels in mononucleated cells of HIV-infected patients before and after initiation of PI- versus NNRTI-containing HAART.

To compare CC chemokine mRNA levels from native peripheral blood mononucleated cells (PBMCs) before and 6 months after the initiation of two different regimens of highly active antiretroviral therapy (HAART), we treated group 1 (n = 11) with two nucleoside analogues and the protease inhibitor (PI) indinavir boosted by ritonavir (800/100 mg b.i.d.

Influence of HLA-B57 on clinical presentation and viral control during acute HIV-1 infection.

Background: HLA-B57, as well as cytotoxic T-lymphocyte (CTL) responses restricted by this allele, have been strongly associated with long-term non-progressive chronic HIV-1 infection. However, their impact on viral replication during acute HIV-1 infection is not known.

Methods: Clinical and immunological parameters during acute and early HIV-1 infection in individuals expressing HLA-B57 were assessed.