Key Research From IDSA 2007: The 45th Annual Meeting of the Infectious Diseases Society of America This activity is supported by an educational grant from San Diego, California | October 4-7, 2007 Faculty Eric Daar, M.D.

The Body PRO The Body PRO Covers IDSA 2007 IDSA 2007: Faculty for This Activity Eric Daar, M.D. Dr. Daar is the chief of HIV medicine at Harbor-UCLA Medical Center in Los Angeles, Calif., and a professor of medicine at the University of California-Los Angeles' David Geffen School of Medicine. He has been an active HIV physician and researcher since the 1980s; during the past three decades, he has led dozens of studies on a vast range of HIV-related issues, with a particular focus on coinfections and other health complications associated with HIV and HIV treatment, including hepatitis C, metabolic complications, cardiovascular disease and psychosocial issues such as depression.

The Body PRO The Body PRO Covers IDSA 2007 IDSA 2007: Key Research About This Presentation This presentation was created to accompany The Body PRO's podcast summary of key research presented at IDSA 2007, featuring an interview with Eric Daar, M.D. For more information about this program, please visit us on the Web at: TheBodyPRO.com/IDSA2007 Please feel free to use this slide presentation for personal reference or for your own presentations; however, we ask that you not modify any aspects of the slides contained within this presentation so proper attribution can be retained. If you would like to publish all or part of this presentation, or repost any of these slides online, you must first obtain permission from Body Health Resources Corporation. Our gratitude goes out to all who granted permission for their slides to be adapted for this presentation. Disclaimer Knowledge about HIV changes rapidly. Note the date of this presentation's publication, and before treating patients or employing any therapies described in these materials, verify all information independently. If you are a patient, please consult a doctor or other medical professional before acting on any of the information presented in this presentation.

The Body PRO The Body PRO Covers IDSA 2007 New Antiretroviral Options: Emerging Data From Recently Approved Agents or Agents Available in Expanded Access

The Body PRO The Body PRO Covers IDSA 2007 TITAN: Study Design W. David Hardy et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 TITAN: Virologic Response Through Week 48 (ITT-TLOVR) – All Patients W. David Hardy et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 TITAN: Difference in Virologic Response (VL <50 Copies/mL) at Week 48: Univariate Analysis W. David Hardy et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 TITAN: Baseline Characteristics W. David Hardy et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 TITAN: NRTIs and NNRTIs Used in the Optimized Background Regimen W. David Hardy et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 TITAN: Impact of IAS-USA Primary PI Mutations* at Baseline on VL <50 Copies/mL at Week 48 W. David Hardy et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 TITAN: Difference in Virologic Response (VL <50 Copies/mL, ITT-TLOVR): Multivariate Analyses W. David Hardy et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 Summary of Virologic Responses Without (-) and With (+) Enfuvirtide (ENF) Adapted from Jacob P. Lalezari et al. IDSA 2007; abstract 964.

The Body PRO The Body PRO Covers IDSA 2007 DUET 24-Week Efficacy: Patients With Viral Load <50 Copies/mL at Week 24 (Primary Endpoint; ITT-TLOVR) Charles Hicks et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 DUET 24-Week Efficacy: Mean Viral Load Reduction From Baseline (ITT NC=F) Charles Hicks et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 DUET 24-Week Efficacy: CD4 Cell Count Increase to 50 Cells/mm 3 or Above Charles Hicks et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 DUET 24-Week Efficacy: Response (<50 Copies/mL) According to Number of Active Background Antiretrovirals Charles Hicks et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 DUET 24-Week Efficacy: Response (<50 Copies/mL) According to Baseline Viral Load and CD4 Cell Count Charles Hicks et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 DUET 24-Week Efficacy: Mutations Associated With a Decreased Response to TMC125 Charles Hicks et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 DUET 24-Week Efficacy: Response (<50 Copies/mL) According to Number of TMC125 RAMS Charles Hicks et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 DUET 24-Week Safety: Overview of Adverse Events Parameter, % TMC125 group (n=599) Placebo group (n=604) Any AE (any cause)9293 Grade 3 AE2225 Grade 4 AE79 Serious AE (SAE)1319 Death (any cause)12 Discontinuation due to AE64 Most common AEs (>10% in either group, regardless of severity and causality)* Rash (any type)17 § 9 Diarrhea1520 Nausea1411 Headache912 AEs leading to death were not reported in more than one patient except for pneumonia and sepsis (n=2 each) in the placebo group None of the deaths in the TMC125 group were considered related to TMC125 *excluding injection site reactions; § p= vs placebo; AE = adverse event Richard Haubrich et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 AE regardless of causality, n (%) TMC125 group (n=599) Placebo group (n=604) Any grade 3/4 AE2527 Most common grade 3/4 clinical AEs (>0.5% in pooled TMC125 group)* Rash (any type)1.30 Peripheral neuropathy1.00 Pancreatitis0.70 Pneumocystis jiroveci pneumonia0.7 Renal failure *excluding injection site reactions and grade 3/4 laboratory abnormalities reported as AEs DUET 24-Week Safety: Grade 3 and 4 Adverse Events Richard Haubrich et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 DUET 24-Week Safety: Rash In the TMC125 group: –Early onset: Median 12 days. –Limited duration: Median 11 days. –Low severity: Most mild to moderate; 1.3% grade 3, none grade 4. Mostly maculopapular; no mucosal involvement. –Infrequently led to discontinuation: 2.2% of patients (0% with placebo). Most resolved with continued treatment. Clinical associations with rash –No association with baseline CD4 cell count. –No increased risk with prior NNRTI-related rash. Investigator assessment of cause of rash, % TMC125 group (n=599) Placebo group (n=604)Significance Any cause179.4p<0.001 Possibly related to study medication124.8 Richard Haubrich et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 DUET 24-Week Safety: Psychiatric Disorders Patients experiencing psychiatric-related AEs, % TMC125 group (n=599) Placebo group (n=604) Grade Grade Most common (reported in ≥1.0% of patients in the TMC125 group) Insomnia 67 Depression 35 Anxiety 33 Sleep disorder 11 Similar incidence to placebo: 13% in TMC125 group versus 15% in placebo group (p=0.3). Low severity: mostly grade 1 and 2. Infrequently lead to discontinuation: 1 patient (0.2%) in each group. No increased risk in patients with a history of psychiatric disorders. Abnormal dreams/nightmares in 5 patients (0.8%) in each group and no episodes of hallucinations, suicidal ideation or manic symptoms with TMC125. Richard Haubrich et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 High Density Lipoprotein Low Density Lipoprotein Calculated DUET 24-Week Safety: Lipid Changes Over Time Total Cholesterol/High Density Lipoprotein Triglycerides Change from baseline (mg/dL) Week TMC125 group Placebo group Richard Haubrich et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 DUET 24-Week Safety: Hospitalizations Patients hospitalized at least once by 24 weeks (%) 16% 11% Placebo groupTMC125 group p= Cumulative days hospitalized by 24 weeks Richard Haubrich et al. IDSA 2007; abstract Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 A : Phase 2b Pilot Study Evaluating the Safety of Maraviroc in Patients With Non-R5 HIV-1 J.M. Goodrich et al. IDSA 2007; abstract LB-2. Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 A : Baseline Characteristics J.M. Goodrich et al. IDSA 2007; abstract LB-2. Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 A : Baseline Characteristics – Primary Study Population J.M. Goodrich et al. IDSA 2007; abstract LB-2. Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 A : Percentage of Patients With Undetectable HIV-1 RNA Over 48 Weeks J.M. Goodrich et al. IDSA 2007; abstract LB-2. Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 A : Mean Change From Baseline in CD4+ Count J.M. Goodrich et al. IDSA 2007; abstract LB-2. Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 A : Summary of Week 48 Safety Results J.M. Goodrich et al. IDSA 2007; abstract LB-2. Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 A : Number of Category C Events J.M. Goodrich et al. IDSA 2007; abstract LB-2. Reprinted with permission.

The Body PRO The Body PRO Covers IDSA 2007 Visit The Body PRO for comprehensive coverage of IDSA This presentation was created to accompany The Body PRO's summary of key research presented at IDSA 2007, by Eric Daar, M.D. Learn more at: TheBodyPRO.com/IDSA2007 In addition, be sure to browse through The Body PRO’s extensive coverage of IDSA 2007, which includes: –A full written summary with expert discussion and analyses of key research. –Downloadable MP3s: listen on your computer or download to your MP3 player. –Slides and in-depth data analyses. Visit TheBodyPRO.com/IDSA2007 today for a full listing of our conference materials! IDSA 2007: Key Research