Pegylated-liposomal doxorubicin is more effective and less toxic than the standard combination chemotherapy regimen ABV for treatment of AIDS-KS.

Roche.

Pegylated-liposomal doxorubicin offers a new alternative for treatment of patients who have experienced failure of standard chemotherapy for AIDS-KS.

The relationship between depression and neuropsychological test performance in HIV-1 seropositive individuals is unclear. The present study was conducted to determine whether different patterns of neuropsychological test performance would be present in depressed vs. nondepressed individuals infected by the Human Immunodeficiency Virus (HIV-1). It was hypothesized that subjects evidencing depressed mood would demonstrate greater difficulty on measures of neuropsychological function. The subjects were 54 mostly symptomatic HIV-1 seropositive homosexual/bisexual males aged 20 to 60. A neuropsychological test battery together with the Beck Depression Inventory (BDI) was administered to all subjects. Stepwise multiple regression analysis revealed a significant relationship only between scores on the BDI and the Grooved Pegboard test and Trial 6 of the RAVLT. Subjects were then dichotomized using the BDI into high-BDI (M = 28.9) and low-BDI (M = 6.3) groups. Analysis of variance failed to reveal significant group differences between the depressed vs. the non-depressed groups on the neuropsychological measures despite their marked separation on the BDI. Similarly, examination of individual neuropsychological outliers again failed to demonstrate an increased number of outliers in the high- and low-BDI groups. These results suggest that the presence of clinically significant levels of depression in a non-elderly HIV-1 seropositive sample does not necessarily lead to significant neuropsychological dysfunction.

No abstract

on behalf of the JUMP-C Investigators* Mericitabine is a selective nucleoside analog inhibitor of the hepatitis C virus (HCV) NS5B RNA-dependent RNA polymerase, with activity across all HCV genotypes. Treatment-naïve patients infected with HCV genotype 1 or 4 were randomized to 24 weeks of double-blind treatment with either mericitabine 1,000 mg (N 5 81) or placebo (N 5 85) twice-daily (BID) in combination with pegylated interferon alpha-2a (Peg-IFNa-2a)/ribavirin (RBV). Patients randomized to mericitabine with HCV RNA <15 IU/mL from week 4 to 22 (extended rapid virologic response; eRVR) stopped all treatment at week 24; all other patients continued Peg-IFNa-2a/RBV to complete 48 weeks of treatment. The primary efficacy endpoint was sustained virologic response (SVR; HCV RNA <15 IU/mL after 24 weeks of treatment-free follow-up). SVR was achieved in 56.8% (95% confidence interval [CI]: 45.9-67.0) of mericitabine-treated patients and 36.5% (95% CI: 27.0-47.1) of placebo-treated patients (D 5 20.3%; 95% CI 5.5-35.2). SVR rates were higher in mericitabine-than placebo-treated patients when subdivided by IL28B genotype (CC, 77.8% versus 56.0%; non-CC, 44.1% versus 16.2%) and hepatic fibrosis (noncirrhotic, 63.3% versus 41.9%; cirrhotic, 38.1% versus 21.7%). Overall relapse rates were 27.7% and 32.0% in mericitabine-and placebo-treated patients, respectively. No evidence of NS5B S282T-variant virus or phenotypic resistance to mericitabine was observed in the one patient who experienced partial response. No S282T variants were detected in any baseline samples. The safety profile of mericitabine was similar to that of, and fewer patients in the mericitabine than in the placebo group discontinued treatment for safety reasons. Conclusion: A 24-week response-guided combination regimen of mericitabine 1,000 mg BID plus Peg-IFNa-2a/RBV is well tolerated and more effective than a standard 48-week course of Peg-IFNa-2a/RBV. (HEPATOLOGY 2013;58:514-523) See Editorial on Page 488

on behalf of the PROPEL Investigators* Mericitabine is a nucleoside analog polymerase inhibitor of hepatitis C virus (HCV). Treatment-naïve HCV genotype 1 or 4 patients were randomized to double-blind treatment with oral mericitabine at a dosage of 500 mg twice-daily (BID) for 12 weeks (A), 1,000 mg BID for 8 (B) or 12 weeks (C and D), or placebo BID for 12 weeks (E). All patients received pegylated interferon alpha-2a (Peg-IFNa-2a; 40 kD)/ribavirin (RBV) at standard doses for 24 or 48 weeks during and after mericitabine/placebo therapy. Patients in arms A-C who maintained a virologic response (VR) (HCV RNA <15 IU/mL) from weeks 4 to 22 stopped all treatment at week 24; all other patients (arms A-E) continued Peg-IFNa-2a/RBV to complete 48 weeks. The primary outcome was sustained VR (SVR) (HCV RNA <15 IU/mL after 24 weeks of untreated follow-up; SVR-24). VR rates were higher in arms A-D than in arm E at weeks 4 and 12 overall, in patients with and without cirrhosis and in patients with CC and non-CC IL28B genotypes. However, the overall SVR-24 rate in arms D (50.6%) and E (placebo, 51.2%) was similar and those in the response-guided therapy arms A, B, and C were lower (48.8%, 42.0%, and 32.9%, respectively). No viral breakthrough or mericitabine-resistance mutations (S282T) were observed during mericitabine therapy. Conclusion: Treatment with mericitabine plus Peg-IFNa-2a/ RBV for 8 or 12 weeks provided potent suppression of HCV RNA, was well tolerated, and did not select resistant variants, but did not increase SVR rates, compared to placebo. IFN-free and IFN-containing trials of mericitabine of longer treatment duration are ongoing. (HEPATOLOGY 2013;58:524-537) See Editorial on Page 488 P egylated interferon (Peg-IFN)/ribavirin (RBV) treatment produces sustained virologic response (SVR) rates of approximately 50% in patients with chronic hepatitis C virus (HCV) and was standard of care for all chronic hepatitis C (CHC) patients for a decade.1,2 The approval of the first HCV NS3/4A protease inhibitors (PIs), boceprevir and telaprevir, has established a new era of direct-acting antiviral (DAA) therapy for CHC.3 Most importantly, the combination of a PI and Peg-IFN/RBV increases SVR rates in both treatment-naïve and previously treated patients with HCV genotype (G) 1 infection.4-8 Furthermore, responseguided therapy (RGT) is possible with both of these PIs, which decreases treatment duration for many patients. These benefits have established PI-based triple therapy as the new standard of care for HCV G1 patients. 3,9

Objective: To evaluate the safety, dose tolerance, and anti-tumor effects of 9-cis-retinoic acid in the treatment of Kaposi sarcoma (KS) related to acquired immunodeficiency syndrome (AIDS). Design: Phase 2, open-label clinical trial of oral doses of 9-cis-retinoic acid increasing in 40-mg increments every 2 weeks from 60 mg/m 2 per day to a maximum of 140 mg/m 2 per day. Setting: Five hospital or health maintenance organization outpatient clinics. Patients: Fifty-seven adult male patients with human immunodeficiency virus and biopsy-proven KS. Main Outcomes Measures: Safety was evaluated by adverse events, physical examination, laboratory test abnormalities, treatment-limiting toxic effects, and reasons for early withdrawal. Response (Ն50% improvement) was evaluated by an overall KS response and by the area and height from 6 index lesions selected at baseline. Results: Patients tolerated 60 and 100 mg/m 2 per day. Most patients found 140 mg/m 2 per day intolerable owing to headache. Common treatment-related adverse events were headache, xerosis, rash, alopecia, and hyperlipemia. The patient response rate for the overall KS disease was 19% (11/57), including 1 patient with clinically complete response. The response rate assessed by measuring 6 index lesions during treatment was 39% (22/57). Sixteen responding patients (73%) were refractory to at least 1 previous anti-KS therapy. Patients with CD4 + counts of 150 cells/µL or lower were as likely to respond as patients with counts of higher than 150 cells/ µL. The median time to response was 8.5 weeks (range, 4.0-21.1 weeks). The median duration of treatment was 15.1 weeks (range, 0.14 to Ն62 weeks). Conclusion: 9-cis-retinoic acid capsules have moderate activity and provide durable responses, but substantial toxic effects at higher doses limit its suitability as an anti-KS therapy.