Protease inhibitor-sparing simplified maintenance therapy: a need for perspective

Body fat changes and metabolic abnormalities such as hyperlipidaemia and diabetes have been increasingly reported following the successful introduction of highly active antiretroviral therapy (HAART). These side effects were attributed initially to the use of protease inhibitors (PIs). As a consequence, a series of trials were conducted where patients with well-controlled HIV viraemia either continued on PIs or were switched to a simplified maintenance therapy (SMT) without PIs. Evidence from these trials is still insufficient to show that switching from PIs to either abacavir, nevirapine or efavirenz is safe. However, patients with suboptimal pre-HAART treatment are at increased risk of virological failure if switched to an SMT. Patients switched from PI regimens tend to stay longer on an SMT and those switched to abacavir show a reduction in total cholesterol, but there is no evidence of any additional benefit from non-PI-based SMT. There is a clear need for a better understanding of HAART-related lipodystrophy and metabolic toxicity, and pharmacogenetic tests to identify those patients most at risk. The advent of simpler formulations for all drug classes, and new PIs with less metabolic toxicity, is likely to reshape completely the role of SM

Intranasal Influenza Vaccine in a Working Population

In the present study, we assessed the incidence of adverse events and influenza-like symptoms in a working population in Switzerland that was vaccinated against influenza. A total of 12,582 individuals of working age (<65 years old) were offered a free influenza vaccine of their choice (injectable or intranasal vaccine) in October and November 2000. Of these individuals, 1600 were vaccinated against influenza. Ninety-seven percent of the vaccine recipients chose the intranasal vaccine, and 3% chose the injectable influenza vaccine. The incidence of influenza-like symptoms and side effects was 13% and 36%, respectively. Individuals who chose the intranasal vaccine were more likely to report side effects (OR, 3.23; 95% CI, 1.29-8.08). Facial paralysis was observed in 11 patients and was the most severe adverse event associated with the intranasal influenza vaccine. As a result of these adverse events, the intranasal vaccine was removed from the market in the fall of 200

Antiretroviral therapy of late presenters with advanced HIV disease

Potent antiretroviral therapy (ART) has dramatically improved the prognosis of HIV-1-infected individuals. However, 10% to 30% of patients in Western countries still present late for care, when CD4 T cells are below 200 cells/mm3 and symptomatic HIV disease has occurred. Clinical considerations for advanced HIV disease are paramount as morbidity and mortality are directly correlated with a low initial CD4 T cell count, which is commonly associated with the simultaneous occurrence of co-morbidities, particularly opportunistic infections. Upon start of ART, the clinical entity of immune reconstitution inflammatory syndrome may occur and, in this context, raise the question of early versus delayed ART in patients treated for opportunistic infections. Recent data clearly indicate that an earlier start of ART is warranted in this latter situation. Guidelines for specific antiretroviral treatment for late-presenting patients are lacking. Knowledge about drug-drug interactions and co-morbidities should guide treatment choices and influence the clinical management and monitoring of drug-related side effects and interactions. Importantly, the outlook of patients who present late is very much dependent upon the initial response to ART. Nevertheless, even if optimal response to treatment has been achieved, long-term prognosis may be impaired in patients who initially presented with advanced HIV disease. We encourage physicians to perform HIV testing more frequently in order to detect HIV-infected individuals in tim

Antiretroviral Therapy Reduces Markers of Endothelial and Coagulation Activation in Patients Infected with Human Immunodeficiency Virus Type 1

We investigated the effect of antiretroviral therapy on vascular activation in 41 human immunodeficiency (HIV)—infected patients receiving a regimen that included either at least 1 protease inhibitor (PI; n = 21) or a nonnucleoside reverse-transcriptase inhibitor (NNRTI; n = 20). Acontrol group of 21 healthy subjectswas included for comparison. Levels of endothelialmarkers (soluble vascular cell adhesion molecule [sVCAM]-1, soluble intercellular adhesionmolecule-1, and vonWillebrand factor) were higher in HIV-infected persons before treatment than in control subjects anddecreasedsignificantlyafter 5-13 months of treatment. Levels of sVCAM-1 and vonWillebrand factor correlated significantly with initial virus load. D-dimer concentrations also decreased significantly after initiation of treatment. PI- and NNRTI-containing regimens had similar effects. Therapy did not reduce levels of the soluble platelet (sP) activation markers sP-selectin and CD40 ligand. The inhibition of markers of vascular activation may counterbalance sequelae of therapy-induced dyslipidemia and potentially prevent development of atherosclerosis in HIVinfected patient