Complete Viral Suppression Research Articles

Analogs in the treatment of chronic hepatitis B: real life experience with tenofovir and entecavir

INTRODUCTION: Tenofovir and entecavir are potent antiviral agents. By suppressing viral replication, they induce histological improvement and finally delay the progression of chronic hepatitis B and the development of complications. They are rarely associated with serious side effects. Our data from a real life experience support data from the literature and suggest some minimal difference that may be useful in tailoring therapy.PATIENTS AND METHODS: We retrospectively analyzed 54 patients affected by chronic hepatitis B (31 and 23 treated by entecavir and tenofovir, respectively). Eight patients were cirrhotic. At baseline and 4-12 and 24 weeks after starting therapy, biochemical and virological analysis were performed in all patients. Renal function tests (serum creatinine, creatinine clearance and blood urea), serum (calcium and phosphate blood level) and urine electrolyte were also studied.RESULTS: All the patients reached virological control within 24 weeks. Only in the group treated by tenofovir we observed a complete viral suppression within 12 weeks. Some patients treated with tenofovir showed increased creatinine clearance without serum creatinine alteration. No significant side effects were reported with the exception of one case of persistent headache in the entecavir group for which the drug was suspended.CONCLUSIONS: Entecavir and tenofovir are effective in suppressing viral replication in patients with chronic hepatitis B. Tenofovir is more potent than entecavir and viral replication is blocked within 12 weeks of therapy. Tenofovir administration is associated with slight increase of creatinine clearance without alteration of serum creatinine levels. The choice of one or the other should be made according to target and specific patients characteristics. In patients with high serum viral load where the complete and quick control of viral replication is the main target, tenofovir may represent the best choice.

Comparison Between Tenofovir and Entecavir Treatment in Real-World Clinical Practice

Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are effective as two first-line anti-viral therapies for chronic hepatitis B (CHB); however, data are limited on directly comparing these two antivirals. This study aimed to compare the effectiveness and safety of TDF and ETV initial treatment of CHB patients. From October 2008 to December 2013, 257 consecutive treatment-naive CHB patients receiving TDF (n = 79) or ETV (n = 178) at Taipei Veterans General Hospital were enrolled. The baseline characteristics were comparable between the two groups. Kaplan-Meier curve estimated probability of complete HBV DNA suppression was 56.5% vs 75.9% at 6 months (P = .003), 81.7% vs 89.9% at 12 months (P = .098) and 93.3% vs 96.2% at 24 months (P = .565) in ETV and TDF group, respectively. Multivariate Cox regression indicated that treatment with TDF compared to ETV was a significant predictor of HBV DNA suppression (HR = 1.33; 95% CI 1.01-1.76; P = .045). In addition, HBAg positive (HR = 0.70; 95% CI 0.52-0.96; P = .025) and higher baseline HBV DNA level (HR = 0.84; 95% CI 0.76-0.92; P < .001) were significant negative predictors for viral suppression. The ALT normalization rate between these two treatment groups were not statistically significant (P = .114). Estimated glomerular filtration rate (eGFR) calculated by MDRD formula significantly decreased in both group at 24 months (-6.4027 in ETV vs -16.0556 in TDF, P = .006). Multivariate analysis indicated that TDF and baseline eGFR were independent factors associated with change of eGFR at 24 months. However, a small amount of patients progressed into moderate renal dysfunction during 24 months (0.7% vs 5.6%, P = .058). TDF was significantly more effective in achieving complete viral suppression, whereas it was also more significant in reduction of eGFR than ETV group.

Nanoformulation of antiretroviral drugs enhances their penetration across the blood brain barrier in mice

Eradication of virus by sanctuary sites is a main goal in HIV management. The central nervous system (CNS) is a classic model of sanctuary where viral replication occurs despite a complete viral suppression in peripheral blood. In recent years, nanotechnologies have provided a great promise in the eradication of HIV from the CNS. We hereby demonstrate for the first time that the structurally complex antiretroviral drug enfuvirtide (Enf), which normally is unable to penetrate the cerebrospinal fluid, is allowed to cross the blood brain barrier (BBB) in mice by conjugation with a nanoconstruct. Iron oxide nanoparticles coated with an amphiphilic polymer increase Enf translocation across the BBB in both in vitro and in vivo models. The mechanism involves the uptake of nanoconjugated-Enf in the endothelial cells, the nanocomplex dissociation and the release of the peptide, which is eventually excreted by the cells in the brain parenchyma. From the Clinical EditorDespite the success of cocktail therapy of antiretroviral drugs, the complete eradication of HIV remains elusive, due to existence of viral sanctuary sites. The authors showed in this study that an antiretroviral drug complexed with iron oxide nanoparticles and coated with PMA amphiphilic polymer crosses the blood brain barrier. Furthermore, there was significant anti-viral activity. The results would aid further drug designs to eradicate HIV.

HIV Drug Therapy in the Americas 16-18 April 2015, Mexico City, Mexico.

HIV Drug Therapy in the Americas 16-18 April 2015, Mexico City, Mexico.

Factors Associated with Immunological Discordance in HIV-Infected Patients Receiving Antiretroviral Therapy with Complete Viral Suppression in a Resource-Limited Setting.

"Immunological discordance," i.e., immunological failure despite complete viral suppression in human immunodeficiency virus (HIV)-infected patients receiving antiretroviral therapy (ART), is associated with increased risk of AIDS or death. To evaluate risk factors for immunological discordance in a resource-limited setting in which patients usually present late with low CD4 cell counts, we conducted a case-control study among HIV-infected patients receiving ART and having undetectable HIV RNA. The study included patients with immunological discordance (cases), which was defined as CD4 cell count < 30% above baseline and absolute CD4 cell count < 200 cells/mm(3) at the first 12 months of undetectable HIV RNA (<50 copies/mL). Patients without immunological discordance were included as controls. Of 142 patients (44 cases; 98 controls), the mean age was 38.6 ± 9.4 years and 67.6% were men; 65.5% had history of opportunistic infections. In multivariate analysis, only baseline CD4 cell count < 100 cells/mm(3) (odd ratio [OR], 2.53; 95% confidence interval [CI], 1.04-6.14; P = 0.040) and history of lost to follow-up (OR, 11.04; 95% CI, 2.87-42.46; P < 0.001) were significantly associated with immunological discordance. Early initiation of ART and intervention to improve regular clinic visit compliance and adherence to ART are crucial to prevent immunological discordance among HIV-infected patients.

Safety and efficacy of entecavir in adefovir-experienced patients.

Suboptimal viral suppression with adefovir (ADV) poses a challenge in managing chronic hepatitis B. Few studies have evaluated the efficacy of entecavir (ETV) in ADV-experienced patients. Our aim is to assess treatment effectiveness of ETV in ADV-experienced patients. ADV-experienced patients switched to ETV were enrolled from six US clinics. Patients completed a median of 24 months of ETV after switch. Patients were categorized into partial responders (detectable HBV-DNA at switch) or complete responders (undetectable HBV-DNA at switch) to ADV. Primary and secondary outcome measurements were complete viral suppression (CVS, HBV-DNA < 60 IU/mL) and biochemical response (BR, alanine aminotransferase [ALT] < 40 U/L), respectively. A total of 120 patients were included in the analysis (80 ADV partial responders; 40 ADV complete responders). In partial responders, CVS rate was 84% after 24 months of ETV. BR rate was 58% at switch to ETV and increased to 90% after 24 months. All complete responders continued to experience CVS after switch. On multivariate analysis inclusive of age, male gender, ALT level at switch, and history of lamivudine (LAM) exposure, we identified positive, hepatitis B e antigen status before ADV and higher HBV-DNA level at time of switch as significant independent negative predictors of CVS. In eight patients with ADV resistance, seven achieved CVS after 24 months of ETV, and all achieved BR. In ADV-experienced patients, high rates of CVS and BR can be achieved/sustained after switching to ETV, including those with ADV resistance or with prior exposure to LAM.

Tenofovir‐based alternate therapies for chronic hepatitis B patients with partial virological response to entecavir

Entecavir (ETV) is a first-line antiviral therapy for treating chronic hepatitis B (CHB); however, some patients have suboptimal response to ETV. Currently, there are limited data on how to approach these patients. Therefore, our aim was to compare the effectiveness of two alternate therapies--tenofovir (TDF) monotherapy and combination therapy of ETV+TDF--in CHB patients with ETV partial virological response. We conducted a retrospective study of 68 patients who had partial virological response to ETV, defined as having detectable HBV DNA following at least 12 months of ETV, and were switched to TDF monotherapy (n = 25) or ETV+TDF (n = 43). Patients were seen in seven US liver/community-based clinics and started on ETV between 2005 and 2009. The majority of patients were male; the vast majority were Asian and had positive hepatitis B e antigen (HBeAg). Patients in both groups had similar pretreatment characteristics. Complete viral suppression (CVS) rates with TDF monotherapy and ETV+TDF were similar after 6 months (71% vs 83%, P = 0.23) and 12 months (86% vs 84%, P = 0.85), and there was no statistically significant difference in CVS rates even when only patients with higher HBV DNA levels at switch (>1000 IU/mL) were evaluated. Multivariate analysis indicated that ETV+TDF was not an independent predictor of CVS compared to TDF monotherapy (OR = 1.19, P = 0.63). In conclusion, TDF monotherapy and ETV+TDF are comparable in achieving CVS in CHB patients with partial virological response to ETV. Long-term alternate therapy with one pill (TDF monotherapy) vs two pills (ETV+TDF) could lead to lower nonadherence rates and better treatment outcomes.

Off-treatment virologic relapse and outcomes of re-treatment in chronic hepatitis B patients who achieved complete viral suppression with oral nucleos(t)ide analogs.

BackgroundThe durability of off-treatment virologic responses has not been fully elucidated in chronic hepatitis B (CHB) patients who have previously achieved complete virologic suppression with nucleos(t)ide analog (NA) therapy. This study aimed to assess off-treatment virologic relapse rates and to characterize the outcomes of subsequent re-treatment in CHB patients who have discontinued oral NA following complete virologic suppression.MethodsNinety-five CHB patients who showed complete virologic suppression were withdrawn from NAs: entecavir, lamivudine, and clevudine in 67, 15, and 13 patients, respectively. Consolidation therapy was given for 6 and 12 months for HBeAg-positive and -negative CHB, respectively, before cessation. Virologic relapse was managed with the same NA that had induced complete virologic response before discontinuation.ResultsThe cumulative rates of virologic relapse at 12 and 24 months were 73.8% and 87.1%, respectively. The relapse rates were independent of HBeAg positivity, HBeAg seroconversion, and type of oral NA. In a multivariate analysis, duration of oral NA therapy was the only significant predicting factor associated with off-treatment virologic relapse. Although the majority of patients regained complete virologic suppression, some patients did not respond to re-treatment with the initial NA and developed genotypic resistance.ConclusionsNA consolidation therapy for 6 and 12 months is associated with high off-treatment virologic relapse in HBeAg-positive and -negative CHB patients, respectively. Drugs with high genetic barriers to resistance should be considered as a rescue therapy for off-treatment relapse in CHB.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2334-14-439) contains supplementary material, which is available to authorized users.

135 HIV-associated immunodeficiency despite potent antiretroviral therapy with CD4 T cell reconstitution

CD4 T cell reconstitution in patients with HIV is associated with increased responses to conventional vaccines and improved resistance to opportunistic infections. However, prolonged therapy fails to replenish a capacity for immune control over HIV and patients who interrupt therapy inevitably rebound to pre-treatment viral burden in plasma. Only elite patients, termed NVS or natural virus suppressors (1), control viremia to undetectable levels in the absence of therapy. Our earlier studies on NVS patients showed that this group was distinguished from all other HIV patients by the presence of normal levels of CD56+ V 2V 2 T cells in blood (2) reflecting reconstitution of the T cell receptor repertoire through new cell synthesis (3). The CD56 marker identifies cytotoxic effector lymphocytes including NK, CD8, T and NKT subsets, but it’s function remains unknown. We have now shown persistent depression of CD56 expression on CD8 T cells from HIV+ individuals except for NVS patients where the levels approach those found in normal controls. The CD56+ CD8 T cell subset is highly responsive to stimulus, expresses high levels of perforin/granzyme and the small population remaining in HIV patients on therapy, also express the immune exhaustion marker TIM-3, indicating cells may be lost through an apoptosis mechanism. The persisting defect in CD56 expression for 2 T cells subsets is consistent with a lack of cytolytic effector function and is present in patients with complete virus suppression for many years due to treatment, long after the T cell population is refreshed by new cell synthesis. The block to lytic effector function may explain why treated patients fail to eradicate viral reservoirs; this mechanism is a key target for new therapies designed to cure HIV disease.1. M. M. Sajadi, A. Heredia, N. Le, N. T. Constantine, R. R. Redfield, HIV-1 natural viral suppressors: control of viral replication in the absence of therapy. AIDS 21, 517 (2007).2. D. J. Riedel et al. Natural viral suppressors of HIV-1 have a unique capacity to maintain gamma delta T cells. AIDS 23, 1955 (2009).3. S. Chaudhry, C. Cairo, V. Venturi, C. D. Pauza, The gamma delta T cell receptor repertoire is reconstituted in HIV patients after prolonged antiretroviral therapy. AIDS epub ahead of print, (2013).

Immune activation despite suppressive highly active antiretroviral therapy is associated with higher risk of viral blips in HIV‐1‐infected individuals

Viral blips are thought to represent random biological variations around a steady state of residual HIV viraemia and to lack clinical significance. We aimed to assess the association of immune activation and the occurrence of blips. HIV-infected patients from our out-patient cohort who developed a blip after having been on fully suppressive highly active antiretroviral therapy (HAART) for at least 180 days were matched with patients without blips according to duration of complete viral suppression (CVS), age, sex and Centers for Disease Control and Prevention (CDC) stage. Frequencies of CD3(+), CD3(+) CD4(+), CD3(+) CD8(+), CD3(+) HLA-DR(+), CD4(+) CD45RA(+), CD16(+) CD56(+) CD3(-) and CD19(+) cells, as well as C-reactive protein (CRP) levels and clinical parameters, were included in conditional logistic regression models. Adherence to HAART was assessed by measuring prescribed nonnucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI) plasma levels in a sample of 57 patients. Eighty-two patients with viral blip were matched with 82 controls from the same cohort. The mean age was 47.2 years [standard deviation (SD) 12.1 years], 80.5% of patients were male and 42.7% had CDC stage C disease. Viral blips occurred after a median of 14 months [interquartile range (IQR) 8-34 months] of CVS. In the logistic regression, activated CD3(+) HLA-DR(+) lymphocytes [odds ratio (OR) 1.25 per 100 cells/μL; 95% confidence interval (CI) 1.02-1.54; P = 0.03] were significantly associated with blips and there was a trend for an association of longer time on HAART with blips (OR 1.31 per year; 95% CI 0.96-1.78; P = 0.09). No between-group difference regarding subtherapeutic drug levels was found (P = 0.46). The occurrence of viral blips after suppressive HAART was associated with elevated markers of T-cell activation. Blips may identify a subset of patients with higher immune activation and increased risk for HIV disease progression.

Tenofovir is superior to entecavir for achieving complete viral suppression in HBeAg‐positive chronic hepatitis B patients with high HBV DNA

Entecavir (ETV) and tenofovir disoproxil fumarate (TDF) are the two first-line anti-viral therapies for chronic hepatitis B (CHB); however, there are limited studies directly comparing their effectiveness. To compare the effectiveness of ETV and TDF in nucleos(t)ide-naïve CHB patients with high hepatitis B virus (HBV) DNA levels, defined as serum HBV DNA greater than 6 log10 IU/mL. We performed a retrospective multicentre cohort study of adult CHB patients who were seen between 2009 and 2012 at four Northern California community gastroenterology and hepatology clinics. We identified 59 consecutive patients treated with TDF and 216 patients treated with ETV. Pre-treatment characteristics were similar between the two groups. Among HBeAg-negative patients, there was no significant difference in viral suppression rates between ETV and TDF (P=0.72). In contrast, among HBeAg-positive patients, those treated with TDF achieved viral suppression significantly more rapidly than those treated with ETV (P<0.0001); the Kaplan-Meier estimated probability of complete suppression was 18% vs. 11% at 6months, 51% vs. 28% at 12months and 72% vs. 39% at 18months respectively. Multivariate Cox proportional hazards analysis indicated that treatment with TDF compared to ETV was a significant predictor of viral suppression, but only for HBeAg-positive patients (HR=2.59; 95% CI 1.58-4.22; P<0.001). Tenofovir is significantly more effective than entecavir for achieving complete viral suppression in HBeAg-positive, nucleos(t)ide-naïve chronic hepatitis B patients with HBV DNA greater than 6 log10 IU/mL.

Maintaining remission in lamivudine‐resistant patients with a virological response to adefovir add‐on lamivudine after stopping lamivudine therapy

We examined the durability of the virological response after discontinuing lamivudine (LVD) in chronic hepatitis B (CHB) patients with LVD-resistant hepatitis B virus (HBV), who responded to LVD plus adefovir (ADV) combination therapy, and the outcome of switching to ADV monotherapy compared to maintaining combination therapy. This study enrolled 72 patients with undetectable viral loads (≤12 IU/ml) and normal alanine aminotransferase levels after ADV add-on therapy for at least 6 months in LVD-resistant CHB patients. The enrolled patients were randomly assigned to continue with LVD-ADV combination therapy or switch to ADV monotherapy (n = 36 per group). Virological rebound was defined as HBV DNA detection at more than 12 IU/ml by quantitative polymerase chain reaction determined on two consecutive measurements. During 96 weeks of follow-up, 100% (36/36) of the patients in the LVD-ADV combination maintained group had persistently undetectable HBV DNA, compared with 94.4% (34/36) patients in the ADV monotherapy switched group. These two patients had undetectable HBV DNA after switching back to LVD-ADV combination therapy. There were no significant differences in the HBsAg levels between the two treatment groups during the 96-week follow-up period. In our study, switching to ADV monotherapy resulted in sustained HBV DNA suppression in 94.4% of the patients for 96 weeks. Prior complete viral suppression with LVD-ADV combination therapy conferred a significant advantage in patients who switched to ADV monotherapy. LVD may be discontinued in patients who show a complete virological response to LVD-ADV combination therapy for at least 6 months.

7.0 Managing virological failure

7.0 Managing virological failure

4.0 When to start

4.0 When to start

Transcriptome analysis of primary monocytes from HIV-positive patients with differential responses to antiretroviral therapy

BackgroundDespite the significant contributions of monocytes to HIV persistence, the HIV-monocyte interaction remains elusive. For patients on antiretroviral therapy, previous studies observed a virological suppression rate of >70% and suggested complete viral suppression as the primary goal. Although some studies have reported genetic dysregulations associated with HIV disease progression, research on ex vivo-derived monocytic transcriptomes from HIV+ patients with differential responses to therapy is limited. This study investigated the monocytic transcriptome distinctions between patients with sustained virus suppression and those with virological failure during highly active antiretroviral therapy (HAART).MethodsGenome-wide transcriptomes of primary monocytes from five HIV+ patients on HAART who sustainably controlled HIV to below detection level (BDL), five HIV+ patients on HAART who consecutively experienced viremia, and four healthy HIV sero-negative controls were analyzed using Illumina microarray. Pairwise comparisons were performed to identify differentially expressed genes followed by quantitative PCR validation. Gene set enrichment analysis was used to check the consistency of our dataset with previous studies, as well as to detect the global dysregulations of the biological pathways in monocytes between viremic patients and BDLs.ResultsPairwise comparisons including viremic patients versus controls, BDL versus controls, and viremic patients versus BDLs identified 473, 76, and 59 differentially expressed genes (fold change > 2 and FDR < 0.05), respectively. The reliability of our dataset was confirmed by gene set enrichment analysis showing that 6 out of 10 published gene lists were significantly enriched (FDR < 0.01) in at least one of the three pairwise comparisons. In the comparison of viremic patients versus BDLs, gene set enrichment analysis revealed that the pathways characterizing the primary functions of monocytes including antigen processing and presentation, FcγR mediated phagocytosis, and chemokine signaling were significantly up-regulated in viremic patients.ConclusionsThis study revealed the first transcriptome distinctions in monocytes between viremic patients and BDLs on HAART. Our results reflected the outcome balanced between the subversion of the monocyte transcriptome by HIV and the compensatory effect adapted by host cells. The up-regulation of antigen presentation pathway in viremic patients particularly highlighted the role of the interface between innate and adaptive immunity in HIV disease progression.

Similar Response to Entecavir 0.5 and 1.0 Mg in Treatment-Naïve Chronic Hepatitis B Patients: A Case-Control Study

The dose recommendation for entecavir (ETV) is 0.5 mg daily for treatment-naïve chronic hepatitis B (CHB) patients and 1.0 mg daily for lamivudine-refractory patients; however, few data are available for the efficacy of a 1.0-mg daily dose in treatment-naïve CHB patients. Our goal is to examine the treatment outcome of treatment-naïve patients placed on ETV 0.5 mg or ETV 1.0 mg daily through week 48. Cases were 40 consecutive hepatitis B e antigen (HBeAg)-positive CHB patients treated with ETV 1.0 mg daily between January 2005 and September 2010, and controls were 40 consecutive CHB patients treated with ETV 0.5 mg daily between January 2005 and September 2010 at three US gastroenterology/liver clinics. Controls were matched for age (±5 years), sex, HBeAg, and baseline hepatitis B virus (HBV) DNA (±0.5 log10 IU/ml). Complete viral suppression was defined as undetectable HBV DNA by polymerase chain reaction (<100 IU/ml). Both groups had similar distributions of age (38 ± 11 years), male patients (55 %), and mean HBV DNA (7.7 ± 1.1 log10 IU/ml). The complete viral suppression rate was similar in both cases and controls through week 24 (15 vs. 15 %, p = 1.00) and week 48 (22 vs. 36 %, p = 0.17). Non-adherence was reported in three patients in the ETV 1.0 mg daily cohort at week 48. There were no significant differences in the proportion of patients with complete viral suppression in patients treated with ETV 0.5 mg daily or the higher daily dose of 1.0 mg.

Relapse of chronic hepatitis B after discontinuation of nucleos(t)ide analogs: Is the glass half full or half empty?

Relapse of chronic hepatitis B after discontinuation of nucleos(t)ide analogs: Is the glass half full or half empty?

Complicated gastrointestinal CMV disease after small bowel transplantation

We report a case of a 52 year old small bowel transplant recipient, with a clinical course complicated by CMV disease. Recipient and donor were CMV-IgG positive. Ganciclovir i.v., followed by valganciclovir was used for CMV-prophylaxis for 100 days. An antilymphocytic induction therapy was performed with Alemtuzumab on days 0 and 1. Immunosuppression was continued with tacrolimus, mycophenolat mofetil, prednisolon. Six months posttransplant the patient presented with CMV tissue invasive disease of the esophagus and stomach, without presence of viremia, tested by quantitative PCR. Treatment with ganciclovir resulted in complete viral load suppression and valganciclovir was initiated for secondary prophylaxis, whereas mycophenolat mofetil and prednisolon were discontinued. Shortly afterwards candida and recurrent CMV based esophagitis was diagnosed, still without viremia. Improvement was achieved with ganciclovir and caspofungin. However, during the following course the patient developed CMV tissue invasive disease of the ileal graft, with persistent absence of viremia. Antiviral coverage was extended with foscarnet and CMV immunoglobulin. Viral load declined to undetectable levels, however the patient failed to improve clinically due to occurrence of graft rejection. Despite infliximab and high dose prednisolon, graft rejection was progressive, requiring surgical explantation of the graft. This case highlights the importance of additional diagnostic tools such as endoscopy including PCR analysis of tissue samples. Extension of primary antiviral prophylaxis interval up to 6 months and prolonged retreatment in recurrent CMV disease may be useful to avoid severe CMV-related complications.

The Predictive Value of On-treatment Virological Response for Sustained Virological Response in Chronic Hepatitis C Patients Receiving a Personalized Treatment Program

Abstract Objective To investigate the effects of individualised treatment with peginterferon alpha-2a (40 kD) plus ribavirin in Chinese patients with CHC. Methods Total of 297 consecutive Chinese patients were enrolled, including 250 naïve cases and 47 cases who were previously treated. Treatment duration was determined according to viral genotypes, prior treatment history and viral responses at week 4, 12 and 24. Results Totally, 235 patients (79.1%) completed treatment and 186 (87.3%) achieved SVR. And 219 out of 289 (75.8%) patients achieved HCV RNA negative at week 4 (RVR) and 259 of 276 (93.8%) at week 12. Among the 164 patients with RVR who completed follow-up, 158 (96.3%) achieved SVR. Patients with RVR had lower baseline viral loads than patients without RVR (P = 0.034). The positive predictive value (PPV) of RVR for SVR was 90.7% (OR 2.10 vs. non-RVR, 95% CI: 0.50 - 8.7). Similar outcomes were observed among patients with HCV undetectable at week 12. Conclusions Complete viral suppression by week 4 is associated with a high rate of treatment success in treatment naïve and experienced patients receiving individualized CHC therapy.

Response to Higher Dose of Entecavir 1.0 mg Daily in Patients With Partial Response to Entecavir 0.5 mg Daily

Despite its high potency against hepatitis B virus (HBV), entecavir (ETV) 0.5 mg daily may not be sufficient to induce complete viral suppression in some patients with very high pretreatment viremia. It is not clear whether ETV 1.0 mg daily would have additive effect in such patients. Our goal was to examine virologic outcome of ETV 1.0 mg daily in patients with partial response to ETV 0.5 mg daily. We retrospectively studied 31 consecutive treatment-naive patients who were switched to ETV 1.0 mg daily after partial response [reduction of HBV DNA ≥2 log10 IU/mL but with detectable HBV DNA levels (>100 IU/mL) after 24 weeks of therapy or longer] with ETV 0.5 mg daily from January 2005 to January 2010 at 2 clinics. All patients were Asians and 90% had positive hepatitis B e antigen. Mean HBV DNA was 8.04±0.65 log10 IU/mL before therapy and 3.64±0.91 log10 IU/mL at the time of switch. Overall rate of complete viral suppression were 29% (n=9/31) after 24 weeks of ETV 1.0 mg daily and 22% (n=5/23) after 48 weeks. Complete viral suppression after 24 weeks with ETV 1.0 mg daily was significantly higher in patients with lower HBV DNA (<3 log10 IU/mL) at time of switch: 75% versus 5%, P<0.0001. The majority of patients with partial response to ETV 0.5 mg daily did not achieve complete viral suppression with the higher dose of ETV 1.0 mg daily except those with minimal residual viremia (HBV DNA <3 log10 IU/mL).