Pegylated interferon alfa-2a (PEG-IFN) may induce sustained virological response (SVR) inS ubstantial advances have been made in the treatment of chronic hepatitis B (CHB) in the past decade. Several nucleos(t)ide analogues are currently approved for the treatment of hepatitis B virus (HBV) infection with a high efficacy in suppressing HBV replication. However, a long duration of treatment is needed to maintain viral suppression, and the major question of whether oral therapy can ever be stopped remains unanswered. 1 In parallel with analogues, the American Association for the Study of Liver Diseases practice guidelines have advocated pegylated interferon alfa-2a (PEG-IFN) as a potential first-line therapy in hepatitis B e antigen (HBeAg)-negative patients. 2 The advantages of PEG-IFN therapy include a limited treatment course, a high rate of HBeAg seroconversion (in HBeAg-positive patients), a 20% to 30% rate of sustained virological response (SVR), the potential for hepatitis B surface antigen (HBsAg) loss or seroconversion, and a lack of resistance development. 3 Nonetheless, the use of PEG-IFN currently accounts for

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HBV genotype has a strong influence on serum HBsAg kinetics during PEG-IFN-alpha2a therapy in HBeAg-negative patients.

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The genotypic inhibitory quotient (GIQ) has been proposed as a way to integrate drug exposure and genotypic resistance to protease inhibitors and can be useful to enhance the predictivity of virologic response for boosted protease inhibitors. The aim of this study was to evaluate the predictivity of the GIQ in 116 protease inhibitor-experienced patients treated with lopinavir-ritonavir. The overall decrease in human immunodeficiency virus type 1 (HIV-1) RNA from baseline to month 6 was a median of ؊1.50 log 10 copies/ml and 40% of patients had plasma HIV-1 RNA below 400 copies/ml at month 6. The overall median lopinavir study-state C min concentration was 5,856 ng/ml. Using univariate linear regression analyses, both lopinavir GIQ and the number of baseline lopinavir mutations were highly associated with virologic response through 6 months. In the multivariate analysis, only lopinavir GIQ, baseline HIV RNA, and the number of prior protease inhibitors were significantly associated with response. When the analysis was limited to patients with more highly mutant viruses (three or more lopinavir mutations), only lopinavir GIQ remained significantly associated with virologic response. This study suggests that GIQ could be a better predictor of the virologic response than virological (genotype) or pharmacological (minimal plasma concentration) approaches used separately, especially among patients with at least three protease inhibitor resistance mutations. Therapeutic drug monitoring for patients treated by lopinavir-ritonavir would likely be most useful in patients with substantially resistant viruses.The development of human immunodeficiency virus (HIV) drug resistance during antiretroviral therapy can compromise the efficacy of subsequent regimens following virologic failure. Several studies have shown that changes in baseline viral genotype, compared to that of wild-type virus, adversely affect the virologic response of antiretroviral-experienced subjects with a subsequent regimen (3,4,19). However, the efficacy of antiretroviral treatment can be impaired by several factors, including poor adherence to treatment regimens, suboptimal antiviral potency and/or drug concentrations, and of course selection of antiretrovirus agent-resistant HIV quasispecies.More information on the effect of these parameters should be beneficial for optimizing the use of protease inhibitors in salvage therapy. The inhibitory quotient, mainly used for the protease inhibitors, has been proposed as a way to integrate drug exposure and viral susceptibility. Defined as the ratio between the trough concentration of a drug in a patient and the susceptibility of the virus in that patient to that drug, the inhibitory quotient has been associated with virologic response to protease inhibitor-based antiretroviral therapy in several studies (6, 17;

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Hepatitis A virus (HAV) is shed in feces but also in saliva. HAV RNA was detected in saliva in five out of six acutely infected patients with HAV viremia. Serum and saliva sequences were identical. The simplicity of obtaining material allows the recommendation of the use of saliva for investigation of outbreaks.

To assess the impact of sequential therapy with adefovir dipivoxil (ADV) and pegylated interferon alfa-2a (PEG-IFN) on virological (serum HBV-DNA) and serological (serum HBsAg) response in 20 consecutive HBeAg-negative patients. Patients received ADV for 20 weeks, then ADV and PEG-IFN for 4 weeks and lastly PEG-IFN for 44 weeks. Serum HBV-DNA and HBsAg were assessed at baseline, during therapy (weeks 20, 44 and 68) and follow-up (weeks 92 and 116). Sustained virological response (SVR) was defined as serum HBV-DNA <10 000 copies/mL (partial) or <70 copies/mL (complete) 24 weeks after stopping treatment. A serological response was defined as a serum HBsAg decrease ≥1 log(10) IU/mL at the end of treatment. Baseline median serum HBV-DNA and HBsAg levels were 7.6 log(10) copies/mL and 3.8 log(10) IU/mL, respectively. Ten patients (50%) achieved SVR, six of them had partial response and four complete response. Four patients (20%) achieved serological response. Complete SVRs showed a major and steep decline in HBsAg level with a median decrease of 0.5, 1.6 and 2.0 log(10) IU/mL at treatment week 20, 44 and 68, respectively. Partial SVRs showed a slight and slow decline in serum HBsAg level (0.1, 0.4, and 0.6 log IU/mL at weeks 20, 44 and 68, respectively). On-treatment serum HBsAg decrease had a high accuracy to predict SVR (AUROC = 0.88). Our results suggest that sequential therapy might be an interesting strategy for HBeAg-negative patients. Serum HBsAg kinetics seem to be an accurate tool to predict SVR. Large clinical trials are needed to explore this strategy with more potent analogues.