Long-term efficacy and safety of fosamprenavir plus ritonavir versus lopinavir/ritonavir in combination with abacavir/lamivudine over 144 weeks.

PURPOSE: The KLEAN study extension assessed the long-term efficacy and safety of fosamprenavir-ritonavir (FPV/r) and lopinavir-ritonavir (LPV/r), both administered with abacavir/lamivudine (ABC/3TC) fixed dose combination, over 144 weeks. METHODS: KLEAN was an open-label, noninferiority study that randomised antiretroviral-naïve patients to FPV/r twice daily (bid) or LPV/r bid with ABC/3TC once daily (qd). Patients with a viral load of <400 copies/mL at Week 48 were eligible to participate in the KLEAN study extension (up to 144 weeks) and continued with their previously randomised therapy. RESULTS: The KLEAN study extension (48 to 144 weeks) randomized 199 patients. The proportion of TLOVR responders (HIV-1 RNA <50 copies/mL) at Week 144 was 73% and 60% in the FPV/r and LPV/r arms, respectively. The proportion of TLOVR responders (<50 copies/mL) was the same irrespective of baseline HIV-1 RNA (>100,000 or 100,000 copies/mL). The Week 144 median (interquartile range) change from baseline CD4+ cell count was 300 (236-433) cells/mm3 and 335 (225-444) cells/mm3 in the FPV/r and LPV/r arms, respectively. Diarrhea was the most frequently reported adverse event. A small proportion of patients (FPV/r, 13%; LPV/r, 9%) discontinued study medication due to adverse events. Three patients (FPV/r, 1; LPV/r, 2) experienced virological failure between Week 48 and Week 144. CONCLUSION: The findings of the KLEAN study extension (48 to 144 weeks) support durable viral suppression with both FPV/r and LPV/r treatment regimens when used in combination with ABC/3TC irrespective of viral load at baseline. Both regimens were well tolerated and had similar safety profiles.

Three-year outcome data of second-line antiretroviral therapy in Ugandan adults: good virological response but high rate of toxicity.

OBJECTIVE: To evaluate the safety and virological response to lopinavir/ritonavir containing second-line therapy after failing a first line nonnucleoside reverse transcriptase inhibitor (NNRTI) based regimen. DESIGN: Prospective 36 months cohort study of patients switched to zidovudine/stavudine plus didanosine plus lopinavir/ritonavir capsules as second-line regimen. METHODOLOGY: Structured interview, medical examination, and laboratory assessment performed every 6 months. RESULTS: We enrolled 40 patients; 1 died and 3 were lost to follow-up. Median CD4+ count at baseline was 108 cell/microL, median log viral load was 4.8 copies/mL. Sixteen (40%) patients had baseline genotypic resistant test, 14 (87%) had lamivudine resistance mutations, and all had NNRTIs resistance mutations. At month 36, 82% of the patients achieved viral suppression (<400 copies/ mL) and the median increase in CD4+ count was 214 cell/microL, (interquartile range: 128-295). Twenty-five patients (62%) experienced at least one adverse event. CONCLUSIONS: Our study confirms lopinavir/ ritonavir-based second-line regimen but with a high rate of toxicities.

Trough concentrations of lopinavir, nelfinavir, and nevirapine with standard dosing in human immunodeficiency virus-infected pregnant women receiving 3-drug combination regimens.

The objective of this study was to evaluate the plasma drug concentrations in human immunodeficiency virus (HIV)-infected pregnant women receiving highly active antiretroviral therapy (HAART) and to define the rate of occurrence of subtherapeutic concentrations for some commonly used antiretroviral drugs during pregnancy. We evaluated HIV-infected women (n = 68) in the third trimester of pregnancy in steady-state treatment with an HAART regimen administrated on a twice a day basis, which included 2 nucleoside reverse transcriptase inhibitors plus nelfinavir (NFV), lopinavir/ritonavir (LPV/r), or nevirapine (NVP). Blood samples were collected at predose (C(trough)). The following thresholds were used to define therapeutic drug concentrations-NFV: 0.8 microg/mL; LPV: 4.0 microg/mL/1.0 microg/mL (experienced/naive); and NVP: 3.1 microg/mL. At predose sampling, adequate drug concentrations were found in a higher proportion of women receiving NFV (70.8%) and LPV (75.0%) than NVP (55.6%). Median C(trough) plasma concentrations were 1.2 microg/mL for NFV, 5.5 microg/mL for LPV, and 3.1 microg/mL for NVP. Women receiving lopinavir/ritonavir had the lowest rates of detectable (>50 copies/mL) HIV RNA (15.4%) compared with rates of 22.2% and 41.7% among women receiving NVP and NFV, respectively. Genotypic resistance was detected in 50% of women with detectable HIV RNA for whom samples were available for testing. Subtherapeutic predose concentrations among HIV-infected pregnant women were more commonly found with NVP than with protease inhibitors. LPV administration was associated with the best viral load suppression.

Initial experience with nifekalant hydrochloride (MS-551), a novel class III antiarrhythmic agent, in patients with acute extensive infarction and severe ventricular dysfunction.

Nifekalant hydrocholoride, a novel class III antiarrhythmic agent, was used as the treatment in 4 patients with extensive anterior infarction and severe ventricular dysfunction. The malignant ventricular tachyarrhythmia was effectively suppressed at a relatively low dose, without compromising the hemodynamics, indicating that this potent K+ channel blocker has therapeutic potential for acute myocardial infarction.