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9th Retrovirus Conference: lipodystrophy, complications, OIs, switching
regimens
Reported by Jules Levin
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At yesterday's oral session on "Opportunistic Infections and Complications of
Antiretroviral Therapy" there were several interesting reports. Here are
brief highlights which will be followed by more detailed reports.
Andrew Carr from Australia, a lipodystrophy reseaercher, reported on his
study intended to establish a case definition of HIV lipodystrophy. The study
was performed at 32 sites in the Americas (15), Europe (11), and Australia
(6). They used a case-control method for identifying clinical, lab, and
imaging features that discriminate lipodystrophy cases. 1081 patients were
recruited (15% female). There 417 cases of lipodystrophy (with at least 1
moderate or severe lipo feature identified by doctor & patient, except
isolated abdominal obesity). There were 371 controls (with no lipo identified
by doctor & patient, and no significant weight change since HIV diagnosis).
And there were 288 noncases & noncontrols. Cases and controls completed all
assessments including ART & metabolic history, fasting metabolic labs, DEXA
and abdominal CT. Carr generated models from 500 randomly selected cases &
controls. Models were validated in the remaining cases & controls. Carr's
definition includes: low trunk:peripheral fat ratio by DEXA, abdominal
bloating, low leg fat % by DEXA (skinny legs), low alcohol use, higher waist:
hip ratio (fat belly), high total chesterol: HDL (good cholesterol ratio,
higher anion gap, report of increased bleeding tendency, highe visceral fat:
subcutaneous fat ratio by CT (fatter belly than periphery).
Switching To Abacavir for Lipodystrophy
Over 100 patients with moderate/severe lipodystrophy receiving d4T (84%) or
AZT (16%), PI use (56%) and stable HIV RNA <400, and no prior abacavir use
were randomized to stay on current therapy or switch d4T or AZT to open-label
abacavir while continuing other HIV meds. 25% of patients had lactic
acidemia. 98% men. 44 yrs of age. CD4 count 577. Mean duration on NRTIs 5
yreas. This study was conducted ny Andrew Carr. Results were reported after
only 6 months. They reported a significant increase in limb fat in the
abacavir group compared to the patients continuing on their current therapy,
and a significant increase in the subcutaneous thigh and abdominal fat areas
for patients switching to abacavir vs those staying on current therapy.
Peripheral fat increases were greater in abacavir patients with higher limb
fat to begin with and with lactate <2 mmol/l. But, patients did not report
seeing any improvement. A 10% improvement in peripheral fat was reported
after 6 months of following patients. There was no significant improvement
reported in intra-abdominal fat.
Metabolic Abnormalities in NNRTI, PI Regimens, and Abacavir Regimens
Researchers from The Netherlands and Denmark reported on differences in
metabolic values (cholesterol, triglycerides, good cholesterol - HDL) between
patients on a NNRTI (nevirapine or efavienz) or PI regimen. The researchers
concluded that patients on a firstline NRTI+NNRTI regimen were less likely to
have bad metabolic lab test results compared to those on a firstline PI_NRTI
regimen (NNRTI group had lower total cholesterol to good cholesterol ratio,
and had better chance of having elevated good cholesterol (HDL). The
researchers said long-term studies are needed to see if this translates into
differences in risk for developing heart disease.
In another study reported by Glaxo Smith Kline and Dr Kumar from Georgetown
University a Combivir/abacavir regimen was compared to 2 nelfinavir/NRTI
regimens for differences in lipids. They looked at over 200 non-diabetic
patients on Combivir/abacavir, Combivir/nelfinavir, or d4T/3TC/nelfinavir for
96 weeks. Cholesterol values went less in the abacir arm than in the other
two arms. LDL (bad cholesterol) increased less in the abacavir arms compared
to the other 2 arms.
Incidence of Grade 4 Events, AIDS, and Death in 3000 Patients
Ron Reisler from the NIH reported on the incidence of grade 4 events, AIDS,
and death in a 3000 patients followed from 5 CPCRA studies. The patients were
treatment naive & experienced and followed for from 1996 to 2001 August
During follow-up all patients were prescribed HAART. 38% had an AIDS
diagnosis at baseline; 45% were treatment naive. Median follow-up was 17
months. The average CD4 count was 240. 600 patients were followed for at
least 30 months. The most common serious life-threatening illness or grade 4
event was liver-related (6%). Coinfection with Hep B or Hep C was the
strongest and only significant predictor of serious liver problems. Other
serious life threatening illnesses occurring less frequently included
neutropenia-type of white blood cells (3.9%), pancreatitis (2.2%), anemia
(2.1%), psychiatric-related problems (2.1%), cardiac and heart disease
(1.6%), kidney disease (1.5%). Only 1.5% experienced kidney related disease
at 30 months but most were African-American. Rates of AIDS were less than
severe life threatening events. This is in part due to the extended lives of
people receiving HAART. Patients with higher CD4 counts had less risk for
developing AIDS, but could still develop life threatening events. 84% of
patients were men, 45% white, 42% African-American, 13% Latino. In the US end
stage renal disease occurs four times more for African-Americans than whites.
Diabetes & hypertension are related. Researchers did not perform analyses to
associate specific regimens or drugs with certain types of grade 4 events,
death, or AIDS. The cumulative % of patients with ant grade grade 4 event at
30 months was 27%, while the 30-month rate of developing an AIDS illness was
13%, and the 30-month death rate was 10%. The risk of death associated with
disease progression was Hazard ratio=6.84 compared to a Hazard ratio=5.77
risk associated with any grade 4 adverse event. In other words if a person
died it was just a litle more likely to result from AIDS than due to an grade
4 event. again, this is in part due to at least AIDS being under control by
HAART and patients living longer.
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