Clinical Impact of New Data From IAS 2019

In partnership with
Clinical Impact of New Data From IAS 2019
This activity is supported by independent educational grants from
Gilead Sciences and ViiV Healthcare
CCO Official Conference Coverage
of the 10th IAS Conference on HIV Science,
July 21-24, 2019; Mexico City, Mexico

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Faculty
Brenda E. Crabtree Ramírez, MD
IAS 2019 Local Scientific Co-Chair
Assistant Professor, HIV Program
Department of Infectious Diseases
Instituto Nacional de Ciencias
Médicas y Nutrición, Salvador Zubirán
Mexico City, Mexico
Anton L. Pozniak, MD, FRCP
IAS 2019 International Scientific
Co-Chair
Consultant Physician
Department of HIV and
Genitourinary Medicine
Chelsea and Westminster Hospital
NHS Foundation Trust
London, United Kingdom

Faculty Disclosures
The faculty reported the following financial relationships or relationships
to products or devices they or their spouse/life partner have with
commercial interests related to the content of this CME/CE activity:
Brenda E. Crabtree Ramírez, MD, has disclosed that she has received
consulting fees from Merck Sharp & Dohme and ViiV Healthcare and
funds for research support from Merck Sharp & Dohme.
Anton L. Pozniak, MD, FRCP, has disclosed that he has received
consulting fees from Cipla, Gilead Sciences, Janssen, Merck, and ViiV
Healthcare.

Tsepamo: Neural Tube Defects and DTG Exposure
 Birth outcomes surveillance study among Botswanan women ± HIV infection
‒ Initial findings in May 2018 found apparent increase in NTD incidence among women
who conceived while receiving DTG[1]
‒ Warnings issued from WHO, EMA, FDA regarding use of DTG at time of conception[2-4]
and some countries halted plans to use DTG-based ART as preferred first-line therapy
 Current analysis reports updated birth outcomes as of March 2019[5,6]
‒ From July to September 2018, surveillance area expanded to capture ~ 72% of all births
in Botswana; data abstracted from obstetric cards of all in-hospital deliveries
‒ Government midwives trained to assess congenital abnormalities performed infant
surface exams; abnormalities photographed with maternal consent and reviewed by
external medical geneticist (blinded to drug exposure history)
1. Zash. NEJM. 2018;379:979. 2. WHO Statement. May 2018. 3. EMA Statement. May 2018.
4. FDA. Sep 2018. 5. Zash. IAS 2019. Abstr MOAX0105LB. 6. Zash. NEJM. 2019;[Epub].

0.09
0.080.030.04
Tsepamo: NTD Prevalence by ARV Exposure
 As of March 2019, rate of NTDs with DTG at
conception lower than initially signaled[1,2]
 No significant difference in major external
structural malformations with DTG vs non-DTG
ART[1,2]
 WHO released updated recommendations
reconfirming use of DTG-based ART as preferred
first-line and second-line therapy[3]
Outcome
At Conception DTG in
Pregnancy
(n = 3840)
HIV Negative
(n = 89,372)
DTG
(n = 1683)
Non-DTG
(n = 14,792)
EFV
(n = 7959)
NTDs per exposures, n/N 5/1683 15/14792 3/7959 1/3840 70/89372
 Prevalence difference, % (95% CI) Reference
0.20
(0.01-0.59)
0.26
(0.07-0.66)
0.27
(0.06-0.67)
0.22
(0.05-0.62)
NTDs per exposures since May 2018, n/N 1/1275 1/3492 0/2172 1/1028 9/23,315
1. Zash. IAS 2019. Abstr MOAX0105LB. 2. Zash. NEJM. 2019;[Epub]. 3. WHO ARV Policy Update. July 2019.
Pre-May 2018
Current analysis
DTG Any Non-
DTG ART
EFV HIV
Negative
Pregnancy
NTDs,%(95%CI)
DTG
Conception
0.30
0.10 0.05
0.00
0.5
1
0
0.94
0.12

Tsepamo: Additional Adverse Birth Outcomes
 No difference between DTG and EFV for any single adverse birth
outcome, including preterm/very preterm birth (< 37/< 32 wks), small
gestational age, stillbirth, in-hospital neonatal death
 Analysis included single births since October 2016
Zash. IAS 2019. Abstr MOAX0105LB. Slide credit: clinicaloptions.com
Birth Outcome, n (%)
DTG at Conception
(n = 1271)
EFV at Conception
(n = 4430)
Adjusted RR
(95% CI)*
Any adverse 422 (33.2) 1550 (35.0) 0.94 (0.86-1.02)
Any severe (SB, NND, vPTB, vSGA) 151 (11.9) 568 (12.8) 0.89 (0.74-1.05)
*Adjusted for maternal age, education, gravida.

Additional NTD Data From Botswana and Brazil
 Prospective birth outcomes surveillance study among Botswanan women commissioned by
Botswana Ministry of Health and Wellness in response to May 2018 Tsepamo findings[1]
‒ Surveillance area included 22 facilities not covered by Tsepamo (October 2018 to March 2019);
potential NTDs evaluated by trained midwives prior to discharge with suspected NTDs reviewed
by blinded geneticist
Outcome
HIV Positive
HIV Negative
(n = 2328)
DTG
(n = 152)
Any Non-DTG ART
(n = 381)
EFV
(n = 261)
NTDs, n (%) [95% CI]
1 (0.66)
[0.02 to 3.69]
0 (0)
[0 to 0.79]
0 (0)
[0 to 1.15]
2 (0.09)
[0.01 to 0.31]
Prevalence difference,
% (95% CI)
Reference
0.66
(-0.73 to 4.16)
0.66
(-1.25 to 4.16)
0.58
(-0.10 to 4.10)
1. Raesima. IAS 2019. Abstr MOAX0106LB. 2. Pereira. IAS 2019. Abstr MOAX0104LB.
 Retrospective cohort of Brazilian women with HIV found no NTDs among births to women
with possible exposure to DTG at conception from 2017-2018 (n = 384)[2]

ImPREP: Same-Day PrEP With TDF/FTC for High-Risk
MSM and TGW in Brazil, Mexico, and Peru
 Prospective, open-label demonstration study of same-day PrEP in MSM and TGW
at high risk of HIV infection (≥ 1 risk criteria)
 Eligible participants were screened and enrolled on the same day to receive a
30-day supply of TDF/FTC
‒ Study enrolled 5019 MSM (94%) and 335 TGW (6%)
 Primary outcomes
‒ PrEP early continuation: attendance to the first 2 follow-up visits within 120 days of
PrEP initiation
‒ PrEP adherence: ≥ 16 days of PrEP medication filled per 30-day period (medication
possession ratio ≥ 0.53)
Veloso. IAS 2019. Abstr TUAC0404LB. Slide credit: clinicaloptions.com

ImPREP: Levels of Early Continuation and Adherence
Veloso. IAS 2019. Abstr TUAC0404LB. Slide credit: clinicaloptions.com
Population
Early
Continuation, %
Medication
Possession Ratio
≥ 0.53, %
Follow-up, PY
HIV Incidence per
100 PY (95% CI)
Brazil 85.4 98.7 1438.6 0.2 (0.1-0.6)
Mexico 84.0 98.0 344.0 0.6 (0.2-2.3)
Peru 52.7 91.0 286.4 2.4 (1.2-5.1)
Overall
 TGW
79.6
55.7
97.2
88.7
2069.0
--
0.6 (0.3-1.0)
--

ANRS Prevenir: Daily vs On-Demand PrEP With FTC/TDF
 Multicenter, open-label, prospective cohort study mainly in MSM (98.6%) from Paris
HIV-negative adults at high risk of
HIV infection with inconsistent
condom use; eGFR ≥ 50 mL/min;
HBsAg negative in on-demand arm
(N = 3045)*
Daily FTC/TDF PrEP†
(n = 1546)
On-Demand FTC/TDF PrEP†
(n = 1499)
*Participants enrolled on arm of their choice with ability to switch. †Plus condoms, gels, risk reduction and adherence counseling, questionnaire on
sexual behavior. Follow-up every 3 mos with STI and/or HIV testing, plasma creatinine measurement.
End of Study
May 31, 2020
Current Analysis
May 2, 2019
Beginning of Study
May 3, 2017
Molina. IAS 2019. Abstr TUAC0202.
 Primary endpoint: ≥ 15% reduction in new HIV diagnoses among MSM in Paris vs rate
reported by National Surveillance network in 2016
 Secondary endpoints: PrEP adherence, sexual behavior, safety

ANRS Prevenir: HIV Incidence
 Global HIV incidence: 0.09/100 PY (n = 2)
‒ PrEP stopped 7-10 wks before infection in both cases
 Mean follow-up: 8.7 mos
 Overall HIV infections averted: n = 143
‒ Assuming incidence of 6.6/100 PY as reported for placebo arm in ANRS IPERGAY study
 Rate of study discontinuation: 8.9/100 PY (n = 196)
Molina. IAS 2019. Abstr TUAC0202. Slide credit: clinicaloptions.com
mITT Analysis
Daily PrEP
(1072.9 PYFU)
On-Demand PrEP*
(1132.7 PYFU)
P Value
HIV incidence/100 PY (95% CI) 0 (0-0.3) 0.2 (0-0.6) .132
*On-demand PrEP strategy not FDA or EMA approved.

Incidence/100 PY
(95% CI)
Daily PrEP
(1072.9 PYFU)
On-Demand PrEP
(1132.7 PYFU)
Drug-related AEs†
 Leading to d/c
11.4 (9.4-13.6)
0 (0-0.3)
13.2 (11.2-15.5)
0.3 (0-0.8)‡
Grade 3/4 AEs 5.3 (4.0-6.9) 4.4 (3.3-5.8)
Viral hepatitis 0.9 (0.5-1.7) 1.2 (0.6-2.0)
ALT abnormality
 Grade 3/4
13.0 (10.9-15.3)
0.8 (0.4-1.6)
10.3 (8.5-12.4)
0.6 (0.3-1.3)
Grade 1 creatinine 15.4 (13.1-17.9) 15.6 (13.4-18.1)
CrCl
 50-70 mL/min
 < 50 mL/min
17.7 (15.3-20.4)
0.8 (0.4-1.6)
18.5 (16.1-21.2)
0.8 (0.4-1.5)
ANRS Prevenir: PrEP Adherence, Sexual Behavior, Safety
 Daily PrEP users had:
‒ More sexual partners
‒ More frequent condomless sex
‒ Higher incidence of bacterial STIs
At Last Sexual
Encounter, n (%)
Daily PrEP
(3806 Acts)
On-Demand PrEP
(3879 Acts)
PrEP use
 Correct*
3705 (97.3)
3613 (97.5)
3188 (82.2)
3072 (96.4)
Condom use 716 (18.8) 851 (21.9)
Participants with adherence data, n = 2134.
*Per protocol, or at least 1 pill before and after within 24 hrs.
†Most were gastrointestinal. ‡Grade 3 vomiting, grade 1 diarrhea,
grade 1 nausea/headache/dizziness; each n = 1.
Molina. IAS 2019. Abstr TUAC0202.

DISCOVER: FTC/TAF vs FTC/TDF as PrEP in MSM, TGW
 International, randomized, double-blind, active-controlled phase III trial
Adult cis-MSM or TGW at
high risk of HIV infection,*
no HBV infection, previous
PrEP use permitted
(N = 5387)
Primary analysis of HIV incidence/100 PY:
Conducted when 100% of patients completed
Wk 48 and 50% completed Wk 96
FTC/TAF 200/25 mg QD
(n = 2694)
FTC/TDF 200/300 mg QD
(n = 2693)
Wk 96Wk 48
0.16
0.34
IRR: 0.47 (95% CI: 0.19-1.15)
Noninferiority established
because upper bound of
95% CI < 1.62
*Defined as ≥ 2 episodes of condomless anal sex within past 12 wks or rectal gonorrhea, chlamydia, or syphilis within past 24 wks.
Spinner. IAS 2019. Abstr TUAC0403LB. Hare. CROI 2019. Abstr 104LB.
 Current analysis assessed whether adherence, PK, sexual behavior, or STI incidence
could account for observed differences in HIV infection rates

DISCOVER: Onset and Duration of Protection With
FTC/TAF vs FTC/TDF as PrEP
 Adherence comparable between arms
by self-report over time, pill count
(median adherence: 98% in each arm),
and TFV-DP levels in DBS
 Steady-state PBMC TFV-DP levels
were 6.3-fold higher with FTC/TAF vs
FTC/TDF
 Modeling found that concentrations
> EC90 would last for 16 days after
final dose of FTC/TAF vs 10 days after
FTC/TDF
FTC/TAF
(n = 158)
FTC/TDF
(n = 151)
PBMCTFV-DPLevels(fmol/106cells)
EC90 = 40 fmol/106 cells
(associated with 90%
HIV risk reduction)
PBMC TFV-DP Levels at 20-28 h Postdose
100,000
10,000
1000
100
10
1
404
61
98% of
participants
> EC90
68% of
participants
> EC90
Spinner. IAS 2019. Abstr TUAC0403LB. Reproduced with permission. Slide credit: clinicaloptions.com

DISCOVER: Sexual Behaviors and STI Incidence
 Sexual behavior and STI incidence comparable between arms
‒ AE-based incidence of chlamydia, gonorrhea, and syphilis: 145/100 PY with FTC/TAF,
139/100 PY with FTC/TDF
Wk
Number of Condomless
Receptive Anal Sex Partners Lab-Based Rectal Gonorrhea/Chlamydia
10
8
6
4
2
0
MeanNo.ofPartners(SD)
0 12 24 36 48 60 72 84 96
FTC/TAF
FTC/TDF
Wk
20
15
10
5
0
Participants(%)
0 12 24 36 48 60 72 84 96

DISCOVER: Adherence by DBS at HIV Diagnosis Visit in
Nested Case-Control Study
 Low adherence (< 2 doses/wk) associated with significantly increased risk of HIV
infection in both arms (both P < .001)
HIV Cases
(n = 7)
FTC/TAF FTC/TDF
HIV-Negative
Controls
(n = 35)
HIV Cases
(n = 15)
HIV-Negative
Controls
(n = 75)
P < .001
P < .001
MedianTFV-DPConcentration,
fmol/punch(es)(Q1,Q3)
2500
2000
1500
900
450
0
≥ 4 doses/wk
2-3 doses/wk
< 2 doses/wk
Adherence
2000
1500
1000
700
350
0

DISCOVER: Rapidity in Achieving EC90
 In a phase I study in healthy volunteers, median PBMC TFV-DP concentration > EC90 reached
within 1-2 hrs (all within 4 hrs) of dosing with FTC/TAF vs 3 days of dosing with FTC/TDF
MedianTFV-DPConcentration,
fmol/106cells(Range)
10000
1000
100
10
1
0.1
FTC/TAF
FTC/TDF
0 2 4 8 24
Hours
EC90
First Dose

ANRS 12300 Reflate TB2: (RAL vs EFV) + 3TC/TDF
in ART-Naive Patients With HIV and Tuberculosis
 International, randomized, open-label phase III noninferiority trial
 Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48 by FDA
Snapshot algorithm in ITT population
‒ Noninferiority margin: -12%
RAL 400 mg BID + 3TC/TDF QD
(n = 228)
EFV 600 mg QD + 3TC/TDF QD
(n = 227)
Wk 48
ART-naive patients with HIV infection,
confirmed or probable TB, and ≤ 8 wks
of standard rifampin-based TB
treatment; no TB meningitis
(N = 455)
Stratified by country
De Castro. IAS 2019. Abstr MOAB0101.

ANRS 12300 Reflate TB2: Primary Endpoint at Wk 48
 RAL 400 mg BID + 3TC/TDF did not meet criteria for noninferior efficacy
vs EFV 600 mg QD + 3TC/TDF
Virologic Outcomes (FDA Snapshot) RAL-EFV Treatment Difference (95% CI)
-13.9 3.7
-5.1
-12% NI margin
-12 -8 -4 0 4 8
RAL + 3TC/TDFEFV + 3TC/TDF
12-16 -14Virologic
Nonresponse
HIV-1 RNA
< 50 c/mL
No Virologic
Data
Patients(%)
60
100
80
20
40
0
66
61
22
29
1210
RAL + 3TC/TDF
EFV + 3TC/TDF
De Castro. IAS 2019. Abstr MOAB0101. Reproduced with permission.

AE, n (%)
RAL +
3TC/TDF
(n = 229)
EFV +
3TC/TDF
(n = 230)
Any AE 207 (90) 208 (90)
Grade 3/4 AEs
 Grade 3
 Grade 4
 Drug related
•Leading to ART d/c
 IRIS
 Hepatotoxicity
 Hypersensitivity
 Renal failure
62 (27)
42 (18)
20 (9)
25 (11)
1 (< 1)
10 (4)
9 (4)
1 (< 1)
0 (0)
68 (30)
41 (18)
27 (12)
22 (10)
3 (< 1)
13 (6)
9 (4)
1 (1)
4 (2)
Endpoint
RAL +
3TC/TDF
(n = 228)
EFV +
3TC/TDF
(n = 227)
HIV-1 RNA < 50 c/mL, n (%) 139 (61) 150 (66)
Virologic nonresponse, n (%)
 HIV-1 RNA ≥ 50 c/mL, n
 D/c for lack of efficacy, n
 D/c for other reasons with
last HIV-1 RNA ≥ 50 c/mL, n
66 (29)
45
13
8
50 (22)
31
9
10
No data in window, n (%)
 D/c for AE or death, n
 D/c for other reason, n
 On study but missing data, n
23 (10)
12
11
0
27 (12)
18
7
2
ANRS 12300 Reflate TB2: Efficacy and Safety at Wk 48
Slide credit: clinicaloptions.comDe Castro. IAS 2019. Abstr MOAB0101.

ADVANCE: First-line DTG/FTC/TAF vs DTG/FTC/TDF vs
EFV/FTC/TDF
 Multicenter, randomized, open-label phase III trial conducted in South Africa
 Primary endpoint: HIV-1 RNA < 50 c/mL, d/c, or missing data at Wk 48 (FDA Snapshot in ITT)
 Secondary endpoints: safety
Venter. IAS 2019. Abstr WEAB0405LB. Venter. NEJM. 2019;[Epub]. Slide credit: clinicaloptions.com
ART-naive patients age ≥ 12 yrs
with HIV-1 RNA ≥ 500 copies/mL,
no ART in prior 6 mos,
no TB or pregnancy,
no BL genotype, and
CrCl > 60 mL/min
(N = 1053)
DTG 50 mg QD + FTC/TAF QD
(n = 351)
DTG 50 mg QD + FTC/TDF QD
(n = 351)
EFV/FTC/TDF QD
(n = 351)
Wk 48
Primary Endpoint Wk 96

ADVANCE: HIV-1 RNA < 50 c/mL Through Wk 48
Venter. IAS 2019. Abstr WEAB0405LB. Venter. NEJM. 2019;[Epub]. Slide credit: clinicaloptions.com
ITT Observed Data
PatientsWithHIV-1RNA<50c/mL(%)
Wk
85
84
79
95
96
96
DTG + FTC/TAF
DTG + FTC/TDF
EFV/FTC/TDF
4 12 24 36 48
0
20
40
60
80
100
0 4 12 24 36 48
Wk
4 12 24 36 48
0
20
40
60
80
100
0 4 12 24 36 48
DTG + FTC/TAF
DTG + FTC/TDF
EFV/FTC/TDF

ADVANCE: Primary Efficacy and Resistance at Wk 48
 Emergent NRTI resistance:
0 DTG + FTC/TAF vs 1 (0.3%) DTG +
FTC/TDF vs 4 (1.0%) EFV/FTC/TDF
 Emergent NNRTI resistance:
0 DTG + FTC/TAF vs 0 DTG +
FTC/TDF vs 3 (1%) EFV/FTC/TDF
 No emergent INSTI resistance
 Among patients with HIV-1 RNA > 50
c/mL at Wk 48, DTG arm had n = 14
with resuppression after adherence
counseling, n = 3 without, n = 2 with
no f/u or early termination; EFV arm
had n = 7 with resuppression after
adherence counselling, n = 7
without, n = 2 with no f/u
Difference in HIV-1 RNA < 50 c/mL (98.3% CI)
-12-10 -8 -6 -4 -2 0 12108642 14
DTG + FTC/TAF
vs DTG + FTC/TDF (P = .68)
DTG + FTC/TDF
vs EFV/FTC/TDF (P = .03)
DTG + FTC/TAF
vs EFV/FTC/TDF (P = .08)
-1.1
-7.7 5.4
6.3
-0.7 13.2
-1.9
5.1
12.2
Venter. IAS 2019. Abstr WEAB0405LB. Reproduced with permission.
-10% NI margin

ADVANCE: Safety at Wk 48
 Impact of treatment on renal, bone,
lipid markers in line with established
safety profiles
 IRIS, including TB-IRIS uncommon
‒ High level of isoniazid use
Venter WF. IAS 2019. Abstr WEAB0405LB. Slide credit: clinicaloptions.com
Safety Outcome,
n (%)
DTG +
FTC/TAF
(n = 351)
DTG +
FTC/TDF
(n = 351)
EFV/
FTC/TDF
(n = 351)
Serious AEs 16 (5) 20 (6) 24 (7)
Grade 3/4 AEs 42 (12) 51 (15) 85 (24)
Drug-related
grade 1-4 AEs
185 (63) 227 (65) 251 (72)
Death 1 (0) 1 (0) 2 (1)
Treatment-Emergent
Grade 3/4 Laboratory
Abnormalities, n (%)
DTG +
FTC/TAF
(n = 351)
DTG +
FTC/TDF
(n = 351)
EFV/
FTC/TDF
(n = 351)
Hematology
 Hemoglobin
 Platelets
 Neutrophil count
3 (1)
2 (1)
0 (0)
7 (2)
0 (0)
0 (0)
10 (3)
2 (1)
0 (0)
Chemistry
 ALT
 AST
 GGT
 LDL cholesterol
 Albumin
9 (3)
6 (2)
4 (1)
8 (2)
0 (0)
7 (2)
6 (2)
6 (2)
1 (0)
0 (0)
18 (5)
14 (4)
33 (9)
7 (2)
0 (0)

NAMSAL and ADVANCE: Study Design
 Multicenter, randomized, open-label phase III trials[1-3]
DTG 50 mg + 3TC/TDF QD
(n = 310)
EFV 400 mg + 3TC/TDF QD
(n = 303)
ART-naive patients (≥ 12 yrs)
with HIV-1 RNA ≥ 500 c/mL
(N = 1053)
ADVANCE: South Africa
Wk 96
DTG 50 mg + FTC/TAF QD
(n = 351)
DTG 50 mg + FTC/TDF QD
(n = 351)
EFV 600 mg/FTC/TDF QD
(n = 351)
1. Hill. IAS 2019. Abstr MOAX0102LB. 2. NCT02777229. 3. NCT03122262.
4. NAMSAL ANRS 12313 Study Group. NEJM. 2019:[Epub]. 5. Venter. NEJM. 2019:[Epub].
ART-naive adults with
HIV-1 RNA > 1000 c/mL
(N = 613)
NAMSAL: Cameroon
Primary Endpoint (Both Trials)
HIV-1 RNA < 50 c/mL at Wk 48 by
FDA Snapshot in ITT population
(noninferiority margin: -10%)[4,5]

NAMSAL and ADVANCE: Progressive Weight Gain and
Clinical Obesity
Outcome
NAMSAL ADVANCE
DTG +
3TC/TDF
(n = 293)
EFV +
3TC/TDF
(n = 278)
P Value
DTG +
FTC/TAF
DTG +
FTC/TDF
EFV/
FTC/TDF
P Value
Mean Δ in weight, kg
 Wk 48
 Wk 96
+5
NA
+3
NA
< .001 +6
+8
+3
+5
+1
+2
< .001
Mean Δ in BMI at Wk 48 +1.7 +1.2 < .001 NR NR NR
Treatment-emergent
overweight (BMI 25-29.9), %
 Wk 48
 Wk 96
16
NA
17
NA
NS 23
25
14
13
9
11
NS
Treatment-emergent obesity
(BMI ≥ 30), %
 Wk 48
 Wk 96
12
NA
5
NA
< .01 14
19
7
8
6
4
< .01
Hill. IAS 2019. Abstr MOAX0102LB.

 Significantly greater weight increase* with DTG vs EFV, with TAF vs TDF; plateauing
in weight gain after Wk 48 observed in men but not in women
ADVANCE: Mean Change in Weight to Wk 96 by Sex
Wk
Women
Hill. IAS 2019. Abstr MOAX0102LB. Reproduced with permission.
MeanWeightChange(kg)
Men
4
2
0
0 4 12 24 36
10
8
6
12
48 60 72 84 96
14
n = 430 418 402 387 376 374 366 292 232 140
+5 kg
+4 kg
+1 kg
NS
*Wilcoxon rank-sum comparison at Wk 96.
WkMeanWeightChange(kg)
4
2
0
0 4 12 24 36
10
8
6
12
48 60 72 84 96
DTG + FTC/TAF
DTG + FTC/TDF
EFV + FTC/TDF
14
n = 549 531 514 488 474 459 441 359 276 175
+10 kg
+5 kg
+3 kg
P<.05P<.001
P<.01
P<.001
P<.01

GEMINI-1 and -2: DTG + 3TC in ART-Naive Adults
 Parallel, international, randomized, double-blind phase III noninferiority studies
 Secondary endpoints at Wk 96: HIV-1 RNA < 50 copies/mL (FDA Snapshot and TRDF
analyses); AEs; resistance; changes from BL in bone, renal, and lipid parameters
ART-naive adults with
HIV-1 RNA 1000-500,000 copies/mL,
≤ 10 days on previous ART, no major
RT or PI resistance mutations, no HBV
infection or HCV requiring therapy
(N = 1433)
DTG + 3TC PO QD
(n = 716)
DTG + FTC/TDF PO QD
(n = 717)
Wk 144
Primary Endpoint
Wk 48
Stratified by HIV-1 RNA (≤ vs > 100,000 copies/mL),
CD4+ cell count (≤ vs > 200 cells/mm³)
Screening within 28 days of study start; studies double-blinded until Wk 96, open-label until Wk 144.
Continuation of
DTG + 3TC
permitted
Current Analysis
Wk 96
Cahn. IAS 2019. Abstr WEAB0404LB. NCT02831673. NCT02831764.

GEMINI-1 and -2: Virologic Response
 DTG + 3TC met criteria for noninferior efficacy vs DTG + FTC/TDF at Wk 96
*Adjusted for BL HIV-1 RNA, BL CD4+ cell count, and study.
Endpoint, % (n)
DTG + 3TC
(n = 716)
DTG + FTC/TDF
(n = 717)
Difference,* %
(95% CI)
Responders 86.0 (616) 89.5 (642) -3.4 (-6.7 to 0)
HIV-1RNA<50copies/mL,
%(95%CI)
100
80
60
40
20
0
0 4 8 12 16 24 36 48 60 72 84 96
Wk
87.0
93.2 91.5 87.2 86.0
89.589.4
93.393.4
84.4
Cahn. IAS 2019. Abstr WEAB0404LB. Reproduced with permission.
Rates of HIV-1 RNA ≥ 50 copies/mL unchanged from Wk 48 to 96.
D/c for reasons other than AEs or death higher with DTG + 3TC at Wk 96 (8% vs 5% with 3-drug ART).

GEMINI-1 and -2: Virologic Response at Wk 96 by
Baseline HIV-1 RNA and CD4+ Cell Count
FDA Snapshot Analysis TRDF Analysis*
> 100,000≤ 100,000
BL HIV-1 RNA,
copies/mL
> 200 ≤ 200
BL CD4+ Cell Count,
cells/mm3
> 200 ≤ 200
BL CD4+ Cell Count,
cells/mm3
BL HIV-1 RNA,
copies/mL
499/
576
510/
564
117/
140
132/
153
573/
653
594/
662
43/
63
48/
55
560/
576
545/
564
132/
140
146/
153
633/
653
638/
662
59/
63
53/
55
n/N =
DTG + 3TC DTG + FTC/TDF
*Accounts for CVW, withdrawal for lack of efficacy or treatment-related AEs, and participants meeting protocol-defined stopping criteria.
PatientsWithHIV-1RNA
<50copies/mL(%)
100
80
60
40
20
0
87 90
84 86 88 90
68
87
PatientsWithoutTRDF(%)
n/N =
100
80
60
40
20
0
97 97 9794 9495 96 96
Cahn. IAS 2019. Abstr WEAB0404LB. Reproduced with permission.
> 100,000≤ 100,000

GEMINI-1 and -2: Safety and Resistance at Wk 96
 Lower risk of drug-related AEs with DTG +
3TC vs DTG + FTC/TDF
 Weight gain reported as an AE in 1.8% of
patients receiving DTG + 3TC, 1.4% receiving
DTG + FTC/TDF
 Low rates of confirmed virologic withdrawal
(≤ 1.5%) across arms
‒ No treatment-emergent resistance
observed in any of these patients
 Renal and bone changes significantly favored
DTG + 3TC
 Non-HDL lipid changes significantly favored
DTG + FTC/TDF
Safety Event, n (%)
DTG
+ 3TC
(n = 716)
DTG
+ FTC/TDF
(n = 717)
Any AE in ≥ 10% in either arm
 Nasopharyngitis
 Diarrhea
 Headache
591 (83)
71 (10)
89 (12)
79 (11)
609 (85)
114 (16)
93 (13)
87 (12)
Drug-related AEs*
 Grade 2-5 in ≥ 1% of patients
• Headache
140 (20)
50 (7)
8 (1)
179 (25)
57 (8)
8 (1)
AEs leading to withdrawal
 Neuropsychiatric
 Renal-related
 Osteoporosis
24 (3)
10 (1)
2 (< 1)
0
23 (3)
5 (< 1)
7 (< 1)
2 (< 1)
Any serious AE† 64 (9) 67 (9)
*For DTG + 3TC, relative risk ratio: 0.78 (95% CI: 0.64-0.95).
†Death (n = 3); all with DTG + 3TC, considered unrelated to study treatment.
Cahn. IAS 2019. Abstr WEAB0404LB.

GEMINI-1 and -2: Viral Rebound Through Wk 48
 Elevated viral load cases: DTG + 3TC, n = 125; DTG + FTC/TDF, n = 130
‒ Most commonly transient “blips” with immediate re-suppression
Category of Viral Rebound, n (%)
DTG + 3TC
(n = 716)
DTG + FTC/TDF
(n = 717)
HIV-1 RNA 50 to < 200 c/mL (never ≥ 200 c/mL after achieving < 50 c/mL)
 Adjacent values < 50 c/mL (ie, blips)
 Occurs ≥ 2 consecutive times
98 (14)
83 (12)
15 (2)
101 (14)
93 (13)
8 (1)
HIV-1 RNA ≥ 200 c/mL at least once after achieving < 50 c/mL
 Single occurrence with adjacent values < 200 c/mL
 Occurs ≥ 2 consecutive times (ie, confirmed virologic withdrawal)
19 (3)
14 (2)
5 (< 1)†
22 (3)
19 (3)
3 (< 1)‡
HIV-1 RNA < 50 c/mL never achieved* 8 (1) 7 (1)
*Most had only Day 1 visits. †1 CVW in DTG + 3TC arm did not achieve HIV-1 RNA < 50 c/mL and is counted in category directly
below. ‡1 CVW in DTG + FTC/TDF arm confirmed after Wk 48 at Wk 60 and is counted in category directly above.
Underwood. IAS 2019. Abstr MOPEB231.

GEMINI-1 and -2: Viral Rebound Through Wk 48 by
Baseline HIV-1 RNA
 No patient with confirmed virologic withdrawal experienced “blips” beforehand
 In subgroup with BL HIV-1 RNA > 100,000 c/mL, “blips” were numerically more
frequent with DTG + FTC/TDF vs DTG + 3TC, although patient numbers were small
Outcome by BL HIV-1 RNA
All Patients ≤ 100,000 c/mL > 100,000 c/mL
DTG
+ 3TC
(n = 716)
DTG
+ FTC/TDF
(n = 717)
DTG
+ 3TC
(n = 576)
DTG
+ FTC/TDF
(n = 564)
DTG
+ 3TC
(n = 140)
DTG
+ FTC/TDF
(n = 153)
Confirmed virologic withdrawal,* n 6 4 4 3 2 1
Type of elevated HIV-1 RNA, n (%)
 Blip
 50 to < 200 c/mL twice
 ≥ 200 c/mL once
 ≥ 200 c/mL twice
 < 50 c/mL never achieved
83 (11.6)
15 (2.1)
14 (2.0)
5 (0.7)
8 (1.1)
93 (13.0)
8 (1.1)
19 (2.6)
3 (0.4)
7 (1.0)
51 (8.9)
7 (1.2)
11 (1.9)
4 (0.7)
6 (1.0)
47 (8.3)
2 (0.4)
14 (2.5)
2 (0.4)
7 (1.2)
32 (22.9)
8 (5.7)
3 (2.1)
1 (0.7)
2 (1.4)
46 (30.1)
6 (3.9)
5 (3.3)
1 (0.7)
0
Underwood. IAS 2019. Abstr MOPEB231.

TANGO: Switch to DTG/3TC vs Continuing TAF-Based ART
 International, randomized, open-label phase III noninferiority study
Adults with HIV-1 RNA < 50 c/mL for
> 6 mos on stable TAF-based ART*;
no prior VF, NRTI or INSTI resistance,
HBV infection or HCV requiring tx
(N = 741)
Switch to DTG/3TC
(n = 369)
Continue TAF-Based Regimen
(n = 372)
Wk 196
Primary Analysis
Wk 48
Stratified by BL third agent class
Continuation
of DTG/3TC
permitted
Wk 148
*Initial regimen of FTC/TAF + PI, NNRTI, or INSTI, or TDF switched to TAF ≥ 3 mos prior to screening with no other regimen changes.
DTG/3TC
Van Wyk. IAS 2019. Abstr WEAB0403LB. NCT03446573.
 Primary endpoint: virologic failure at Wk 48 by FDA Snapshot analysis (ITT-E)
‒ Noninferiority margin: 4%
 Secondary endpoint: safety

0.5
Difference (%)
-3.4
0.2
-8 -6 -4 -2 0 2 4 6 8
3.9
Key Secondary Endpoint
(HIV-1 RNA < 50 c/mL)
DTG/3TC noninferior to
continued TAF-based ART
-8% NI
margin
TANGO: Virologic Outcomes by FDA Snapshot at Wk 48
TAF-Based ARTDTG/3TC
TAF-Based ART DTG/3TC
-1.2 0.7
-0.3
-8 -6 -4 -2 0 2 4 6 8
Patients(%)
100
80
40
60
20
0
HIV-1 RNA
≥ 50 c/mL
HIV-1 RNA
< 50 c/mL
No Virologic
Data
0.3
93.2 93.0
6.5 6.5
Switch to DTG/3TC
(n = 369)
Continue TAF-based ART
(n = 372)
Virologic Outcomes (ITT-E) Adjusted Treatment Difference (95% CI)*
Primary Endpoint
(HIV-1 RNA ≥ 50 c/mL)
DTG/3TC noninferior to
continued TAF-based ART
4% NI
margin
*Adjusted for baseline third agent class.
van Wyk. IAS 2019. Abstr WEAB0403LB.
 No CVW in DTG/3TC arm, CVW in 1 (< 1%) patient in
TAF-based ART arm; no resistance detected at failure
 All 7 patients (4 in DTG/3TC group, 3 in TAF-based ART
group) with proviral M184V/I mutation at baseline
maintained HIV-1 RNA < 50 c/mL at Wk 48

TANGO: Safety at Wk 48
 Mean weight gain and frequency of weight gain
comparable between arms
 Significantly higher elevation in some bone and
renal markers with DTG/3TC
Van Wyk J. IAS 2019. Abstr WEAB0403LB. Slide credit: clinicaloptions.com
AE, n (%)
DTG + 3TC
(n = 369)
TAF-Based
ART
(n = 371)
Any AE
 Nasopharyngitis
 Upper RTI
 Diarrhea
 Headache
 Syphilis
 Back pain
 Fatigue
 Bronchitis
295 (80)
43 (12)
31 (8)
30 (8)
24 (7)
24 (7)
21 (6)
20 (5)
8 (2)
292 (79)
41 (11)
32 (9)
26 (7)
17 (5)
13 (4)
28 (8)
3 (1)
20 (5)
AE, n (%)
DTG + 3TC
(n = 369)
TAF-Based
ART
(n = 371)
Drug-related grade 2-5 AE 17 (6) 3 (< 1)
Drug-related grade 2-5 AE
occurring in ≥ 0.5%*
 Insomnia
 Constipation
 Flatulence
 Headache
4 (1)
2 (1)
2 (1)
2 (1)
0
1 (< 1)
0
0
AEs leading to withdrawal
 Drug-related AEs
leading to withdrawal
13 (4)†
9 (2)
2 (1)
1 (< 1)
Any serious AE‡ 21 (6) 16 (4)
*All drug-related AEs were grade 2 severity. †Includes 1 fatal AE due
to homicide. ‡None was drug related.

Study 380-4030: Switch to BIC/FTC/TAF From
DTG + FTC/(TAF or TDF)
 Randomized, double-blind, active-controlled phase III noninferiority trial
Sax. IAS 2019. Abstr MOAB0105. Slide credit: clinicaloptions.com
Adults receiving DTG + FTC/(TAF or TDF) with
HIV-1 RNA < 50 copies/mL for ≥ 3-6 mos,* no known
INSTI resistance,† and no previous VF on INSTI
(N = 565)
BIC/FTC/TAF QD
(n = 284)
DTG + FTC/TAF QD
(n = 281)
Wk 48
*3 mos if no known NRTI resistance mutations, 6 mos with known/suspected resistance.
†Documented or suspected NRTI, NNRTI, or PI resistance permitted.
Stratified by known/suspected NRTI resistance at BL
(K65R or ≥ 3 TAMs vs other NRTI RAMs vs none)
 Primary endpoint: HIV-1 RNA ≥ 50 c/mL at Wk 48 by FDA Snapshot algorithm
‒ Noninferiority margin: 4%

 Switch to BIC/FTC/TAF noninferior to remaining on DTG-based ART; HIV-1 RNA
≥ 50 copies/mL not observed in any patient with preexisting NRTI resistance
HIV-1 RNA
< 50 c/mL
HIV-1 RNA
≥ 50 c/mL
No Virologic
Data
1/
284
3/
281
265/
284
256/
281
22/
281
18/
284
Study 380-4030: Virologic Outcomes at Wk 48
Sax. IAS 2019. Abstr MOAB0105. Reproduced with permission. Slide credit: clinicaloptions.com
Virologic Outcomes (FDA Snapshot)
BIC/FTC/TAF
(n = 284)
DTG + FTC/TAF
(n = 281)
Patients(%)
n/N =
100
80
40
60
20
0
< 1 1
93 91
6 8
-4 -2 0 2 4
Favors DTG + FTC/TAFFavors BIC/FTC/TAF
-0.7
1.0-2.8
HIV-1 RNA ≥ 50 copies/mL
Treatment Difference, % (95% CI)

Study 380-4030: Resistance Analyses
 Among patients with virologic rebound (n = 3 in DTG + FTC/TAF arm),
no treatment-emergent resistance through Wk 48
Predictor of Preexisting
NRTI Resistance
Any NRTI Mutation Present M184V/I Present*
OR (95% CI) P Value OR (95% CI) P Value
Time since ART start (per yr) 1.1 (1.1-1.2) < .0001 1.1 (1.1-1.1) < .0001
Prior PI-containing regimen 2.0 (1.2-3.5) .0116 2.2 (1.1-4.2) .0189
Black race (vs nonblack) 2.1 (1.2-3.6) .0106 2.5 (1.4-4.6) .0026
History of PI resistance 3.0 (1.3-6.9) .0123 2.6 (1.1-6.0) .0295
History of NNRTI resistance 2.4 (1.4-4.0) .0014 2.7 (1.5-4.7) .0007
*Preexisting M184V/I mutation present in 42% with PI resistance, 35% with NNRTI resistance.

Study 380-4030: Safety
Adverse Events
BIC/FTC/TAF
(n = 284)
DTG + FTC/TAF
(n = 281)
AE leading to study drug discontinuation, n (%) 6 (2.1) 6 (2.1)
Deaths,* n (%) 2 (< 1) 1 (< 1)
All grade AEs, %
 Any AE
 AEs in ≥ 10% of patients in either group
– Nasopharyngitis
– Diarrhea
– Upper respiratory tract infection
83
11
8
7
86
10
11
11
Any drug-related AE, %
 AEs in ≥ 2% of patients in either group
– Diarrhea
– Headache
14
1
1
10
2
2
*Included cardiopulmonary arrest (treatment emergent) and acute cerebral infarction (not treatment emergent) in the BIC/FTC/TAF group and
suspected myocardial infarction (treatment emergent) in the DTG + FTC/TAF group.
 No difference between arms in changes in fasting lipids or weight from BL to Wk 48

ATLAS and FLAIR Pooled Analysis: Long-Acting
Injectable CAB + RPV vs Daily Oral Three-Drug ART
 Multicenter, randomized, open-label phase III noninferiority trials
 Primary endpoint for both trials: HIV-1 RNA ≥ 50 copies/mL at Wk 48 by FDA Snapshot in ITT-E
LA CAB 400 mg + RPV 600 mg IM Q4W
(n = 303)
Continue Baseline ART PO
(n = 308)
Adults on stable ART (either first
or second regimen) with
HIV-1 RNA < 50 copies/mL for
≥ 6 mos with no previous VF
(N = 616)
Comparator arm
patients eligible to
receive CAB + RPV
in extension phase
after Wk 52
(ATLAS-2M study)
Wk 48 Primary Endpoint
ATLAS
LA CAB 400 mg +
RPV 600 mg IM Q4W
(n = 278)
Continue DTG/ABC/3TC PO QD
(n = 283)
ART-naive patients with
HIV-1 RNA ≥ 1000 copies/mL,
HBsAg negative, no NNRTI RAMs
but K103N permitted
(N = 629)
CAB 30 mg +
RPV 25 mg PO QD
(n = 283)
Wk 48 Primary EndpointWk 4
DTG/ABC/3TC PO QD
Wk 96Day 0
Wk 20FLAIR
Overton. IAS 2019. Abstr MOPEB257.
CAB 30 mg +
RPV 25 mg PO QD
(n = 308)
Wk 4Day 0

ATLAS and FLAIR Pooled Analysis:
Efficacy at Wk 48 in ITT-E Population
Overton. IAS 2019. Abstr MOPEB257. Reproduced with permission.
Participants(%)
100
80
40
60
20
0
Virologic
Nonresponse
(≥ 50 c/mL)
Virologic
Success
(< 50 c/mL)
No Virologic
Data
1.9 1.7
93.1 94.4
5.1 3.9
LA CAB + RPV
(n = 591)
Continue oral ART
(n = 591)
Oral ARTLA CAB + RPV
Difference (%)
Oral ART LA CAB + RPV
-4.1
-1.4
-10 -8 -6 -4 -2 0 2 4 6 8 10
1.4
-1.4 1.7
0.2
-10 -8 -6 -4 -2 0 2 4 6 8 10
4% NI
margin
-10% NI
margin
*Adjusted for sex and
BL third agent class.
Key Secondary Endpoint
(HIV-1 RNA < 50 copies/mL)
LA CAB + RPV noninferior to
continued BL ART
Primary Endpoint
(HIV-1 RNA ≥ 50 copies/mL)
LA CAB + RPV noninferior to
continued BL ART

ATLAS: Health Status and Treatment Acceptance of
Long-Acting CAB + RPV
 Health status scores by SF-12 (mental and
physical) statistically similar between
arms at baseline, Wks 24 and 48
 Treatment acceptance by ACCEPT
questionnaire significantly higher with LA
CAB + RPV switch vs continued BL oral
ART at Wks 8, 24, and 48
*LOFC analysis adjusted for sex, age, race (white vs nonwhite), and
third agent class (INSTI vs PI vs NNRTI).
Mean Score* (± SD) LA CAB + RPV Oral ART
Mental component
 Baseline
 Wk 24
 Wk 48
53.13 (8.19)
53.49 (8.59)
53.8 (8.84)
53.68 (7.34)
53.43 (8.58)
53.57 (8.04)
Physical component
 Baseline
 Wk 24
 Wk 48
55.24 (5.74)
55.75 (5.55)
55.80 (5.51)
54.61 (5.76)
54.66 (5.96)
54.79 (6.23)
Adjusted Mean Δ
From BL in General
Acceptance
Domain*
LA CAB
+ RPV
Oral
ART
Difference
(95% CI)†
Wk 8 8.9 1.0 7.9 (4.1-11.7)
Wk 24 12.3 5.5 6.9 (3.3-10.4)
Wk 48 13.7 3.0 10.7 (7.1-14.4)
Murray. IAS 2019. Abstr MOAB0103.
†P < .001 for all listed differences.

ATLAS: Patient Views on Long-Acting CAB + RPV
 86% to 90% of LA CAB + RPV recipients
scored ISRs and pain at Wk 48 as totally
or very acceptable in PIN questionnaire
 Greater improvement in treatment
satisfaction by HIVTSQ at Wks 24, 44
with LA CAB + RPV vs daily oral ART
Slide credit: clinicaloptions.comMurray. IAS 2019. Abstr MOAB0103.
Acceptability, %
LA CAB + RPV
Wk 5 (n = 296) Wk 48 (n = 303)
ISRs
 Totally
 Very
 Moderately
 A little
 Not at all
48
26
18
5
3
67
23
7
3
1
Pain
 Totally
 Very
 Moderately
 A little
 Not at all
29
35
20
10
6
55
31
9
4
1
P < .001 for Δ over time in “acceptability of ISRs” domain of PIN.
Patient Preference for
ART Delivery Method
by Population, % (n/N)
Long-acting
IM
Daily
PO
ITT-E 86 (266/308) 2 (7/308)
Responding patients 97 (266/273) 3 (7/273)
Adjusted Mean Δ
From BL in Tx
Satisfaction*
LA CAB +
RPV
BL Oral
ART
Difference
(95% CI)†
Wk 24 6.43 1.05 5.39 (4.17-6.60)
Wk 44 6.12 0.44 5.68 (4.37-6.98)
*Adjusted for BL score, sex, age, race, and BL third agent class.
†P < .001 for all listed differences.

ANRS 170 QUATUOR: Study Design
 Multicenter, randomized, open-label phase III noninferiority study
HIV-infected adults with HIV-1 RNA < 50 c/mL
for ≥ 12 mos on ART,* no genotypic resistance,
CD4+ cell count > 250 cells/mm3
(N = 640)
ART on 4 Days Out of 7 (4D/7)
(n = 320)
ART on 7 Days Out of 7 (7D/7)
(n = 320)
Primary Endpoint
Wk 48Stratified by 3rd agent
*ART regimen based on either PI, NNRTI, or INSTI with 2 NRTIs.
All participants
receive open-label
4D/7 through Wk 96
Landman. IAS 2019. Abstr WEAB0406LB.
 Primary endpoint: HIV-1 RNA < 50 copies/mL and no strategy
interruption (except for pregnancy and within-class switches)

ITT - KM
PP - KM
ANRS 170 QUATUOR: Treatment Success at Wk 48 in ITT
Population (Primary Endpoint)
 VF not associated with ARV class
 Emergent resistance detected in 3 of 6
failing 4D/7 vs 1 of 4 failing 7D/7
Slide credit: clinicaloptions.comLandman. IAS 2019. Abstr WEAB0406LB. Reproduced with permission.
Therapeutic Success
Patients(%)
100
80
40
60
20
0
Therapeutic
Success
No Virologic
Data
1.9 1.3
95.6 97.2
2.5 1.6
4D/7 (n = 318)
7D/7 (n = 318)
Virologic
Failure
4D/77D/7
-1.3
-1.6
-5 -4 -3 -2 -1 0 1 2 3 4 5
NI margin -1.6
ITT - KM
PP - KM
ITT - Snapshot
Virologic Failure
0.6
-5 -4 -3 -2 -1 0 1 2 3 4 5
0.6
Difference (95% CI)
NI margin

ANRS 170 QUATUOR: Treatment Failure by Third Agent
Slide credit: clinicaloptions.comLandman. IAS 2019. Abstr WEAB0406LB. Reproduced with permission.
Virologic Failure
by Third Agent, n/N
4D/7 7D/7
INSTI 3/152 1/152
NNRTI 3/148 3/148
PI 0/18 0/18
Virologic Failure
Difference (95% CI) of Proportion
4D/77D/7
0.0
1.4
-5 -4 -3 -2 -1 0 1 2 3 4 5
0.0
INSTI
NNRTI
PI
Third Agent

ANRS 170 QUATUOR: Safety at Wk 48
Median Change in Laboratory Parameters and
Weight Between BL and Wk 48
P < .05
Landman. IAS 2019. Abstr WEAB0406LB. Reproduced with permission.
15
5
10
0
-5
4D/7
7D/7
 No difference in overall safety
between strategies
 Significantly greater eGFR elevation
with 4D/7 vs 7D/7 from BL to Wk 48
(P < .05)
AEs
4D/7
(n = 318)
7D/7
(n = 318)
P Value
All AEs, % 72.3 73.9 .721
Grade 3/4 AEs, % 7.9 9.4 .594
Death, n 2 0 .499
D/c due to AE, n 1 0 1.000

BRIGHTE: Fostemsavir in Heavily Treatment–
Experienced Adults With Multidrug Resistant HIV
 Wk 96 analysis of randomized, double-blind phase III trial in heavily treatment–experienced adults
failing current ART with confirmed HIV-1 RNA ≥ 400 c/mL
‒ At BL: median HIV-1 RNA, 4.6 log10 c/mL; median CD4+ cell count, 80 cells/mm3; AIDS history, 86%
Randomized Cohort
1-2 remaining ARV classes
(≥ 1 fully active§ approved agent/class),
cannot construct viable regimen with
remaining agents
(n = 272)
*Blinded. †Day 8 adjusted by Day 1. ‡Open-label. §No evidence of resistance; patient eligible for, tolerant of, willing to receive the ARV. ║Measured from start of open-label tx.
Study conducted until another option, rollover study, or approved ARV available.
Primary Endpoint
Mean Δ in HIV-1 RNA,†
log10 c/mL (95% CI)
-0.79 (-0.88 to -0.70)
-0.17 (-0.33 to -0.01)
Day 9
FTR 600 mg BID +
Failing Regimen*
(n = 203)
Placebo +
Failing Regimen*
(n = 69)
FTR 600 mg BID + OBT‡
FTR 600 mg BID + OBT‡
Treatment ∆: -0.63
Nonrandomized Cohort
No remaining ARV classes and no
fully active§ approved agents
(n = 99)
FTR 600 mg BID + OBT‡ (investigational agents allowed)
Day 1
Lataillade. IAS 2019. Abstr MOAB0102. Pialoux. IAS 2018. Abstr THPEB045.
Day 8 Wk 96‖

BRIGHTE: ITT-E Virologic Response Through Wk 96
Lataillade. IAS 2019. Abstr MOAB0102. Reproduced with permission.
Randomized Cohort (n = 272)
Nonrandomized Cohort (n = 99)
HIV-1RNA<40copies/mL(%)
*Snapshot analysis excluded baseline data. 1 patient had BL HIV-1 RNA < 40 copies/mL.
100
80
60
40
20
0
Baseline* Wk 24 Wk 48 Wk 72 Wk 96
53 54 53
60
37 38 35 37
Outcome at Wk 96, n (%)
Randomized
Cohort
(n = 272)
Nonrandomized
Cohort
(n = 99)
HIV-1 RNA < 40 copies/mL 163 (60) 37 (37)
HIV-1 RNA ≥ 40 copies/mL
 Data in window not below
threshold
 D/c for lack of efficacy
 D/c for other reason while
not below threshold
 Change in ART*
81 (30)
33 (12)
10 (4)
17 (6)
21 (8)
43 (43)
15 (15)
3 (3)
6 (6)
19 (19)
No virologic data
 D/c due to AE or death
 D/c for other reasons
 Missing data during
window
28 (10)
15 (6)
8 (3)
5 (2)
19 (19)
14 (14)
4 (4)
1 (1)
 Mean change from BL to Wk 96 in CD4+ count, cells/mm3: randomized cohort, 205; nonrandomized cohort, 119
 In the randomized cohort, mean CD4+/CD8+ cell ratio increased from BL (0.2) to Wk 96 (0.443)

BRIGHTE: Safety Through Wk 96
Slide credit: clinicaloptions.comLataillade. IAS 2019. Abstr MOAB0102.
Cumulative Safety Outcomes
Through Wk 96, n (%)
Randomized Cohort
(n = 272)*
Nonrandomized Cohort
(n = 99)
All Treated Patients
(N = 371)
Any event 249 (92) 98 (99) 347 (94)
 Any grade 2-4 AE 216 (79) 87 (88) 303 (82)
 Drug-related grade 2-4 AEs 57 (21) 22 (22) 79 (21)
 Any grade 3/4 AE 78 (29) 49 (49) 127 (34)
 Any serious AE 92 (34) 48 (48) 140 (38)
 Drug-related serious AE 9 (3) 3 (3) 12 (3)
 Any AE leading to d/c 14 (5) 12 (12) 26 (7)
 Any CDC class C event 23 (8) 15 (15) 38 (10)
 Death 12 (4) 17 (17) 29 (8)†
*Includes patients initially randomized to placebo. Data are from initiation of open-label fostemsavir.
†AIDS-related events or acute infections, n = 18 (1 case of IRIS considered treatment-related); occurring after study d/c, n = 5.

Study 380-4449: Switch to BIC/FTC/TAF in
Adults ≥ 65 Yrs of Age
 Multicenter, open-label, single-arm phase IIIb study in adults ≥ 65 yrs of age with
virologic suppression on stable ART for ≥ 3 mos (N = 86)
‒ Switch from EVG/COBI/FTC/TAF or FTC/TDF + third agent to BIC/FTC/TAF
Maggiolo. IAS 2019. Abstr MOPEB238. Slide credit: clinicaloptions.com
HIV-1 RNA ≥
50 copies/mL
HIV-1 RNA
< 50 copies/mL
(Primary Endpoint)
n/N =
Participants(%)
100
80
60
40
20
0
No Virologic Data
in Window
84/86
2
98
0/86 2/86
Virologic Outcomes at Wk 24 (FDA Snapshot)
 Median change in CD4+ cell count at
Wk 24: -7 cells/mm3 (IQR: -80 to 90)

Study 380-4449: Safety
 No grade 3/4 treatment-related
AEs
 1 treatment-related AE resulted
in study drug discontinuation
Maggiolo. IAS 2019. Abstr MOPEB238. Slide credit: clinicaloptions.com
Median Δ From BL to Wk 24 BIC/FTC/TAF
Weight, kg 0
eGFR, mL/min -4.5
Lipid parameters
 Total cholesterol, mg/dL
 LDL cholesterol, mg/dL
 HDL cholesterol, mg/dL
 Triglycerides, mg/dL
 Total cholesterol:HDL
-14
-7
-3
-17
0.1
Renal biomarkers, %
 β2-microglobulin:creatinine
 RBP:creatinine
-20.8
-15.6

Early-Phase Investigational ART

DRIVE2Simplify Part 2: Islatravir + Doravirine vs
DOR/3TC/TDF in ART-Naive Adults
 Current analysis of Part 2 for international, randomized, double-blind phase IIb trial
Slide credit: clinicaloptions.comMolina. IAS 2019. Abstr WEAB0402LB.
 Primary endpoints: rate of HIV-1 RNA < 50 c/mL at Wks 24 and 48 (FDA Snapshot), AEs, AE-related d/c
Treatment-naive adults with
HIV-1 RNA ≥ 1000 c/mL,
CD4+ count ≥ 200 cells/mm3,
no ARV drug resistance,
no active HCV or HBV
coinfection
(N = 121)
Part 1:
3-Drug Dose Ranging
ISL 0.25 mg + DOR + 3TC QD*
(n = 29)
DOR/3TC/TDF QD†
(n = 31)
(n = 30)
(n = 31)
Stratified by screening HIV-1 RNA
(≤ vs > 100,000 c/mL)
ISL 0.25 mg + DOR QD
(n = 29)
DOR/3TC/TDF QD
(n = 28)
(n = 30)
(n = 27)
ISL at selected dose +
DOR QD
DOR/3TC/TDF QD
Part 2:
2-Drug Dose Ranging
Part 3:
Maintenance
If HIV-1 RNA < 50 c/mL at Wk 20
without meeting any VF criteria‡
Wk 24 Wk 48 Wk 96
*Received placebo for DOR/3TC/TDF. †Received placebo for ISL + DOR + 3TC QD.
‡If HIV-1 RNA ≥ 50 c/mL at Wk 20, continued Part 1 until HIV-1 RNA < 50 c/mL
and, if not meeting any VF criteria, transitioned to Part 2.

0/28
DRIVE2Simplify Part 2: Virologic Outcomes at Wk 24
Upon Entry to Part 2 (FDA Snapshot)
HIV-1 RNA < 50 c/mL HIV-1 RNA ≥ 50 c/mL No Virologic Data in Window
Patients(%)
25/28 27/30 24/27 27/28 2/28 2/30 1/27 1/28 1/28 1/30 2/27n/N =
Slide credit: clinicaloptions.comMolina. IAS 2019. Abstr WEAB0402LB. Reproduced with permission.
ISL 0.25 mg + DOR + 3TC
DOR/3TC/TDF
100
80
60
40
20
0
83.9 90 88.9
96.4
7.1 6.7 3.7 3.6 3.6 3.3
7.4

Patients(%)
26/29 27/30 24/31 2/29 2/30
DRIVE2Simplify Part 2: Virologic Outcomes at Wk 48
(FDA Snapshot)
Slide credit: clinicaloptions.comMolina. IAS 2019. Abstr WEAB0402LB. Reproduced with permission.
 All patients with PDVF had confirmatory HIV-1 RNA < 80 c/mL;
no patients met criteria for resistance testing
HIV-1 RNA < 50 c/mL HIV-1 RNA ≥ 50 c/mL No Virologic Data in Window
26/31 4/31 2/31 1/29 1/30 3/31 3/31n/N =
ISL 0.25 mg + DOR
ISL 0.75 mg + DOR
ISL 2.25 mg + DOR
DOR/3TC/TDF
100
80
60
40
20
0
89.7 90
77.4
83.9
7.1 6.7
12.9
6.5
3.4 3.3
9.7 9.7

DRIVE2Simplify Part 2: Adverse Events Through Wk 48
 No deaths reported
 Numerically greater frequency of drug-related AEs with DOR/3TC/TDF vs any dose
of ISL
Slide credit: clinicaloptions.comMolina. IAS 2019. Abstr WEAB0402LB.
Safety Outcome,
n (%)
ISL 0.25 mg
Arm
(n = 29)
ISL 0.75 mg
Arm
(n = 30)
ISL 2.25 mg
Arm
(n = 31)
All ISL
Arms
(n = 90)
DOR/3TC/TDF
Arm
(n = 31)
≥ 1 AE 21 (72.4) 26 (86.7) 19 (61.3) 66 (73.3) 24 (77.4)
Drug-related AE 0 3 (10.0) 4 (12.9) 7 (7.8) 6 (19.4)
Serious AE 1 (3.4) 2 (6.7) 0 3 (3.3) 2 (6.5)
D/c due to AE 0 0 2 (7.4)* 2 (2.2) 1 (3.2)†
*1 case each of diarrhea/nausea/vomiting with onset at Day 200 lasting ~ 2 wks and reactivated HBV with onset at Day 201.
†1 case of worsening congenital long QT syndrome.

Select Agents Under Early Investigation For the
Prevention and Treatment of HIV
Agent MOA Phase n Key Findings
Ad26.Mos4.HIV and either
clade C gp140 or bivalent
gp140[1]
Vaccine I/IIa 126
 Both regimens induced immune responses against a broad
range of HIV-1 subtypes in healthy adults; well tolerated
Islatravir (ISL; MK-8591)[2] NRTTI I 12
 Drug-eluting implants projected to provide HIV prophylaxis for
≥ 1 yr; well tolerated. ISL + DOR tx regimen in phase IIb[3]
2-hydroxypropyl--
cyclodextrin cabotegravir
nanochannel delivery
implant[4]
INSTI PK
6
(rats)
 Clinically-relevant plasma CAB concentrations and drug
penetration into relevant tissues; no AEs observed
GS-6207[5] HIV-1 capsid
inhibitor
Ib 18
 Single SC 50-450 mg dose provided potent antiviral activity,
well tolerated in PLWH naive to capsid and integrase inhibitors
VRC01LS and VRC07-523LS[6] HIV-1 bNAbs I 16
 Decreased HIV-1 RNA following 1 IV dose in viremic PLWH;
well tolerated
Vesatolimod (GS-9620)[7] TLR 7 agonist Ib 36
 Induced immune activation at doses ≥ 4 mg in virologically-
suppressed PLWH; well tolerated
1. Stieh. IAS 2019. Abstr TUAC0402LB. 2. Matthews. IAS 2019. Abstr TUAC0401LB. 3. Molina. IAS 2019. Abstr WEAB0402LB. 4. Pons-Faudoa.
IAS 2019. Abstr TUPEA106. 5. Daar. IAS 2019. Abstr LBPEB13. 6. Chen. IAS 2019. Abstr WEAA0305LB. 7. Riddler. IAS 2019. Abstr WEAA0304.

HPTN 078: Intervention to Engage Virologically
Unsuppressed MSM Living With HIV
Remien. IAS 2019. Abstr MOAX0101LB. Slide credit: clinicaloptions.com
MSM living with HIV infection,
detectable HIV-1 RNA
(N = 144)
Enhanced Case Management
(n = 72)
Standard of Care
(n = 72)
12 Mos
 Enhanced case management: access to a case manager and referral services, counseling
using motivational interviewing, and automated adherence and motivational messaging
‒ Intervention intensity was participant driven (by choosing frequency and content of interactions)
 Study population: predominantly black (84%), educated (≥ 90% had high school diploma),
low income (65% earned < $20,000 annually), and ART experienced (86%)
‒ Median HIV-1 RNA at baseline: 19,459 copies/mL

HPTN 078: Virologic Suppression Rates Similar With
Enhanced Case Management vs Standard of Care
Remien. IAS 2019. Abstr MOAX0101LB. Slide credit: clinicaloptions.com
 At Month 12, 91% of participants were retained and 48% were virologically
suppressed
 No significant difference in virologic suppression rates between enhanced case
management and standard of care (OR: 0.615; 95% CI: 0.315-1.197; P = .1526)
Enhanced case management
Standard of care
Month 3
n/N =
HIV-1RNA
<200copies/mL(%)
100
80
60
40
20
0
20/72
2928
Month 6 Month 9 Month 12
21/72 26/72
3636
26/72 28/72
3939
28/72 30/72
54
42
38/72

Rosuvastatin for Atherosclerotic Progression in People
With HIV at Moderate Cardiovascular Risk
 Randomized, double blind, placebo-controlled, multinational trial
 Study population consisted primarily of white males; mean age: 54 years
 Approximately one third of participants were current smokers, and approximately one third had a family
history of heart attack
 Approximately one quarter of participants were receiving abacavir
Trevillyan. IAS 2019. Abstr MOAB0201. Slide credit: clinicaloptions.com
Patients with HIV infection (> 30 yrs
of age) with moderate coronary heart
disease risk* and no indication for
initiation of statin therapy; on stable
ART for > 3 mos and HIV-1 RNA
< 200 copies/mL for ≥ 6 mos
(N = 84)
Rosuvastatin 20 mg QD†
(n = 44)
Placebo
(n = 40)
*Framingham risk score: 10-15%.
†Participants on a boosted PI or COBI received 10 mg rosuvastatin.
Wk 96

Rosuvastatin vs Placebo: Outcomes at Wk 96
 Decreases in total and LDL cholesterol with rosuvastatin vs placebo
 Greater incidence of adverse events in rosuvastatin vs placebo arm
‒ 75% vs 27% of participants experienced ≥ 1 AE
‒ 16% vs 0% experienced grade 3/4 AEs
Trevillyan. IAS 2019. Abstr MOAB0201. Slide credit: clinicaloptions.com
Mean Common Carotid IMT (SD) Rosuvastatin
(n = 44)
Placebo
(n = 40)
P Value†
Baseline 0.722 (0.032) 0.772 (0.033) .115
48 wks 0.726 (0.032) 0.771 (0.033) .158
96 wks (primary endpoint) 0.726 (0.032) 0.779 (0.033) .097
P value* .319 .115
*Baseline vs Wk 96 within each arm.
†Difference between arms at each time point.

BRAHMS: STIs Among MSM in Germany
 Multicenter, prospective study in MSM aged 18-45 yrs at risk of HIV
infection (N = 1040)
‒ Eligibility criteria: in last 24 wks, documented syphilis, rectal gonorrhea,
or chlamydia OR condomless anal intercourse with ≥ 2 unique male
partners whose HIV status was positive or unknown
 Participants screened for STIs every 3 mos by blood, urine, anal swab,
and oropharyngeal swab; also given sexual behavior questionnaires
 At BL, 45% were receiving PrEP, 18% initiated PrEP after risk reduction
counseling, and 37% chose not to receive PrEP
Slide credit: clinicaloptions.comStreeck. IAS 2019. Abstr TUPDC0106.

BRAHMS: STI Prevalence
 No difference in STI point prevalence
by PrEP status; all cases of HIV in
non-PrEP users
 25% of participants had > 1 STI
 Most STIs were rectal, asymptomatic
STI Point Prevalence (N = 1040) Chlamydia
(n = 155)
Mycoplasma
(n = 231)
Gonorrhea
(n = 134)
17%
15%
68%
15%
26% 59%
44%
7%
49%
Streeck. IAS 2019. Abstr TUPDC0106. Reproduced with permission.
Non-PrEP
PrEP
Cases
250
200
150
100
50
0
Point Prevalence, % 12
12.6
11.4
19
18.5
19.7
9.2
8.5
10.2
4.6
4
5.5
0.4
0.7
0.2
0.4
0.6
0.2
Overall
Non-PrEP
PrEP
Anal
Urine
Throat

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