INDICATIONS AND USAGE
LEXIVA is indicated in combination with other antiretroviral agents for the treatment of HIV infection in adults. The following points should be considered when initiating therapy with LEXIVA/ritonavir in protease inhibitor-experienced patients (see Description of Clinical Studies).
- The protease inhibitor-experienced patient study was not large enough to reach a definitive conclusion that LEXIVA/ritonavir and lopinavir/ritonavir are clinically equivalent.
- Once-daily administration of LEXIVA plus ritonavir is not recommended for protease inhibitor-experienced patients.
Description of Clinical Studies: Therapy-Naive Patients: Study APV30001: APV30001 was a randomized, open-label study, comparing treatment with LEXIVA Tablets (1,400 mg twice daily) versus nelfinavir (1,250 mg twice daily) in 249 antiretroviral treatment-naive patients. Both group s of patients also received abacavir (300 mg twice daily) and lamivudine (150 mg twice daily).
The mean age of the patients in this study was 37 years (range 17 to 70 years), 69% of the patients were males, 20% were CDC Class C (AIDS), 24% were Caucasian, 32% were black, and 44% were Hispanic. At baseline, the median CD4+ cell count was 212 cells/mm3(range: 2 to 1,136 cells/mm3; 18% of patients had a CD4+ cell count of <50 cells/mm3 and 30% were in the range of 50 to <200 cells/mm3). Baseline median HIV-1 RNA was 4.83 log10 copies/mL (range: 1.69 to 7.41 log10 copies/mL; 45% of patients had >100,000 copies/mL).
The outcomes of randomized treatment are provided in Table 7.
Table 7. Outcomes of Randomized Treatment Through Week 48 (APV30001)
Outcome
(Rebound or discontinuation = failure)
|
LEXIVA
1,400 mg b.i.d.
(n = 166) |
Nelfinavir
1,250 mg b.i.d.
(n = 83)
|
|
Responder *
|
66% (57%) |
52% (42%) |
|
Virologic failure
|
19%
|
32%
|
|
Rebound
|
16%
|
19%
|
Never sup pressed
through Week 48
|
3%
|
13%
|
|
Clinical progression
|
1%
|
1%
|
|
Death
|
0%
|
1%
|
Discontinued due to
adverse reactions
|
4%
|
2%
|
Discontinued due to
other reasons **/* |
10%
|
10%
|
|
*Patients achieved and maintained confirmed HIV-1 RNA <400 copies/mL (<50 copies/mL) through Week 48 (Roche AMPLICOR HIV-1 MONITOR Assay Version 1.5).
|
| **/* Includes consent withdrawn, lost to follow up, protocol violations, those with missing data, and other reasons.
|
|
Treatment response by viral load strata is shown in Table 8.
Table 8. Proportions of Responders Through Week 48 by Screening Viral Load (APV30001)
Screening Viral Load HIV-1 RNA
(copies/mL) |
LEXIVA
1,400 mg b.i.d.
|
Nelfinavir
1,250 mg b.i.d.
|
|
|
<400 copies/mL
|
n
|
<400 copies/mL
|
n
|
|
|
65%
|
93
|
65%
|
46
|
|
>100,000
|
67%
|
73
|
36%
|
37
|
|
Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 201 cells/mm3 in the group receiving LEXIVA and 216 cells/mm3 in the nelfinavir group.
Study APV30002: APV30002 was a randomized, open-label study, comparing treatment with LEXIVA Tablets (1,400 mg once daily) plus ritonavir (200 mg once daily) versus nelfinavir (1,250 mg twice daily) in 649 treatment-naive patients. Both treatment group s also received abacavir (300 mg twice daily) and lamivudine (150 mg twice daily).
The mean age of the patients in this study was 37 years (range 18 to 69 years), 73% of the patients were males, 22% were CDC Class C, 53% were Caucasian, 36% were black, and 8% were Hispanic. At baseline, the median CD4+ cell count was 170 cells/mm3(range: 1 to 1,055 cells/mm3; 20% of patients had a CD4+ cell count of <50 cells/mm3 and 35% were in the range of 50 to <200 cells/mm3). Baseline median HIV-1 RNA was 4.81 log10 copies/mL (range: 2.65 to 7.29 log10 copies/mL; 43% of patients had >100,000 copies/mL).
The outcomes of randomized treatment are provided in Table 9.
Table 9. Outcomes of Randomized Treatment Through Week 48 (APV30002)
Outcome
(Rebound or discontinuation = failure)
|
LEXIVA
1,400 mg q.d./
Ritonavir 200 mg q.d.
(n = 322) |
Nelfinavir
1,250 mg b.i.d.
(n = 327) |
|
Responder *
|
69% (58%) |
68% (55%) |
|
Virologic failure
|
6%
|
16%
|
|
Rebound
|
5%
|
8%
|
Never sup pressed
through Week 48
|
1%
|
8%
|
|
Death
|
1%
|
0%
|
Discontinued due to
adverse reactions
|
9%
|
6%
|
Discontinued due to
other reasons **/* |
15%
|
10%
|
|
*Patients achieved and maintained confirmed HIV-1 RNA <400 copies/mL (<50 copies/mL) through Week 48 (Roche AMPLICOR HIV-1 MONITOR Assay Version 1.5).
|
| **/* Includes consent withdrawn, lost to follow up, protocol violations, those with missing data, and other reasons.
|
|
Treatment response by viral load strata is shown in Table 10.
Table 10. Proportions of Responders Through Week 48 by Screening Viral Load (APV30002)
Screening Viral Load HIV-1 RNA
(copies/mL) |
LEXIVA 1,400 mg q.d./
Ritonavir 200 mg q.d.
|
Nelfinavir
1,250 mg b.i.d.
|
|
<400 copies/mL
|
n
|
<400 copies/mL
|
n
|
|
|
72%
|
197
|
73%
|
194
|
|
>100,000
|
66%
|
125
|
64%
|
133
|
|
Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 203 cells/mm3 in the group receiving LEXIVA and 207 cells/mm3 in the nelfinavir group.
Protease Inhibitor-Experienced Patients: Study APV30003: APV30003 was a randomized, open-label, multicenter study comparing 2 different regimens of LEXIVA plus ritonavir (LEXIVA Tablets 700 mg twice daily plus ritonavir 100 mg twice daily or LEXIVA Tablets 1,400 mg once daily plus ritonavir 200 mg once daily) versus lopinavir/ritonavir (400 mg/100 mg twice daily) in 315 patients who had experienced virologic failure to 1 or 2 prior protease inhibitor-containing regimens.
The mean age of the patients in this study was 42 years (range 24 to 72 years), 85% were male, 33% were CDC Class C, 67% were Caucasian, 24% were black, and 9% were Hispanic. The median CD4+ cell count at baseline was 263 cells/mm3(range: 2 to 1,171 cells/mm3). Baseline median plasma HIV-1 RNA level was 4.14 log10 copies/mL (range: 1.69 to 6.41 log10 copies/mL).
The median durations of prior exposure to NRTIs were 257 weeks for patients receiving LEXIVA/ritonavir twice daily (79% had >/=3 prior NRTIs) and 210 weeks for patients receiving lopinavir/ritonavir (64% had >/=3 prior NRTIs). The median durations of prior exposure to protease inhibitors were 149 weeks for patients receiving LEXIVA/ritonavir twice daily (49% received >/=2 prior PIs) and 130 weeks for patients receiving lopinavir/ritonavir (40% received >/=2 prior PIs).
The time-averaged changes in plasma HIV-1 RNA from baseline (AAUCMB) at 48 weeks (the endpoint on which the study was powered) were -1.4 log10 copies/mL for twice-daily LEXIVA/ritonavir and -1.67 log10 copies/mL for the lopinavir/ritonavir group.
The proportions of patients who achieved and maintained confirmed HIV-1 RNA <400 copies/mL (secondary efficacy endpoint) were 58% with twice-daily LEXIVA/ritonavir and 61% with lopinavir/ritonavir (95% CI for the difference -16.6, 10.1). The proportions of patients with HIV-1 RNA <50 copies/mL with twice-daily LEXIVA/ritonavir and with lopinavir/ritonavir were 46% and 50%, respectively (95% CI for the difference -18.3, 8.9). The proportions of patients who were virologic failures were 29% with twice-daily LEXIVA/ritonavir and 27% with lopinavir/ritonavir.
The frequency of discontinuations due to adverse events and other reasons, and deaths were similar between treatment arms.
Through 48 weeks of therapy, the median increases from baseline in CD4+ cell counts were 81 cells/mm3 with twice-daily LEXIVA/ritonavir and 91 cells/mm3 with lopinavir/ritonavir. This study was not large enough to reach a definitive conclusion that LEXIVA/ritonavir and lopinavir/ritonavir are clinically equivalent.
Once-daily administration of LEXIVA plus ritonavir is not recommended for protease inhibitor-experienced patients. Through Week 48, 50% and 37% of patients receiving LEXIVA/ritonavir once daily had plasma HIV-1 RNA <400 copies/mL and <50 copies/mL, respectively.
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