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15th Conference on Retroviruses and Opportunistic Infections


Boston, Massachusetts - February 3-6, 2008


VICRIVIROC, A NEXT GENERATION CCR5 ANTAGONIST, EXHIBITS POTENT, SUSTAINED SUPPRESSION OF VIRAL REPLICATION IN TREATMENT-EXPERIENCED ADULTS: VICTOR-E1 48-WEEK RESULTS

Conf Retrovir Opportunistic Infect 2008 Feb 3-6;15: (abstract no. 39LB)

Barry Zingman1, J Suleiman2, E DeJesus3, J Slim4, M McCarthy5, E Lee5, N Case5, C Mak5, and L Dunkle5
1Montefiore Med Ctr, Bronx, NY, US; 2Brazilmed Assistencia Medica e Pesquisa, Sao Paolo; 3Orlando Immunology Ctr, FL, US; 4St Michael`s Med Ctr, Newark, NJ, US; and 5Schering-Plough Res Inst, Kenilworth, NJ, US

BACKGROUND: Vicriviroc (VCV) is a potent CCR5 antagonist with predictable pharmacokinetics dosed once daily with a ritonavir (RTV)-boosted protease inhibitor (PI) -containing regimen. Sustained efficacy was shown previously with 10 and 15 mg once daily.

METHODS: VICTOR E-1, a double-blind trial, compared VCV 20 and 30 mg once daily to placebo in CCR5-tropic HIV patients experienced with ≥3 classes of ART. Subjects had HIV RNA ≥1000 copies/mL despite stable ART for ≥6 weeks. VCV was dosed with a new RTV-boosted, PI-containing optimized background therapy (OBT) containing ≥3 drugs. The primary endpoint was change in HIV RNA at week 48. Secondary endpoints included % achieving <400 and <50 copies/mL.

RESULTS: Of 116 subjects, 78% were male, 68% Caucasian, 71% Latino, and 5% HIV/hepatitis C virus (HCV) co-infected. Mean baseline HIV RNA was 4.5, 4.5, and 4.6 log10 copies/mL in the VCV 30 mg, 20 mg, and placebo arms, respectively. Mean baseline CD4 counts were 202, 202, and 226 cells/mm3. Of the total, 33 (85%), 35(88%), and 18(49%) completed the study in the 3 groups. Mean HIV RNA declines at week 48 were –1.77, –1.75, and –0.79log10, respectively. Mean CD4 changes at week 48 were +102, +136, and +63 cells/mm3. Emergence of detectable X4 tropic HIV occurred mostly in the first 8 weeks of treatment and did not necessarily coincide with virologic failure. There were no apparent dose or drug-related toxicities. Most treatment-emergent adverse events were evenly distributed across treatment arms. Cmin at 30 mg was above the 100 ng/mL threshold in almost all subjects, supporting this dose.

Intent-to-treatanalysis(all treated subjects)

VCV 30 mg once daily+ OBT

(n=39)

VCV 20 mg once daily+

OBT

(n=40)

Placebo +

OBT

(n=35)

%<50 copies/mL

(pvalue vs placebo)

22 (56%)

(0.0002)

21(52%)

(0.0004)

5 (14%)

Subset analyses

Subjects <50copies/mL

Baseline RNA ≥100,000

Baseline RNA <100,000

4/12 (33%)

18/27 (67%)

2/12 (17%)

19/28 (68%)

1/10 (10%)

4/25 (16%)

DRV-containing OBT n (%)

9/12 (75%)

6/9 (67%)

2/6 (33%)

#active drug(s) in OBT:

 

≥3

1-2

0

*OSS missing at baseline 3 subjects

5/7 (71%)

14/22 (64%)

2/7 (29%)

 

 

5/6 (83%)

15/26 (58%)

1/8 (12%)

 

 

0/6 (0%)

5/22 (23%)

0/7 (0%)

% Patients with/Cmin >100 ng/mL

92%

82%

0

Safety analyses

 

Virologic failure

5 (18)

3 (8)

14 (40)

Emergence detectable X4 virus

 

9 (23)

 

7 (10)

 

3 (9)

Grade 3/4 adverse events n(%)

 

8/39 (21%)

 

8/40 (20%)

 

7/35 (20%)

CONCLUSIONS: VCV 30 or 20 mg once daily plus RTV-containing OBT provided sustained viral suppression in treatment-experienced subjects and increased CD4 cell counts regardless of the # of active drugs in OBT. VCV 30 mg showed superior efficacy based on % fully suppressed (<50 copies/mL) and was well tolerated. Phase 3 trials are ongoing.

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2008-02-03
39LB

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