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Richard Haubrich, M.D., of UC San Diego AntiViral Research Center, presents "CROI Review: ARV and other Issues of Interest" at AIDS Clinical Rounds
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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
Recommended