No abstract

Study M98-863 was a double-blind, randomized, phase 3 study that compared lopinavir/ritonavir with nelfinavir, each coadministered with stavudine and lamivudine, in 653 antiretroviral therapy-naive human immunodeficiency virus (HIV) type 1-infected subjects. The incidence of HIV drug resistance was analyzed using baseline and rebound virus isolates from subjects with plasma HIV RNA >400 copies/mL from weeks 24 to 108 of therapy. No evidence of genotypic or phenotypic resistance to lopinavir/ritonavir, defined as any active site or primary mutation in HIV protease, was detected in virus isolates from 51 lopinavir/ritonavir-treated subjects with available genotypes. Primary mutations related to nelfinavir resistance (D30N and/or L90M) were observed in 43 (45%) of 96 nelfinavir-treated subjects. Resistance to lamivudine and stavudine was also significantly higher in nelfinavir-treated versus lopinavir/ritonavir-treated subjects. These differences suggest substantially different genetic and pharmacological barriers to resistance for these 2 protease inhibitors and may have implications for strategies for initiating antiretroviral therapy.

CPOP-R is an active regimen with modestly lower response rates than CHOP-R but similar PFS and event-free survival. This study demonstrates a substantially lower cardiotoxicity of pixantrone compared with doxorubicin when used as first-line therapy in DLBCL.

Pixantrone is a potentially more effective, less cardiotoxic alternative to doxorubicin for patients with aggressive non-Hodgkin lymphoma (aNHL). This phase I/II non-comparative study evaluated pixantrone in place of doxorubicin in the standard CHOP regimen (cyclophosphamide, doxorubicin, vincristine, and prednisone), i.e. CPOP (cyclophosphamide, pixantrone, vincristine, and prednisone), in patients with relapsed aNHL who had previously received CHOP ± rituximab. Patients were administered pixantrone on day 1 of each 21-day cycle. Phase I (n = 35) dose escalation from 80 mg/m(2) to 180 mg/m(2) established the phase II (n = 30) dose as 150 mg/m(2). In phase II, 20 patients (67%) received all six planned cycles. The objective response rate was 73%, complete response/complete response unconfirmed (CR/CRu) rate was 47%, and median overall survival was 17.9 months. Myelosuppression was nearly universal. Six patients (20%) developed febrile neutropenia. Overall, left ventricular ejection fraction (LVEF) declines ≥10% occurred in 14 patients; declines seemed transient and unrelated to dose. Symptomatic cardiac failure occurred in four patients; however, pre-existing conditions confounded causality.

HAART initiation is associated with increased HCV loads and ALT levels. A low baseline CD4+ cell count is associated with persistent increases in the HCV RNA load in nelfinavir-treated patients. These results warrant careful interpretation of abnormalities in the ALT load after HAART initiation in HCV-HIV-coinfected patients to prevent premature discontinuation of treatment.