Abacavir
is generally well tolerated, but can cause hypersensitivity reactions in a small
percentage of patients. The risk of such reactions has fallen with the introduction
of the HLA-B*5701
genetic test, which shows which patients are at risk and should therefore
avoid abacavir.
Tenofovir
is widely used (especially as part of the 1-pill once-daily Atripla
coformulation) and is also well tolerated, though a small percentage of patients
may develop kidney toxicity and some (albeit mixed) data suggest a potential association
with bone loss.
The HEAT study evaluated the efficacy and safety of the
2 backbones in combination with lopinavir/ritonavir
(Kaletra) soft-gel capsules once daily in patients starting antiretroviral
therapy for the first time (the study began before the new "Meltrex"
formulation of Kaletra was approved).
The randomized, double-blind, 96-week,
non-inferiority trial included 688 treatment-naive participants at multiple U.S.
sites. Most (82%) were men and the average age was 38 years; half were white and
36% were African American. Patients started with a plasma HIV RNA level >
1000 copies/mL, as were stratified as having greater or less than 100,000 copies/mL.
The baseline CD4 cell counts were 214 cells/mm3 in the Epzicom
arm and 193 cells/mm3 in the Truvada
arm.
Virological failure was defined as failure to achieve a viral load
< 200 copies/mL by week 24, or confirmed rebound to > 200 copies/mL.
Patients were allowed to make certain therapy switched due to toxicity and remain
in the study. HLA-B*5701 screening for abacavir hypersensitivity was not performed
in advance.
The primary efficacy endpoint was the proportion of patients
with viral load < 50 copies/mL at week 48; non-inferiority was analyzed using
a 12% threshold. The primary safety endpoint will be safety at week 96; the study
was only partially unblinded to allow the interim efficacy analysis.
Results
•
At 48 weeks, percentages of patients with
HIV RNA < 50 copies/mL were as follows:
•
68% in the Epzicom arm and 67% in the Truvada
arm in an intent-to-treat analysis with missing = failure and patients who switched
included in the analysis (P = 0.91).
•
64% and 62%, respectively, in an intent-to-treat
analysis with missing = failure, but patients who discontinued or switched excluded
from the analysis.
•
63% and 61%, respectively, in a TLOVR (time
to loss of virological response) analysis (P = 0.68).
•
84% and 87%, respectively, in an observed (as-treated) analysis (P = 0.40).
•
Percentages with HIV RNA < 400 copies/mL
were as follows:
•
75% in the Epzicom arm and 71% in the Truvada
arm in an intent-to-treat, missing = failure, switch included analysis (P = 0.25).
•
94% and 92%, respectively, in an observed
analysis (P = 0.47).
•
Confirmed virological failure occurred in
12% of patients in the Epzicom arm and 11% in the Truvada arm.
•
The median increases in CD4 count from baseline
were 201 cells/mm3 in the Epzicom arm and 173 cells/mm3 in the Truvada arm.
•
Percentages of patients who withdrew from
the study early for any reason were 20% in the Epzicom arm and 24% in the Truvada
arm.
•
19% and 24%, respectively, discontinued due
to adverse events.
•
Moderate-to-severe (Grade 2-4) adverse event
rates were 45% and 44%, respectively.
•
Rates of diarrhea (18% vs 19%), nausea (7%
vs 6%), and elevated triglycerides (6% vs 5%) were similar in both arms.
•
Elevated cholesterol occurred in 6% of Epzicom
patients and 3% of Truvada patients.
•
4% in the Epzicom arm and 1% in the Truvada
arm stopped due to a suspected abacavir hypersensitivity reaction.
•
0% and 1%, respectively, developed proximal
renal tubular dysfunction (a potential indicator of kidney toxicity), though glomerular
filtration rate decreases occurred in 5% of patients in both arms.
•
34% taking Epzicom and 53% taking Truvada
developed treatment-emergent resistance mutations.
•
M184V or mixtures were the most common mutations
in both arms, but were twice as common in the Truvada arm; a few previously unreported
M184A mutations were noted in the Truvada arm.
Conclusion
Based
in these results, the investigators concluded, "Abacavir/3TC was non-inferior
to tenofovir/[emtricitabine] when combined with once-daily lopinavir/ritonavir.
Median CD4 increase was greater in the abacavir/3TC arm at week 48."
"Both
once-daily treatment regimens were well tolerated with few discontinuations due
to adverse events in either arm," they added.
The study is ongoing
and 96 week safety will be reported when it becomes available.
Rush
Univ Medical Center, Chicago, IL; Johns Hopkins Univ School of Medicine, Baltimore,
MD; Southwest Infectious Disease Assoc, Dallas, TX; North Texas Infectious Disease
Consultants, Dallas, TX; ID Consultants, Charlotte, NC; GlaxoSmithKline, Research
Triangle Park, NC.
2/5/08
Reference K
Smith, D Fine, P Patel, and others. Efficacy and Safety of Abacavir/Lamivudine
Compared to Tenofovir/Emtricitabine in Combination with Once-daily Lopinavir/Ritonavir
through 48 Weeks in the HEAT Study. CROI 2008. Boston, MA. February 3-6, 2008.
Abstract 774.
Abacavir/3TC
(Epzicom) Matches Tenofovir/Emtricitabine (Truvada) for Treatment-naive Patients:
HEAT Study 
