96 weeks combination of adefovir dipivoxil plus emtricitabine vs. adefovir dipivoxil monotherapy in the treatment of chronic hepatitis B.

BACKGROUND/AIMS: In order to prevent the occurrence of drug-resistant mutants associated with treatment for chronic hepatitis B virus (HBV) infection, combination therapy is being developed. To determine the efficacy of adefovir dipivoxil (ADV) plus emtricitabine (FTC) combination therapy in chronic HBV infection. METHODS: Thirty treatment-nai ve, HBeAg-positive patients were randomized to combination ADV plus FTC (n=14) or ADV plus placebo monotherapy (n=16) for 96 weeks. HBV DNA was measured by polymerase chain reaction. Treatment was stopped in those with HBeAg seroconversion. RESULTS: The median decrease in HBV DNA at week 96 was higher in the combination group (-5.30 vs. -3.98 log(10)copies/ml, p=0.05). More patients in the combination group had normalization of alanine aminotransaminase and HBV DNA<300 copies/ml at week 96 when compared with the monotherapy group [11 of the 14 patients (78.6%) vs. 6 of the 16 patients (37.5%), p=0.03]. However, HBeAg seroconversion at week 96 was similar in the 2 groups [2/14 (14.3%) vs. 4/16 (25.0%), p=NS]. No ADV or FTC resistance was detected at week 96. In those with HBeAg seroconversion, 50.0% had post-treatment relapse. CONCLUSIONS: Combination ADV plus FTC resulted in more potent suppression of HBV DNA over 96 weeks of therapy.

Baseline genotype as a predictor of virological failure to emtricitabine or stavudine in combination with didanosine and efavirenz.

The presence of drug-associated mutations among ART-naive, HIV-1(+) patients may compromise the response to antiviral therapy. We evaluated the effect of preexisting drug-associated resistance mutations to the response in treatment-naive patients to therapy with emtricitabine (FTC) or stavudine (d4T) in combination with didanosine (ddI) and efavirenz (EFV). Study FTC-301A compared emtricitabine once daily (QD) with stavudine twice daily in combination with didanosine and efavirenz in ART-naive patients. Genotypic analysis was performed on baseline plasma HIV-1 RNA for all available samples and at time of virologic failure (VF). Drug resistance mutations present at baseline were evaluated as predictors of VF using logistic regression. VF rates were compared between subgroups using a two-sided exact test. Baseline drug resistance mutations were observed in 90/546 (16.5%) patients: 56/90 (62.2%) with nonnucleoside analogue (NNRTI) mutations and 42/90 (46.6%) with nucleoside analogue mutations. In a stepwise, multiple regression analysis, the presence of the K103N mutation at initiation of therapy was associated with VF in both arms (p = 0.001), however, there was a higher incidence of VF in the stavudine arm compared to the emtricitabine arm regardless of the presence or absence of mutations at baseline (p = 0.001). In this study, the presence of drug-associated resistance mutations in ART-naive patients was significantly correlated with subsequent development of virologic failure underscoring the utility of testing for resistance in addition to the use of potent and well-tolerated first line regimens in treatment-naive patients.

Comparison of real-time PCR assays for monitoring serum hepatitis B virus DNA levels during antiviral therapy.

The performance characteristics of the RealART and Molecular Beacons assays were compared with those of the Digene Hybrid Capture II assay (ultrasensitive). The results of the RealART and Digene Hybrid assays were related (r = 0.94; P < 0.001) and diverged by 2 orders of magnitude. The RealART assay can be used to effectively monitor serum hepatitis B virus DNA levels.

Age-related immune dysfunction in health and in human immunodeficiency virus (HIV) disease: association of age and HIV infection with naive CD8+ cell depletion, reduced expression of CD28 on CD8+ cells, and reduced thymic volumes.

Older age is a strong predictor of accelerated human immunodeficiency virus (HIV) disease progression. We investigated the possible immunologic basis of this interaction by comparing older (>/=45 years) and younger (