Report from the 21st International AIDS Conference – 2016 Durban, RSA Charles Hicks, M.D. September 2, 2016 UCSD HIV & Global Health Rounds

2. Report from the 21st International AIDS
Conference – 2016
Durban, RSA
Charles Hicks, M.D.
Professor of Clinical Medicine
September 2, 2016

3. Speaker Disclosures – September 2016
Charles Hicks, MD
• Royalties: UpToDate, Inc.
• Consulting Fees: BMS, Gilead, ViiV, Merck, Janssen Virology
• IDMC: Medimmune (D5170C00002 Study)
• Other: Massachusetts Medical Society/NEJM: Associate
Editor and Contributor for Journal Watch-ID

6. Time for “Sundowners”….

7. Another happy customer

8. UNAIDS Report 2016: Number of People Living with
HIV on Antiretroviral Therapy, Global 2010-2015
• 36.7 million people living with HIV infection
• 46% of people living with HIV infection are on ARVs
UNAIDS Report, 2016. unaids.org
PeopleonAntiretroviralTherapy
0
2
4
6
8
10
12
14
16
18
2010 2011 2012 2013 2014 2015
7.5
Million
9.1
Million
10.9
Million
15.0
Million
17.0
Million
12.9
Million
2015 target within the 2011
United Nations Political
Declaration on HIV and AIDS

9. UNAIDS Report 2016: ARV Coverage and AIDS
Related Deaths, Global 2000-2015
UNAIDS Report, 2016. unaids.org
0
1
2
3
0
10
20
30
40
50
60
2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
NumberofAIDS-relateddeaths(Millions)
AntiretroviralTherapyCoverage(%)
HIV treatment coverage (all ages) AIDS-related deaths (all ages)

10. UNAIDS Report 2016:
From Durban to Durban and Beyond
People Living with HIV on Antiretroviral Therapy, Global (Millions)
<1 17 30
New HIV Infections (Millions)
3.2 2.1 <0.5
New HIV infections Among Children (Thousands)
490 150 <50
AIDS Related Deaths (Millions)
1.5 1.1 <0.5
Investments for the HIV Response ($ Billion)
5 19 26
Countries that Criminalize Same Sex Relationships
92 74 0
2000 2015 2020 Target
UNAIDS Report, 2016. unaids.org

11. Goal:
73%
0%
10%
20%
30%
40%
50%
60%
70%
80%
ProportionofpeoplelivingwithHIV
withviralsuppression
www.HIV90-90-90watch.org
Towards 90-90-90: Countries Reporting More Than
50% of People Living with HIV with Viral Suppression
Granich R, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. WEAE0201.
70% 68%70%
67% 64%
62%63%
59% 58%
54%
53% 52% 52% 50%
36%

13. 0
2000
4000
6000
8000
10000
12000
14000
16000
Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4 Q1 Q2 Q3 Q4
*
Unique Individuals Starting FTC/TDF for PrEP in US
2012 2013 2014 2015
79,684 unique individuals started FTC/TDF for PrEP:
1,671 in Q4 2012 → 14,000 in Q4 2015
18,812 women, 60,872 men
738% increase
Cities with ≥500 individuals on PrEP: New York, San Francisco, Chicago,
Washington DC, Los Angeles, Seattle, Boston, Atlanta, Philadelphia
McCallister S, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. TUAX0105LB.
* CDC Guidelines for PrEP issued

14. Open Label Extension IPERGAY Trial:
On-Demand PrEP with TDF/FTC
• 86% rate of protection in blinded phase
• 362 (368 eligible) enrolled in open extension, 299 (83%) completed
• HIV incidence: 1 infection in 515 pt-yrs of follow-up
• 0.19 (0.01-1.08)
Proportion Pts with Condomless Sex for Last Receptive Anal Intercourse
Blinded
Molina JM, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. WEAC0102.
0
10
20
30
40
50
60
70
80
90
100
J0
(208)
M2
(163)
M4
(149)
M6
(134)
M8
(106)
M10
(83)
M12
(67)
M14
(65)
M16
(56)
M18
(47)
M20
(50)
M22
(35)
M24
(38)
J0O
(203)
M2O
(190)
M4O
(190)
M6O
(158)
M8O
(154)
M10O
(137)
M12O
(144)
M14O
(140)
M16O
(136)
M18O
(72)
Time (n Participants)
Open-Label
86%
77%
D0

15. Risk for Drug Resistance with PrEP in Oral
TDF/FTC Trials
Infected at Entry Incident Infection
Study Drug Placebo Study Drug Placebo
Study Resist/Tot Resist/Tot Resist/Tot Resist/Tot
iPrEx 2/2 1/8 0/48 0/83
Partners PrEP 1/3 0/6 0/13 0/52
TDF2 1/1 0/2 0/9 0/24
FEM-PrEP 0/1 0/1 4/33 1/35
VOICE 2/9 0/1 1/61 0/60
Total %
(95% CI)
6/16
37.5%
(18 to 61%)
1/18
5%
(1 to 26%)
5/164
3%
(1 to 7%)
1/254
0.3%
(.06 to 2%)
• 9 excess DR infections: 11 active, 2 placebo
• 92 infections averted by TDF/FTC PrEP = (254+18)-(164+16)
• 8 (92/9) infections averted per DR infection overall
• Overall risk of resistance 5/9222 (0.05%) participants
• # Needed to Harm = 1844; # needed to prevent HIV: 13 - 60
Grant R, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. TUAC0104.

16. • Ages 15-17; born male
• MSM At high risk of HIV
• Tests HIV antibody negative
at time of screening
• Daily TDF/FTC
ATN 113 Study: PrEP Demonstration Project for
Adolescent MSM Ages 15-17 in the US
Approached for Pre-screening
(N = 2,864)
Pre-screened eligible
(n=260)
In-person Screening Visit
(n=108)
79 Enrolled
• 32 Prematurely Discontinued
• LTFU (19)
• W/D consent (3)
• Moved (3)
• Failed to complete Wk 0 (5)
• Mother’s request (1)
• Inadvertent enrollment (1)
Refused study participation: 152
Hosek S, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. TUAX0104LB.

17. WK 4 WK 8 WK 12 WK 24 WK 36 WK 48
ATN 113 Study: Adherence
0%
10%
20%
30%
40%
50%
60%
70%
80%
90%
100%
3 incident HIV infections: 6.41 per 100 person-years (95% CI: 4.9-25.8)
60
52.4 55
31.5 22.7
28.2
>700 (4 or more days)
<350-699 (2-3 days)
<350 (<2 days)
BLQ
Hosek S, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. TUAX0104LB.
TFV-DP (fmol/punch) via Dried Blood Spots with Dosing Estimates

18. ATN 113: Adherence
 Drop off in TFV-DP levels between Wk 12 and Wk 24 corresponded to reduced
frequency of scheduled study visits (from every 4 wks to every 12 wks)
Slide credit: clinicaloptions.com
Hosek S, et al. AIDS 2016. Abstract TUAX0104LB.
Reproduced with permission.
1200
1000
800
600
400
200
0
TFV-DP(fmol/punch)
viaDriedBloodSpot
0 12 24 36 48
Overall
White
Latino
Mixed
Black
Wk
4 8

20. • For couples initiating ART at
enrollment, PrEP was offered
through 6 months, then stopped:
• For couples in which the infected
partner delayed or declined ART,
PrEP was continued until 6
months after ART initiation:
Combining ART and PrEP for HIV Discordant
Couples in Africa
Protection through sustained
ART use 
PrEP prior to viral
suppression in HIV+
partner
ART
PrEP
HIV+
partner
HIV-
partner
0
1
2
3
4
5
6
N=83 infections
incidence = 4.9
(95% CI 3.9-6.0)
N=4 infections
incidence = 0.2
(95% CI 0.1-0.6)
95% reduction
(95% CI 87-98%)
P<0.0001
Expected Observed
Baeten J, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. WEAC0105.
Protection through
sustained ART use 
PrEP prior to ART initiation
and then prior to viral
suppression in HIV+ partner
PrEP
HIV+
partner
HIV-
partner
ART
delayed ART

22. Slide credit: clinicaloptions.com
MTN-020/ASPIRE: Dapivirine Vaginal Ring
for HIV Prevention in Women
 Multicenter, double-blind, placebo-controlled, randomized phase III
trial in Malawi, South Africa, Uganda, and Zimbabwe
 Silicone elastomer vaginal matrix ring containing NNRTI dapivirine
25 mg; ring replaced every 4 wks
 Primary endpoints: efficacy and safety
 HIV protection efficacy: 27% reduced incidence of HIV infection with
dapivirine ring vs placebo (P = .046)
Brown E, et al. AIDS 2016. Abstract TUAC0105LB.
Baeten JM, et al. N Engl J Med. 2016;[Epub ahead of print].
Dapivirine 25 mg Vaginal Ring Q4W
+ HIV Prevention Service Package
(n = 1313)
Placebo Vaginal Ring Q4W
+ HIV Prevention Service Package
(n = 1316)
Sexually active HIV-
uninfected adult
women
(N = 2629)
≥ 1 yr; endpoint-
driven duration

23. Slide credit: clinicaloptions.com
MTN-020/ASPIRE Subcohort: Adherence
by Residual Dapivirine in Vaginal Ring
Brown E, et al. AIDS 2016. Abstract TUAC0105LB. Reproduced with permission.
Outcome Placebo Nonadherent
(≥ 23.5 mg*)
Low-High Adherence
(< 23.5 mg*)
Med-High Adherence
(< 22 mg*)
HIV infections, n 50 13 14 7
HIV incidence/100 PY 4.6 3.6 1.9 1.5
Risk reduction vs PBO,
% (95% CI; P value)
--
31
(-28 to 63; .24)
56
(20 to 76; .007)
65
(22 to 84; .01)
*Residual levels of dapivirine remaining in returned rings.
 A lower level of
residual dapivirine in
the returned ring is
indicative of higher
adherence
16 18 20 22 24 26 28
Dapivirine Remaining (mg)
Expected level of ring
used for 28 days: 20-21 mg
Expected level of
unused ring: 24-25 mg

24. MTN020 – ASPIRE: Adherence to Dapivirine Vaginal
Ring and Rate of HIV Protection
Proportion of f/u 20% 27% 27% 27%
Placebo
100%
Incidence /100 p-y
(# infections)
4.9 (10) 3.1 (8) 1.9 (5) 0.4 (1) 4.7 (47)
Ring Data Three Months Prior to Detection
Brown E, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. TUAC0105LB.
Risk reduction
11%
(95% CI -78-55)
No Use
Poor
Risk reduction
29%
(95% CI -52-66)
Bottom Third
T1
Risk reduction
58%
(95% CI -7-83)
Middle Third
T2
Risk reduction
92%
(95% CI 38-99)
Top Third
T3
RiskReduction
Adherence
100
50
-50
0

25. Lactobacillus Dominant non- Lactobacillus dominant
Tenofovir Placebo Tenofovir Placebo
# HIV-1 infections 9 22 14 17
HIV-1 incidence
per 100 person-years
2.7 6.9 6.4 7.8
HIV-1 protection effectiveness
95% CI, P-value
61%
(11, 84), p=0.013
18%
(-77, 63), p=0.644
Tenofovir Vaginal Gel Less Protective in Absence
of Lactobacillus Dominance in Vaginal Microbiome
Burgener A, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. TUSS0605.
P=0.013
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
ProbabilityofHIVinfection
Years in Study
B. Non-Lactobacillus dominant
Tenofovir Placebo
P=0.644
Efficacy, 18%
95% CI, -77 to 63%
HR=0.82 (95% CI: 0.40; 1.65)
0 0.5 1 1.5 2 2.50 0.5 1 1.5 2 2.5
Efficacy, 61%
95% CI, 11 to 84%
HR=0.39 (95% CI: 0.20; 0.83)
0.00
0.05
0.10
0.15
0.20
0.25
0.30
0.35
0.40
ProbabilityofHIVinfection
Years in Study
A. Lactobacillus dominant
Tenofovir Placebo

26. Mechanisms for Alteration of Risk for HIV Infection
by Vaginal Microbiome
Association Between HIV Acquisition in Women with Prevotella bivia2
• Analysis of vaginal microbiome in women in CAPRISA trial
• 19.2 – fold increase risk of vaginal mucosa inflammation with P bivia
• 12.7 – fold increase risk of HIV infection
1. Burgener A, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. TUSS0605.
2. Passmore JA, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. TUSS0604.
0.00
0.50
1.00
1.50
Tenofovirfold-change
Tenofovir (Supernatant)
Time (hours)
0 10 20 30
Abiotic L. iners
0.00
0.01
0.02
0.03
Tenofovir(mg/mL)
Tenofovir (Cell)
0 10 20 30
Time (hours)
G. vaginalis
Intravaginal Tenofovir is rapidly depleted by Gardnerella Vaginalis1

27. Key Points
• The proportion of HIV infected individuals continues to grow
and is now galvanized by the UNAIDS 90:90:90 treatment
paradigm
• The uptake of PrEP is increasing in the US (and
internationally)
• Efforts to develop alternatives to a daily ARV combination for
PrEP continue and include long-acting agents and
microbicides
• Adherence to all prevention strategies remain a big challenge
• The failure of vaginal microbicides may be due, in part, to
biological factors (it may not always be poor adherence)

29. Studies in Treatment-naïve Patients

30. Guidelines for Treatment-Naive Patients
Regimen DHHS[1] IAS-USA[2] BHIVA[3] EACS[4] GeSIDA[5]
DTG/3TC/ABC*
DTG + TDF/FTC
DTG + FTC/TAF
EVG/COBI/TDF/FTC
EVG/COBI/FTC/TAF
RAL + FTC/TAF
RAL + TDF/FTC
ATV/r + TDF/FTC
DRV/r + TDF/FTC
DRV/r + FTC/TAF
RPV/TDF/FTC
Recommended Alternative Not included1. DHHS Guidelines. July 2016.
2. Günthard H, et al. JAMA. 2016;316(2):191-210.
3. BHIVA Guidelines. 2015.
4. EACS HIV Guidelines. V 8.0. October 2015.
5. GeSIDA. Enferm Infecc Microbiol Clin 2016. doi:10.1016/j.eimc.2016.02.028

31.  Initial ART with RAL 800 mg QD (two 400-mg tablets) inferior to RAL
400 mg BID, each with FTC/TDF, in previous QDMRK trial[1]
 ONCEMRK: Multinational, randomized, double-blind phase III study of
QD RAL 1200 mg using reformulated RAL 600 mg tablets[2]
– Primary endpoint: Wk 48 HIV-1 RNA < 40 copies/mL
Slide credit: clinicaloptions.com
ONCEMRK: RAL 1200 mg QD vs
400 mg BID + TDF/FTC in ART-Naive Pts
1. Eron JJ Jr, et al. Lancet Infect Dis. 2011;11:907-915. 2. Cahn P, et al.
AIDS 2016. Abstract FRAB0103LB.
RAL 1200 mg* QD +
TDF/FTC
(n = 533)
RAL 400 mg BID +
TDF/FTC
(n = 269)
ART-naive adults
with HIV-1 RNA
≥ 1000 copies/mL
(N = 802)
96 wks
Randomized 2:1
48 wks – primary endpoint
 Baseline HIV-1 RNA > 100,000 copies/mL: 28.1% to 28.6%
*Two 600-mg tablets.

32. Slide credit: clinicaloptions.com
ONCEMRK: RAL 1200 mg QD Noninferior
to RAL 400 mg BID at Wk 48
Cahn P, et al. AIDS 2016. Abstract FRAB0103LB.
Reproduced with permission.
 Wk 48 HIV-1 RNA < 40 copies/mL in pts with BL HIV-1 RNA > 100,000 copies/mL:
RAL QD, 86.7%; RAL BID, 83.8% (∆ 2.9; 95% CI: -6.5-14.1)
 RAL QD associated with overall safety profile similar to RAL BID
100
80
60
40
20
0
PtsWithHIV-1RNA
<40copies/mL(%)
0 4 8 12 16 20 24 28 32 36 40 44 48
Treatment Wk
RAL 1200 mg QD + TDF/FTC
RAL 400 mg BID + TDF/FTC
88.388.786.583.5
78.2
51.9
53.5
76.3
82.1 87.4 87.2 88.9

33. ONCEMRK Study: Resistance
• 6.8% of subjects in each treatment group had PDVF
• RAL QD group: 14 subjects tested, 9 had no resistance or failed testing
• 5 (0.9%) had documented resistance (including RAL resistance in 4)
• RAL BID group: 3 subjects tested – 2 had no resistance; 1 failed all testing
Failure Type/
Time
RAL FTC TDF Comments
1 NR / wk 24 V151l, N155H M184V -
2 NR / wk 24 N155H M184M/I/V -
BL RNA >106, CD4 <20
Resistance test wk 48
3 NR / wk 24 L74M, E92Q M184V - BL RNA >106, CD4 <20
4 NR / wk 16 N155H, I203M M184V - Resistance test wk 36
5 NR / wk 24 - V118I - Resuppressed
Cahn P, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. FARB0103LB.
NR= non-response, RB=rebound
Resistance rates in other large RAL BID studies (STARTMRK, ACTG 5257):
2-3% for any resistance and 1.4-1.8% for Integrase resistance

35. Viral load was measured at baseline, days 2, 4, 7, 10,
and weeks 2, 3, 4, 6, 8, 12, 24, 36 and 48
Second cohort enrolled after confirming
success of first cohort at week 8
PADDLE Study: DTG + 3TC in Naïve Patients
Study Design
DTG 50 mg QD
3TC 300 mg QD
DTG 50 mg QD
3TC 300 mg QD
Phase IV, pilot, open-label, single arm exploratory trial
1st cohort
(n=10)
2nd cohort
(n=10)
Cahn P, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. FARB0104LB.
ARV- naïve patients,
≥18 years
HIV-1 RNA
>5,000 copies/mL and
≤100,000 copies/mL
CD4 count ≥200
cells/mL
HB(s)Ag negative
(n=20)
DTG 50 mg QD
3TC 300 mg QD

36. PADDLE Study: Efficacy
# SCR BSL DAY 4 DAY 7 W.2 W.3 W.4 W.6 W.8 W.12 W.24 W.36 W.48
1 5.584 10.909 383 101 <50 <50 <50 <50 <50 <50 <50 <50 <50
2 8.887 10.233 318 <50 <50 <50 <50 <50 <50 <50 <50 <50 <50
3 67.335 151.569 1.565 1.178 97 53 <50 <50 <50 <50 <50 <50 <50
4 99.291 148.370 3.303 432 178 55 <50 <50 <50 <50 <50 <50 <50
5 34.362 20.544 1.292 570 107 <50 <50 <50 <50 <50 <50 <50 <50
6 16.024 14.499 1.634 162 <50 <50 <50 <50 <50 <50 <50 <50 <50
7 37.604 18.597 819 61 <50 <50 <50 <50 <50 <50 <50 <50 <50
8 25.071 24.368 1.377 Not done 105 <50 <50 <50 <50 <50 <50 <50 <50
9 14.707 10.832 516 202 <50 <50 <50 <50 <50 <50 <50 SAE
10 10.679 7.987 318 <50 <50 <50 <50 <50 <50 <50 <50 <50 <50
11 50.089 273.676 68.129 3.880 784 290 288 147 <50 <50 <50 <50 <50
12 13.508 64.103 3.296 135 351 84 67 <50 <50 <50 <50 <50 <50
13 28.093 33.829 26.343 539 61 <50 <50 <50 <50 <50 <50 <50 <50
14 15.348 15.151 791 198 <50 61 64 <50 <50 <50 <50 <50 <50
15 23.185 23.500 4.217 192 <50 <50 <50 Not done <50 <50 <50 <50 <50
16 11.377 3.910 97 143 <50 <50 <50 <50 <50 <50 <50 <50 <50
17 39.100 25.828 1.970 460 52 <50 <50 <50 <50 <50 <50 <50 <50
18 60.771 73.069 2.174 692 156 <50 <50 <50 <50 <50 <50 <50 <50
19 82.803 106.320 2.902 897 168 76 <50 <50 <50 <50 <50 PDVF
20 5.190 7.368 147 56 <50 <50 <50 <50 <50 <50 <50 <50 <50
Cahn P, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. FARB0104LB.
SAE = serious adverse event PDVF = protocol defined virologic failure

37. SCR BSL W.2 W.3 W.4 W.6 W.8 W.12 W.24 W.36
Dec
2015
retest
Jan
2016
W.48
Feb
2016
DV
Mar
2016
PADDLE Study: Patient with Protocol Defined
Virologic Failure
Cahn P, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. FARB0104LB.
GENOTYPE
RT: no mutations; integrase and
protease regions did not amplify
DTG 50mg/d plus 3TC 300 mg/d
61
246
99
76
168
82,803
106,320100,000
10,000
1,000
100
10
1
Patient was discontinued from study and counted as a failure, but followed up
to week 48. He resuppressed without changes in ARV regimen.

39. ARIA Study: DTG/ABC/3TC vs. ATV/r + TDF/FTC in
Naïve Women - Study Design
• Key eligibility criteria: women, ART-naïve, HLA-B*5701 negative,
HIV-1 RNA >500 c/mL, hepatitis B negative
• Stratification: by HIV-1 RNA (≤ or >100,000 copies/mL),
CD4+ count (≤ or >350 cells/mm3)
ATV/r + TDF/FTC FDC
DTG/ABC/3TC FDC
DTG/ABC/3TC FDC
Continuation phaseOpen-label
1:1
randomization
Randomization Week 48
primary analysis
Orrell C, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. THAB0205LB.

40. ARIA Study: Efficacy and Resistance
• 6 confirmed virologic failure in DTG/ABC/3TC and 4 in ATV/r + TDF/FTC (1 with M184V)
• Virologic non response 6% vs 14%
• No virologic data 12% vs 15%
Orrell C, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. THAB0205LB.
82 83
80
85
78
71
74
64
72 71
0
20
40
60
80
100
Overall ≤100,000 >100,000 ≤350 >350
HIV-1RNA<50c/mL,%
DTG/ABC/3TC (ITT-E, n=248)
HIV-1 RNA c/mL CD4+ count cells/mm3
9,7
10,5
-12-10 -8 -6 -4 -2 0 2 4 6 8 10 12 14 16 18 20
ATV/r + TDF/FTC DTG/ABC/3TC
Treatment Differences (95% CI)
3.1 17.8
2.6 16.8
ITT
PP
ITT-E
(primary)

41. Other Observations in Naive Patients
START Study
(Molina JM, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. THAB0201)
• Patients with age > 50 yrs, viral load > 50,000 c/ml, and
Framingham score > 10 benefited from early therapy
• Number needed to treat for benefit in these patients fell from 128  45
INTENSIVE ART INDUCTION IN AFRICA
(Kityo C, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. FRAB0102LB)
• 12-week raltegravir-intensified quadruple therapy versus triple
first-line ART reduces viral load more rapidly, but does not
reduce mortality, in severely immunosuppressed African HIV-
infected adults and older children

42. Key Points
• Few differences in major ART Treatment Guidelines in
recommended initial regimens
• More data supportive of the use of INSTIs in naïve patients
• New reformulated RAL once daily was non-inferior to standard
RAL twice daily
• Minor increase in risk of resistance?
• DTG-3TC in the PADDLE study still promising at wk 48
• DTG/3TC/ABC superior to ATV/r + TDF/FTC in women in both
virologic outcome and toxicity
• HIV+ patients benefitting most from early ART in START were
older, with higher viral load and higher Framingham CV risk
score

44. Novel Strategies and Treatment-
experienced Patients

45. SEARCH 019 Study: Vorinostat, Maraviroc,
Hydroxychloroquine + ART for Acute HIV
• Randomized, open-label trial comparing ART vs ART
plus vorinostat, maraviroc, hydroxychloroquine
• All patients diagnosed and treated during acute HIV
• Endpoints of interest:
• Time to virologic rebound
• Size of latent reservoir
Ananworanich J, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. TUAX0101LB.
Adults treated
in Fiebig III/IV
acute HIV
VL <50
for >2 yrs
ART only
(n=5)
VHM + ART
(n=10)
Viral load post
interruption
ART if VL>1000
ART if VL>1000
Weekly VL monitoring
Wk 0
start VHM
Wk 10
stop VHM,
Begin interruption
Wk 34
End of study
Vorinostat 400mg/day 14 days on/off
3 cycles
(10 weeks)
Hydroxychloroquine 200mg/dose 2 times/day 10 weeks
Maraviroc 600mg/dose 2 times/day 10 weeks

46. SEARCH 019 Study: Results
Ananworanich J, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. TUAX0101LB.
0 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16
HIVRNA
(copies/mL)
Weeks after Treatment Interruption
VHM+ART
ART
100000
10000
1000
100
10
(Viral load kinetics following treatment interruption in VHM+ART vs. ART arms)

47. IMMEDIATE ART Study: Randomized Trial of Same-
Day ART vs Standard of Care
• 762 newly diagnosed patients in Haiti
• Excluded if active opportunistic infection or suspected
TB on CXR, or if did not want to start ART
• Randomized to same-day ART initiation vs start at 3rd visit
in 21 days (after counseling and other non-ART interventions)
• 762 enrolled; mean age 38, female 51%, mean CD4 244
• Study stopped early by DSMB due to better outcome
in same-day ART group
Koenig S, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. WEAE0202.

48. Standard Group
(n=285)
Same-Day ART Group
(n=279)
P-value
Initiated ART 262 (92%) 279 (100%) p<0.001
Died 19 (7%) 8 (3%) p=0.035
Alive and in care 201 (71%) 224 (80%) p=0.007
In care with VL
<50 copies/ml
120 (42%) 151 (54%) p=0.004
In care with VL
<1000 copies/ml
143 (50%) 171 (61%) p=0.008
Koenig S, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. WEAE0202.
IMMEDIATE ART Study: 12 Month Outcomes

50. REALITY Study:
Enhanced Prophylaxis in Advanced HIV Disease
Hakin J, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. FRAB0101LB.
ART-naïve HIV-infected adults & children >5 years with CD4<100 cells/mm3
Characteristic Enhanced Px (N=906) Standard Px (N=899)
Male 477 (53%) 484 (54%)
Age (Years) 36 (29-42) [6-71] 36 (30-42) [5-78]
5-17 Years 39 (4%) 33 (4%)
Current TB Disease 122 (13%) 125 (14%)
WHO Stage 1 or 2 436 (48%) 418 (46%)
CD4 (cells/mm3) 38 (16-64) 36 (16-60)
0-24 cells/mm3 323 (36%) 333(37%)
VL (c/mL) N=1568) 229,690 230,540
>100,000 c/mL 574/782 (73%) 563/786 (72%)
EFV-based ART 820 (91%) 799 (89%)
TDF/FTC NRTI Backbone 716 (79%) 706 (79%)
Initiated ART and Randomized 1:1
Enhanced Prophylaxis: CTX* +
12 weeks INH/B6* 300/25 mg/d (anti-TB)
12 weeks fluconazole 100 mg/d (anti-fungal)
5 days azithromycin 500 mg/d (anti-bacterial & anti-protozoal)
Single-dose albendazole 400 mg (anti-helminth)
Standard Prophylaxis: CTX* +
(Most received additional INH/B6* from
12 weeks depending on national guidelines)

51. • Mortality at 24 weeks: 8.9% enhanced Px vs 12.2% standard Px
• Second randomization to standard ART vs ART plus raltegravir:
faster HIV RNA decline, CD4 increase but no clinical benefit
REALITY Study: Results
Hakin J, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. FRAB0101LB.
0.00
0.05
0.10
0.15
0.20
Died
Week Since Randomisation (ART Initiation)
W24: HR=0.73
(95%CI 0.54-0.97)
p=0.03
W24: HR=0.75
(95%CI 0.58-0.98)
p=0.04
3.3 lives saved for
every 100 treated
NNT=30
Standard Prophylaxis
Enhanced Prophylaxis
14.4%
11.0%
12.2%
8.9%
0 8 16 24 32 4840
No. at Risk (Deaths)
Standard 899 (67) 816 (27) 786 (13) 768 (7) 754 (7) 739 (6) 637
Enhanced 906 (55) 839 (16) 816 (8) 807 (6) 797 (6) 787 (7) 689

52. LATTE-2 Study: Maintenance Therapy With
Injectable Cabotegravir and Rilpivirine
Induction period
Week 32
Primary analysis
Dosingregimen
selection
Day 1
Randomization
2:2:1
Week 48
Analysis
Dosing regimen
confirmation
CAB 400 mg IM + RPV 600 mg IM
Q4W (n=115)
CAB 600 mg IM + RPV 900 mg IM
Q8W (n=115)
CAB 30 mg + ABC/3TC PO QD (n=56)
Week 96b
CAB loading dose at Day 1
CAB loading doses at Day 1 and Week 4
CAB 30 mg +
ABC/3TC for
20 weeks
(N=309)
Maintenance period
Add RPV
4 weeks
Margolis D, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. THAB0206LB

53. LATTE-2 Study: 48 Week Results
Margolis D, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. THAB0206LB
0
10
20
30
40
50
60
70
80
90
100 92
<1
8 9
91 89
7
<1 2
Virological
success
Virological
non-response
No virologic
data
Q8W (n=115)
Q4W (n=115)
CAB 744 (n=56)
Virologic Outcomes Treatment Differences (95% CI)
IMOral
Q8W IM
-12 -10 -8 -6 -4 -2 0 2 4 6 8 10 12 14
2.9
12.4-6.6
Q4W IM
-12 -10 -8 -6 -4 -2 0 2 4 6 8 10 12 14
2.0
11.6-7.6
Both Q8W and Q4W comparable to Oral CAB at Week 48
HIV-1RNA<50c/mL,%

54. LATTE-2 Study: 48 Week Results and Resistance
Analysis
Week 48 outcome
Q8W IM
(n=115)
Q4W IM
(n=115)
Oral CAB
(n=56)
Virologic success 106 (92%) 105 (91%) 50 (89%)
Virologic non-response 8 (7%) 1 (<1%) 1 (2%)
Data in window not <50 c/mLa 6 (5%) 1 (<1%) 0
Discontinued for lack of efficacy 1 (<1%) 0 1 (2%)
Discontinued for other reason while
not <50 c/mL
1 (<1%) b 0 0
No virologic data in window 1 (<1%) 9 (8%) 5 (9%)
Discontinued due to adverse event or death 0 6 (5%) 2 (4%)
Discontinued for other reasons 1 (<1%) 3 (3%) 3 (5%)
• One patient in the Q8W group developed resistance: NNRTI—K103N,
E138G, and K238T (FC RPV=3.3; Etravirine=1.9); INI—Q148R (FC
CAB=5.1; Dolutegravir=1.38
• Patient satisfaction scores favored IM over PO
• Q4W dosing frequency selected for phase 3 program
Margolis D, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. THAB0206LB

55. Diaz A, et al: Dolutegravir (DTG) Plus Rilpivirine
(RPV) in Suppressed Patients with Resistance
• Patients with virologic suppression, multiple ART failures, resistance, offered DTG + RPV
if susceptible to both drugs
• Baseline characteristics (n=38):
Diaz A, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. TUPDB0106.
Variable
Age, median 53.4 years
Gender Women 34%
AIDS 34%
Prior IDU/HCV+ 68%/70%
Nadir CD4+ T cell count, median 179 cells/mm3
Baseline CD4+ T cell count, median 592 cells/mm3
Variable Results
Time on ART, median 19.4 years
Time HIV RNA<50 6.7 years
Number of pills 4.3
Reasons for prescribing
DTG + RPV
DDI: 38%
Toxicity: 33%
Simplification: 25%
NRTI NNRTI PI INI
Treated, n (%) 38 (100) 34 (90) 37 (97) 24 (62)
Failure, n (%) 38 (100) 26 (68) 27 (71) 3 (8)
Resistance mutations4, n (%) 25 (65) 14 (37) 12 (32) NA
Number of mutations, median 3.8 2.0 4.2 NA
Most significant major
resistance mutations
M184V (59%), M41L
(50%), L210W
(36%), T215Y (36%),
K65R (9%)
K103N (43%),
G190A/S (28%),
H221Y (14%), A98G
(7%) V179D (7%)
M46I/L (50%), V82AT (42%),
I54V (33%), L33F (33%),
L90M (25%), I84V (16%),
I50V (8%).
NA
Characteristics of the Study Population (n=38)
Previous treatment and resistance mutations

56. Diaz A, et al: Results
• 35/38 (92%) virologically suppressed at week 48
• No virologic failures – 3 d/c’d
(GI toxicity; need for omeprazole; MD decision)
• Safety:
Diaz A, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. TUPDB0106.
1.1
44 41
78
94
0.68
27 27
52
84
0
20
40
60
80
100
Bt AST ALT GGT Palc
Liver Toxicity
Baseline 48w
1.11 1.21 1.22 1.24
85
75 76 76
0
20
40
60
80
100
Baseline 4w 24w 48w
Renal Function
Cr CKD-EPI
188
49
115
133
202
45
123
173
0 50 100 150 200 250
Ct
HDL
LDL
TG
Lipid Profile
Baseline 48w

57. Key Points
• Adding vorinostat, maraviroc, & hydroxychloroquine to ART in
acute HIV does not delay time to rebound or reduce reservoir
• In Haiti, ART provided on the same day as HIV diagnosis
improves virologic suppression rates, survival, & retention in
care
• REALITY: In advanced disease, enhanced prophylaxis
improves survival; RAL added to standard ART yields no
clinical benefit
• LATTE-2: Injectable cabotegravir and rilpivirine maintains
virologic suppression comparable to oral therapy; dosing
every 4 weeks had fewer virologic failures than every 8 weeks

58. Other stuff (Filler)

60. STRIIVING Study: Switching to ABC/3TC/DTG
Lake J, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. THAB0203.
Open-label
randomized
1:1
DTG/ABC/3TC
DTG/ABC/3TCCurrent ART
Screening 0 Week 24 Week 48
Countries: US, Canada, Puerto Rico
Primary endpoint at 24
weeks: VL <0 c/mL
(Snapshot)
• Virologically suppressed
(confirmed HIV-1 RNA <50 c/mL)
• HLA-B*5701 negative
Inclusion Criteria

61. STRIIVING Study: Results
48 Week Early Switch Arm Week 24 and 48
Lake J, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. THAB0203.
HIV-1RNA<50copies/mL,%
0
10
20
30
40
50
60
70
80
90
100
85
88
83
14
10
17
Virological
success
Virological
non-response
No virologic
data
DTG/ABC/3TC,
Day 1-Week 24 (n=275)
cART, Day 1-Week 24
(n=278)
DTG/ABC/3TC,
Day1-Week 48 (n=275)
1 1 <1

62. STRIIVING Study: Virologic Endpoints
• No subjects met protocol-defined virologic failure in either
study arm
• 4 subjects >50 at Week 48 window: ES (51), LS (54, 53, 156);
All 4 resuppressed <50 c/mL
Lake J, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. THAB0203.
Early Switch Late Switch
DTG/ABC/3TC
N=275
Day 1 to Wk 24
DTG/ABC/3TC
N=275
Day 1 to Wk 48
DTG/ABC/3TC
N=244
Wk 24 to Wk 48
PDVF 0 0 0
Viral load ≥50 c/mL (snapshot) 3 (1%) 1 (<1) 3 (1%)

64. 110
I
100
I
90
I
80
I
• 15,156 patients. Median age was 35.4 years (IQR 29.9 to 42.0), median
CD4 cell count was 168 cells/µL (IQR 83 to 243), and median eGFR was
99.6 mL/min (IQR 85.7 to 116.3)
• Median follow-up duration on tenofovir was 12.9 months
(IQR 5.1 to 23.3)
I
0
I
3
I
6
I
9
I
12
I
15
I
18
I
21
I
24
Time (months)
eGFR(mL/min)
Baseline eGFR ≥90 mL/min (n=7335)
Baseline eGFR <90 mL/min (n=3858)
De Waal R, et al: Change in eGFR by Baseline on
TDF Regimens
12 Month change by baseline
-4.4 (95% CI -4.9 to -4.0) if >90ml/min
+11.9 mL/min (95%CI 11.0 to 12.7) if < 90 mL/min
De Waal R, et al. AIDS 2016; Durban, South Africa; July 18-22; Abst. TUPEB035.

66. MACS Study:
Replete Vitamin D at ART Start and CD4 Recovery
Abraham A, et al. AIDS 2016; Durban, South Africa; July 18-22, 2016; Abst. WEPEB089.
300
400
500
600
CD4+TCellCount(cells/mm3)
0 2 4 6 8 10
75th %ile of Post-HAART 25OHD
25th %ile of Post-HAART 25OHD
Rate: 10% faster/10 ng/mL 25OHD (p<0.01)
Plateau: 3% higher/10 ng/mL 25OHD (p<0.01)
Time (years)