Good Safety Profile and Efficacy of Leucocyte Interferon-α in Combination with Oral Ribavirin in Treatment-Naive Patients with Chronic Hepatitis C

Background: The differential tolerability profile of various interferon (IFN)-α preparations used in combination with ribavirin for the treatment of chronic hepatitis C needs to be elucidated. Approximately 8% of patients receiving recombinant IFNα-2b plus ribavirin discontinue treatment because of adverse events. Human leucocyte IFNα is deemed to have a better safety profile than recombinant IFNα. We therefore compared the safety profile and efficacy of ribavirin combined with leucocyte IFNα or with recombinant IFNα-2b in treatment-naive patients with chronic hepatitis C. Study design: We randomised 423 patients to either leucocyte IFNα 3MU three times weekly plus ribavirin (210 patients) or the same dose of recombinant IFNα-2b plus ribavirin (213 patients). Patients were treated for 24 weeks and followed-up for a further 48 weeks. The primary endpoint was the safety profile of the two therapies; the secondary endpoint was the rate of sustained response. Results: In patients receiving leucocyte IFNα, the total number of adverse events was lower than in the group receiving recombinant IFNα (259 vs 441 patients), and the percentage of patients discontinuing treatment because of adverse events or laboratory abnormalities was significantly reduced (4% vs 11%; p = 0.013). Sustained response was observed in 47% of patients receiving leucocyte IFNα plus ribavirin and in 44% of patients receiving IFNα-2b plus ribavirin. Conclusions: Both therapeutic regimens were effective in inducing a sustained response in naive patients. However, the safety profile of leucocyte IFNα plus ribavirin was more favourable than that observed with the administration of recombinant IFNα-2b plus ribavirin, suggesting that leucocyte IFNα may be an alternative option in patients with reduced tolerability to other IFNs.     

Interfreron-α Alone versus Interferon-α plus Ribavirin in Patients with Chronic Hepatitis C Not Responding to Previous Interferon-α Treatment

OBJECTIVE: To study the effects of monotherapy with leucocyte interferon-alpha (IFNalpha) versus IFNalpha + ribavirin in patients with chronic hepatitis C who were nonresponders to previous courses of recombinant or lymphoblastoid IFNalpha. DESIGN AND SETTING: This was a nonblind randomised study of outpatients at 3 centres in Palermo, Sicily, Italy. PATIENTS AND PARTICIPANTS: We recruited 72 patients (48 males, 24 females), mean age 48.8 +/- 6.6 years (range 31 to 63 years), with biopsy-proven chronic hepatitis C, predominantly genotype 1b. INTERVENTIONS: 24 patients (group A) received IFNalpha 6MU 3 times weekly for 6 months, and 48 patients (group B) received IFNalpha 6MU 3 times weekly + ribavirin 1200 mg/day for 6 months. ALT levels and adverse effects were monitored monthly, and hepatitis C virus (HCV) RNA levels were measured at study entry, at the end of treatment and after a 6-month follow-up. RESULTS: At baseline all patients were HCV-RNA positive and had ALT levels greater than twice normal. Mean post-treatment serum HCV-RNA levels were below baseline in group A, but the virus was eradicated in only 1 patient; 6 patients had normalised serum ALT levels. In group B at end of treatment, 12 patients were negative for HCV-RNA and serum ALT levels were normal in 18. At follow-up, all group A patients had elevated ALT levels and positive HCV-RNA. In group B, 3 patients were still negative for HCV-RNA and 4 had normal ALT. In 4 patients in group B, therapy was suspended because of anaemia, depression and decrease in neutrophil count; a flu-like syndrome was recorded with no frequency difference between groups. CONCLUSIONS: These results suggest that patients with chronic hepatitis C unresponsive to IFNalpha monotherapy could benefit from combination therapy with IFNalpha + ribavirin.     

Efficacy of prolonged entecavir monotherapy in treatment-na?ve chronic hepatitis B patients exhibiting a partial virologic response to entecavir

Background/Aims

The optimal management of patients exhibiting a partial virologic response (PVR) to entecavir (ETV) has not been determined. The aim of this study was to determine the long-term efficacy of prolonged ETV monotherapy in treatment-naïve chronic hepatitis B (CHB) patients exhibiting a PVR to ETV therapy.

Methods

This study included 364 treatment-naïve CHB patients treated with ETV for ≥48 weeks and who received continuous ETV monotherapy for ≥96 weeks. PVR was defined as a decrease in serum hepatitis B virus (HBV) DNA of more than 2 log₁₀ IU/mL from baseline but with detectable HBV DNA by real-time PCR assay at week 48.

Results

Fifty-two of the 364 patients (14.3%) showed a PVR. Among them, 41 patients received continuous ETV monotherapy for ≥96 weeks (median duration 144 weeks, range 96-312 weeks), and 40 of these patients (95%) achieved a virologic response (VR, HBV DNA <20 IU/mL) during prolonged ETV monotherapy (median duration 78 weeks, range 60-288 weeks). The cumulative probabilities of a VR at weeks 96, 144, and 192 from treatment initiation were 78.0%, 92.7%, and 95.1%, respectively. The VR rate was 97.2% (35/36) in HBeAg-positive patients and 100% (5/5) in HBeAg-negative patients. In multivariate analysis, HBeAg positivity (odds ratio [OR], 9.231; 95% confidence interval [CI], 1.03-82.91; P=0.047) and a high baseline HBV DNA level (OR, 0.170; 95% CI, 0.08-0.37; P=0.000) were independently associated with a delayed virologic response. No patient developed genotypic resistance to ETV during follow-up.

Conclusions

Long-term ETV monotherapy is effective for achieving a VR in treatment-naïve CHB patients exhibiting a PVR to ETV. HBeAg positivity and high baseline HBV DNA level were independently associated with a delayed virologic response.     

Peginterferon-α-2a (40kD) and Ribavirin in Patients with Chronic Hepatitis C

Background and aims: Addition of a 40kD polyethylene glycol moiety to interferon-α-2a [peginterferon-α-2a (40kD)] improves pharmacokinetic properties over those of standard interferon. We conducted a phase II study to assess the safety and initial efficacy of peginterferon-α-2a (40kD) plus ribavirin combination therapy in patients with chronic hepatitis C (CHC). Methods: Twenty patients received open-label 180μg peginterferon-α-2a (40kD) subcutaneously once weekly and oral ribavirin 1000 or 1200mg daily for patients weighing <75 or ≥75kg, respectively, for a period of 24 weeks. Patients with hepatitis C virus (HCV) genotype 1 and a virological response at week 24 received study drugs for an additional 24 weeks. Results: A sustained virological response, defined as undetectable HCV RNA 24 (i.e. <100 copies/ml) weeks after completing the therapy, was achieved in 50% of patients in an intent-to-treat analysis (6/16 genotype 1 and 4/4 genotype non-1). Adverse events were similar to those reported with unmodified interferon plus ribavirin combination therapy. Anaemia led to ribavirin dose reduction in five patients. Neutropenia led to dose reduction in three patients treated with peginterferon-α-2a (40kD). Conclusions: The addition of ribavirin to a once-weekly peginterferon-α-2a (40kD) regimen should be investigated in larger clinical trials.     

Tenofovir disoproxil fumarate monotherapy for nucleos(t)ide analogue-na?ve and nucleos(t)ide analogue-experienced chronic hepatitis B patients

Background/Aims

This study investigated the antiviral effects of tenofovir disoproxil fumarate (TDF) monotherapy in nucleos(t)ide analogue (NA)-naive and NA-experienced chronic hepatitis B (CHB) patients.

Methods

CHB patients treated with TDF monotherapy (300 mg/day) for ≥12 weeks between December 2012 and July 2014 at a single center were retrospectively enrolled. Clinical, biochemical, and virological parameters were assessed every 12 weeks.

Results

In total, 136 patients (median age 49 years, 96 males, 94 HBeAg positive, and 51 with liver cirrhosis) were included. Sixty-two patients were nucleos(t)ide (NA)-naïve, and 74 patients had prior NA therapy (NA-exp group), and 31 patients in the NA-exp group had lamivudine (LAM)-resistance (LAM-R group). The baseline serum hepatitis B virus (HBV) DNA level was 4.9±2.3 log IU/mL (mean±SD), and was higher in the NA-naïve group than in the NA-exp and LAM-R groups (5.9±2.0 log IU/mL vs 3.9±2.0 log IU/mL vs 4.2±1.7 log IU/mL, P<0.01). The complete virological response (CVR) rate at week 48 in the NA-naïve group (71.4%) did not differ significantly from those in the NA-exp (71.3%) and LAM-R (66.1%) groups. In multivariate analysis, baseline serum HBV DNA was the only predictive factor for a CVR at week 48 (hazard ratio, 0.809; 95% confidence interval, 0.729-0.898), while the CVR rate did not differ with the NA experience.

Conclusions

TDF monotherapy was effective for CHB treatment irrespective of prior NA treatment or LAM resistance. Baseline serum HBV DNA was the independent predictive factor for a CVR.     

Do Anti-TNF Agents Increase the Risk of Inflammatory Bowel Disease Evolution in Patients with Ankylosing Spondylitis? Real Life Data

ObjectiveThe aim of this study was to determine whether there is any association with anti-tumor necrosis factor (TNF) agent administration and development of new-onset inflammatory bowel disease (IBD) in ankylosing spondylitis (AS) patients.MethodsRecords of the patients who met 1984 modified New York criteria for AS between 1998 and 2016 at Rheumatology Department were evaluated retrospectively and data about the patients, IBD properties and medication were obtained.ResultsAmong 420 patients, 310 were male, the average age was 42.9 ± 1.3 years, average disease duration was 16.7 ± 10.4 years. Anti-TNF agents were in use by 154 patients, 52 patients were receiving etanercept (ETN), infliximab (INF), adalimumab (ADA), and golimumab (GO) treatments were ongoing in 50, 41, and 11 patients, respectively. New-onset IBD developed in 10 patients; 3 from the group treated with non-anti-TNF drugs (1.1%) and 7 from the group treated with anti-TNF agents (4.5%) (p = 0.042). No significant difference was detected between three anti-TNF agent forms in relation with the risk of IBD onset. In AS patients, existence of familial AS (OR 4.69 (95%CI 1.28-17.19, p = 0.020) and anti-TNF agent treatment (OR 4.17 (95%CI 1.06-16.38, p = 0.041) were independent risk factors for new-onset IBD development.ConclusionDespite the increased risk of new-onset IBD development during the course of AS, paradoxical response to anti-TNF drugs must also be considered as a source that triggers onset of IBD.     

How Many Valid Measurements Are Necessary to Assess Liver Fibrosis Using FibroScan? in Patients with Chronic Viral Hepatitis? An Analysis of Subjects with at Least 10 Valid Measurements

Purpose

Using FibroScan® to obtain a reliable liver stiffness measurement (LSM) may require more than 10 valid measurements (VMs), according to the manufacturer''s recommendations. However, this requirement lacks scientific evidence in support thereof. We investigated the minimal number of VMs required to assess liver fibrosis without significant loss of accuracy in patients with chronic hepatitis B (CHB) and C (CHC) and predictors of discordance between LSM and liver biopsy (LB).

Materials and Methods

Between January 2005 and December 2009, we prospectively enrolled 182 patients with CHB and 68 patients with CHC who were to undergo LB and LSM before starting antiviral treatment. Only LSMs with at least 10 VMs were considered reliable. The Batts and Ludwig scoring system was used for histologic assessment.

Results

The mean age and body mass index were 46.0 years and 23.4 kg/m² in patients with CHB and 49.7 years and 23.1 kg/m² in those with CHC, respectively. The median elasticity scores from the first 3, first 5, and all VMs taken significantly predicted fibrosis stages ≥F2 and F4 (all p<0.05) without significant differences (all p>0.05 by DeLong''s method). Alanine aminotransferase (ALT) was the only predictor of discordance in fibrosis stage as estimated by the median elasticity score from the first 3 VMs and by LB in patients with CHB, whereas no significant predictor was identified in those with CHC.

Conclusion

After comparison of patients who had more than 10 valid measurements for LSM, three VMs may be enough to assess liver fibrosis using LSM without significant loss of accuracy in patients with CHC and patients with CHB. However, ALT should be considered when interpreting LSM for patients with CHB.     

Interleukin 18 Promoter Variants (−137G>C and −607C>A) in Patients with Chronic Hepatitis C: Association with Treatment Response

Background

Recently, two functional IL18 promoter variants, ?607C>A (rs1946518) and ?137G>C (rs187238), were associated with viral clearance in patients with hepatitis C. The present study focused on their relevance for treatment response.

Methods

Seven hundred fifty-seven chronically infected European patients and 791 controls were enrolled in the study. IL18 genotyping was performed by allele-specific PCR. Liver histology was available in 67.9%.

Results

Genotype and allele frequencies were equally distributed in patients and controls. No significant association with various disease characteristics was observed. However, when comparing patients with sustained virological response (SR) and non-SR, statistically significant associations were found for both variants (p?=?0.0416 and p?=?0.0274, respectively). In viral genotype 1, the ?607A allele was positively associated with treatment response (p?=?0.0190; OR 1.537; 95% CI, 1.072–2.205) and the ?137G allele with a higher rate of nonresponse (p?=?0.0302; OR 1.524; 95% CI, 1.040–2.233).

Conclusions

The association of IL18 variants with treatment response in genotype 1 hepatitis C patients implies a predictive and modifying role of these genetic variants.

     

Tenofovir disoproxil fumarate monotherapy for nucleos(t)ide-na?ve chronic hepatitis B patients in Korea: data from the clinical practice setting in a single-center cohort

Background/Aims

This study assessed the antiviral efficacy and safety of tenofovir disoproxil fumarate (TDF) for up to 12 months in Korean treatment-naïve chronic hepatitis B (CHB) patients.

Methods

A total of 411 treatment-naïve CHB patients who had been treated with TDF for at least 3 months (median 5.6) were consecutively enrolled. Clinical, biochemical, virological parameters and treatment adherence were routinely assessed every 3 months.

Results

The median age was 51.3 years, 63.0% of the patients were male, 49.6% were HBeAg (+), and 210 patients had liver cirrhosis. The median baseline HBV DNA was 5.98 (SD 1.68) log₁₀ IU/mL. Among the patients completing week 48, 83.3% had a complete virologic response (CVR, <12 IU/mL by HBV PCR assay), and 88.2% had normalized levels of alanine aminotransferase (ALT). The cumulative probabilities of CVR at 3, 6, 9 and 12 months were 22.8%, 53.1%, 69.3% and 85.0%. During the follow-up period, 9.8% patients achieved HBeAg loss and 7.8% patients achieved HBeAg seroconversion. There was no virological breakthrough after initiating TDF. The most common TDF-related adverse event was gastrointestinal upset, and three patients discontinued TDF therapy. However, no serious life-threatening side effect was noted.

Conclusions

In a clinical practice setting, TDF was safe and highly effective when administered for 12 months to Korean treatment-naïve CHB patients.     

Interleukin-2 Plus Ribavirin Versus Interferon-α-2b Plus Ribavirin in Patients with Chronic Hepatitis C Who Did Not Respond to Previous Interferon-α-2b Treatment

BACKGROUND: Interferon (IFN)-alpha-2b therapy has been shown to improve clinical conditions of patients with chronic hepatitis C. Several studies showed that the addition of ribavirin to IFNalpha-2b greatly improved the biochemical as well as the virologic and histological response rate in patients with chronic hepatitis C. The aim of this study was to evaluate biochemical, virologic, and histological responses as well as adherence to a treatment employing ribavirin plus low doses of recombinant interleukin (IL-2) or IFNalpha-2b in subjects with chronic active hepatitis C, which relapsed or did not respond to previous treatment with interferon alone. PATIENTS AND METHODS: We evaluated all 75 consecutive adult patients with chronic hepatitis C admitted to our department, who were previously treated with one course of recombinant or lymphoblastoid IFNalpha-2b (3 million to 6 million IU three times a week for at least 4 months), and either relapsed or did not respond to this treatment. Sixty patients met the inclusion criteria for enrollment in our study. Randomization was performed on the basis of a computer-generated list. The treatment schedule was based on subcutaneous administration of recombinant IFNalpha-2b (Intron A) at a dosage of 3 million IU every day, or IL-2 (aldesleukin) at a dose of 1 million IU every day, with oral ribavirin administered 400 mg twice daily (morning and night) [for patients weighing <75 kg] or 500 mg twice daily (for those weighing > or = 75 kg). The planned treatment period was 6 months. RESULTS: Both IFN and IL-2 treatment groups achieved a significant biochemical response with respect to baseline values at the end of the treatment (p < 0.0001 for both) and at the end of the follow up (p < 0.001 for both). The differences between the two groups at the end of treatment and at the end of the follow up were significant (p < 0.04 and p < 0.003 respectively) in favor of IL-2-treatment. The virologic response rate for IL-2-treated patients was significantly higher than for IFN-treated patients at months 3 (p < 0.05) and 6 (p < 0.05) of the treatment. Both groups showed significant improvement in histological activity index with respect to baseline values, but the difference between the groups was not significant. No withdrawals have been registered. CONCLUSION: The combination of IL-2 and ribavirin seems to increase the probability of a sustained biochemical and virologic response in patients with chronic hepatitis C that is unresponsive to IFN. Our study showed that IL-2 plus ribavirin may provide a clinically important option that appears to be well tolerated and effective in patients with chronic hepatitis C virus infection.     

Once-Daily Abacavir/Lamivudine and Ritonavir-Boosted Atazanavir for the Treatment of HIV-1 Infection in Antiretroviral-Naïve Patients: A 48-Week Pilot Study

Abstract

Purpose: To assess the efficacy and safety of a once-daily (QD) regimen consisting of the co-formulation of abacavir/lamivudine (ABC/3TC) and atazanavir plus ritonavir (ATV-RTV) in antiretroviral (ART)-naïve patients with plasma HIV-1 RNA >5,000 copies/mL. Method: This open-label, multicenter study conducted between September 2004 and June 2006 included 112 patients who received ABC 600 mg/3TC 300 mg and ATV 300 mg-RTV 100 mg QD. Drug switches were permitted for ABC hypersensitivity and ATV-related hyperbilirubinemia. Primary endpoints were proportion of patients achieving HIV-1 RNA <50 copies/mL at Week 48 and treatment discontinuation due to study drugs. Results: A total of 111 patients were treated. At Week 48, the proportion of patients achieving HIV-1 RNA <50 copies/mL was 77% (85/111) by intent-to-treat (ITT) missing=failure, switch included response rate. Drug substitutions occurred in 8 (7%) patients for suspected ABC hypersensitivity reaction (HSR) and in 6 (5%) patients for ATV-related toxicities; only 1 patient discontinued study due to ABC HSR. Four patients met confirmed virologic nonresponse (HIV RNA ?400 copies/mL). Treatment-emergent drug resistance was rare, and no patient had virus that developed reduced susceptibility to ATV. Median change from baseline (95% confidence interval) in fasting lipids at Week 48 was 39 (26–66) mg/dL for triglycerides, 28 (22–38) mg/dL for total cholesterol (C), 14 (10.5–16) mg/dL for HDL-C, and 8 (2–16.5) mg/dL for LDL-C. Conclusion: ABC/3TC and ATV-RTV QD is an effective and well-tolerated regimen in ART-naïve patients through 48 weeks, with a modest impact on fasting lipids.     

Efficacy of toltrazuril (Baycox? 5% suspension) in natural infections with pathogenic Eimeria spp. in housed lambs

A field study was conducted to evaluate the effect of a single oral treatment with 20 mg/kg body weight (BW) of toltrazuril (Baycox? 5% suspension)—TOL—in comparison to a single oral treatment with 1 mg/kg BW of diclazuril (Vecoxan? suspension orale, 2.5 mg/ml)—DIC—and an untreated control group (CTRL) on naturally acquired Eimeria infections in lambs. On a French sheep farm with a known history of coccidiosis, 75 housed lambs aged 10–14 days were randomised and allocated to one of three groups. During an observation period of 60 days after treatment, clinical (faecal consistency, BW) and parasitological parameters (oocyst excretion) were evaluated. Excretion in the negative control group started 3 days after treatment and peaked on the 31st day with a prevalence of 80%. Animals were predominantly infected with Eimeria ovinoidalis. Treatment with toltrazuril, but not with diclazuril, resulted in significantly reduced numbers of excreting animals. The number of excretion days and the average oocyst excretion decreased significantly in both the TOL and the DIC groups compared to the CTRL, with the TOL group showing significantly fewer excretion days and excretion intensities than the DIC group. Changes in the faecal consistency were moderate throughout the study and not significantly different between the groups. Daily weight gains were higher in the TOL group compared to the DIC and CTRL groups which did not differ. This study demonstrates the good efficacy of toltrazuril administered orally to lambs in the prepatent period in subclinical natural Eimeria infections in housed lambs.     

Spotlight on Peginterferon-α-2a (40 kD) Plus Ribavirin in the Management of Chronic Hepatitis C Mono-Infection

Peginterferon-α-2a (40 kD) [Pegasys®] is a conjugate of recombinant interferon-α-2a and a 40 kD branched polyethylene glycol (PEG) moiety that is highly active against hepatitis C virus (HCV). Ribavirin (Copegus®) is a synthetic nucleoside analog that acts in synergy with the antiviral activity of peginterferon-α-2a (40 kD). The combination of subcutaneous peginterferon-α-2a (40 kD) once weekly plus oral ribavirin twice daily is widely approved for use in adult patients with chronic hepatitis C, including those with persistently ‘normal’ ALT activity or HIV-HCV co-infection, and is recommended as a first-line treatment option for patients with chronic hepatitis C and compensated liver disease. In randomized, phase III trials, the combination has consistently demonstrated good therapeutic efficacy (i.e. high sustained virologic response [SVR] rates) and has been generally well tolerated in both treatment-naïve and treatment-experienced patients with chronic hepatitis C, including those with compensated, advanced liver disease. Several baseline and dynamic (on-treatment) predictors of an SVR that can be used to guide and optimize therapy were also determined in these trials and in subsequent analyses. By utilizing these predictors, therapy with peginterferon-α-2a (40 kD) plus ribavirin can be individualized to achieve the optimal balance between efficacy and tolerability, further increasing the usefulness of this drug combination. Thus, peginterferon-α-2a (40 kD) plus ribavirin remains a valuable therapy in patients with chronic hepatitis C, as a first-line option in those with compensated liver disease and as a second-line therapy in those with advanced liver disease.     

Transcranial Alternating Current Stimulation in Patients with Chronic Disorder of Consciousness: A Possible Way to Cut the Diagnostic Gordian Knot?

Unresponsive wakefulness syndrome (UWS) is a chronic disorder of consciousness (DOC) characterized by a lack of awareness and purposeful motor behaviors, owing to an extensive brain connectivity impairment. Nevertheless, some UWS patients may retain residual brain connectivity patterns, which may sustain a covert awareness, namely functional locked-in syndrome (fLIS). We evaluated the possibility of bringing to light such residual neural networks using a non-invasive neurostimulation protocol. To this end, we enrolled 15 healthy individuals and 26 DOC patients (minimally conscious state—MCS- and UWS), who underwent a γ-band transcranial alternating current stimulation (tACS) over the right dorsolateral prefrontal cortex. We measured the effects of tACS on power and partial-directed coherence within local and long-range cortical networks, before and after the protocol application. tACS was able to specifically modulate large-scale cortical effective connectivity and excitability in all the MCS participants and some UWS patients, who could be, therefore, considered as suffering from fLIS. Hence, tACS could be a useful approach in supporting a DOC differential diagnosis, depending on the level of preservation of the cortical large-scale effective connectivity.     

The Safety and Efficacy of Switching Stavudine to Tenofovir DF in Combination with Lamivudine and Efavirenz in HIV-1—Infected Patients: Three-Year Follow–up After Switching Therapy

Abstract

Background: Study 903 is a phase 3 trial with a completed 144-week, double-blind phase comparing tenofovir DF (TDF) with stavudine (d4T), in combination with lamivudine (3TC) and efavirenz (EFV), and an ongoing 336-week open-label extension phase. Method: Patients in 3 countries completing the d4T treatment phase were allowed to switch d4T to TDF and receive once-daily TDF+3TC+EFV in the extension phase. Results: At the time of switch, 100% and 99% of patients (n = 85; 60% male, 64% White; mean age 37 years; mean CD4 = 650 cells/mm3) had HIV RNA <400 and <50 copies/mL. At 144 weeks after the switch, 89% (missing = failure) had HIV RNA <400 copies/mL and 87% had HIV RNA <50 copies/mL. Mean CD4 cell count increased 155 cells/mm3. No patient had virologic failure. Significant decreases from switch to week 144 in mean fasting total cholesterol (?22 mg/dL, p < .0001) and triglycerides (?78 mg/dL, p < .0001) were observed. Mean limb fat increased significantly from 4.5 kg to 5.8 kg, 144 weeks after switch (p < .0001). Conclusion: In virologically suppressed patients, switching d4T to TDF as part of a once-daily regimen with 3TC and EFV resulted in maintenance of virologic suppression and continued CD4 cell increases through 144 weeks, with significant improvements in metabolic parameters.