HIV
and Hepatitis.com Coverage of the 14th
Annual Conference on Retroviruses and Opportunistic Infections (14th CROI) February
25 - 28, 2007, Los Angeles, CA
Significant
Sparing of Lipoatrophy Results from Treatment of HIV Patients with Kaletra + Combivir
Induction followed by Kaletra Monotherapy Compared with Sustiva + Combivir
It
is widely accepted that lipoatrophy
(fat loss) in HIV patients is related to treatment with antiretrovirals of
the nucleoside analogue reverse transcriptase (NRTIs) drug class. However, the
association of the HIV
protease inhibitors (PIs) alone to lipoatrophy and to other aspects of the
HIV-related lipodystrophy syndrome remains unclear.
The objective of the
current study, conducted at medical centers in the US, Canada and Spain and presented
in an oral session at the 14th CROI in Los Angeles this week, was to evaluate
body fat changes and their potential causes in treatment-naïve HIV patients.
The patients were randomized to receive induction therapy with
lopinavir/ritonavir (LPV/r; Kaletra) plus zidovudine/lamivudine
(ZDV/3TC; Combivir) followed by LPV/r monotherapy vs efavirenz
(EFV; Sustiva) plus ZDV/3TC
for 96 weeks.
The 155 randomized study participants underwent induction
therapy with LPV/r + ZDV/3TC for 24 to 48 weeks. One hundred four (104) of these
patients then received LPV/r monotherapy. The remaining 51 patients received EFV
+ ZDV/3TC.
All patients had DEXA scans every 24 weeks for 96 weeks. The
researchers assessed both lipohypertrophy (defined as > 20% trunk fat gain)
and lipoatrophy (defined as >20% limb fat loss) and they evaluated various
metabolic parameters and their association with body fat changes in the patients
who completed 96 weeks of therapy.
Results
•
In the LPV/r
arm, 74 patients (71%) and, in the EFV arm, 32 patients (63%) had DEXA scans every
24 weeks for 96 weeks.
•
No
baseline differences in DEXA measurements were observed.
•
A
significant difference in limb fat change from baseline was observed at week 96
(median +18% LPV/r, -9% EFV, p <0.001 between groups), while trunk fat changes
were similar (+14% LPV/r, +15% EFV).
•
Lipoatrophy
was observed in 5% in the LPV/r arm and 34% in the EFV arm (p <0.001) and lipohypertrophy
was observed in 45% and 44%, respectively (p >0.99);
•
0%
(LPV/r arm) and 16% (EFV arm) had both lipoatrophy and lipohypertrophy.
•
Baseline
and changes from baseline in lipids and metabolic parameters were comparable between
treatment groups, except for a higher median triglyceride increase in the LPV/r
group (+0.67 vs +0.47 mM/L, p = 0.02).
•
Subjects
with low baseline CD4 counts were more likely to have limb fat increases.
•
Age,
other baseline demographics, and levels of blood lipids and TNF soluble receptors
1 and 2 were not associated with limb or trunk fat changes.
•
The
difference between treatment groups in limb fat changes remained significant after
adjusting for baseline CD4 count (p <0.001).
•
There
was no statistically significant change in peripheral blood mononuclear cell mtDNA
in either group.
Based
on these findings, the study authors conclude, "Treatment with LPV/r monotherapy
(compared with EFV+ZDV/3TC) was significantly and independently associated with
sparing of peripheral lipoatrophy."
Univ
of Ottawa at The Ottawa Hosp, Canada; Abbott Labs, Abbott Park, IL, US; Hosp La
Paz, Madrid, Spain; Hosp Univ Doce de Octubre, Madrid, Spain; and Mercer Univ
Sch of Med, Macon, Georgia, US.
