Copyright ©2011 Merck & Co., Inc., Whitehouse Station, New Jersey, USA, All Rights ReservedIAS 2011_ Abstract # WEPDB0102

Sustained Efficacy and Tolerability of Raltegravir after 240 Weeks of

Combination ART in Treatment-Naive HIV-1 Infected Patients:

Final Analysis of Protocol 004

E. Gotuzzo1, B.-Y. Nguyen2, M. Markowitz3, F. Mendo4, W. Ratanasuwan5, C. Lu2, S. Bhanja2,

H. Teppler2, and the Protocol 004 Part II Study Team

1Hospital Nacional Cayetano Heredia, Lima, Peru; 2Merck Research Labs, North Wales, PA, United States; 3Aaron Diamond AIDS Research Center,

New York, NY, United States; 4Hospital Nacional Edgardo Rebagliati, Lima, Peru; 5Siriraj Hospital, Bangkok, Thailand

Copyright ©2011 Merck & Co., Inc., Whitehouse Station, New Jersey, USA, All Rights ReservedIAS 2011_ Abstract # WEPDB0102

• Percentage of Patients with HIV RNA < 50 copies/mL (NC=F)

• Change from Baseline in CD4 Cell Counts (OF)

160 155 153 146 143 138 134 129 129 121 12338 38 36 36 35 33 34 32 32 31 31

llmk0518p4CD4obsCombinewk240_color June 8, 2011

MK-0518 CombinedEfavirenz 600 mg q.d.

0 24 48 72 96 120 144 168 192 216 240

Weeks

0

50

100

150

200

250

300

350

Cha

nge from

Bas

eline

in CD

4 Cell C

ount

Number of Contributing Patients

160 160 160 160 159 159 158 159 160 159 16038 37 38 38 38 38 38 38 38 38 38

llmk0518p4Hit50ncCombinewk240_color June 8, 2011

MK-0518 CombinedEfavirenz 600 mg q.d.

0 24 48 72 96 120 144 168 192 216 240

Weeks

0

20

40

60

80

100

Pe

rcen

t of P

atie

nts w

ith

HIV

RN

A <

50

Co

pie

s/mL

Number of Contributing Patients

Virologic and Immunologic Responses

301.7

275.6

63.2%

68.8%

160 155 153 146 143 138 134 129 129 121 12338 38 36 36 35 33 34 32 32 31 31

llmk0518p4CD4obsCombinewk240_color June 8, 2011

MK-0518 CombinedEfavirenz 600 mg q.d.

0 24 48 72 96 120 144 168 192 216 240

Weeks

0

50

100

150

200

250

300

350

Change from

Baseline

in CD

4 Cell C

ount

Number of Contributing Patients

Week 240 (OF approach): RAL 89% EFV 77%

Raltegravir

Copyright ©2011 Merck & Co., Inc., Whitehouse Station, New Jersey, USA, All Rights ReservedIAS 2011_ Abstract # WEPDB0102

Safety Summary: Week 240• Overall adverse event (AE) profiles, all causality

– Generally similar for RAL and EFV (other than neuropsychiatric AEs)– Similar frequencies reported at Weeks 192 and 240

• Drug-related clinical AEs – Less common with RAL than EFV: 55% vs 76% (p=0.017)

• Neuropsychiatric symptoms*– Most occurred by Week 48– At Week 240: 38% for RAL vs 63% for EFV

• Malignancies† – 3.1% (5/160 pts) in RAL group, none considered drug-related – 2.6% (1/38 pts) in EFV group, 1 event (GI carcinoma) possibly drug-related

• Grade 3 / 4 lab abnormalities uncommon– Similar frequencies reported at Weeks 192 and 240

• Minimal effect of RAL on serum lipids*Abnormal dreams, adjustment disorder with depressed mood, depressed mood, depression, dizziness, insomnia,

nightmare, psychotic disorder, somnolence, suicidal ideation, suicide attempt.

† Cases included: in RAL group: 1 pt with B-cell lymphoma, 2 pts with Kaposi’s sarcoma, 1 pt with basal cell carcinoma and squamous cell carcinoma (SC), and 1 pt with non-small cell lung carcinoma; in EFV group: 1 pt with gastrointestinal carcinoma (possibly drug-related) and SC.

Copyright ©2011 Merck & Co., Inc., Whitehouse Station, New Jersey, USA, All Rights ReservedIAS 2011_ Abstract # WEPDB0102

Exploratory Analysis: Prognostic Factors Associated With CD4 Cell Count at Yearly Time Points

Prognostic FactorP-value†

Wk 48 Wk 96 Wk 144 Wk 192 Wk 240

Baseline CD4 cell count (cells/mm3)

<0.0001 <0.0001 <0.0001 <0.0001 <0.0001

Week 8 HIV RNA decline (log10 copies/mL)

0.0005 <0.0001 <0.0001 <0.0001 <0.0001

Treatment Group 0.2887 0.3592 0.9778 0.6421 0.6057

† p-Value calculated from a linear regression model with CD4 cell count separately at each time point as the dependent variable adjusted for baseline CD4 cell count (c/mm3), Week 8 HIV RNA decline (log10 copies/mL) and treatment group.

Significant predictors for CD4 cell count (at 0.05 critical value) at each time point were: (1) baseline CD4 count and (2) log HIV RNA decline at week 8.

Copyright ©2011 Merck & Co., Inc., Whitehouse Station, New Jersey, USA, All Rights ReservedIAS 2011_ Abstract # WEPDB0102

CONCLUSIONS

• RAL + TDF/3TC demonstrated sustained antiretroviral efficacy through 5 years, similar to EFV + TDF/3TC:– HIV RNA <50 copies/mL in 69% of RAL patients vs 63% of EFV

patients– CD4 counts continued to increase through 5 years in both groups

• RAL was generally well tolerated over 5 years:– Safety profile similar to Week 144 (3 years) and Week 192 (4 years)– Drug-related AEs less frequent with RAL than EFV– RAL has minimal effect on LDL-cholesterol and triglycerides

• In an exploratory analysis, statistically significant predictors for CD4 cell count at each yearly time point were baseline CD4 count and early (week 8) log HIV RNA decline.