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Safety Profile of HIV-1 Attachment Inhibitor Prodrug BMS-663068 in Antiretroviral-Experienced Subjects: Week 24 Analysis

J Lalezari1, GH Latiff2, C Brinson3, J Echevarría4, S Treviño-Pérez5, JR Bogner6, D Stock7, SR Joshi7, GJ Hanna8, M Lataillade7, for the AI438011 study team1Quest Clinical Research, San Francisco, CA, USA; 2Maxwell Clinic, Durban, South Africa; 3Central Texas Clinical Research, Austin, TX, USA; 4Hospital Nacional Cayetano Heredia, Lima, Peru; 5Mexico Centre for Clinical Research, Mexico City, Mexico;

6Hospital of the University of Munich, Munich, Germany; 7Bristol-Myers Squibb, Wallingford, CT, USA; 8Bristol-Myers Squibb, Princeton, NJ, USA

Max Lataillade, DO MPH Bristol-Myers Squibb

Research and Development Wallingford

CT 06492 USA

Email: [email protected] Phone: 203-677-7991

Poster 1574

BACKGROUND ■ Despite the success of combination antiretroviral therapy, some HIV-positive patients may have

limited treatment options owing to: — presence of viral mutants causing reduced antiretroviral (ARV) drug susceptibility — emergence of drug toxicities from long-term ARV therapy — contraindications from the need to manage associated co-infections and morbidities1,2

■ Consequently, there is a continued need to develop novel ARVs that have: — unique resistance profiles — well-tolerated safety profiles — limited or manageable drug–drug interactions

■ BMS-663068 is a prodrug metabolized to the active moiety BMS-626529 (Figure 1), a first-in-class attachment inhibitor that binds to HIV-1 gp120, preventing initial viral attachment and entry into the host CD4+ T cell (Figure 2)3,4

■ BMS-626529 has in vitro activity against HIV-1 viruses, with the exception of subtype AE and Group O5

■ By binding directly to the virus, BMS-626529 is not affected by co-receptor tropism and is therefore active against CCR5-, CXCR4- and dual-tropic (R5X4) strains of HIV-14,6-8

■ BMS-626529 has a unique resistance profile with no in vitro cross-resistance to other classes of antiretrovirals6

■ AI438011 is an ongoing Phase IIb study investigating the efficacy, safety and dose response of BMS-663068 versus atazanavir/ritonavir (ATV/r) in HIV-1-infected, treatment-experienced subjects

■ Through Week 24, BMS-663068 + tenofovir-disoproxil fumarate (TDF) + raltegravir (RAL) demonstrated comparable efficacy to ATV/r + TDF + RAL (modified intent-to-treat SnapShot, Table 1)

Gastrointestinallumen

BMS-663068(prodrug)

BMS-626529(active moiety)

BMS-626529Blood plasma

Alkalinephosphatase

Figure 1. Conversion of BMS-663068 to BMS- 626529

Figure 2. BMS-626529 attachment inhibitor: Proposed mechanism of action

Table 1. AI438011 efficacy summary: Week 24 SnapShot: modified intent-to-treat (Presented at CROI 20149)

BMS-663068 + TDF + RAL ATV/r + TDF + RAL

400 mg BIDN=50

800 mg BID N=49

600 mg QD N=51

1200 mg QD N=50

300 mg/100 mg QD N=51

HIV-1 RNA <50 c/mL, % 40 (80.0%) 34 (69.4%) 39 (76.5%) 36 (72.0%) 38 (74.5%)

HIV-1 RNA ≥50 c/mL, % 8 (16.0%) 10 (20.4%) 11 (21.6%) 13 (26.0%) 9 (17.6%)

No virologic data at Week 24

Discontinued due to adverse event or death, n (%) 1 (2.0%) 2 (4.1%) 0 1 (2.0%) 2 (3.9%)

Discontinued for other reasons, n (%) 1 (2.0%) 3 (6.1%) 1 (2.0%) 0 2 (3.9%)

Missing data during window but on-study, n (%) 0 0 0 0 0

ATV/r, ritonavir-boosted atazanavir; BID, twice daily; QD, once daily; RAL, raltegravir; TDF, tenofovir-disoproxil fumarate.Modified intent-to-treat population: all subjects receiving ≥1 dose of study drug.

OBJECTIVES ■ To assess the safety and tolerability through Week 24 of BMS-663068, when combined with RAL

and TDF, in HIV-1-infected subjects by measuring frequency of: — adverse events (AEs) — serious AEs (SAEs) and — AEs leading to discontinuation

ACKNOWLEDGMENTS ■ We would like to thank all of the AI438011 clinical trial participants and their families ■ AI438011 Investigators: JD Altclas, PE Cahn, SH Lupo, MD Martins, AI Arango-Duque, OA Sussmann-Pena, G Amaya-Tapia,

JF Andrade-Villanueva, ER Granados-Reyes, JG Sierra-Madero, SC Trevino-Perez, WM Casapia-Morales, JI Echevarria, JR Lama-Valdivia, MY Leon-Paredes, FC Mendo-Urbina, Y Pinedo-Ramirez, MR Salazar-Castro, R Bardinas-Rodriguez, C Brinson, E Dejesus, R Elion, J Ernst, J Feinberg, S Hassler, C Hicks, J Lalezari, AR Scribner, L Sloan, M Thompson, K Arastéh, J Bogner, J Rockstroh, A Stoehr, IG Diaconescu, LJ Prisacariu, S Rugina, OA Tsybakova, EE Voronin, AA Yakovlev, NG Zakharova, J Fourie, D Johnson, R Kaplan, G Latiff, B Clotet

■ Bristol-Myers Squibb: A Rightmire, M DeGrosky, J Coumbis, N Ray, N Cusack, M Krystal, C Hwang and T Correll ■ Other: P Lill and J Riefler (ICON CRO) ■ Professional medical writing and editorial assistance was provided by MediTech Media and was funded by Bristol-Myers Squibb

REFERENCES1. Wainberg M et al. JAMA 1998; 279:1977–1983.2. Wittcop L et al. Lancet Infect Dis 2011; 11:363–371.3. Brown J et al. J Pharm Sci 2013: 102:1742–15124. Langley DL et al. Manuscript in development5. Varghese V et al. J Acquir Immune Defic Syndr 2009;

52:309–315.

6. Li Z et al. AAC 2013; 57:4172–4180.7. Nowicka-Sans B et al. AAC 2012; 56:3498–3507.8. Ray N et al. JAIDS 2013; 64:7–15.9. Lalezari J et al. CROI 2014: Oral Abstract 86.10. Bristol-Myers Squibb. Reyataz prescribing information. 2013.

Available at: http://packageinserts.bms.com/pi/pi_reyataz.pdf. Accessed April 2014.

CONCLUSIONS ■ BMS-663068 was generally well tolerated across all arms:

— no related SAEs or AEs leading to discontinuation — no dose-related safety signals

■ Across the BMS-663068 arms, there were no trends for Grade 2–4 AEs or Grade 3–4 clinical laboratory abnormalities

■ These results support continued development of BMS-663068 ■ An analysis of BMS-663068 efficacy by subgroup through Week 24 will be presented on

Thursday, October 9th at 3pm by Brinson et al (Oral 540)

METHODSAI438011 study design

■ Phase IIb, randomized, active-controlled, blinded-to-BMS-663068 dose trial (NCT01384734) ■ Consisted of a 7-day elective monotherapy substudy and the main study (Figure 3) ■ For the main study, subjects were randomized 1:1:1:1:1 into five treatment arms: four treatment

groups of BMS-663068 (400 mg twice daily [BID], 800 mg BID, 600 mg once daily [QD], or 1200 mg QD), and a reference group (ATV/r 300/100 mg QD), each with a backbone of RAL 400 mg BID + TDF 300 mg QD (Figure 3)

Primary endpointWeek 24

BMS-

Day 1

Week 8 Data monitoring committee assessment

BMS-663068 400 mg BID

+ RAL + TDFN=50

BMS-663068800 mg BID

+ RAL + TDFN=50

BMS-663068600 mg QD

+ RAL + TDFN=50

Primary study - start of combination therapy

BMS-663068 monotherapy substudy: 10 patients per study arm

Long-term follow-up through Week 48/96Week 48/96

BMS-6630681200 mg QD+ RAL + TDF

N=50

ATV/r300/100 mg QD

+ RAL + TDFN=50

Part

ial b

lind*

Figure 3. AI438011 study design

* Blinded to BMS-663068 dose. ATV/r, ritonavir-boosted atazanavir; BID, twice daily; QD, once daily; RAL, raltegravir; TDF, tenofovir-disoproxil fumarate.

Eligibility criteria ■ Main inclusion criteria:

— antiretroviral treatment-experienced (defined as current or previous exposure to ≥1 antiretroviral for ≥1 week)

— plasma HIV-1 RNA ≥1000 c/mL — CD4+ T-cell count >50 cells/mm3

— susceptibility to RAL, TDF and ATV — BMS-626529 IC50 <100 nM as determined by screening Phenosense® entry assay (Monogram Biosciences - LabCorp)

— no other significant abnormalities on medical history, physical examination, 12-lead electrocardiograms (ECGs), and clinical laboratory evaluations

— aged 18–49 years — body mass index 18–32 kg/m2

■ Main exclusion criteria: — pregnancy or breast feeding — any significant acute or chronic medical illness — liver enzymes (aspartate aminotransferase [ALT]/alanine aminotransferase [AST]) >5 times the upper limit of normal

— positive blood screen for hepatitis B surface antigen or hepatitis C antibodies/RNA

Assessments ■ Safety assessments included:

— vital signs and physical examinations — recording of AEs (SAEs, AEs and Centers for Disease Control Class C AIDS events) — measurements of changes in fasting lipids — laboratory abnormalities and ECG measurements

■ Assessments were performed at Weeks 4, 8, 12, 16, 20, 24 ■ AEs were coded according to MedDRA version 15.1 and the severity and relationship to study

drug was assessed by the corresponding investigator

RESULTSBaseline characteristics

■ Baseline demographic and disease characteristics were broadly similar across all treatment groups (Table 2)

— Median age range was 37–40 years; 60.0% male — 66.0% of subjects had HIV-1 subtype B — Median baseline HIV-1 RNA: 4.85 log10 copies/mL — Median baseline CD4+ T-cell count: 229.5 cells/µL — ~ 50.0% of subjects had at least one major protease inhibitor (PI), nucleoside reverse transcriptase inhibitor or non-nucleoside reverse transcriptase inhibitor resistance-associated mutation at baseline (M184V/I, 31.0%; K103N, 29.0%; thymidine analogue mutations, 13.0%; major PI mutations, 2.0%)

Table 2. Baseline characteristics

BMS-663068 + TDF + RAL ATV/r + TDF + RAL

400 mg BIDN=50

800 mg BIDN=49

600 mg QDN=51

1200 mg QDN=50

300 mg/100 mg QD N=51

Median age, years (range) 39 (22–57) 37(23–60) 40(26–58) 40 (20–67) 39 (20–68)

Male, % 62.0% 57.1% 56.9% 68.0% 56.9%

Race, %

White 40.0% 38.8% 33.3% 32.0% 45.1%

Black/African-American 28.0% 30.6% 31.4% 36.0% 25.5%

Other 32.0% 30.6% 35.3% 32.0% 29.4%

HIV subtype, n (%)

B 70.0% 59.2% 68.6% 64.0% 66.7%

C 16.0% 24.5% 21.6% 20.0% 17.6%

Other* 14.0% 16.2% 9.9% 16.0% 15.6%

HIV-1 RNA

Median, log10 c/mL 4.97 5.01 4.88 4.78 4.78

≥100,000 c/mL, % 46.0% 51.0% 45.1% 36.0% 35.3%

CD4+ T-cell count

Median, cells/μL 214 237 226 224 249

<200 cells/μL, % 38.0% 32.6% 41.2% 42.0% 37.3%* Majority of subjects within the “other” category reported themselves as multiracial. ATV/r, ritonavir-boosted atazanavir; BID, twice daily; QD, once daily; RAL, raltegravir; TDF, tenofovir-disoproxil fumarate.

Subject disposition ■ 581 subjects enrolled, 254 randomized and 251 treated (Figure 4) ■ Screen failures were primarily due to failure to meet study criteria; most common reasons (not

mutually exclusive) were: — a screening plasma HIV-1 RNA of <1000 copies/mL — failure of the resistance assay(s) to provide a genotypic and/or phenotypic result for ≥1 of the study drugs

■ Of those receiving treatment, 32/200 (16.0%) across the BMS-663068 arms and 9/51 (17.6%) in the ATV/r arm failed to complete 24 weeks’ treatment (Figure 4)

BMS-663068 (400 mg BID) + TDF + RAL

Participated, n=7 Participated, n=5 Participated, n=10 Participated, n=10

BMS-663068(800 mg BID) + TDF + RAL

BMS-

BMS-663068(600 mg QD) + TDF + RAL

BMS-663068(1200 mg QD) + TDF + RAL

Randomized (n=254)

Assessed for eligibility (N=581)

Randomized, n=52Treated, n=50*

Randomized, n=50Treated, n=49†

Randomized, n=51Treated, n=51

Randomized, n=50Treated, n=50

Randomized, n=51Treated, n=51

Ongoing at time of analysis (n=44 )

Ongoing at time of analysis (n=38)

Ongoing at time of analysis (n=44)

Ongoing at time of analysis (n=42)

Ongoing at time of analysis (n=42)

Discontinued (n=6) 1 adverse event 1 withdrew consent 2 lost to follow-up 1 poor/ non-compliance 1 other

Discontinued (n= 11) 2 adverse events 2 withdrew consent 2 pregnancies 1 no longer met study criteria 3 lack of efficacy 1 poor/ non-compliance

Discontinued (n=7) 1 pregnancy 2 lost to follow-up 1 no longer met study criteria 2 poor/ non-compliance 1 other

Discontinued (n=8) 1 adverse event 1 withdrew consent 3 lost to follow-up 1 request to discontinue 1 no longer met study criteria 1 lack of efficacy

Excluded (n=327) Did not meet inclusion criteria (n=303) Declined to participate (n=9) Lost to follow-up (n=3) Other reasons (n=11) Not reported (n=1)

Discontinued (n=9) 2 adverse events 3 withdrew consent 2 pregnancies 1 administration- related 1 poor/ non-compliance

ATV/r(300/100 mg QD)

+ TDF + RAL

Monotherapysubstudy

Assigned to receive

Primarystudy

Figure 4. Subject disposition

* Two subjects did not receive allocated intervention: one withdrew consent, one randomized in error; † One subject did not receive allocated intervention: withdrew consent. ATV/r, ritonavir-boosted atazanavir; BID, twice daily; QD, once daily; RAL, raltegravir; TDF, tenofovir-disoproxil fumarate.

Table 3. Overall safety summary ■ A summary of AI438011 safety data through Week 24 is shown in Table 3

BMS-663068 + TDF + RAL ATV/r + TDF + RAL

Total number of subjects, n (%)

400 mg BIDN=50

800 mg BIDN=49

600 mg QDN=51

1200 mg QDN=50

300 mg/100 mg QD N=51

SAEs 4 (8.0%) 4 (8.2%) 3 (5.9%) 2 (4.0%) 5 (9.8%)

Grade 2–4-related AEs 6 (12.0%) 3 (6.1%) 2 (3.9%) 6 (12.0%) 14 (27.5%)

AEs leading to discontinuation 1 (2.0%) 2 (4.1%) 0 1 (2.0%) 2 (3.9%) AE, adverse event; SAE, serious AE; ATV/r, ritonavir-boosted atazanavir; BID, twice daily; QD, once daily; RAL, raltegravir; TDF, tenofovir-disoproxil fumarate.

Grade 1–4 adverse events ■ A summary of Grade 1–4 AEs is shown in Table 4

■ The most commonly reported AE across the BMS-663068 arms was headache (mostly Grade 1),

which occurred in:

— 28/200 (14.0%) of subjects in the BMS-663068 arms versus 5/51 (9.8%) in the ATV/r arm

Table 4. All Grade 1–4 adverse events occuring in ≥10% of subjects

BMS-663068 + TDF + RAL ATV/r + TDF + RAL

Parameter, n (%) 400 mg BIDN=50

800 mg BIDN=49

600 mg QDN=51

1200 mg QDN=50

300 mg/100 mg QD N=51

Total subjects with an event 44 (88.0%) 40 (81.6%) 41 (80.4%) 42 (84.0%) 48 (94.1%)

Infections and infestations 32 (64.0%) 28 (57.1%) 28 (54.9%) 26 (52.0%) 31 (60.8%)

Urinary tract infection 4 (8.0%) 8 (16.3%) 4 (7.8%) 5 (10.0%) 3 (5.9%)

Nasopharyngitis 6 (12.0%) 3 (6.1%) 6 (11.8%) 3 (6.0%) 4 (7.8%)

Bronchitis 4 (8.0%) 1 (2.0%) 4 (7.8%) 5 (10.0%) 1 (2.0%)

Herpes zoster 2 (4.0%) 5 (10.2%) 1 (2.0%) 0 0

Gastrointestinal disorders 16 (32.0%) 16 (32.7%) 15 (29.4%) 20 (40.0%) 19 (37.3%)

Diarrhea 7 (14.0%) 4 (8.2%) 6 (11.8%) 4 (8.0%) 8 (15.7%)

Nausea 3 (6.0%) 3 (6.1%) 3 (5.9%) 5 (10.0%) 6 (11.8%)

Nervous system disorders 16 (32.0%) 9 (18.4%) 11 (21.6%) 11 (22.0%) 13 (25.5%)

Headache 11 (22.0%) 4 (8.2%) 7 (13.7%) 6 (12.0%) 5 (9.8%)

General disorders and administration site conditions

6 (12.0%) 3 (6.1%) 4 (7.8%) 8 (16.0%) 7 (13.7%)

Fatigue 2 (4.0%) 1 (2.0%) 1 (2.0%) 5 (10.0%) 3 (5.9%)

ATV/r, ritonavir-boosted atazanavir; BID, twice daily; QD, once daily; RAL, raltegravir; TDF, tenofovir-disoproxil fumarate.

Serious adverse events

■ SAEs were reported in 13/200 (6.5%) subjects across the BMS-663068 treatment arms and 5/51 (9.8%) in the ATV/r arm (Table 5)

■ Most were secondary infections and none were related to BMS-663068 or ATV/r

■ Through Week 24, no deaths occurred

Table 5. Serious adverse events*

BMS-663068 + TDF + RAL ATV/r + TDF + RAL

Parameter, n (%) 400 mg BIDN=50

800 mg BIDN=49

600 mg QDN=51

1200 mg QDN=50

300 mg/100 mg QD N=51

Total subjects with an event 4 (8.0%) 4 (8.2%) 3 (5.9%) 2 (4.0%) 5 (9.8%)

Infections and infestations 2 (4.0%) 2 (4.1%) 2 (3.9%) 1 (2.0%) 3 (5.9%)

Injury, poisoning and procedural complications 1 (2.0%) 0 1 (2.0%) 1 (2.0%) 0

Musculoskeletal and connective tissue disorders 0 1 (2.0%) 0 1 (2.0%) 0

Gastrointestinal disorders 0 0 0 0 1 (2.0%)

Hepatobiliary disorders 0 0 0 0 1 (2.0%)

Nervous system disorders 0 0 0 0 1 (2.0%)

Pregnancy, puerperium and perinatal conditions 0 1 (2.0%) 0 0 0

Renal and urinary disorders 0 1 (2.0%) 0 0 0

Respiratory, thoracic and mediastinal disorders 1 (2.0%) 0 0 0 0

* A single patient may have had more than one event.ATV/r, ritonavir-boosted atazanavir; BID, twice daily; QD, once daily; RAL, raltegravir; TDF, tenofovir-disoproxil fumarate.

Grade 2–4 related adverse events

■ Across the BMS-663068 arms, 17/200 (8.5%) subjects had Grade 2–4-related AEs; however most were single instances with no relationship to dose (Table 6)

■ In the ATV/r arm, 14/51 (27.5%) subjects had Grade 2–4-related AEs, which were mostly gastrointestinal and hepatobiliary disorders associated with hyperbilirubinemia (Table 6)

Table 6. Select Grade 2–4-related adverse events*

BMS-663068 + TDF + RAL ATV/r + TDF + RAL

Parameter, n (%) 400 mg BIDN=50

800 mg BIDN=49

600 mg QDN=51

1200 mg QDN=50

300 mg/100 mg QD N=51

Total subjects with Grade 2–4-related AEs 6 (12.0%) 3 (6.1%) 2 (3.9%) 6 (12.0%) 14 (27.5%)

Gastrointestinal disorders 0 1 (2.0%) 0 2 (4.0%) 5 (9.8%)

Hepatobiliary disorders 0 0 0 0 7 (13.7%)

Hyperbilirubinemia 0 0 0 0 4 (7.8%)

Jaundice 0 0 0 0 2 (3.9%)

DILI 0 0 0 0 1 (2.0%)

Nervous system disorders 0 1 (2.0%) 0 1 (2.0%) 2 (3.9%)

Headache 0 1 (2.0%) 0 0 2 (3.9%)

Renal and urinary disorders 0 1 (2.0%) 1 (2.0%) 0 0

Hematuria 0 0 1 (2.0%) 0 0

Proteinuria 0 0 1 (2.0%) 0 0

Acute renal failure 0 1 (2.0%)† 0 0 0

Injury and poisoning 1 (2.0%) 0 0 0 0

Overdose 1 (2.0%) 0 0 0 0

Skin and subcutaneous disorders 0 1 (2.0%) 0 0 0

Hyperhidrosis 0 1 (2.0%) 0 0 0* Select events presented. A single patient may have had more than one event. † TDF induced acute renal failure.AE, adverse event; ATV/r, ritonavir-boosted atazanavir; BID, twice daily; DILI, drug-induced liver injury; QD, once daily; RAL, raltegravir; TDF, tenofovir-disoproxil fumarate.

Adverse events leading to discontinuation ■ A summary of AEs leading to discontinuation is shown in Table 7

— No BMS-663068-related SAEs or AEs leading to discontinuation

Table 7. Adverse events leading to discontinuation*

BMS-663068 + TDF + RAL ATV/r + TDF + RAL

Parameter, n (%) 400 mg BIDN=50

800 mg BIDN=49

600 mg QDN=51

1200 mg QDN=50

300 mg/100 mg QD N=51

Total subjects: AE leading to discontinuation 1 (2.0%) 2 (4.1%) 0 1 (2.0%) 2 (3.9%)

Gastrointestinal disorders 0 0 0 0 2 (3.9%)

Abdominal distention 0 0 0 0 1 (2.0%)

Flatulence 0 0 0 0 1 (2.0%)

Nausea 0 0 0 0 1 (2.0%)

Infections 0 1 (2.0%) 0 1 (2.0%) 0

Bone tuberculosis 0 1 (2.0%) 0 0 0

Disseminated tuberculosis 0 0 0 1 (2.0%) 0

Hepatobiliary 0 0 0 0 1 (2.0%)

Jaundice 0 0 0 0 1 (2.0%)

Musculoskeletal 0 0 0 1 (2.0%) 0

Back pain 0 0 0 1 (2.0%) 0

Renal 0 1 (2.0%) 0 0 0

Acute renal failure 0 1 (2.0%) 0 0 0

Vascular 1 (2.0%) 0 0 0 0

Ischemia (likely related to cocaine use) 1 (2.0%) 0 0 0 0

* A single patient may have had more than one event.AE, adverse event; ATV/r, ritonavir-boosted atazanavir; BID, twice daily; QD, once daily; RAL, raltegravir; TDF, tenofovir-disoproxil fumarate.

Grade 3–4 laboratory abnormalities ■ Across the BMS-663068 arms, no noticeable trend for Grade 3–4 lab abnormalities was observed

(Table 8) — Grade 3–4 hematologic changes (neutropenia, 5/196 [2.6%]) were uncommon — Liver chemistry elevations (AST/ALT elevations, 2/196 [1.0%]) were uncommon

■ In the ATV/r arm 25/51 (49.0%) of subjects had elevations in total bilirubin, consistent with the known profile of ATV10

Table 8. Select Grade 3–4 laboratory abnormalities

BMS-663068 + TDF + RAL ATV/r + TDF + RAL

Parameter, n (%) 400 mg BIDN=50

800 mg BIDN=49

600 mg QDN=51

1200 mg QDN=50

300 mg/100 mg QD N=51

HematologyHemoglobin/hematocrit 0 0 0 0 0Platelet 0 0 0 0 0Neutrophils 1 (2.0%) 1 (2.0%) 2 (3.9%) 1 (2.0%) 0

Liver and kidney functionAlkaline phosphatase 0 0 0 1 (2.0%) 0Alanine aminotransferase 0 0 0 2 (4.0%) 1 (2.0%)Aspartate aminotransferase 0 1 (2.0%) 0 1 (2.0%) 0

Bilirubin 0 0 0 0 25 (50.0%)Estimated creatinine clearance 0 0 0 0 0

Other chemistry testingCreatinine kinase 0 1 (2.0%) 1 (2.0%) 1 (2.0%) 0

ATV/r, ritonavir-boosted atazanavir; BID, twice daily; QD, once daily; RAL, raltegravir; TDF, tenofovir-disoproxil fumarate.

Changes from baseline in fasting lipids ■ No clinically significant changes in total cholesterol, low-density lipoprotein and triglycerides from

baseline observed across the BMS-663068 arms (Figure 5) — No dose relationship observed

400 mg BID

800 mg BID

600 mgQD

1200 mg QD

300 mg/100 mg QD

BMS-663068 + TDF + RAL ATV/r + TDF + RAL

-60

-50

-40

-30

-20

-10

0

10

20

Mea

n (S

E) c

hang

e in

fast

ing

lipid

s fr

om b

asel

ine,

mg/

dL Total cholesterolLDLTriglycerides

Figure 5. Mean change in total cholesterol, low-density lipoprotein and triglycerides from baseline through Week 24

ATV/r, ritonavir-boosted atazanavir; BID, twice daily; LDL, low-density lipoprotein; QD, once daily; RAL, raltegravir; SE, standard error; TDF, tenofovir-disoproxil fumarate.

IDWeek 20148–12 October 2014, Philadelphia, PA, USA