the 6th ias conference on hiv pathogenesis, treatment and prevention rome, italy july 17-20, 2011

The 6th IAS Conference on HIV Pathogenesis,

Treatment and Prevention

Rome, ItalyJuly 17-20, 2011

CME Disclaimer

These slides may not be published, posted online, and/or presented

for Continuing Medical Education credit without written permission from Rush University Medical Center

and Practice Point Communications

Rush University Medical Center is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. Rush University Medical Center designates this enduring material for a maximum of 1 AMA PRA Category 1 Credit™. Physicians should claim only credit commensurate with the extent of their participation in the activity.

The University of Florida College of Pharmacy is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education (UAN #0012-9999-11-097-H02-P). This slide kit is accredited for one hour of continuing education credit. The University of Florida College of Pharmacy will mail Statements of Continuing Education Credit within 30 working days after receiving evidence of successful completion of the course. Successful completion means that you must attend the entire program and complete an evaluation form.

Supported by an independent educational grant from Gilead Sciences Medical Affairs.

Accreditation and Designation

The Association of Nurses in AIDS Care is an approved provider of continuing nursing education by the Virginia Nurses Association Continuing Education Approval Committee, an accredited approver by the American Nurses Credentialing Center’s Commission onAccreditation.

This activity is approved for 1.0 contact hours by the Association of Nurses in AIDS Care.

This program contains 1.0 hour of pharmacology content.

Faculty:CME Course Director

Harold A. Kessler, MDProfessor of Medicine and Immunology/Microbiology

Associate Director, Section of Infectious DiseasesRush University Medical Center

Chicago, Illinois

Faculty:Content Development and Training

Calvin J. Cohen, MD, MScResearch DirectorCRI New England

Harvard Vanguard Medical AssociatesClinical Instructor

Harvard Medical SchoolBoston, Massachusetts

Ian Frank, MDProfessor of Medicine

Director, Anti-Retroviral Clinical Research

University of PennsylvaniaPhiladelphia, Pennsylvania

W. David Hardy, MDDirector, Division of Infectious Diseases

Cedars-Sinai Medical CenterAssociate Professor of Medicine-in Residence

David Geffen School of Medicine at UCLALos Angeles, California

Paul E. Sax, MDClinical Director

Division of Infectious Diseases & HIV ProgramBrigham & Women’s Hospital

Associate Professor of MedicineHarvard Medical SchoolBoston, Massachusetts

Faculty:CME Reviewer

David M. Simon, MD, PhDAssociate Professor

Section of Infectious DiseasesRush University Medical Center

Chicago, Illinois

Disclosure Information

• It is the policy of the Rush University Medical Center Office of Continuing Medical Education to ensure that its CME activities are independent, free of commercial bias and beyond the control of persons or organizations with an economic interest in influencing the content of CME

• Everyone who is in a position to control the content of an educational activity must disclose all relevant financial relationships with any commercial interest (including but not limited to pharmaceutical companies, biomedical device manufacturers, or other corporations whose products or services are related to the subject matter of the presentation topic) within the preceding 12 months

• If there are relationships that create a conflict of interest, these must be resolved by the CME Course Director in consultation with the Office of Continuing Medical Education prior to the participation of the faculty member in the development or presentation of course content

Disclosure Information:CME Course Director

• Harold A. Kessler, MD− Grants/Research Support

− None− Consultant

− None− Speakers’ Bureau

− None− Stock Shareholder

− Abbott Laboratories, GlaxoSmithKline, Merck− Other Financial or Material Support

− None


• Calvin J. Cohen, MD, MSc− Grants/Research Support

− Bristol Myers Squibb, Gilead Sciences, Merck, Tibotec− Consultant

− Bristol Myers Squibb, Gilead Sciences, Merck, Tibotec− Speakers’ Bureau

− Bristol Myers Squibb, Gilead Sciences, Merck, Tibotec− Stock Shareholder

− None− Other Financial or Material Support

− None


• Ian Frank, MD− Grants/Research Support

− GlaxoSmithKline− Consultant

− Gilead Sciences, Tibotec− Speakers’ Bureau



− None


• W. David Hardy, MD− Grants/Research Support

− Bionor, Gilead Sciences, GlaxoSmithKline, Pfizer, ViiV− Consultant

− Bionor, Gilead Sciences, GlaxoSmithKline, Pfizer, ViiV− Speakers’ Bureau


− Merck (< $5,000)− Other Financial or Material Support

− None


• Paul E. Sax, MD− Grants/Research Support

− Gilead Sciences, GlaxoSmithKline, Merck, Tibotec− Consultant

− Abbott, Bristol-Myers Squibb, Gilead Sciences, GlaxoSmithKline, Merck, Tibotec

− Speakers’ Bureau− None

− Stock Shareholder− None

− Other Financial or Material Support− None

Disclosure Information:CME Reviewer

• David M. Simon, MD, PhD− Grants/Research Support

− None− Consultant

− None− Speakers’ Bureau



− None

Opinions and Off-Label Discussions

The opinions or views expressed in this educational program are those of the participants and do not necessarily reflect the opinions

or recommendations of Gilead Sciences Medical Affairs,Rush University Medical Center, Association of Nurses in AIDS Care,

or the University of Florida College of Pharmacy

The faculty may have included discussion on unlabeled usesof a commercial product or an investigational use of a

product not yet approved for this purpose

Please consult the full prescribing information before usingany medication mentioned in this program

Learning Objectives (CME, CE)

• Upon completion of this activity, the participant intends to incorporate the following objectives into their practice of medicine:− Initiate ARV therapy in ARV-naïve patients based upon the most

current clinical data indicating when the potential benefits of ARV therapy outweigh the potential risks.

− Prescribe ARV therapy in ARV-naïve patients based upon the most current clinical data indicating which ARV regimens are superior regarding efficacy and avoidance of toxicity and adverse events.

− Utilize recent study results regarding the medical management of HIV-positive patients in your clinical practice to improve patient care.

− Utilize the data presented regarding viral hepatitis to improve the health care you provide to HIV-positive patients.

Learning Objectives (CPE)

• Upon completion of this activity, the pharmacist should be able to:− Determine when the most current clinical data indicates the

potential benefits of ARV therapy outweigh the potential risks in ARV-naïve patients.

− Recommend the most appropriate ARV therapy for ARV-naïve patients based on efficacy and avoidance of toxicity and adverse events according to the most current clinical data.

− Utilize recent study results regarding the pharmacological management of HIV-positive patients in your clinical practice to improve patient care.

− Utilize the data presented regarding viral hepatitis to improve the health care you provide to HIV-positive patients.

Studies in ARV-Naïve Patients

W. David Hardy, MDDirector, Division of Infectious Diseases

Cedars-Sinai Medical CenterAssociate Professor of Medicine-in-Residence

David Geffen School of Medicine at UCLALos Angeles, CA

HIV-infected Subjects with CD4 350 to 550 Cells/mm3

Serodiscordant Couples

HPTN 052: Study Design

Immediate ART CD4 350-550

Delayed ART CD4 <250

Randomization

886 Index Partners 877 Index Partners

184 Initiated Therapy886 Initiated Therapy

Hessinapour M. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. MOAX0104.

HPTN 052: Baseline Characteristics

ImmediateN=886

DelayedN=877

Female sex 49% 50%

Age 18-25 16% 18%

26-40 63% 62%

>40 21% 19%

Continent Asia 30% 30%

North/South America 16% 16%

Africa 54% 54%

CD4 cell counts (cells/mm3) 442 428

HIV-1 RNA (log10 copies/mL) 4.4 4.4

Prophylactic TMP/SMX use 7% 7%

Prophylactic INH use 4% 4%


HPTN 052: Virologic and Immunologic Response to ART

• Virologic Efficacy:− Immediate arm: 90% (90% non-

Africa; 91% Africa) had viral load <400 cps/mL at 1 year

− Delayed arm: 93% (96% non-Africa; 85% Africa) had viral load <400 cps/mL at 1 year

• Virologic failures: Immediate 5.1% vs. 2.7% Delayed

• 67% began a second regimen (Immediate) vs. 60% (Deferred)

Delayed

Immediate

Immunologic Response

Subjects Contributing Data

39033

57755

78596

842149

880183


HPTN 052: Clinical Endpoints

• 105 individuals had a primary clinical endpoint: Immediate 40 vs. 65 delayed [HR=0.6 (0.4,0.9), P=0.01]

• Development of extrapulmonary TB was the main difference between the two groups (P<0.002)

• Increased mortality with delayed treatment, but not significant [HR=0.77, (0.34,1.76), P>0.5]

• Adverse events: immediate 24% vs. 5% delayed

Immediate Delayed

Total (N=129) 53 76

Tuberculosis 17 33

Severe bacterial infection

16 11

Death 10 13

Chronic herpes simplex

3 7

Bacterial pneumonia (recurrent)

2 2

Esophageal candidiasis

2 2

Grinstein B, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. MOAX0105.

SENSE: Trial Design

• Double-blinded, active controlled to Week 48• Inclusion: Treatment naïve, HIV RNA >5,000 copies/mL• No genotypic mutations to NRTIs, NNRTIs or PIs• Predicted Phenotypic sensitivity to NNRTIs and selected NRTIs

157 subjects

ETR 400 mg OD+ 2 NRTIs (n=79)

EFV 600 mg OD+ 2 NRTIs (n=78)

Two investigator-selected NRTIs (AZT+3TC; ABC+3TC; TDF+FTC)Primary endpoint: Neuropsychiatric adverse events up to Week 12

Follow-up

Follow-up

Unblinding

Unblinding

6 weeks 48 weeks 2-8 weeks 4 weeks

Rockstroh J, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TULBPE025.

SENSE: Baseline Characteristics (ITT)

ETR arm

(n=79)

EFV arm

(n=78)

Age, mean (years)

Male

Caucasian

Weight (mean)

CDC C

38

85%

92%

72 kg

3%

38

77%

85%

75 kg

1%

CD4 count, cells/uL, mean (range)

Mean baseline HIV RNA (log10 copies/mL)

Screening HIV RNA >100,000

Duration of HIV infection (years, mean)

IAS-USA NNRTI mutations*

IAS-USA NRTI mutations*

331 (74-638)

4.9

32%

2.5

13 (16%)

5 (6%)

302 (91-722)

4.9

33%

2.9

4 (5%)

0 (0%)

* Significant difference in baseline NRTI/NNRTI resistance between arms, but most patients had single mutations and were still NRTI/NNRTI sensitive (5 were protocol violators)


SENSE: Grade 1 - 4 Drug-related Neuropsychiatric Adverse Event Prevalence

through 48 Weeks (ITT)

P<0.001P<0.001 P=0.001P=0.001 P=0.013P=0.013 P=0.014P=0.014 P=0.111P=0.111 P=0.011P=0.011


SENSE: Summary Efficacy at Week 48 (ITT TLOVR) – by Type of Response (%)

Mean change in CD4 cell count from BL at week 48 (observed data): EFV 236 cells/mm3 vs. ETR 232 cells/mm3


SPRING-1: Dolutegravir (DTG, S/GSK1349572) in ART-naïve Adults

• Phase IIb dose-ranging, partially-blinded, N ~200 ART-naïve patients

• All arms include 2 NRTI backbone given once daily • Primary endpoint: % <50 c/mL at 16 weeks (TLOVR)

van Lunzen J, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TUAB0102.

HIV-1 RNA >1,000 c/mL

CD4 ≥200 cells/mm3

1:1:1:1 Randomization

EFV 600 mg

DTG 50 mg

DTG 25 mg

DTG 10 mg

50 mg DTGSelected Dose

EFV 600 mg

Wk 48 Interim Analysis

Stratified by• HIV RNA >100,000 or ≤ 100,000• ABC/3TC and TDF/FTC

Wk 96

SPRING-1: Baseline Characteristics

DTG10 mg(N=53)

DTG25 mg(N=51)

DTG50 mg(N=51)

EFV600 mg(N=50)

Age (Median and Range in Years) 32 (21 – 61) 38 (20-64) 37 (22 – 55) 40 (20 – 79)

Male 42 (79%) 46 (90%) 45 (88%) 44 (88%)

Race

African American/African 7 (13%) 6 (12%) 8 (16%) 4 (8%)

White 41 (77%) 42 (82%) 38 (75%) 43 (86%)

Baseline HIV-1 RNA

Mean (log10 c/mL) 4.42 4.38 4.58 4.46

>100,000 c/mL 11 (21%) 10 (20%) 12 (24%) 11 (22%)

Baseline CD4 (mean, cells/mm3) 309.4 333.8 327.2 327.5

Investigator-selected NRTIs

TDF/FTC 36 (68%) 34 (67%) 34 (67%) 34 (68%)

ABC/3TC 17 (32%) 17 (33%) 17 (33%) 16 (32%)


SPRING-1: Antiviral Activity through Week 48

• Mean CD4 cell changes from BL: EFV: +180 cells vs. DTG: +200-240 cells (P=0.076)• Resistance: 3/150 (2%) DTG VFs (>400 c/mL); none in 50 mg arm 1 - M184V; No integrase mutations


DTG10 mg(N=53)

DTG25 mg(N=51)

DTG50 mg(N=51)

DTGSubtotal(N=155)

EFV600 mg(N=50)

Grade 2-4 Drug Related (All) 5 (9%) 4 (8%) 4 (8%) 13 (8%) 10 (20%)

Gastrointestinal 1 (2%) 1 (2%) 1 (2%) 3 (2%) 2 (4%)

Psychiatric disorders 0 0 0 0 3 (6%)

Metabolic disorders 0 3 (6%) 1 (2%) 4 (3%) 0

Skin disorders 0 0 0 0 2 (4%)

Infections 2 (4%) 0 0 2 (1%) 0

General disorders 1 (2%) 0 1 (2%) 2 (1%) 1 (2%)

Serious Adverse Events (All) 3 (6%) 1 (2%) 4 (8%) 8 (5%) 4 (8%)

AEs Leading to WD/IP Discontinuation 0 1 (2%) 1 (2%) 2(1%) 4 (8%)

SPRING-1: Adverse Events

• Events leading to withdrawal:− DTG (n=2): dyspepsia and Burkitt’s lymphoma− EFV (n=4): abnormal dreams, suicide attempt, drug intolerance, drug hypersensitivity

• Small changes in serum creatinine (0.1 – 0.15 mg/dL) observed consistent with inhibition of the renal transporter responsible for tubular secretion of creatinine


Study A4001078: MVC + ATV/r vs. FTC/TDF + ATV/r in Treatment-naïve Patients

Patient Eligibility Criteria •R5 HIV at screening•≥16 years of age•HIV-1 RNA ≥1,000 copies/mL•CD4 ≥100 cells/mm3

•No evidence of resistance to ATV/r, TDF, or FTC

Portsmouth S, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TUAB0103.

Randomization 1:1

N=121 MVC (150 mg QD) + ATV/r (300/100 mg QD)

FTC/TDF + ATV/r (300/100 mg QD)

0 24 wk 48 wkScreening(6 weeks) 16 wk

Week 2First 15 US patients

Serial PK of MVC

Interim analyses Primary analysis

Study A4001078: Baseline Characteristics

MVC + ATV/r n=60

FTC/TDF + ATV/r n=61

Mean age, years (range) 38.3 (21–61) 35.3 (18–68)

Male, n (%) 56 (93.3) 52 (85.2)

Race, n (%)

White

Black

Asian

Other

45 (75.0)

13 (21.7)

0

2 (3.3)

46 (75.4)

11 (18.0)

3 (4.9)

1 (1.6)

Median CD4 count, cells/mm3 (range) 344 (160–744) 358 (110–902)

Mean HIV-1 RNA, log10 copies/mL (range) 4.6 (3.4–5.9) 4.7 (3.3–5.9)

HIV-1 RNA ≥100,000 copies/mL, n (%) 16 (27) 22 (36)


Study A4001078: HIV-1 RNA <50 copies/mL at Week 48

• Change in median CD4+ cell count over 48 weeks (LOCF): MVC+ATV/r 173 vs. TDF/FTC + ATV/r 187 cells/mm3

• VF and Resistance: 7/9 MVC and 3/3 TDF/FTC subjects >50 cps/mL at 48 weeks resuppressed post 48 wks

• No genotypic or phenotypic resistance observed


Study A4001078: Safety

MVC + ATV/r n=60

FTC/TDF + ATV/r n=61

Any AE, n (%) 58 (96.7) 60 (98.7)

Serious AE, n (%) 10 (16.7) 12 (19.7)

Grade 3 or 4 AE, n (%) 29 (48.3) 18 (29.5)

Discontinued due to AE, n (%) 2 (3.3) 0

Hyperbilirubinemia, n (%)

AE related

Grade 3 or 4 AE related

Grade 3 or 4 laboratory*

27 (45.0)

22 (36.7)

39 (65.0)

21 (34.4)

12 (19.7)

32 (52.5)

7 patients in the MVC + ATV/r group and 3 patients in the FTC/TDF group switched their ATV/r to DRV/r or LPV/r per protocol due to intolerability or hyperbilirubinemia7 patients in the MVC + ATV/r group and 3 patients in the FTC/TDF group switched

their ATV/r to DRV/r or LPV/r per protocol due to intolerability or hyperbilirubinemia


ECHO and THRIVE: 96 Week Follow-Up

*Investigator’s choice: TDF/FTC; AZT/3TC; ABC/3TC

48 Weeks Primary Analysis

96 Weeks Final Analysis

N=690 Patients

RPV 25 mg qd + TDF/FTC + EFV placebo qd (N=346)

EFV 600 mg qd + TDF/FTC + RPV placebo qd (N=344)

ECHO (TMC278-C209)

1:1

N=678 Patients

RPV 25 mg qd + 2 N(t)RTIs* + EFV placebo qd (N=340)

EFV 600 mg qd + 2 N(t)RTIs* + RPV placebo qd (N=338)

THRIVE (TMC278-C215)

1:1

Cohen C, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TULBPE032.

Pooled ECHO and THRIVE: VL <50 copies/mL Over 96 Weeks

(ITT-TLOVR)

Mean change in CD4 cell count from baseline at Week 48 (NC=F): RPV +228 vs. EFV +219 cells/mm3

Mean change in CD4 cell count from baseline at Week 48 (NC=F): RPV +228 vs. EFV +219 cells/mm3

RPV 25 mg qd (N=686)

EFV 600 mg qd (N=682)

78%78%

Time (weeks)

Res

po

nd

ers

(%,

95%

CI)

Per protocol responses: RPV: 79% EFV: 78%

Snapshot responses:RPV: 76% EFV: 77%

Per protocol responses: RPV: 79% EFV: 78%

Snapshot responses:RPV: 76% EFV: 77%

00 22 44 88 1212 1616 2424 3232 4040 4848 6060 7272 8484 969600

2020

4040

6060

8080

100100


Pooled ECHO and THRIVE: Virologic Outcomes and Resistance

After 96 Weeks

• Similar rates of VF in both groups after 48 wks

• Emergence of mutations after 48 wks was similar in both groups RPV 7 (39%) vs. EFV 6 (43%)

• Pooled Grade 2-4 adverse events from wk 48-96: RPV 14 (2%) vs. EFV 26 (4%) (P<0.001)

VFres, n (%) RPVN=686

EFVN=682

VFres (All) 96 (14.0)

52 (7.6)

Rebounder 52 (8) 34 (5)

Never suppressed 44 (6) 18 (3)

VFres (up to week 48) 73 (11) 36 (5)

Rebounder 29 (4) 18 (3)

Never suppressed 44 (6) 18 (3)

VFres (after Week 48 and up to Week 96)

22 (3) 16 (2)

Rebounder 21 (3) 15 (2)

Never suppressed 1 (0.1) 1 (0.1)


Treatment Experienced Patients and New AntiviralsCalvin J. Cohen, MD, MSc

Research Director, CRI New EnglandHarvard Vanguard Medical Associates

Clinical InstructorHarvard Medical School

Boston, MA

FTC/TDF + PI/rn=155

3TC/ABC + PI/rn=156

48 weeks

• N=311

• On ABC/3TC + any PI/r for ≥3 mo

• HIV RNA <200 c/mL ≥3 mo

• Any CD4 count

• No hx of resistance to study drugs

• N=311

• On ABC/3TC + any PI/r for ≥3 mo

• HIV RNA <200 c/mL ≥3 mo

• Any CD4 count

• No hx of resistance to study drugs

SWIFT: ABC/3TC to TDF/FTC Switch Trial

• Primary Endpoint was the percentage who had a viral load <200 c/mL through 48 weeks• Used TLOVR definition of failure: virologic failure, premature discontinuations, ARV

changes• -12% margin for definition of Non-inferiority

LPV/r ATV+RTV

FTC/TDF 31% 40%

3TC/ABC 34% 38%

Most Frequent PI used• >10% use in both arms

Campo R, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. WELBB03.

SWIFT: Primary Endpoint

Virologic Failure (>200 c/mL): •3 TDF/FTC, 11 ABC/3TC•No resistance detected in the subset of virologic failures that qualified for genotyping

%

TL

OV

R R

esp

on

der

s H

IV-1

RN

A <

200

c/m

L

TLOVR Response RateDifference: 3% (-5%, +11%)


SWIFT: Changes in Fasting Lipids at Week 48

Lipid Fraction TDF/FTC ABC/3TC P value

Total Cholesterol

-21 mg/dL -3 mg/dL <0.001

LDL Cholesterol -7 mg/dL +2 mg/dL 0.007

HDL Cholesterol -1 mg/dL 0 NS

Triglycerides -18 mg/dL -9 mg/dL 0.07

40

All Changes in mg/dL


SWIFT: Estimated GFR Outcomes Through 48 Weeks

41

155 153 147 144 139 137156 153 150 146 142 139

FTC/TDF3TC/ABC

MDRD Results: ABC/3TC -4.2 vs. TDF/FTC -9.2 (P=0.008)

Est

imat

ed G

FR

by

IBW

CG

(m

L/m

in)

P=0.012

-4.5- 8.3

Week

Cockcroft-Gault

FTC/TDF3TC/ABC

0 4 12 24 36 480

20

40

60

80

100

120


Subanalysis of MOTIVATE 1 and 2: Maraviroc QD or BID Plus boosted-PI in Treatment-

Experienced Patients

• MOTIVATE 1 and 2: Maraviroc vs. placebo in treatment experienced patients

• Comparison of MVC 150 mg QD, MVC 150 mg BID and placebo in pts also taking a boosted PI− PK exposures to MVC 150 mg QD in presence of most ritonavir boosted

PIs similar to currently approved dose in treatment-naïve patients− Analysis restricted to those confirmed R5 by ESTA test

Difference and 97.5% CI: MVC QD vs. PBO: 28% (16-39) MVC BID vs. PBO: 31% (18-43)

Difference and 97.5% CI: MVC QD vs. PBO: 28% (16-39) MVC BID vs. PBO: 31% (18-43)

85/187 84/176 14/85

Hardy D, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TUAB0106.

Elvitegravir vs. Raltegravir:Study Design

N = 702

1:1 randomization

N = 702

1:1 randomization RAL 400 mg BID

Protease Inhibitor/r

3rd ARV

EVG Placebo QD

Molina JM, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. WELBB05.

• Choice of fully active PI and 3rd agent were based on resistance testing

• If M184V or M184I, optional to also add FTC or 3TC

• Primary Endpoint: HIV-1 RNA <50 c/mL through 48 weeks (FDA TLOVR)• Non-inferiority Study

− Lower limit of the 95% Conf Interval: -10%

Elvitegravir (EVG) QD

Protease Inhibitor/r

3rd ARV

RAL Placebo BID

EVG vs. RAL: Baseline Characteristics and Background Regimens

44

CharacteristicEVG

(n = 351)RAL

(n = 351)

HIV RNA (log10 copies mL), Median 4.35 4.42

CD4 count (cells/mm3), Mean 259 264

Baseline Resistance Mutations

NRTI 69% 68%

NNRTI 63% 60%

Primary PI 31% 34%

Two or more classes 64% 60%

PIs Used

Darunavir 58%

Lopinavir 19%

Third Agent

NRTIs only 80%

- TDF 59%

- TDF/FTC 27%


EVG vs. RAL: Week 48 Results

Outcomes, %EVG

(n=351)

RAL

(n=351)

Responder1 (Per Protocol Analysis)* 59 58

Virologic Failure 20 22

Rebound 11 16

Never suppressed 8 5

Switched background regimen 1 1

Deaths <1 2

Drug discontinuation due to AE 2 3

Drug discontinuation due to Other2 19 15

45

*1. Responder: achieved and maintained confirmed HIV-1 RNA <50 copies/mL through Week 482. Drug DC due to Other: Lack of Efficacy, Lost to Follow-up, Non-compliance, Investigator Discretion, Pregnancy, Protocol Violation, Withdrew Consent

CD4 Change:RAL: +147/mm3

EVG: +138/mm3

Integrase Resistance:RAL: 21%EVG: 27%


95%CI: -6% to 8.2%, p=0.001 for noninferiority

EVG vs. RAL: Select Adverse Events and Labs

46

Grade 3-4 Labs, n (%)EVG

(n=354)

RAL

(n=358)

Cholesterol 12 (4%) 13 (4%)

Triglycerides 11 (4%) 11 (4%)

ALT 6 (2%)** 18 (5%)

AST 5 (1%)*** 18 (5%)

Adverse Event (Treatment Emergent) EVG

(n=354)RAL

(n=358)

Diarrhea 12%* 7%

Nausea 4% 2%

*Diarrhea nearly all grade 2 (P-value=0.023)**P-value=0.020***P-value=0.009


Lersivirine in ARV-Naïve Patients: Phase 2b Trial Design

• Planned interim analysis at week 24• Primary endpoint at week 48: HIV RNA <50 c/mL• Pts followed to week 96• Eligibility criteria

− HIV-1 RNA ≥1,000 c/mL− CD4 >200/mm3

− Absence of any RT mutations (using standard genotyping)• Randomization stratified by:

− Viral load (< or ≥100,000 c/mL)− Geographic region

47

Double Blind StudyRandomized 1:1:1

TDF/FTC plus EFV 600 mg QD

TDF/FTC plus LRV 750 mg QD

TDF/FTC plus LRV 500 mg QD

Vernazza P, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TUAB0101.

Lersivirine: Week 48 Virologic Outcomes

Treatment<50 c/mL

(ITT, NC=F)Difference from EFV

SE Diff (80% CI)

LRV 500 mg QD 79% -9%7%

(18.1,0.8)

LRV 750 mg QD 79% -8%7%

(-17,1.2)

EFV 600 mg QD 86%

48


Lersivirine: Reported Adverse Events

Number with Adverse Event (All Grades) n (%)

LRV 500 mgN = 65

LRV 750 mg N = 65

EFV 600 mg N = 63

Nausea 15 (23) 27 (42) 8 (13)

Headache 15 (23) 11 (17) 9 (14)

Abnormal dreams 5 (8) 5 (8) 12 (19)

Dizziness 5 (8) 4 (6) 13 (21)

Rash 3 (5) 1 (2) 7 (11)

Abdominal pain 2 (3) 6 (9) 7 (11)

Vomiting 2 (3) 10 (15) 9 (14)

Diarrhea 10 (15) 10 (15) 10 (16)

Insomnia 5 (8) 9 (14) 5 (8)

49


Metabolic and Other Adverse Events

Paul E. Sax, MDClinical Director,

Division of Infectious Diseases and HIV ProgramBrigham and Women's Hospital

Associate Professor of Medicine, Harvard Medical School

Boston, MA

Aging of HIV Population: San Francisco

• Population-based HIV registry from 2006-2010• Registry increased from 9,001 to 9,673 mostly due to decline in

deaths• Those older than 50 now 53% of population, up from 41% in 2006 --

fastest growing subset of patients

Scheer S, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TUPE131.

Age Trends of Persons Living with HIV/AIDS in San Francisco

ECHO/THRIVE: Change in Lipids through 96 Weeks


p<0.0001*

p<0.0001*

p<0.0001*

p<0.0001*

Efavirenz Rilpivirine

RADAR: Fasting Lipids and Renal Function

Serum creatinine increased 0.06 mg/dL in both groups.

Bedimo R, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. MOPE214.

TC LDL HDL TG

SENSE: Lipid Abnormalities at 48 Weeks


0

Grade 3/4 Lipid Abnormalities at 48 Weeks

Prevalence of Lipodystrophy in Current ART Era

• Cross-sectional study of HIV patients at Australian clinic, comparing 1998 to 2010− Definition of lipodystrophy (LD) from original case definition

• Results:− Participants older, healthier from HIV and CV risk factor perspective− Prevalence of study-defined LD has declined from 69 to 58%− In multivariate analysis, use of tenofovir or abacavir associated with significantly lower risk

• Conclusion: Although prevalence of LD has declined, it remains relatively common – especially in long-term survivors

Price J, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. MOPE264.

Characteristic 1998 (n=144)* 2010 (n=100)* p-value

Age (years) 42.1 ± 0.74 51.8 ± 0.87 <0.0001

Smoking: n (%) 73 (51) 36 (36) <0.0001

HIV Duration (mos.) 86.2 ± 4.6 165.0 ± 10.4 <0.0001

ART Duration (mos.) 36 (21-72) 129 (51-169) <0.0001

CD4 Count (cells/mm3) 320 (178-560) 585 (403-754) <0.0001

HIV VL (copies/mL) 250 (250-9800) 250 (250-250) <0.0001

Undetectable VL: n (%) 78 (57) 90 (90) <0.0001

Raltegravir Substitution for Lipohypertrophy

• Prospective study of women (n=37) with VL <50 on 2NRTIs + PI or NNRTI and lipohypertrophy – randomized to continue current ART or switch PI to RAL

• Results at 24 weeks:− No statistically significant changes

in adipose tissue, anthropometrics, or glucose metabolism

− Improvement in lipids observed in those switching from PI

Lake J, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. MOPE263.

Immediate Delayed

-40.0

-30.0

-20.0

-10.0

0.0

10.0

20.0

30.0

40.0

TotalCholesterol

LDL HDL Triglycerides

mg

/dl

P=0.04P=0.04 P=0.22 P=0.26

VAT Change SAT Change

% C

han

ge

0.43 P=0.932

-25

-20

-15

-10

-5

10

15

2025

0

5

Pooled ECHO and THRIVE: DEXA Substudies

Tebas P, et al. 13th ADRC; Rome, Italy; July 14-16, 2011. Abst. O23.

• Within group changes at Weeks 48 and 96 from baseline, P<0.0001

• Differences between treatment groups not statistically significant at any timepoint

+734 g

+704 g

Time (Weeks)

N=209 196 173

N=204 183 180

Parameter Week RPV EFV

Limb fat↓ from baseline 48 N=196 N=183

≥10% 12.8% 14.8%

≥20% 3.6% 5.5%

96 N=173 N=180

≥10% 15.6% 17.2%

≥20% 6.9% 10.0%

Aquitaine Cohort: Risks for Chronic Kidney Disease

• Aquitaine cohort, 2004-2008 − Eligible: Baseline creatinine

clearance >60 mL/min/1.73m2 by MDRD

− CKD definition 2 consecutive measurements <60

• Incidence: 10.1 cases per 1,000 person-years

• Risks by MV analysis: preexisting mild renal dysfunction, female, older age, DM, HTN, lower CD4, TDF exposure – risk increased if also given with PI/r

Variables

Women 75.7%

Intravenous Transmission of HIV 17.7%

Current Injection Drug Users 3.9%

ART-naïve Patients 21.2%

Age (years)

<45 65.1%

45-60 29.1%

>60 5.1%

Creatinine Clearance (mL/min/1.73m2)

60-70 9.9%

70-80 18.5%

80-90 22.6%

>90 49.0%

Morlat P, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. WEPDB0104.

Patient’s Characteristics at BaselineAquitaine Cohort 2004-2008, N=2693

Risk of Chronic Kidney Disease: Role of PI/r

• CANOC cohort, 2000-2010 (n=965)1

− Eligible: ARV Tx naïve, starting TDF (682) or ABC (283) based ART; normal renal function

• After controlling for known causes of renal impairment:− LPV/r and ATV/r associated with increased risk of CKD− No association with TDF use (vs. ABC)

• Chelsea-Westminster Cohort: Among 2,115 patients (86% also on TDF), exposure to ATV/r and LPV/r (but not DRV/r) associated with increased risk of CKD2

1. Hosein SR, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TUPE254; 2. Rockwood N, et al. ibid. Abst. TUPE250.

Total Duration of Follow-up (Patient Years) Hazard Ratio (95% CI) P Value

LPV/r 267 1.69 (1.1 to 2.6) 0.017

ATZ/r 562 1.52 (1.14-2.03) 0.004

DRV/r 451 1.31 (0.94-1.81) 0.108

EFV 1,400 1

Bone Turnover Markers in SMART

• SMART study: Bone density decreased more in virologic suppression (VS) than drug conservation (DC) group

• Markers of bone formation and resorption both higher in VS group

Bone Formation Markers

P <0.001 <0.001 <0.00 <0.001 0.007 0.01 0.01 0.01 <0.001 <0.001

Bone Resorption Markers

DC GroupVS Group

Hoy J, et al. 13th ADRC; Rome, Italy; July 14-16, 2011. Abst. O05.

Risk of Osteoporotic Fractures

• Data Source: Veterans Affairs’ Clinical Case Registry

• Predictors: − Antiretroviral exposure: PY of exposure to NRTIs

(TDF, ABC, AZT or D4T), NNRTI, boosted PI.− Age, race, smoking, BMI, type 2 diabetes, HCV co-

infection, chronic kidney disease• Outcome: Incident osteoporotic fracture defined

as any vertebral, hip, or wrist fracture by ICD-9 codes

Bedimo R, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. MOAB0101.

VA: Antiretroviral Exposure and Risk of Osteoporotic Fractures

*MV Model 1: Controlling for CKD, age, race, tobacco use, diabetes and BMI; **MV Model 2: Controlling for Model 1 variables + concomitant exposure to other ARVs.

Univariate

MV Model 1*

MV Model 2**

Bedimo R, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. MOAB0101.

STEAL: Changes in BMD by Switch to TDF/FTC or ABC/3TC

P=0.006P<0.001 P=0.017

ABC-3TC N=153 151 147 N=153 151 147

TDF-FTC N=160 154 154 N=160 155 155

Despite differences in BMD, no significant difference in fracture rate

Carr A, et al. 13th ADRC; Rome, Italy; July 14-16, 2011. Abst. O06.

Progress: BMD Changes by LPV/r + RAL or TDF/FTC

Qaqish R, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TULBPE021.

CASTLE:Changes in Bone Density

• Randomized comparison of ATV/r and LPV/r, both with TDF/FTC

• DEXA performed at baseline and weeks 48, 96; paired results available on 176 study subjects to assess bone mineral density (BMD)

• Results:− Both study arms experienced decline in BMD− ATV/r was associated with smaller declines in BMD

compared to LPV/r, with differences of 0.8%, 0.8%, and 1.1% for arms, legs, and total body, respectively (P=NS)

Moyle G, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TUPE244.

Management

Ian Frank, MDProfessor of Medicine

Director, Anti-Retroviral Clinical ResearchUniversity of Pennsylvania

Philadelphia, PA

The Rome Statement for an HIV Cure

Major HIV/AIDS Stakeholders Call for HIV Cure Research to be Accelerated

The year 2011 marks 30 years since the first AIDS cases…development of efficient antiretroviral drugs and their expanding availability have ensured that millions of people living with HIV live a healthy life…

Nevertheless…This life-long requirement is both an individual and public health burden…Investments to develop new therapeutic strategies that will ultimately allow HIV infected patients to discontinue their treatment are of the utmost urgency.

A functional HIV cure can only be achieved through an increased and concerted international effort engaging not only the scientific community but also stakeholders involved in the HIV/AIDS response and global health.Now, more than ever, it is time to seriously start looking for an HIV cure.

http://www.iasociety.org/Default.aspx?pageId=583

Early or Late Initiation of ARVs to Prevent Transmission: HPTN 052

• Design: Early vs. delayed ART (start when CD4 count <250 cells/mm3) to infected partner in discordant couple with CD4+ count of 350-550 cells/mm3 at enrollment

• Population – 1,763 couples− 98% heterosexual

• DSMB stopped trial April 28, 2011• Number of transmissions

− Total - 39− 4 early therapy (0.3/100 py)− 35 delayed therapy (2.2/100 py)

− Linked - 28− Transmissions linked by pol

sequences− 23/28 linked transmissions in

African sites• Conclusion: Treatment is

prevention

Cohen M, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. MOAX0102; Cohen MS, et al. N Engl J Med. July 18, 2011.

Delayed

Early

1/1,585 p/yr

27/1,557 p/yr

High Drug Concentrations and Low Amounts of Virus in Cervicovaginal

Fluid of Women on ART• Goal: Evaluate the level of HIV

RNA and drug concentrations in blood and CVF in women on TDF/FTC + ATV/r

• Design: 20 women had samples collected at 6 time points during menstrual cycle (absence of menses)

• HIV RNA >50 c/mL detected in blood in 13/119 (11%) of evaluations and in CVF in 0/119 (0%)

• HIV DNA detected in 100% of blood specimens and 36% of CVF specimens

• Conclusions: Low levels of HIV and high levels of drug in female genital secretions

Sheth A, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. MOAC0204.

*FGT: Plasma C24h Geometric Mean Ratio, 95%CI

Mea

n lo

g10

Co

nce

ntr

atio

n

(ng

/mL

), 9

5% C

I

1,428 ng/mL (1035-1970)

560 ng/mL

(433-724) 236

ng/mL (157-354)

67 ng/mL (53-85)

909 ng/mL

(644-1283)

75 ng/mL (58-96)

12.2

(8.71–17.0)

3.42 (2.17–

5.39)

2.49 (1.80–

3.44)

Antiretroviral Drug C24h (N=119)

FGT*Plasma

Benefit of PrEP in Heterosexual Men and Women in Botswana: TDF2 Study

• Design: Placebo-controlled, trial of daily TDF/FTC

• Population− 1,200 followed for seroconversion− 33% did not complete study− 45% women− 94% married

• Results− 33 seroconverters

− 21 women (7 on TDF/FTC and 14 PLC)

− 12 men (2 on TDF/FTC and 10 PLC)

• Conclusions− PrEP beneficial in this population− Protection in women in contrast

with results of FEM-PrEP trial • 9 HIV-infected in TDF-FTC group and 24 HIV-infected in placebo group

• Overall protective efficacy 62.6% (95% CI 21.5 to 83.4, P=0.0133)

Thigpen MC, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. WELBC01.

Time to Event Analysis of Seroconverter DataAnalysis using all 33 Seroconverters

Years

Per

cen

t S

ero

conv

ers

ions

PrEP among Heterosexual Africans: The Partners PrEP study

• Phase III, placebo-controlled comparison of oral TDF, TDF/FTC and placebo to prevent HIV transmission in heterosexual discordant couples

• 4,758 couples enrolled; HIV neg partner - 38% women, 62% men

• Safety: no difference in renal function; more diarrhea with active agents

TDF FTC/TDF Placebo

Number of HIV infections 18 13 47

HIV incidence, per 100 p/yr 0.74 0.53 1.92

HIV protection efficacy 62% 73%

95% CI (34-78%) (49-85%)

P-value 0.0003 <0.0001

Baeten J, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. MOAX0106.

Primary Results (mITT)

Risk Compensation among MSM Following iPrEx

• Internet surveys of MSM in San Francisco1 and Boston2 asking about knowledge and attitudes of PrEP

SF – 1155 responders• Heard of PrEP: 70.0%

post-iPrEx• Would use PrEP: 69%

somewhat to extremely likely to use

• Similar findings among 4,325 responders Boston− 0.8% have used PrEP− 78.4% would use PrEP− Men would obtain PrEP from PCP (40.9%) Internet (28.3%)

or other provider (22.7%)

1. Irvin R, et al. 6th IAS; Rome Italy; July 17-20, 2011. Abst. TUAC0104. 2. Mayer K, et al. 6th IAS; Rome Italy; July 17-20, 2011. Abst TUPE360.

Given that the daily pill is 44% effective in preventing HIV, how would this affect your use of condoms if you

were taking the pill?

7%

75%

8% 10%

Change in Frequency of Condom Use if Using PrEP

Pe

rce

nt

Higher Clearance Rate Than Expected of HCV in MSM

• Prospective survey of acute HCV in MACS cohort (n = 6,972 MSM)• 103 seroconverters: 83% HIV+, 16% with IVDU history

• Conclusion: HCV clearance rate considerably higher than previously reported

Cle

aran

ce P

rob

abili

ty

Months following HCV incidence

1.0

0.8

0.6

0.4

0.2

0.0

0 3 6 9 12# at risk:

ABC

161465

81052

8848

7844

6643

C. HIV+/RNA ˃400 (32%)

B. HIV+/RNA ≤400 (50%)

A. HIV- (63%)

P=0.02

Time to HCV Clearance – By HIV/RNA

Cle

aran

ce P

rob

abili

ty

Months following HCV incidence

1.0

0.8

0.6

0.4

0.2

0.0

0 3 6 9 12# at risk:

AB

8914

6313

5513

4913

4413

B. IDU (7%)

A. Non-IDU (49%)

P=0.01

Time to HCV Clearance – By IDU history

Seaberg EC, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TUPE182.

Factors Associated with SVR on Boceprevir Therapy in HCV

Monoinfected Patients

SPRINT-2•IFN naïve•BOC vs. Placebo + IFN + RBV x 24 (RGT) or 44 week

RESPOND-2•Previous IFN failure•BOC vs. Placebo + IFN + RBV x 32 (RGT) or 44 week•IL28B CC genotype and >1 log decline in HCV RNA at week 4 predictive in both studies

RGT = response guided therapyOnly covariates remaining significant at α=0.05 after adjustment for the other variables were retained in the model as shown in the table

Tondolo F, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TULBPE020.

SPRINT-2:Effect

Odds Ratio(95% CI) p-value

BOC/PR48 vs. PR48 7.0 (4.1, 12.0) ˂0.0001

BOC/RGT vs. PR48 6.0 (3.5, 10.2) ˂0.0001

Baseline HCV-RNA: ≤400,000 vs. ˃400,000 IU/mL 5.8 ( 1.9, 17.5) 0.002

Log decline in HCV-RNA at TW 4(continuous variable) 2.6 (2.1, 3.00 ˂0.0001

Genotype: 1b/others vs. 1a 2.3 (1.5, 3.6) ˂0.001

BMI: 25-30 kgm2 vs. ˃30 kg/m2 2.3 (1.4, 3.9) 0.002

BMI: ≤25-30 kgm2 vs. ˃30 kg/m2 1.9 (1.1, 3.3) 0.02

RESPOND-2:Effect

Odds Ratio(95% CI) p-value

BOC/PR48 vs. PR48 11.4 (4.6–28.0) ˂0.0001

BOC/RGT vs. PR48 7.9 (3.3–18.9) ˂0.0001

Previous Response: Relapser vs. Nonresponder 2.2 (1.2–4.3) 0.01

Log decline in HCV-RNA at TW 4(continuous variable) 1.8 (1.3–2.4) ˂0.0001

BMI: ≤25-30 kgm2 vs. ˃30 kg/m2 3.4 (1.4–8.2) 0.01

A5269: Nitazoxanide Increases Rate of Early Virologic Response When Added to Peg-IFN + RBV

for HCV Genotype 1 Infection:

• Single-arm, open-label study with historical comparison• Nitazoxanide 500 mg BID x 4 wks, then add Peg-IFNa-2a + RBV

1,000 – 1,200 mg QD• 68 subjects enrolled

− 78% men, 48% AA− 91% on ART− 73% HIV RNA <detectable

• Response rates− RVR – 10.4%− cEVR – 38.8%− EVR – 65.7%

• GI toxicity – diarrhea, nausea, vomiting most common

• Conclusion: Nitazoxanide can potentiate the effects of IFN+RBV compared to historical populations

cEVR and EVR: Comparison with prior study – A5178 at week 12

Amorosa V, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TUPE176.

Pe

rce

nt

Maraviroc to Prevent HCV-Related Liver Fibrosis in HIV Coinfection

• Proof of concept, open-label trial of maraviroc to prevent acceleration of liver fibrosis

• HIV/HCV coinfection with undetectable VL on TDF/FTC + ATV/r

• Addition of maraviroc 150 mg BID vs. maintenance therapy x 96 wk

• Liver stiffness measured by elastography

• Results of safety on first 60 patients prior to continued enrollment

• Possible delay in fibrosis as evidenced by shift towards Stage I and II fibrosis after 24 weeks of therapy

60

50

40

30

20

10

0

Control n=21 Maraviroc n =23Stage I II III IV I II III IV

12(57,1%)

10(47,6%)

4(19%)

6(28,6%)

2(9,5%)

3(14,3%)

5(23,8%)

8(34,8%)

10(43,5%)

6(26,7%)

7(30,4%)

5(24,7%)

2((8,7%)

4(17,4%)

Baseline

Week 24

Nasta P, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. WEAB0105.

Grade of Liver Stiffness from Baseline to Week 24

Tryptophan Catabolism Correlates with CD4+ T Cell Recovery and Survival

• Background: Tryptophan depletion can diminish T cell proliferation

• Goal: Evaluate the relationship between tryptophan catabolism and CD4 count increases after ART initiation and survival

• Design: Measurement of kynurenine:tryptophan (K/T) ratio in 500 Ugandans starting ARVs

• Results: Higher K/T ratio associated with higher baseline VL and lower CD4 count

• Conclusion: Tryptophan catabolism may be cause, or just another marker, of immune activation

Hunt P, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. MOAA0105.

Tryptophan Catabolism Predicts Mortality during Suppressive ART

(VL <400 at Month 6 of ART)

Tertile of Month 6K/T Ratio

1 (˂0.06)2 (0.06-0.08)3 (˃0.08)

P for Trend =.012

Per

cen

t M

ort

alit

y

Month After ART Initiation

10

8

6

4

2

0

0 12 24 36 48

Hydroxychloroquine (HCQ) to Treat Immune Activation – No Benefit in ARV

Naïve Patients

• HCQ is a candidate drug to decrease immune activation• HCQ 400 mg vs. placebo in ARV naïve patients x 48 weeks• Activation markers, CD4 counts and HIV RNA levels tracked

logrank P=0.030

.00

0.2

50

.50

0.7

51

.00

Pro

po

rtio

n E

ven

t F

ree

42 30 23 20 15HCQ41 34 32 27 15Placebo

Number at risk

0 12 24 36 48Weeks from Randomization

PlaceboHCQ

Time to CD4 below 350 mm3 or ART initiation

Change at Week 48

Marker (Mean)

HCQ Placebo p-value

CD8CD38DR+ % -4.22 -3.59 0.08

CD4CD38DR+ % 0.90 0.04 0.3

log10 IL-6 0.01 -0.05 0.6

log10 D-dimer -0.02 0.03 0.4

Log10 HIV RNA 0.28 0.14 0.1

Paton N, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. MOPE269.

Acyclovir Delays CD4 Decline in HIV/HSV2 Co-Infection

• Objective: Compare effect of acyclovir 400 mg BID vs. placebo on progression to CD4+ count <250 cells/mm3 or WHO Stage IV endpoints

• 440 HIV/HSV2 coinfected participants with CD4 counts 300 – 400 cells/mm3

• Benefits only seen for those with BL VL >50,000 c/mL

• Change in VL over time− Placebo +0.402 log− ACV -0.061 log− Difference -0.46 log (P=0.001)

• Conclusion: Use of acyclovir can slow progression of HIV

0.0

00

.15

0.3

00

.45

0.6

00

.75

0 90 180 270 360 450 540 630 720

Placebo

Treatment

Pro

bab

ilit

y o

f A

RT

Eli

gib

ilit

y

Total Follow-up Time (days)

Enrolment viral load 50,000+ copies/mL

Cumulative probability of ART Eligibility

AHR 0.62 (95% CI 0.43-0.96, P=0.03)

Reynolds S, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TUAB0104.

Therapeutic Vaccines – May Be Possible

• Vacc-4x is peptide vaccine with highly conserved and immunogenic p24 domains

• Design: Vacc-4x or placebo (2:1) at weeks 1, 2, 3, 4, 16, 18 with analytical STI at week 28 for up to 24 weeks− Treatment resumed for fall in

CD4+ count to <350 cells/mm3

• Results− 135 enrolled (92 Vacc-4x, 43

PLC)− Vacc-4x safe and well tolerated

• Conclusion: More effective control of HIV following vaccination

Difference in viral load at week 52:

•44 Vacc-4x and 18 PLC off ART

•HIV RNA 0.55 log10 c/mL lower in Vacc-4x recipients (P=0.0003)

Rockstroh JK, et al. 6th IAS; Rome, Italy; July 17-20, 2011. Abst. TULBPE028.

Trend in Viral Load Set Point Following Treatment Interruption

0.5

0.0

1.0

1.5

2.0

28 5236 44

WeekGroup Placebo Vacc-4x

32 40 48

HIV

-RN

A r

elat

ive

to p

re-A

RT

Outcomes Measurement Reminder

• CME providers are required to assess “changes in learners competence, performance or patient outcomes achieved as a result of their participation in a CME sponsored educational activity”

• As a result of this requirement you will receive via e-mail a short 1-page survey 2 to 3 months after completing this course− We consider the survey to be an additional component of your overall

participation in this educational activity and would urge you to reflect on what you learned in the activity and then complete this survey

• Please be certain that you have correctly written your e-mail address on the CME evaluation form that you complete at the end of today’s activity

The 6th IAS Conference on HIV Pathogenesis,

Treatment and Prevention

Rome, ItalyJuly 17-20, 2011

the 6th ias conference on hiv pathogenesis, treatment and prevention rome, italy july 17-20, 2011

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