The Gemini Study Saquinavirr SQVr vs lopinavirr LPVr plus emtricitabinetenofovir FTCTDF as initial t

1
The Gemini StudySaquinavir/r (SQV/r) vs
lopinavir/r (LPV/r) plus emtricitabine/tenofovir
(FTC/TDF) as initial therapy in HIV-1 infected
patients

• Walmsley S,1 Ruxrungtham K,2 Slim J,3 Ward D,4
  Larson P,5 and Raffi F6

1University of Toronto, Toronto, Canada
2HIV-NAT, Thai Red Cross AIDS Research Centre,
Bangkok, Thailand 3St Michaels Medical Center,
Newark, NJ, USA 4Dupont Circle Physicians Group,
Washington DC, USA 5 Roche, Nutley, NJ, USA
6University Hospital, Nantes, France.
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Gemini Study Design

• Prospective, randomized, multicenter, open-label
  trial
• N 337
• USA, Canada, France, and Thailand
• Duration 48 weeks
• Inclusion criteria
• Treatment naive
• CD4 count 350 cells/mm3
• HIV-1 RNA gt10,000 copies/mL
• Exclusion criteria
• Previous treatment with antiretrovirals (2 weeks
  exposure)
• Evidence of OI or intercurrent illness

11 randomization
Saquinavir/Ritonavir (SQV/r) 1000 mg/100 mg
BID FTC/TDF 200 mg/300 mg QD
Lopinavir/Ritonavir (LPV/r) 400 mg/100 mg
BID FTC/TDF 200 mg/300 mg QD
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Gemini Subject Disposition
337 participants
167 participants randomized to SQV/r (ITT)
170 participants randomized to LPV/r (ITT)
163 in safety analysis
168 in safety analysis
145 in per-protocol analysis (PP)
148 in per-protocol analysis (PP)
128 participants reached week 48
135 participants reached week 48
17 participants in SQV/r and 25 in LPV/r arm
excluded from PP analysis primarily because of
entry criteria violations HIV-1 10,000
copies/mL, CD4 count gt350 cells/mm3, and HBsAg.
Two additional participants in the SQV/r arm were
excluded 1 for use of prohibited medication and
1 for a major protocol violation.
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Gemini Study Objective and End Points

• To demonstrate non-inferiority SQV/r vs LPV/r at
  week 48 in treatment-naïve, HIV-1 infected adults
  
• Non-inferiority defined as lower CI threshold of
  -12
• Primary efficacy end point
• Patients () with HIV-1 RNA lt50 copies/mL at week
  48
• Secondary efficacy and tolerability endpoints
• Time course of virologic suppression (lt50
  copies/mL and lt400 copies/mL)
• Time course of CD4 cells/mm3 increase
• Safety as assessed by clinical and laboratory
  AEs, SAEs, and deaths

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Gemini Demographics and Baseline Characteristics
ITT Population lipid data-safety population
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Gemini Subject Discontinuations
a7 total 3 deaths occurred outside of treatment
period in LPV/r group (after withdrawal or during
follow-up period) hepatic failure (possibly
related to study drug), Burkitt's lymphoma, PML
bCause of death victim of crime (remotely
related to study drug), drowning, sepsis cCause
of death suicide
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Gemini HIV-1 Virological Response (ITT
missing non-response)
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Gemini HIV-1 Virological Response (ITT
missing non-response)
Patients (95 CI)
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Gemini HIV-1 Viral Load, Mean Change From BL
(ITT observed values)
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Gemini Absolute CD4 Median Change From BL (ITT
observed values)
CD4 Cells/mm3 (95 CI)
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Gemini Adverse Events (all grades)
Multiple occurrences of the same AE in one
individual are counted only once
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Gemini Virological Failures
Virological failure defined as 2 consecutive
counts of HIV RNA gt400 copies/mL at week 16 or
after aDocumented poor adherence also had
M184V bNew PI mutations were described at week 24
in 2 separate subjects. On further ongoing
analyses, in 1 subject, the D60E mutation was
subsequently confirmed in the baseline sample
for the subject presented here, L10I/V was
confirmed to be new, but baseline sample could
not be amplified past codon 46
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Gemini Median Change in Fasting Lipid Levels
(mg/dL)
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Gemini Median Change in Fasting TC/HDL Ratio
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Gemini Subjects Exceeding Lipid Levels that May
Warrant Clinical Intervention
Based on NCEP and ACTG guidelines fasting
samples
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Gemini Conclusions

• Gemini demonstrates non-inferiority of SQV/r (
  subjects reaching VR lt50 copies/mL) to LPV/r in
  the treatment of HIV-1 infected ARV-naïve
  adults
• In this study population with advanced untreated
  HIV disease, both regimens showed substantial CD4
  cell count increases
• Adverse events were reported with similar
  frequency and resulted in few discontinuations in
  either arm
• Significantly lower elevations from baseline in
  median triglycerides were observed with SQV/r at
  weeks 24 and 48
• Decrease in TC/HDL ratio for SQV/r at week 24
  (but not at week 48) was significantly greater
  than for LPV/r

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Gemini Conclusions

• Overall, these results confirm that SQV/r is an
  efficacious and well-tolerated PI for use in
  treatment-naïve patients with HIV-1 infection
• Gemini provides further evidence for the lack of
  emergence of PI resistance with failure of
  first-line boosted PI regimens

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Gemini Acknowledgements
Subjects who participated in this study

• The following investigators
• Jonathan B. Angel, MD
• Christian Aquilina, MD
• Jean-François Bergmann, MD, PhD
• Robert Bolan, MD
• Philip Brachman, MD
• U. Fritz Bredeek, MD, PhD
• Jason Brunetta, MD
• Robert Catalla, MD
• Catherine Creticos, MD
• Charles P. Craig, MD
• Frederick A. Cruickshank, MD
• Yasmine Debab, MD
• Edwin DeJesus, MD
• Pierre Dellamonica, MD
• Serge Dufresne, MD
• Joseph Gathe, Jr, MD
• Barbara Hanna, MD

• Caroline Lascoux-Combe
• Jean-Michel Livrozet, MD
• Mona Loutfy, MD, MPH
• Iván Meléndez-Rivera, MD
• Karam Mounzer, MD
• Gerald Pierone, MD
• Isabelle Poizot-Martin, MD, PhD
• David Prelutsky, MD
• Anita R. Rachlis, MD, MEd
• François Raffi, MD
• Isabelle Ravaux, MD
• Kiat Ruxrungtham, MD
• Dominique Salmon, MD, PhD
• Anne Simon, MD
• Jihad Slim, MD
• Fiona M. Smaill, MD
• Christian Trepo, MD, PhD