Bisher AKIL, MD

Archive for March 22nd, 2009|Daily archive page

IL-2 increases CD4+ count but no clinical improvement

In Immune System on March 22, 2009 at 11:35 pm

Previous studies have suggested that adding Interleukin (IL)-2 will increase CD4+ cell count. The clinical benefit for such increase was inferred but not proven. In February 2009, during the 16th Conference on Retroviruses and Opportunistic Infections (CROI), two studies attempted to show the clinical benefit.
In the SILCAAT trial [Abstract 90bLB], 1695 patients who had CD4 counts <300 cells/mm3 while receiving antiretroviral therapy (ART) were randomized either to continue ART alone or to also receive IL-2 (4.5 million IU, delivered subcutaneously twice daily in at least 6 cycles of 5 days each, separated by 8-week intervals). The median nadir CD4 count was 60 cells/mm3, and the median entry CD4 count was 202 cells/mm3; 81% of patients had viral loads 500 copies/mL. The two treatment groups were well matched at baseline. During follow-up (median, 7.6 years), the IL-2 group averaged 57 more CD4 cells/mm3 than did the ART-alone group, but the rate of opportunistic disease or death was similar between the groups. Adverse event rates were also similar, except in the first year, when the IL-2 group had a higher rate of grade 4 events (mostly psychiatric and gastrointestinal).
The second study, ESPRIT trial, [Abstract 90aLB], had the same study design as SILCAAT, but the 4111 patients had baseline CD4 counts 300 cells/mm3, and the IL-2 was dosed differently (7.5 million IU, delivered subcutaneously twice daily in at least 3 cycles of 5 days each, separated by 8-week intervals). The overall median nadir CD4 count was 197 cells/mm3, and the mean enrollment CD4 count was 457 cells/mm3; 80% of patients had viral loads 500 copies/mL. Results were similar to those of the SILCAAT study: The IL-2 group gained more CD4 cells than did the ART-alone group (average difference, 153 cells/mm3) but did not have a lower rate of opportunistic disease or death. Again, the IL-2 group had an excess of grade 4 adverse events (this time, mostly vascular complications).
Comments: Why? usually more CD4+ cell count means better immune system and less infections, less death…etc. There is no clear answer, but there is no shortage of possibilities: maybe the cells generated are not as good as the cells one gets from ART; maybe IL-2 does something bad, maybe…etc. In the meantime, these were unexpected results _ BA

Treatment Induced Changes in HDL , LDL and Heart Disease

In Heart on March 22, 2009 at 11:06 pm

High-density lipoprotein (HDL) cholesterol level is associated independently and inversely with coronary heart disease risk. However, evidence that treatment-mediated increases in HDL cholesterol levels lower risk for heart disease is lacking. In analysis of 108 randomized trials (Briel M et al. Association between change in high density lipoprotein cholesterol and cardiovascular disease morbidity and mortality: Systematic review and meta-regression analysis. BMJ 2009 Feb 16; 338:b92.), involving nearly 300,000 patients, investigators assessed whether changes in HDL and Low -density lipoprotein (LDL) as a result of medical treatment was associated with changes in the risk for heart disease.
All but five trials involved lipid-modifying drugs. After adjustment for changes in LDL cholesterol levels related to treatment and drug class, no associations were noted between treatment-mediated changes in HDL cholesterol levels and all-cause death. However, changes in LDL cholesterol levels were associated with significant outcomes: For a 10 mg/dL reduction in LDL cholesterol level, relative risks were lowered for all-cause death by 4.4%, for coronary heart disease-related death by 7.2%.
Comments: the good news is that is the LDL is lowered using medications, there is clear and significant benefit; on the other hand, changes in HDL did not seem to make a difference, in this analysis. This analysis may not reveal hidden benefits for increasing HDL, but it makes it clear that the goal of treatment should be lowering LDL _ BA