Safety and tolerability of sequential pegylated IFN-alpha2a and tenofovir for hepatitis B infection in HIV(+) individuals.

Chronic hepatitis B virus infections are a major cause of morbidity and mortality in HIV co-infected patients. The standard of care for treating HCV co-infection has been guided by major clinical trials, but the treatment of HBV co-infection has not been as thoroughly studied and the standard of care remains largely untested. The single pill formulation of tenofovir with emtricitabine has become a standard treatment approach in HBV co-infected patients. WU114 was a phase 1 clinical trial that examined the safety and tolerability of sequential treatment of HBV with pegylated interferon-alpha2a plus delayed-initiation tenofovir in HIV co-infected individuals. We postulated that initial HBV viral load reduction with pegylated interferon prior to initiation of nucleoside/nucleotide therapy would increase seroconversion events and durability of HBV virologic suppression. No severe pegylated IFN-alpha2a drug toxicities were seen in either the monotherapy or delayed tenofovir arms. Sequential pegylated interferon and tenofovir-based therapy was tolerable and should be compared with dual nucleoside/nucleotide suppression to determine relative frequencies of seroconversion and durability of HBV suppression in co-infected patients.

Increasing prevalence of resistance mutations in antiretroviral-naïve individuals with established HIV-1 infection from 1996-2001 in St. Louis.

BACKGROUND: Transmission of drug-resistant virus in HIV-1 infected individuals is well documented, particularly in patients with primary infection. Prevalence in chronically infected antiretroviral-naïve patients is reportedly low. Routine genotyping in this population is not recommended. PURPOSE: The purpose of this study was to evaluate resistance profiles in patients with established HIV infection in St. Louis. METHOD: We selected specimens from drug-naïve individuals (CD4 >300 cells/mL and VL >1000 copies/mL) with established HIV infection between 1996-2001. 62 of 75 specimens were available for genotyping. We excluded patients with evidence of acute HIV infection and long-term nonprogressors. RESULTS: The overall prevalence of resistance was 11% (7/62). From 1996 to 1998, a prevalence of 4% was observed (1/27 individuals). During the subsequent period from 1999 to 2001, the frequency increased to 17% (6/35 participants; p =.08; 95% CI 5-29%). CONCLUSION: The results suggest that the prevalence of primary resistance is increasing in our region to the point that it justifies genotypic testing in all individuals before the initiation of antiretroviral therapy. This has to be considered when designing antiretroviral clinical trials.