CROI 2014: ARV and other issues of interest

Richard Haubrich, MD Professor of Medicine

Division of Infectious Diseases Director, California Collaborative Treatment Group

University of California, San Diego

OUTLINE • Epidemiology

– TDR (CDC and Margott) • ARV treatment naïve studies

– ACTG 5257: three EFV sparing regimens – Neat 001: DRV with NRTI or RAL – DTG 96 weeks – Prelude to long acting therapy: LATTE 1

• ARV complications? – DAD (again), Kaiser to block? – ACTG 5280- save the bones?

• PrEP – long acting 744, proof of concept

Is there a difference in efficacy between ATVr and DRVr

1. Yes 2. No

Are all DHHS guidelines preferred regimens equivalent?

1. Yes 2. No 3. I don’t read the guidelines, so

who cares!

Do you think there is adequate evidence to suggest ABC has increased CV risk (all

other factors equal) 1. Yes 2. No 3. I am agnostic

Calcium and vitamin D can prevent ART related bone loss

1. yes 2. no 3. stop the @$#^! questions and tell me the

answers

TDR EPIDEMIOLOGY

Sensitive Screening Reveals Widespread Underestimation of Transmitted HIV Drug Resistance

• 2009-2011; 895 samples • Allele specific PCR: RT mutations

– M41L, K103N, Y181C, M184V and K65R. • Prevalence

– Bulk: 7.9% – Sensitive: 13.6%

Jonson, et al. 21st CROI. Boston, 2014. Abstract 87.

Demographics

• Age: < 20 5%; 20-40 63%; > 40 32% • Race/ Ethnicity

– Black- 54% – White- 29% – Hispanic- 14%

• Sex- 86% male • Risk: MSM 71%

Jonson, et al. 21st CROI. Boston, 2014. Abstract 87.

Black: 15%, Hispanic 6%. White 16%

TDR: Naïve Gilead Studies (2000-2013) • Retrospective analysis

– 4 studies: prior to treatment • IN (n=1617, 100 from early studies) • PR-RT (n=2531) • Subtype B: 92%

– Enrollment years • 2000 (study 903), 2003 (study 934), 2013 (studies 104 and 111)

• Transmitted resistance trends – INST: 1 T66T/I mixture 2000, 0 in 2003, 1.4% T97A – NNRTI and PI: increased presence – NRTI: stable presence of NRTI

Margot NA, et al. 21st CROI. Boston, 2014. Abstract 578.

Resistance-Associated Mutation

0

1

2

3

4

5

6

7

8

9

10

NNRTI PI INSTI

Patie

nts (

%)

8.7%

2.4%

3.2%

1.0% 1.4%

0% 0.5%

4.2%

1.2%

NRTI

2.9% 2.6%

2000 2003 2013

HPTN 061: “TDR” Black MSMs

• Longitudinal cohort black MSM in 6 US cities – HIV uninfected (n=1167) – HIV infected (n=348)

• Genotyped with resistance results (n=169 with HIV RNA >200 copies/mL)

• ART drug resistance: 28% – In 3 cities, >40% had drug-

resistance HIV – Multiclass resistance: 11% – 23% of newly infected had drug-

resistant Chen I, et al. 21st CROI. Boston, 2014. Abstract 581.

ART Drug Resistance in Black MSM (2009-2011)

0

10

20

30

40

50

60

70

Boston (n=14)

LA (n=41)

Atlanta (n=30)

Patie

nts

(%)

50%

30%

17% 17%

10%

20%

7%

41%

4%

Any resistance Multi-class resistance

50%

8%

20%

SF (n=10)

DC (n=24)

NYC (n=50)

‘some’ on arv based on drug levels

ARV Treatment: Naïve

Efficacy and Tolerability of Atazanavir, Raltegravir, or Darunavir with FTC/TDF: ACTG A5257

Landovitz RJ, Ribaudo HJ, Ofotokun I, Wang H, Baugh BP, Leavitt RY, Rooney JF, Seekins D, Currier JS, and Lennox JL for the A5257 Study Team

Background • DHHS Guidance for initial treatment of HIV-1

infection includes TDF/FTC with EFV, ATV/r, DRV/r, INI’s*

• Globally, EFV most commonly prescribed, following WHO guidelines

• Patients with transmitted drug resistance, psychiatric disorders, and women who are contemplating pregnancy** are not good EFV candidates

• A5257 designed to provide a comprehensive comparison of non-EFV based regimens

*ABC/3TC may be used with DTG; ** If other options are available

ACTG A5257 Study • Open-label, naïve, n=1809

– HIV RNA >1000 – Any CD4 count

• Randomized to TDF/FTC plus: – ATVr (n=605) – RAL bid (n=603) – DRVr QD (n=601)

• Primary endpoints – Time to HIV RNA >1000 at weeks

16-24, or >200 at or after week 24 – Time to discontinuation for toxicity

Landovitz RJ, et al. 21st CROI. Boston, 2014. Abstract 85.

BASELINE Patients (n=1809)

Age (years) 37 Male (%) 76 Race/ethnicity (%) Black Hispanic

42 42

CD4 Median % <200

308 30

HIV RNA Median % >100K % >500K

4.6 30 7

Cumulative Incidence of Virologic Failure

Difference in 96 wk cumulative incidence (97.5% CI)

-20 0 -10 10 20

3.4% (-0.7%, 7.4%)

5.6% (1.3%, 9.9%)

-2.2% (-6.7%, 2.3%)

ATV/r vs RAL

DRV/r vs RAL

ATV/r vs DRV/r

Cumulative Incidence of Tolerability Failure

Difference in 96 wk cumulative incidence (97.5% CI)

-20 0 -10 10 20

13% (9.4%, 16%)

3.6% (1.4%, 5.8%)

9.2% (5.5%, 13%)

ATV/r vs RAL

DRV/r vs RAL

ATV/r vs DRV/r

Favors RAL

Favors DRV/r

Cumulative Incidence of Virologic or Tolerability Failure

Difference in 96 wk cumulative incidence (97.5% CI)

-20 0 -10 10 20

15% (10%, 20%)

7.5% (3.2%, 12%)

7.5% (2.3%, 13%)

ATV/r vs RAL

DRV/r vs RAL

ATV/r vs DRV/r

Favors RAL

Favors RAL

Favors DRV/r

*Consistent results seen with TLOVR at a 200 copies/ml threshold

Tolerability Failure Toxicity Associated Discontinuation of randomized ART *

ATV/r (N=605)

RAL (N=603)

DRV/r (N=601)

Any toxicity discontinuation 95 (16%) 8 (1%) 32 (5%) Gastrointestinal toxicity 25 2 14 Jaundice/Hyperbilirubinemia 47 0 0 Other hepatic toxicity 4 1 5 Skin toxicity 7 2 5 Metabolic toxicity 6 0 2 Renal toxicity (all nephrolithiasis) 4 0 0 Abnormal chem/heme (excl. LFTs) 0 0 2 Other toxicity 2 3 4

*Participants allowed to switch therapy for intolerable toxicity

Proportion VL ≤50 copies/mL ITT, regardless of ART change ITT, off-ART=failure (SNAPSHOT)

96 ATV/r 88% RAL 94%

DRV/r 89%

96 ATV/r 63% RAL 80%

DRV/r 73%

Resistance to Study Agents*

75/94 VF Available

RAL

99/115 VF Available

9 Any Resistance (1.5% of ATV/r)

18 Any Resistance (3% of RAL)

4 Any Resistance (<1% of DRV/r)

ATV/r DRV/r

295 Virologic Failures 1 Baseline Missing 56 VF Failed to Amplify

1809 Participants

65/85 VF Available

*Stanford University Genotypic Resistance Interpretation Algorithm V 6.3.1

Resistance to Study Agents

75/94 VF Available

RAL

99/115 VF Available

9 Any Resistance (1.5% of ATV/r)

18 Any Resistance (3% of RAL)

4 Any Resistance (<1% of DRV/r)

ATV/r DRV/r

295 Virologic Failures 1 Baseline Missing 56 VF Failed to Amplify

1809 Participants

65/85 VF Available

5 isolated M184V 1 integrase mutation

2 T69D/T215A/T 1 K70N + M184V

7 isolated M184V 1 isolated integrase mutation

7 integrase + M184V 3 integrase + M184V + K65R

3 isolated M184V

1 integrase mutation

*Stanford University Genotypic Resistance Interpretation Algorithm V 6.3.1

Additional Clinical Outcomes Mean change in CD4 count from baseline

• CD4 increase at week 96 • ATV/r: 284 • RAL: 288 • DRV/r: 256

• Both PI/r arms had greater increases in

LDL and triglycerides than the RAL-arm (p<0.001)

Conclusions • ATV/r, RAL, and DRV/r were equivalent for virologic efficacy • ATV/r was less well tolerated than DRV/r or RAL

– Largely due to cosmetic hyperbilirubinemia • RAL was superior to both PI/r regimens for combined tolerability and virologic

efficacy – DRV/r was superior to ATV/r

• VF with resistance was rare – More frequently observed with RAL

• Analyses are ongoing to evaluate: – Cardiovascular, metabolic, skeletal, fat, inflammatory biomarkers, behavior,

adherence, and key subgroup differences

either with DRVr QD

NEAT 001/ARNS 143: Raltegravir + Darunavir/r in Treatment-Naïve Patients

Randomization 1:1

TDF + FTC (n=404)

RAL bid (n=401) Phase 3 study (96 weeks)

Treatment-naïve Open-label, non-inferiority HIV RNA >1000 copies/mL

CD4 <500 cells/mm3

No major IAS-USA resistance mutations

No HBV

Primary endpoint: time to virologic or clinical failure (any of the following):

• Viral failure • Death due to any cause. • Any new or recurrent AIDS-defining event. • Any new serious non-AIDS-defining event.

Raffi F, et al. 21st CROI. Boston, 2014. Abstract 84LB

NEAT 001/ARNS 143: Raltegravir + Darunavir/r in Treatment-Naïve Patients

• DRVr + RAL – Non-inferior at week 96 (adjusted

difference 3.7% [-1.1%, 8.6%]; P=0.12)

– Inferior to TDF/ FTC with CD4 <200 cells/mm3

• Similar safety between the 2 arms • Treatment-emergent resistance

with available genotype at failure – RAL: 18% (5/28)

• 4/5 with baseline HIV RNA >500K copies/mL

– FTC/TDF: 0% (0/16)

Raffi F, et al. 21st CROI. Boston, 2014. Abstract 84LB.

Key Week 96 Outcomes RAL

(n=401) TDF/ FTC

(n=404)

Virologic/clinical failure (%) Overall Baseline CD4 <200 Baseline HIV RNA >100K

17 39 36

14 21 27

Secondary HIV RNA <50 (%) CD4 gain Lipid changes (%) Total cholesterol LDL-C HDL-C Triglycerides Change in eGFR (mL/min)

89

267

+0.9 +0.5 +0.2 +0.3 +0.9

93 266

+0.5* +0.4* +0.1* +0.2 -3.8*

Raffi F, et al. 21st CROI. Boston, 2014. Abstract 84LB

Walmsley et al. CROI 2014: 543

DTG vs EFV (Single)- WEEK 96

• Randomized, PC, double blind • Treatment naïve, HLA-B*5701 negative • Randomized to:

– DTG + ABC/3TC – EFV/TDF/FTC

Walmsley et al. CROI 2014: 543

CD4 increase: 325 DTG vs 281, p = 0.004 Viral failure: 6% (25 subjects) in each arm

HIV RNA < 50 (FDA snapshot)

HIV RNA < 50: snapshot by VL subgroup

Walmsley et al. CROI 2014: 543

Treatment related adverse events

Walmsley et al. CROI 2014: 543

• HIV-1 integrase inhibitor, dolutegravir analogue

• Oral drug (t½ = 40 hours) • Long-acting SC or IM injection

(apparent t½ ≈ 40 days) • Good virologic response at 5

and 30 mg/day as oral 10-day monotherapy

GSK1265744 (744)

Margolis et al. CROI 2014; Boston, MA. Abstract 91LB. Spreen et al. HIV Clin Trials. 2013;14:192-203.

LATTE Study: 744 + Rilpivirine as 2-Drug Oral Maintenance Therapy

Margolis D, et al. 21st CROI. Boston, 2014. Abstract 91LB.

Efavirenz + 2 NRTIs*

744 (10, 30, 60 mg) + 2 NRTIs*

Phase 2b study (96 weeks)

Treatment-naïve Open-label

HIV RNA >1000 copies/mL CD4 >200 cells/mm3

Stratified by HIV RNA and NRTI

Week 0 24 48 96 Primary Endpoint

HIV RNA <50 copies/mL (FDA “Snapshot”)

744 (10, 30, 60 mg) + Rilpivirine

Induction (24 weeks)

Maintenance (72 weeks)

Patients in the 744 arm with HIV RNA <50 copies/mL at week 20 were switched to maintenance regimen at week 24.

Baseline: CD4 ~ 400; HIV RNA ~ 4.2

Primary Endpoint Virologic Success: HIV-1 RNA <50 c/mL by FDA Snapshot (ITT-E)

Week

744 overall response W48 82%

EFV response W48 71%

744 overall response W24 87%

EFV response W24 74%

Median (IQR) change from baseline CD4+ cell count (cells/mm3)

Week 48 744 overall +219 (141,343)

EFV +227 (134,369)

Prop

ortio

n, %

24 2 4 8 12 16 40 32 48 36 26 28 BL 0

20

40

60

80

100

744 10 mg (N=60) 744 30 mg (N=60) 744 60 mg (N=61) EFV 600 mg (N=62)

Induction Phase Maintenance Phase

Margolis et al. CROI 2014; Boston, MA. Abstract 91LB.

Secondary Endpoint – Maintenance Population Virologic Success: HIV-1 RNA <50 c/mL by Snapshot (ITT-ME)

24 Week

Prop

ortio

n, %

2 4 8 12 16 40 32 48 36 26 28 BL

*EFV patients with a week 24 visit 0

20

40

60

80

100

744 10 mg (N=52) 744 30 mg (N=53) 744 60 mg (N=55) EFV 600 mg (N=47)

Induction Phase Maintenance Phase

Margolis et al. CROI 2014; Boston, MA. Abstract 91LB.

Treatment Outcomes - Maintenance Population HIV-1 RNA <50 c/mL by Snapshot (ITT-ME)

Outcome at Week 48

744 total

n=160

EFV 600 mg n=47*

Virologic success 149 (93%) 44 (94%)

Virologic failure 9 (6%) 2 (4%)

Data in window not <50 c/mL 7 (4%) 1 (2%)

Discontinued for lack of efficacy 0 1 (2%)

Change in ART 2 (1%) 0

No virologic data at Week 48 2 (1%) 1 (2%)

Discontinued due to AE‡ 2 (1%) 1 (2%) *EFV patients with a W24 visit †Carried forward from Induction Phase ‡Abnormal ECG (10 mg); anxiety (60 mg); colitis (EFV) Margolis et al. CROI 2014; Boston, MA. Abstract 91LB.

LATTE Study – Week 48 Analysis Conclusions

Margolis et al. CROI 2014; Boston, MA. Abstract 91LB.

• Following induction therapy, oral 744+RPV maintained virologic suppression at a rate similar to EFV+NRTIs

• Primary Endpoint: 82% of 744+RPV and 71% of EFV+NRTIs subjects had HIV-1 RNA <50 copies/mL

• Secondary Endpoint (ITT-ME): 93% of 744+RPV and 94% of EFV+NRTIs subjects had HIV-1 RNA <50 copies/mL

• Similar response rate across 744 10mg, 30mg, and 60mg arms • One subject, with persistently low 744 and RPV drug concentrations, developed

treatment emergent INI and NNRTI mutations

• 744+RPV was well tolerated, with few drug related AEs leading to withdrawal

• Long-term data needed, however, these regimen POC results support evaluation of long-acting injectable regimen of 744 LA + TMC278 LA as maintenance therapy

Based on A5257 would you use ATVr:

1. More 2. Less 3. The same 4. I don’t use ATVr

When would you use a two drug regimen (i.e. PIr + INSTI or NNRTI)?

1. Never 2. For maintenance in patients that develop NRTI

toxicity 3. For patients with high CD4 and low HIV RNA

ARV Complications?

D:A:D Study: Update on MI Risk and Abacavir Exposure

• Prospective cohort (2000-2013) – >49,000 HIV-positive patients from 11

cohorts in Europe, Australia, US • Current abacavir use was associated with

a 98% increase in MI rate – No difference between pre- and post-2008 – Results unchanged after stratifying by

Framingham risk group, as well as by other factors (eg, renal function, dyslipidemia, hypertension)

• Current findings argue against channeling bias

Sabin CA, et al. 21st CROI. Boston, 2014. Abstract 747LB.

PY: person-years.

Adjusted Relative MI Rate and Current Abacavir Use

1.98

Reference No Abacavir

5

4

3

2

1

0.7

1.97 1.97

Overall Pre

3/2008 Post

3/2008

No ABC Events/PYs Rate/PYs (95% CI)

600/2,95,642

0.20 (0.19, 0.22)

425/169,417

0.25 (0.23, 0.28)

175/126,225

0.14 (0.12, 0.16)

On ABC Events/PYs Rate/PYs (95% CI)

341/71,917

0.47 (0.42, 0.52)

247/40,833

0.61 (0.53, 0.68)

94/31,084

0.30 (0.24, 0.36)

Kaiser Permanente, Northern California: MI Risk and HIV Infection Status

• Population-based cohort (1996-2011) – Male: 91% – HIV negative (n=257,600)

• MI events: 2483 • Follow-up: 1,506,676 person-years

– HIV positive (n=24,768) • MI events: 320 • Follow-up: 119,587

• Higher risk of MI among HIV-positive adults is no longer observed in more recent years

– Reduced risk likely due to cardiovascular risk reduction, more lipid-friendly ART, and reduced immunodeficiency

Klein DB, et al. 21st CROI. Boston, 2014. Abstract 737.

MI Rate Ratios for HIV-infected vs negative

0 0.5 1.0 1.5 2.0 2.5 3.0 Adjusted Rate Ratio (95% CI)

1996-1999

2000-2003

2004-2007

2008-2009

2010-2011

1.8

1.7

1.3

Reference HIV-

1.3

1.0

ACTG A5280: Impact of High-Dose Vitamin D and Calcium on Bone Loss With ART

• Double-blind, prospective, 48-week trial in treatment-naïve patients initiating efavirenz/ emtricitabine/tenofovir DF

– Vitamin D level <75 to >10 ng/mL • Randomized arms

– Vitamin D3 4000 IU/ calcium 1000 mg – Placebo

• Primary endpoint – Percent change from baseline in total hip BMD at

week 96

Baseline Characteristics

Overton ET, et al. 21st CROI. Boston, 2014. Abstract 133.

Vitamin D Calcium (n=79)

Placebo (n=86)

Age (years) 36 31

Male (%) 91 90

Race/ethnicity (%) White Black Hispanic

35 30 29

38 35 21

BMI (kg/m2) 25.0 24.0

HIV RNA (log10 copies/mL) 4.5 4.5

CD4 (cells/mm3) 339 342

Estimated daily intake Calcium (mg) Vitamin D (IU)

813 120

811 137

ACTG A5280: Impact of High-Dose Vitamin D and Calcium on Bone Loss With ART

• HIV outcomes – HIV RNA <50 copies/mL: 90% – Similar CD4 gains in both arms

• Change in 25(OH) vitamin D3 levels – Vitamin D/calcium arm

• Increased from 26.7 ng/mL at baseline to 55.6 and 56.4 ng/mL at weeks 24 and 48, respectively

– Placebo arm: no change from baseline levels (25.1 ng/mL)

• Vitamin D3 and calcium – Reduced hip and spine BMD loss by 50% with ART – Attenuated bone turnover

• Adverse events – Kidney stone (n=1, placebo) – No hypercalcemia, hypophosphatemia

Overton ET, et al. 21st CROI. Boston, 2014. Abstract 133.

Week 96 Change in BMD

-4

-3

-2

-1

0

1

Lumbar Spine

Total Hip

Wee

k 48

Cha

nge

(%)

-1.4%

-2.9%

-1.4%

-3.2%

Vitamin D and calcium (n=79) Placebo (n=86)

P<0.001 P<0.08

ACTG A5257 Substudy: Impact of Raltegravir- and PI-Based Regimens on BMD

• Open-label, treatment-naïve patients (n=328) – HIV RNA >1000 copies/mL

• Randomized groups – Raltegravir + FTC/TDF (n=106) – Atazanavir/r + FTC/TDF (n=109) – Darunavir/r + FTC/TDF (n=113)

• Week 96 change in BMD – Reduced BMD with all 3 arms – Raltegravir arm had significantly less BMD loss at lumbar

spine and total hip versus PI-based arms (P<0.01) – Less loss in total body BMD

• Raltegravir versus atazanavir/r (P=0.004) • Darunavir/r versus atazanavir/r (P=0.001)

Brown TT, et al. 21st CROI. Boston, 2014. Abstract 779LB.

Week 96 Change in BMD

-5

-4

-3

-2

-1

0

1

Lumbar Spine

Total Body

Total Hip

Wee

k 96

Cha

nge

(%)

-3.6%

-2.9%

-1.6%

-2.4%

-3.4%

-3.9%

-1.8%

-4.0%

-1.7%

Raltegravir (n=106) Atazanavir/r (n=109) Darunavir/r (n=113)

When would you use vitamin D and Ca++?

1. For post menopausal women 2. For all patients on EFV 3. For high-risk patients on EFV 4. After a fracture 5. Never- not enough data

Do you consider ABC-related CV effects in selection of regimens for naïve patients?

1. Never 2. In a patient with moderate CV risk 3. In a patient with high CV risk 4. I don’t use ABC

PrEP

US PrEP Demonstration Project: Implementation of PrEP (2012-2014)

• STD clinics in San Francisco, Miami, Washington, DC (n=831)

– MSM, transgender women (1.4%) – Clinic referrals (63%) – Self-referrals (37%): more likely to be white, higher

education level, higher sexual risk behaviors and risk perception versus clinic referrals

• Offered up to 48 weeks of open-label emtricitabine/tenofovir DF

– Accepted PrEP: 60.4% • 77% had TDF-DP levels consistent with taking >4

doses/week

• PrEP uptake associated with – Self-referral, prior PrEP awareness, higher-risk

sexual behaviors

BLD: below limit of detection.

Cohen SE, et al. 21st CROI. Boston, 2014. Abstract 954.

Tenofovir-DP Levels (Week 4)

0

10

20

30

40

50

60

<250 250-550 >550-950 BLD

Sam

ples

(%)

18%

43%

14%

5% 2%

>950

2%

11%

27%

4% 4%

52%

43% 40%

35%

Miami (n=157) Washington, DC (n=100) San Francisco (n=300)

Doses/Week: <2 <2 2 4 >4

Tenofovir-DP (fmol/punch)*

0%

*femtomole/punch: measure of flux density.

Partners PrEP Study: Low Frequency Resistance Testing Among Seroconverters

• Double-blind, phase 3 study of serodiscordant, heterosexual couples

– PrEP significantly reduced the risk of HIV infection by 67% to 75% (P<0.0001)

– Ultra-deep versus standard sequencing • Detect drug resistance at frequencies >1% versus >20%,

respectively

• Ultra-deep sequencing on samples from 121 seroconverters

• Overall resistance: 7.4% (9/121) – HIV positive at enrollment (n=3) – Acquired HIV after enrollment (n=6)

• TDF (2/38): 1 M184V, 1 K65R/M184V • TDF/FTC (5/25): 4 M184V, 1K65R/K70E

• Detection of PrEP drug in blood plasma was associated with an increased risk of resistance (P=0.0009)

Lehman DA, et al. 21st CROI. Boston, 2014. Abstract 590LB.

0

20

40

60

80

100

Resistance Detected Above Frequencies of 1% in 121 Seroconverters

Sero

conv

erte

rs (%

) Overall

(n=25/38/58)

20%

3.5% 5.3%

Before (n=4/8/6)

After (n=21/30/52)

Found to Be HIV Positive Before or After Study Enrollment

Emtricitabine/tenofovir DF Tenofovir DF Placebo

50%

0%

12.5% 14.3%

3.8% 3.3%

0

20

40

60

80

100

0

20

40

60

80

100

PrEP Proof-of-Concept: Long-Acting Integrase Inhibitor in Nanosuspension for Injection

• Macaque model of SHIV transmission • Study 1 (vaginal transmission)

– Low-dose SHIV (50 TCID50) twice a week – GSK744 LA (50 mg/kg) 3 injections at week 0,

4, 8 – 6 of 6 pigtail macaques (lunar menstrual cycles)

protected against SHIV infection • Study 2 (rectal transmission)

– Weekly SHIV (50 TCID50) until systemic infection detected

– One GSK744 LA (50 mg/kg) injection at week 0 – After 1 to 2 challenges, placebo macaques

became infected – With a single GSK744 injection, infection was

delayed by 5 to 10 challenges with SHIV

Radzlo J, et al. 21st CROI. Boston, 2014. Abstract 40LB. Andrews CD, et al. 21st CROI. Boston, 2014. Abstract 39. Andrews CD, et al. Science. 2014;343:1151-1154.

P=0.0005

Week Av

irem

ic (%

)

GSK744 LA (n=6) Placebo (n=6)

Week 0 2 4 6 8 10 12 14 16 30

Vaginal SHIV Exposure

Avire

mic

(%)

GSK744 LA (n=12) Placebo (n=4)

Rectal SHIV Exposure

0 2 4 6 8 10 12 14 16 18 20 22 24

P<0.0001

Summary of Clinically Relevant Points • TDR still alive and well

– Can find more using sensitive techniques – Little evidence of transmitted INSTI

• ARV for naïve – ATV has more tolerability issues than RAL or DRV

(mostly bilirubin) – RAL best tolerated – DTG with ABC/ 3TC superior to EFV/TDF/FTC (tolerability)

Summary of Clinically Relevant Points

• ARV for naïve – Bone loss can be prevented with Ca and vitamin D – ABC cv risk still controversial

• Long acting ART promising for – Maintenance – PrEP