9th Retrovirus Conference Highlights From Late Breakers
Reported by Jules Levin
The Conference ended this morning with the Late Breaker session from 9-12am.
Here are highlights from today which will be followed by more detailed
Sam Bozzette, from the VA system reported on a study evaluating
cardiovascular outcomes from over 30,000 patients in the VA system. He
reported there were no increases in cardiovascular events. He concluded this
data does not support a hypothesis of an association between HAART and
excessive cardiovascular-related death & sickness. I think this is misleading
and a disservice. They followed patients for 6 years. Other studies have
found increased risks in heart related disease in the HAART era. Elevated
lipids from HAART may lead to potential heart-related disease. But, certain
behaviors can be a cause of heart disease and can be controlled by people:
smoking cigarettes, diet, exercise, etc. can play important contributions in
contributing to heart disease.
Michael Dube, from the ACTG & Indiana University, reported on a small study
in 6 HIV-negative individuals who smoked cigarettes and received indinavir
monotherapy for 4 weeks. He reported they did not change their diet or
exercise routines. He found indinavir induces endothelial dysfunction.
Endothelial dysfunction can be an early step in predicting cardiovascular
disease. Endothelial dysfunction can constrict blood flow. Elevated lipids
can contribute to additional risk for developing cardiovascular disease.
These two potential causes for heart disease appear to have independent
affects on increasing potential for heart disease.
J Sutinen and a research group from Finland studied rosiglitazone in patients
on HAART with lipodystrophy. 30 patients were randomized to receive 8 mg of
rosiglitazone or placebo for 24 weeks. Visceral fat and abdominal
subcutaneous fat were measured using MRI. Rosiglitazone is an anti-diabetic
drug that can improve insulin resistance in HIV-negative diabetics. Although
insulin levels went down suggesting improvement in insulin resistance,
subcutaneous fat did not improve. Waist-to-hip ratio did not improve.
Increases in triglycerides were observed. ALT did not increase.
Ray Chung, from Harvard medical School and the ACTG, reported on Pegasys
(pegylated interferon) + ribavirin in HIV/HCV coinfected patients. 133
patients were randomized to receive either Pegasys/ribavirin or standard
interferon + ribavirin. The standard interferon dose was 6 MIU 3x/week for 12
weeks; the Pegasys dose was 180 mcg once per week. Each group received 600 mg
ribavirin escalated to 1000 mg/day. The study is for 48 weeks treatment with
a 24-week followup period. The baseline characteristics of the two groups
were similar. Chung reported preliminary interim data at week 24: by ITT
analysis, 44% undetectable HCV RNA (<60 IU by RocheAmplicor) receiving
Pegasys/RBV compared to 15% receiving standard interferon/ribavirin. Most
study patients were genotype 1 & high viral load. Although there were more
grade 4 toxicity events in the peg group (17 vs 5), premature discontinuation
was lower than might be expected and about the same in both groups (15% Peg
vs 12% IFN). Multivariate statistical analysis found receiving peg
interferon, being Caucasian, having low fibrosis, and a Karnofsky score less
than 100 were jointly associated with viral response. Encouragingly, over a
third of viral nonresponders who underwent biopsy had histologic response
(improvement in liver condition). This suggests benefits can occur without a
viral response, which has been seen in other studies in HCV monoinfected.
Jose Gatell, from Spain, reported on a study of 460 adults receiving PI-HAART
and undetectable HIV RNA (<200 copies/ml) for 6 or more months who were
randomized to switch to nevirapine, efavirenz or abacavir. Gatell reported
baseline characteristics did not differ between the 3 treatment arms in the
study. Gatell said patients with elevated cholesterol & triglycerides who
switched to abacavir saw improvements, while those who switched to nevirapine
or efavirenz did not. The viral response was about the same in the three
switch groups with the exception that patients with prior NRTI resistance who
switched to abacavir saw more viral failures. This is due to NRTI
cross-resistance, as abacavir is an NRTI. The proportion of patients with
cholesterol over 240 at the end of the 48-week study was lower in the
abacavir arm than the efavirenz and nevirapine arms.
These are brief highlights. More detailed reports to follow in extensive
coverage of Retrovirus from NATAP's team. Sleepless in Seattle, Jules Levin