Ulrik Bak Dragsted

Objective: To assess the rate of protocol-defined treatment failure and safety of lopinavir/ritonavir (LPV/r) and saquinavir/ritonavir (SAQ/r). Design: Open-label, prospective, randomized (1:1), international multi-centre trial. Methods: Adult HIV-1-infected patients were assigned LPV/r 400/100 mg twice daily or SAQ/r 1000/100 mg twice daily with two or more nucleoside reverse transcriptase inhibitors (NRTIs)/non-NRTIs. All patients, whether on or off the assigned treatment, were followed for 48 weeks. Results: Of 339 randomized patients, 324 initiated assigned treatment (intention-to-treat/exposed [ITT/e] population). At 48 weeks, treatment failure occurred in 29/163 (18%) and 53/161 (33%) of patients in the LPV/r and SAQ/r arms, respectively (ITT/e, P=0.002, log rank test). In an analysis that also considered those patients who discontinued treatment as having failed treatment (ITT/e/discontinuation=failure), 40/161 (25%) LPV/r-treated individuals versus 63/161 (39%) SAQ/R-treated individuals failed treatment ( P=0.005, log rank test). Discontinuation of the assigned treatment occurred in 23/163 (14%) patients in the LPV/r-treated group, compared with 48/161 (30%) in the SAQ/r-treated group (ITT/e; P=0.001). The primary reasons for premature discontinuation were non-fatal adverse events (LPV/r: 12/163; SAQ/r: 21/161) and patients’ choice (LPV/r: 7/163; SAQ/r: 8/161). In the on-treatment analysis of time to treatment failure, no difference was observed between the two arms ( P=0.27, log rank test). Conclusion: LPV/r had better antiretroviral effects compared with SAQ/r at the doses and in the formulations studied. This may have been a result of patients’ preferences and ability to adhere to assigned therapy, rather than a result of differences in the intrinsic potency of the study protease inhibitors.

In 2002, a sharp increase in outbreaks of norovirus-associated illness, both on cruise ships and on land, encouraged us to examine the molecular epidemiology of detected noroviruses, to identify a common strain or source. Of 14 laboratory-confirmed outbreaks on cruise ships, 12 (86%) were attributed to caliciviruses; among these 12, outbreak characteristics included continuation on successive cruises in 6 (50%), multiple modes of transmission in 7 (58%), and high (110%) attack rates in 7 (58%). Eleven of the 12 calicivirus outbreaks were attributed to noroviruses, 7 (64%) of which were attributed to a previously unreported lineage, provisionally named “the Farmington Hills strain.” From May 2002 to December 2002, 10 (45%) of 22 land-based outbreaks also were attributed to this strain. Nucleotide-sequence analysis provided insights into norovirus transmission, by documenting links among outbreaks, the introduction of strains onto ships, and viral persistence on board (despite cleaning). Control measures for outbreaks should address all routes of transmission. Better outbreak surveillance and collection of data on sequences will help to monitor norovirus strains and to identify common sources.

This trial assessed the rate of virological failure at 48 weeks in adult human immunodeficiency virus (HIV) type 1–infected patients assigned indinav

Antiretroviral combination therapy is the standard of care in the treatment of HIV-infection in the industrialised world. Treatment with antiretroviral drugs provides selective pressure on HIV. Suboptimal anti-HIV treatment increases the risk of resistant mutations developing. Recently, genotypic and phenotypic resistance testing has become available for routine use. So far, few data have been published on the efficacy of this testing and there is no evidence of clinical benefit. The use of genotypic resistance testing should--until further evidence has been provided--be limited to patients with virological failure on a current regimen. Genotypic resistance testing can also be used for epidemiological surveillance.