This study investigated the efficacy, safety, and pharmacokinetics of adefovir dipivoxil (ADV) in children and adolescents with chronic hepatitis B (CHB). A total of 173 treatmentnaive and treatment-experienced children with hepatitis B e antigen (HBeAg)؉ CHB were randomized to ADV or placebo. Randomization was stratified by age (2 to <7 years; >7 to <12 years; >12 to <18 years) and prior treatment. Significantly more ADV-treated subjects aged 12 to <18 years achieved the primary efficacy endpoint (serum hepatitis B virus [HBV] DNA <1,000 copies/mL and normal alanine aminotransferase) compared to placebotreated subjects (23% versus 0%; P ؍ 0.007). In the younger groups, differences between ADV and placebo at the end of blinded treatment were not statistically significant. More ADV-treated subjects had HBeAg seroconversion: 18 of 113 (15.9%) versus three of 57 (5.3%) (but P ؍ 0.051), and more met the combined endpoint of HBeAg seroconversion, HBV DNA <1,000 copies/mL and normal alanine aminotransferase (12/113 versus 0/57; P ؍ 0.009). No subject developed an ADV-associated mutation that has been linked to HBV DNA rebound (that is, mutations rtN236T or rtA181V). ADV plasma concentrations were comparable across groups and within the target range. ADV treatment was well tolerated; no new safety issues were identified. Treatment-related adverse events were reported for 12% of ADV-treated and 10% of placebo-treated subjects. After 48 weeks of ADV treatment, antiviral efficacy in subjects ages 12 to <18 years with HBeAg؉ CHB was similar to that observed in a study in adult treatment-naive subjects with HBeAg؉ CHB. ADV was not different from placebo in subjects aged 2 to 11 years despite adequate plasma ADV exposure in all three age groups. Conclusion: ADV showed significant antiviral efficacy in subjects aged 12 to 17 years with HBeAg؉ CHB, but was not different from placebo in subjects aged 2 to 11 years. (
The QuantiFERON-TB Gold In-Tube test is a specific test for M tuberculosis exposure in children, with performance characteristics similar to those for adults residing in regions with low levels of endemic disease. Concerns about test sensitivity, especially for children <2 years of age, will require additional prospective long-term evaluation.
CD4؉ T cells are thought to be critical in the maintenance of virus-specific CD8 ؉ cytotoxic T-cell (CTL) responses. In human immunodeficiency virus type 1 (HIV-1) infection, a selective decline in HIV-1-specific CTL as the CD4 ؉ T-cell count decreases has been reported. Using HLA-peptide tetrameric complexes, we show the presence at high frequency of HIV-1-and cytomegalovirus-specific CD8 ؉ T cells when the peripheral CD4 ؉
T-cell count was low or zero in three HIV-1-infected patients. No direct virus-specific CD8؉ -mediated effector activity was seen in these subjects, suggesting antigen unresponsiveness, although tetramer-sorted cells could be expanded in vitro in the presence of interleukin-2 into responsive effector cells. Thus, virus-specific CD8 ؉
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