(Lexiva) Is Equally Effective with a Lower 100 mg Ritonavir (Norvir) Boosting
treatment guidelines recommend that protease
inhibitors (PIs) should be used with a small amount of ritonavir
(Norvir) in order to "boost" levels of the main PI in the body.
However, ritonavir is associated with a variety of side effects, including elevated
blood lipid levels.
the 48th International Conference on Antimicrobial Agents
and Chemotherapy (ICAAC 2008) last week in Washington, DC, researchers presented
data from 2 studies looking at the safety and efficacy of reducing the ritonavir
boosting dose from 200 mg to 100 mg when used with fosamprenavir
(Lexiva). Fosamprenavir/ritonavir at a dose of 1400/100 mg once-daily
was recently approved by the U.S. Food and Drug Administration for treatment-naive
the open-label Phase 3b LESS trial (Lexiva Simplification Study), patients who
achieved HIV suppression < 400 copies/mL for at least 3 months while taking
a fosamprenavir regimen boosted with 200 mg ritonavir (once-daily [QD] 1400/200
mg or twice-daily [BID] 700/200 mg) were randomized 2:1 to either decrease their
ritonavir dose to 100 mg or continue on the original regimen.
209 participants included in the intent-to-treat population were mostly men (about
80%), 67% were white, the median age was 44 years, and the median CD4 count was
about 435 cells/mm3. The most common nucleoside/nucleotide reverse transcriptase
(NRTI) backbone was abacavir (Ziagen)
+ lamivudine (3TC; Epivir) at about 45%, followed by tenofovir
(Viread) + emtricitabine (Emtriva) at about 25%, and zidovudine
(AZT; Retrovir) + lamivudine at about 19%.
At week 24, 92% of 140 patients in the
100 mg ritonavir arm and 94% of 69 in the 200 mg arm had not experienced viral
rebound to > 400 copies/mL (not a statistically significant difference).
In a "time to loss of virological
failure" (TLOVR) analysis, 83% of patients in the 100 mg ritonavir arm and
85% in the 200 mg arm achieved HIV RNA < 50 copies/mL.
Proportions achieving viral load <
400 copies/mL were 92% and 94%, respectively.
Median CD4 cell increases were 446 and
438 cells/mmm3, respectively.
34% of patients taking 100 mg ritonavir
experienced any grade 2-4 adverse events (AEs), compared with 36% of those taking
The proportions of patients who experienced
drug-related grade 2-4 AEs were 4% and 7% respectively.
The most common AE was diarrhea, occurring
in 1% and 3%, respectively.
No patient in either arm experienced treatment-related
No patient in the 100 mg group and 2 people
in the 200 mg group experienced hypercholesterolemia (elevated cholesterol).
Overall median changes in lipid parameters
at week 24 were similar in the 100 and 200 mg ritonavir dose arms.
However, patients taking 100 mg ritonavir
had a significantly larger decrease in triglycerides (-21 vs -1 mg/dL).
findings led the investigators to conclude that, "A regimen of fosamprenavir
1400 mg + ritonavir 100 mg demonstrated non-inferiority to full boosted fosamprenavir/ritonavir
(700/100 mg BID or 1400/200 mg QD) over a 24 week period in virologically stable
"These results support the safety and efficacy of
the once-daily treatment option of Lexiva and 100 mg dose of ritonavir for patients
with HIV/AIDS," said Mark Shaefer, PharmD, Director of Clinical Development
at GlaxoSmithKline in a press release issued by the company. "Once-daily
dosing with 100 mg of ritonavir not only reduces the pill burden on patients but
also simplifies the treatment regimen."
Community Res. Initiative,
Boston, MA; Orlando Immunology Ctr., Orlando, FL; Therafirst Med. Ctr., Fort Lauderdale,
FL; North Texas IDC, Dallas, TX; Univ. of Colorado, Denver, CO; GlaxoSmithKline,
Research Triangle Park, NC.
Safety and Efficacy at 96 Weeks
a related study, COL100758, researchers compared the safety and efficacy of 100
vs 200 mg doses of ritonavir to boost 1400 mg once-daily fosamprenavir; in this
trial, all patients received abacavir/lamivudine as their NRTI backbone.
randomized, open-label trial enrolled 115 participants. Most (81%) were men, 53%
were black, 41% were white, 16% were Hispanic/Latino, and the median age was 39
years. The median baseline CD4 count was higher in the 100 mg ritonavir arm (259
vs 179 cells/mm3).
46 of 58 patients (79%) in the 100 mg
ritonavir arm and 33 of 57 (58%) in the 200 mg arm completed the study.
At 96 weeks, 66% in the 100 mg arm and
53% in the 200 mg arm had HIV RNA < 50 copies/mL in an intent-to-treat "missing
= failure" analysis (not a statistically significant difference).
In an observed (as-treated) analysis,
the corresponding percentages were 83% and 94%, respectively.
In a TLOVR < 50 copies/mL analysis,
the proportions were 57% and 49%, respectively.
Median CD4 cell increases were 265 in
the 100 mg arm and 260 in the 200 mg arm.
41% and 44%, respectively, experienced
any grade 2-4 treatment-related AEs.
14% and 18%, respectively, experienced
grade 2-4 diarrhea.
Low-density lipoprotein (LDL or "bad")
cholesterol and triglycerides increased less in the 100 mg arm than in the 200
47% of patients in the 100 mg arm maintained
? 95% adherence, compared with 27% in the 200 mg arm (just shy of statistical
Immunology Ctr., Orlando, FL; North Texas ID Consultants, Dallas, TX; Comprehensive
Care Ctr., Ft. Lauderdale, FL; GlaxoSmithKline, Durham, NC, Duke Univ., Durham,
and Bone Mineral Density
another analysis of the same study, researchers compared changes in regional fat
and bone mineral density (BMD) at 96 weeks. Total body DEXA scans were performed
pre-treatment and at week 96; 113 patients had at least 1 scan, and 71 had paired
baseline and week 96 scans (40 in the 100 mg ritonavir arm and 31 in the 200 mg
percentage changes in fat in the upper and lower limbs and trunk, and median percentage
changes in total body and lumbar spine BMD were assessed. Clinically relevant
changes in fat mass were defined as > 20% loss of limb fat and/or > 20%
gain in trunk fat.
Median percentage changes in fat mass
in the 100 mg and 200 mg arms, respectively, were as follows:
-1.5% vs +11.6% for upper limbs;
+10.0% vs +16.3% for lower limbs;
+14.5% vs +18.5% for trunk.
20% fat changes were observed in the following
proportions of patients in the 100 mg and 200 mg arms, respectively:
18% and 13% with > 20% fat loss in
the upper limbs;
15% vs 6% with > 20% fat loss in the
38% vs 45% with > 20% fat gain in the
No patient had both > 20% limb fat
loss and > 20% trunk fat gain simultaneously.
Median total body BMD (g/cm2) percentage
changes were -1.05% in the 100 mg arm and -1.04% in the 200 mg arm.
Among the 27 patients with lumbar spine
data available, the changes were -3.0% and -2.2%, respectively.
96 weeks treatment with once-daily fosamprenavir plus abacavir/lamivudine, "both
limb and trunk fat depots generally increased," the researchers concluded.
However, "[t]he median [percentage] change in fat mass in all regions studied
was not significantly different" between the ritonavir 100 mg and 200 mg
arms. Finally, they noted, "BMD changes were small in both study arms."
of NC, Chapel Hill, NC; Orlando Immun. Ctr., Orlando, FL; North Texas ID Consultants,
Dallas, TX; Comprehensive Care Ctr., Ft. Lauderdale, FL; GlaxoSmithKline, Research
Triangle Park, NC; Duke Univ, Durham, NC.
Cohen, E DeJesus, A Lamarca, and others. Switching from a 200mg-Ritonavir (RTV,
r)-Boosted Fosamprenavir (FPV) Regimen (700mg/200mg BID or 1400mg/200mg QD) to
a 100mg RTV-Boosted FPV Regimen (1400mg/100mg QD) Yields Similar Efficacy and
Safety. 48th International Conference on Antimicrobial Agents and Chemotherapy
(ICAAC 2008). Washington, DC. October 25-28, 2008. Abstract H-1250e.
DeJesus, l Sloan, M Sension, and others. 96-Week Efficacy/Safety Data Comparing
Two Doses of Ritonavir (/r) to Boost Once-Daily (QD) Fosamprenavir (FPV), Used
in Combination with Abacavir (ABC)/Lamivudine (3TC). 48th International Conference
on Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October
25-28, 2008. Abstract H-1246.
Wohl, E DeJesus, L Sloan, and others. Fat changes by total body DEXA after 96
weeks of treatment with once-daily fosamprenavir with either 100 or 200 mg of
ritonavir plus abacavir/lamivudine: COL10075. 48th International Conference on
Antimicrobial Agents and Chemotherapy (ICAAC 2008). Washington, DC. October 25-28,
2008. Abstract H-2302.
GlaxoSmithKline. Data Show that Administration of LEXIVA with Lower
Dose of Ritonavir Is Associated with Similar Efficacy and Safety as Higher Dose.
Press release. October 26, 2008.