An open-label study of tenofovir in HIV-1 and Hepatitis B virus co-infected individuals

Chelsea and Westminster Hospital, London, UK.
AIDS (Impact Factor: 5.55). 02/2003; 17(1):F7-10. DOI: 10.1097/01.aids.0000042959.95433.c1
Source: PubMed


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.
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.
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.
These results indicate that 52 weeks of tenofovir in addition to antiretroviral therapy is active against HBV, and it appears to overcome lamivudine resistance.

7 Reads
  • Source
    • "However we did not observe effect of hepatitis B co-infection but instead hepatitis C coinfection was a significant risk factor for DILI. In HIV-HBV-coinfected patients, in addition to antiretroviral therapy both Lamivudine and Tenofovir promptly inhibit HBV replication and lower HBV DNA viral load as well as alanine aminotransferase [45], [46]. All our study subjects received Lamivudine as part of anti-HIV regimen and this might lead to alleviating HBV co-infection as a risk factor for DILI. "
    [Show abstract] [Hide abstract]
    ABSTRACT: To investigate the timing, incidence, clinical presentation, pharmacokinetics and pharmacogenetic predictors for antiretroviral and anti-tuberculosis drug induced liver injury (DILI) in HIV patients with or without TB co-infection. A total of 473 treatment naïve HIV patients (253 HIV only and 220 with HIV-TB co-infection) were enrolled prospectively. Plasma efavirenz concentration and CYP2B6*6, CYP3A5*3, *6 and *7, ABCB1 3435C/T and SLCO1B1 genotypes were determined. Demographic, clinical and laboratory data were collected at baseline and up to 48 weeks of antiretroviral therapy. DILI case definition was according to Council for International Organizations of Medical Sciences (CIOMS). Incidence of DILI and identification of predictors was evaluated using Cox Proportional Hazards Model. The overall incidence of DILI was 7.8% (8.3 per 1000 person-week), being non-significantly higher among patients receiving concomitant anti-TB and HAART (10.0%, 10.7 per 1000 person-week) than those receiving HAART alone (5.9%, 6.3 per 1000 person-week). Frequency of CYP2B6*6 allele (p = 0.03) and CYP2B6*6/*6 genotype (p = 0.06) was significantly higher in patients with DILI than those without. Multivariate cox regression model indicated that CYP2B6*6/*6 genotype and anti-HCV IgG antibody positive as significant predictors of DILI. Median time to DILI was 2 weeks after HAART initiation and no DILI onset was observed after 12 weeks. No severe DILI was seen and the gain in CD4 was similar in patients with or without DILI. Antiretroviral and anti-tuberculosis DILI does occur in our setting, presenting early following HAART initiation. DILI seen is mild, transient and may not require treatment interruption. There is good tolerance to HAART and anti-TB with similar immunological outcomes. Genetic make-up mainly CYP2B6 genotype influences the development of efavirenz based HAART liver injury in Tanzanians.
    PLoS ONE 07/2012; 7(7):e40180. DOI:10.1371/journal.pone.0040180 · 3.23 Impact Factor
  • Source
    • "In coinfected patients with HBV and HIV the information regarding TDF is rather heterogeneous , and data on efficacy derived from controlled trials is scarce. Analysis of cohorts which have included at least 20 patients with HBV-HIV suggest that TDF containing regimens can suppress HBV DNA levels in the majority of patients [Lacombe et al. 2008; Jain et al. 2007; Benhamou et al. 2006; Schmutz et al. 2006; Stephan et al. 2005; Nelson et al. 2003], with loss of HBeAg ranging from 6% to 40% after 1 year of treatment [Lacombe et al. 2008; Jain et al. 2007; Stephan et al. 2005], and has been shown to be as effective in naı¨ve as in lamivudine-resistant CHB [Schmutz et al. 2006]. These studies have failed to identify any differences when TDF is administered alone or with lamivudine [Schmutz et al. 2006]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Chronic hepatitis B (CHB) is prevalent worldwide. It may cause cirrhosis and hepatocellular carcinoma. Treatment for this condition may need to be lifelong, thus the drugs used must be both efficacious and safe. Clinical trials of tenofovir have demonstrated a good safety profile for this drug and it has potent antiviral properties. However, to better characterize the safety of this drug, the postmarketing surveillance must be taken into account. Clinicians need to be vigilant, as infrequent adverse events may be revealed during this phase. The current review presents a detailed exposé of preclinical and clinical data on tenofovir to increase awareness of possible adverse events and drug-drug interactions, based on the large experience of this drug in human immunodeficiency virus (HIV) treatment (and to date in patients with CHB). Several recommendations that may help the clinician to prevent the development of adverse events associated with tenofovir disoproxil fumarate (TDF) treatment are outlined, along with a suggested surveillance protocol for the timely and proper identification of possible renal and bone toxicity.
    Therapeutic Advances in Gastroenterology 03/2010; 3(2):107-19. DOI:10.1177/1756283X09354562 · 3.93 Impact Factor
  • Source
    • "TDF and FTC are both active against HBV in vitro, in case series (Benhamou et al 2003), and in a small controlled clinical trial with HIV-HBV coinfected subjects (Peters MG et al 2006), but are not approved for that indication. While FTC has no activity against lamivudine-resistant HBV strains, in HIV co-infected patients with a positive HBeAg, the inclusion of TDF in the HIV regimen resulted in a signifi cant reduction of viral load, including those with lamivudineresistant strains (Nelson et al 2003; Dore et al 2004). TDF also may be active against strains of HBV resistant to the NtRTI adefovir and be more potent as well (Qi et al 2007; Lacombe et al 2007). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Highly active antiretroviral therapy has significantly reduced HIV-related morbidity and mortality. Increasingly, fixed-dose antiretroviral combinations with equal or greater potency than traditional antiretrovirals, along with fewer side effects, reduced toxicity, and simplified dosing convenience are being utilized. Tenofovir-emtricitabine (TDF-FTC) represents one of the more recent fixed-dose combinations. In combination with either a ritonavir-boosted protease inhibitor or a non-nucleoside reverse transcriptase inhibitor, TDF-FTC is a preferred choice in recent treatment guidelines on the basis of demonstrated potency in randomized clinical trials, one-pill-a-day dosing convenience, and relatively low toxicity. In addition, the drug is active against hepatitis B virus. Caution must be exercised in patients with renal insufficiency, or when the drug is used with certain other drugs. This manuscript reviews the use of TDF-FTC in the treatment of HIV.
    Therapeutics and Clinical Risk Management 01/2008; 3(6):1097-104. · 1.47 Impact Factor
Show more