In the News

• Hepatitis A Vaccine Safe in HIV Patients
• Combination Therapy for HBV
• Risk of Early Virologic Failure With ddI + TDF + NNRTI
• Tenofovir for the Treatment of Lamivudine-Resistant Hepatitis B Virus (HBV)
• Barriers to Care of HCV for Drug Users

Hepatitis A Vaccine Safe in HIV Patients

Hepatitis A virus (HAV) is common among persons who are at highest risk for HIV infection. One hundred eighty subjects, 90 of whom were HIV-infected were given an inactivated HAV vaccine to determine the safety and efficacy in HIV-infected patients. The HIV-infected subjects were stratified into two groups: one group with CD4 cell counts <300 cells/mm³ and one group with CD4 cell counts >300cells/mm³. Vaccine or placebo was administered at zero and 24 weeks. At week 28, seroconversion rates among HIV-infected and HIV-uninfected subjects were 94% and 100%, respectively. Additionally, HIV-infected subjects with CD4 cell counts <300 cells/mm³ had a seroconversion rate of 87%, while HIV-infected subjects with CD4 cell counts >300 cells/mm³ had a seroconversion rate of 100%. Conclusions drawn from this study are that HAV vaccine is immunogenic and safe among HIV-infected persons, and should be part of their preventative care.
Clin Infect Dis 2004; 39:1207-13.

Combination Therapy for HBV

Thirty treatment naive, hepatitis B virus (HBV) e antigen positive (HBeAg+) patients were randomized to receive adefovir dipivoxil (ADV) plus emtricitabine (FTC) or ADV plus placebo for 48 weeks. The study aims were to compare the efficacy of a new combination therapy of ADV plus FTC versus ADV monotherapy. At baseline, median HBV DNA was 7.6 log copies/ml in the ADV plus FTC arm and 8.5 log copies/ml in the ADV arm. The median log change from baseline HBV DNA was -3.95 for the ADV plus FTC arm and -2.44 for the ADV arm. HBeAg seroconversion occurred in three patients total; two in the combination arm and one in the ADV arm. Additionally, 80% of HbeAg positive patients taking ADV plus FTC had undetectable HBV DNA, versus 20% taking ADV alone at 48 weeks. Combination therapy with ADV plus FTC may be superior to ADV alone, at least in the short term.
NATAP (www.natap.org)

Risk of Early Virologic Failure With ddI + TDF + NNRTI

Two studies reported at the 2004 ICAAC meeting found that regimens combining the nucleoside/nucleotide analogs didanosine (ddI) and tenofovir disoproxil fumarate (TDF), plus either efavirenz (EFV) or nevirapine (NVP) can cause early virologic failure in treatment-naive persons, particularly in those persons commencing treatment with a high viral load. Podzamczer et al. found that 43% of people taking TDF/ddI/efavirenz had virologic failure, defined as less than a two log drop in viral load by month three of their study. None of the subjects taking TDF/ddI/efavirenz plus lopinavir/ritonavir had virologic failure. In a larger study conducted by Moyle et al, 44 subjects were randomized to start TDF/ddI/efavirenz and 36 were randomized to start 3TC/ddI/efavirenz. While adherence exceeded 99% in both groups, virologic failure in the TDF/ddI/efavirenz group and 3TC/ddI/efavirenz group were 12% and 0%, respectively. All people with a virologic failure had a pretreatment CD4 count below 200 cells/uL and a viral load greater than 100,000 copies/mL. The mechanism of early virologic failure in these patients is unclear. Clinicians should use caution when coadministering ddI/TDF and either EFV or NVP in treatment-naive patients with high baseline viral loads.
NATAP (www.natap.org)

Tenofovir for the Treatment of Lamivudine-Resistant Hepatitis B Virus (HBV)

Adefovir dipivoxil, which was recently approved for the treatment of wild-type and lamivudine-resistant HBV infection, and tenofovir disoproxil fumarate (TDF) were compared in a study of 53 subjects to measure the decline of HBV DNA levels in lamivudine-resistant HBV infection. Thirty-five subjects received TDF 300 mg/day for 72-130 weeks, while 18 subjects received adefovir 10 mg/day for 60-80 weeks. The TDF-treated group was further divided into three groups: HBV-infected subjects, HIV/HBV coinfected subjects who had received TDF as a part of antiretroviral therapy, and immunosuppressed HBV-infected subjects following kidney transplantation. None of the adefovir subjects had these comorbidity features. Subjects were matched for age, sex, ALT levels, hepatitis B e antigen (HBeAg) status, and HBV DNA level at baseline. All TDF-treated subjects showed a strong and early suppression of HBV DNA within a few weeks, including the HIV coinfected subjects. At week 48, 100% of the TDF-treated subjects had HBV DNA levels below 105 copies/mL, in contrast to only 44% of those subjects treated with adefovir. While tenofovir has not been approved for the treatment of HBV, this study shows that it may become an effective alternative for the treatment of patients with lamivudine-resistant HBV infection.
Hepatology; 2004: 40:6

Barriers to Care of HCV for Drug Users

Five hundred fifty-seven HIV-seropositive and HIV-seronegative current and former injection drug users were enrolled in a prospective study to gauge the natural history of hepatitis C virus (HCV) infection. The 228 subjects with chronic HCV infection were offered referral for HCV evaluation and treatment; only 56% accepted referrals. Reasons study participants gave for declining referrals included self-reported clinical care elsewhere (62%), not interested or too busy (16%), or not ready (9%). Additional reasons included fear of biopsy or treatment, unable to keep appointments, and end-stage liver disease. Of the 56% of subjects who did accept referrals, only 43% arrived for evaluation, which was located two city blocks from the research site. Additionally, of those who did arrive for evaluation, only 22% had a liver biopsy, and only 7% were treated. Despite counseling about HCV infection and the need for medical evaluation, only a small percentage of subjects actually followed through to treatment. This study suggests that there must be other barriers, besides access to care, that inhibit HCV infected injection drug users from seeking and receiving treatment.
NATAP (www.natap.org)