March 4-7, 2019; Seattle, Washington In this downloadable slideset, expert faculty members summarize key studies from this important annual conference. Format: Microsoft PowerPoint (.ppt) File Size: 576 KB Released: March 22, 2019

1. Clinical Impact of New HIV Data From CROI 2019*
This program is supported by independent educational grants from
Gilead Sciences; Janssen Therapeutics; Merck & Co, Inc; and ViiV Healthcare.
CCO Independent Conference Coverage*
of the 2019 Conference on Retroviruses and Opportunistic Infections,
March 4-7, 2019; Seattle, Washington
*Clinical Care Options (CCO) is an independent medical education organization that provides conference
coverage and other unique educational programs for healthcare professionals.

2. About These Slides
 Please feel free to use, update, and share some or all of these slides in
your noncommercial presentations to colleagues or patients
 When using our slides, please retain the source attribution:
 These slides may not be published, posted online, or used in
commercial presentations without permission. Please contact
permissions@clinicaloptions.com for details
Slide credit: clinicaloptions.com

3. Faculty
W. David Hardy, MD
Adjunct Professor of Medicine
Division of Infectious Diseases
Johns Hopkins University School of
Medicine
Washington, DC
Daniel R. Kuritzkes, MD
Chief, Division of Infectious Diseases
Brigham and Women’s Hospital
Harriet Ryan Albee Professor of
Medicine
Harvard Medical School
Boston, Massachusetts

4. Faculty Disclosures
W. David Hardy, MD, has disclosed that he has received consulting fees
from Gilead Sciences, Merck, and ViiV Healthcare and funds for research
support from Abbott Molecular, Amgen, Gilead Sciences, Janssen, Merck,
and ViiV Healthcare.
Daniel R. Kuritzkes, MD, has disclosed that he has received consulting
fees from Abivax, Gilead Sciences, GlaxoSmithKline, Janssen, Merck, and
ViiV Healthcare; fees for non-CME/CE services from Janssen; and funds
for research support from Abbott, Gilead Sciences, Merck, and ViiV
Healthcare.

5. Pre-Exposure Prophylaxis

6. DISCOVER: FTC/TAF vs FTC/TDF Oral PrEP in cis-MSM
and Transgender Women
 International, randomized, double-blind, active-controlled phase III trial
Hare. CROI 2019. Abstr 104LB. NCT02842086. Slide credit: clinicaloptions.com
Option for
open-label FTC/TAF
up to Wk 144
FTC/TAF 200/25 mg + FTC/TDF Placebo QD
(n = 2694)
FTC/TDF 200/300 mg + FTC/TAF Placebo QD
(n = 2693)
Wk 96
HBV-negative cis-MSM and
transgender women at high risk
of HIV* with eGFR ≥ 60 mL/min;
prior PrEP use permitted
(N = 5387)
*Defined as ≥ 2 episodes of condomless anal sex within past 12 wks or rectal gonorrhea, chlamydia, or syphilis within past 24 wks.
Prevention services (eg, risk reduction, condoms/lubricant) and adherence counseling provided at entry and every 12 wks.
 Primary endpoint: HIV incidence/100 PY
‒ Noninferiority upper bound of 95% CI for
IRR of FTC/TAF vs FTC/TDF: < 1.62
‒ Expected incidence 1.44/100 PY based on
prior studies
 Secondary endpoints: adherence,
resistance, safety, including renal
biomarkers and BMD substudy

7. 2
DISCOVER: FTC/TAF Noninferior to FTC/TDF for Efficacy
 Primary analysis conducted when 100%
completed Wk 48, 50% completed Wk 96
 Noninferiority of FTC/TAF maintained in
sensitivity analysis excluding suspected
BL infections
‒ IRR: 0.55 (95% CI: 0.20-1.48)
Slide credit: clinicaloptions.comHare. CROI 2019. Abstr 104LB. Reproduced with permission.
Outcome, n FTC/TAF FTC/TDF
Possible causes of HIV infection
 Suspected BL infection
 Low TFV-DP in DBS
 Medium/high TFV-DP in DBS
(n = 2694)
1
5
1
(n = 2693)
4
10
1
Resistance genotype performed
 FTC
 TFV
(n = 6)
0
0
(n = 13)
4*
0
*All with suspected BL infection.
FTC/TAF
(n = 2694)
FTC/TDF
(n = 2693)
0.6
0.5
0.3
0.2
0.1
0
HIVIncidence/
100PY
HIV Incidence: 22 Infections in 8756 PYFU
0.4
4386 PY
4370 PY
7 infections
15 infections0.16
0.34
Favors FTC/TAF Favors FTC/TDF
Incidence Rate Ratio (95% CI)
0.19
0.47
0 1 1.62
Noninferiority
margin
1.15

8. DISCOVER: Safety, Incidence of Sexually Transmitted
Infections
 Similar AE rates with FTC/TAF vs FTC/TDF
‒ Study drug–related AEs: 20% vs 23%
‒ AEs leading to d/c: 1% vs 2%
 Similar on-study incidence of gonorrhea,
chlamydia, or syphilis per AE reporting
‒ Incidence per 100 PY: 145.1 vs 138.8
‒ Lab-assessed GC/CT rate steady through
Wk 96 in each arm (~ 10% to 15%)
 Deaths: 1 vs 2
‒ Included traffic accident, metastatic
squamous cell carcinoma, unknown
 Significantly better bone and renal
outcomes with FTC/TAF vs FTC/TDF
Slide credit: clinicaloptions.com
Safety Outcome
Through Wk 48
FTC/
TAF
FTC/
TDF
P
Value
Mean change from BL, %
 Spine BMD
 Hip BMD
0.50
0.18
-1.12
-0.99
< .001
< .001
Median change from BL
in eGFRCG, mL/min
1.8 -2.3 < .001
Renal d/c, n 2 6 --
Fanconi syndrome, n 0 1 --
Hare. CROI 2019. Abstr 104LB.

9. Evaluation for Immediate PrEP Initiation in cis-Gender
Adults From NYC Walk-in Clinic Setting
 NYC sexual health clinics assess individuals for same-day PrEP initiation via
medical history, physical exam, and rapid HIV antibody testing
‒ Looking for history of renal disease or HBV infection, acute HIV signs/symptoms
Slide credit: clinicaloptions.comMikati. CROI 2019. Abstr 962.
If none of these parameters found:
PrEP is delayed (dPrEP) until lab tests
show absence of contraindications*
If any of these parameters found:
If lab results show positive HIV NAAT or
GFR < 60 mL/min, iPrEP is stopped
30-day FTC/TDF immediate PrEP (iPrEP)
provided before lab results available
Return within 60 days for initiation
*GFR < 60 mL/min, positive HIV NAAT or for HBsAg.
 Current analysis of January 2017 - June 2018 medical records evaluated
prevalence of medical contraindications to PrEP in patients initiating iPrEP or
dPrEP (N = 1437)

10. Medical Contraindications to PrEP for cis-Gender Adults
From NYC Walk-in Clinic Setting
 Low rate of contraindications
among iPrEP group: 0.7%
 Only 15/43 (35%) in dPrEP group
without medical contraindications
initiated PrEP at NYC sexual health
clinic within 60 days
 Contraindications in iPrEP group
6 x more likely for those ≥ vs
< 40 yrs of age (3% vs 0.5%; P = .01)
 Women (n = 58) 4 x more likely
than men to qualify for dPrEP
(12.1% vs 3.1%; P < .001), yet no
woman had medical
contraindications
Slide credit: clinicaloptions.com
Medical
Contraindication to
PrEP, n (%)
iPrEP
(n = 1387)
dPrEP
(n = 50)*
P
Value
Any 10 (0.7) 7 (14.0) < .001
 Positive HIV NAAT 2 (0.1) 1 (2.0) .10
 GFR < 60 mL/min 2 (0.1) 4 (8.0) < .001
 Reactive HBsAg 6 (0.5) 2 (4.0) .03
Mikati. CROI 2019. Abstr 962.
*Reasons for delay: acute HIV signs/symptoms (n = 12), history
of CKD (n = 16) or HBV infection (n = 9), other (n = 13).

11. PrEP Drug Resistance Among Individuals Recently
Diagnosed With HIV in NYC Who Previously Used PrEP
 Surveillance study utilizing PrEP use data from cases assigned to partner services, medical
provider report forms, and NYC surveillance field investigation
‒ Data on drug resistance, HIV NAAT, and acute HIV infection obtained from NYC surveillance
registry and laboratory database
 Study compared PrEP users vs never-users regarding PrEP drug resistance (FTC: M184I/V;
TDF: K65R) and diagnosis of acute HIV infection
 Of 3685 patients diagnosed with HIV in previous 12 mos and referred for partner services
in NYC, 91 individuals (2%) used PrEP prior to diagnosis
‒ Median duration between PrEP initiation and HIV diagnosis: 250 days (IQR: 395)
‒ Median duration of PrEP prior to HIV diagnosis: 106 days (IQR: 214)
 PrEP users more likely to be younger (< 30 yrs), cis-men, white, and MSM vs never-users
Misra. CROI 2019. Abstr 107. Slide credit: clinicaloptions.com

12. PrEP Surveillance Study: Resistance Mutations,
Acute HIV Infection
 Identification of FTC, but not TDF,
resistance associated mutations common
among previous PrEP users
 Diagnosis in acute stage more common in
previous PrEP users vs never-users
 In New York, NAAT required prior to PrEP
initiation if symptoms of acute HIV
infection present or if individual reported
condomless sex in previous 4 wks
‒ Only 25% of PrEP users had evidence
of negative NAAT before starting PrEP,
and only 5% had negative NAAT within
0-2 days before PrEP initiation
Outcome, %
PrEP
Users
(n = 91)
Never-
Users
(n = 3594)
Genotype data available 75 63
Resistance mutation
 M184I/V/IV/MV
 K65R
29
0
2
< 1
Acute HIV infection 33 9
Slide credit: clinicaloptions.comMisra. CROI 2019. Abstr 107.

13. EleMENt: PrEP Uptake and Persistence Among Young
Black MSM
 Prospective observational cohort study of 298 HIV-negative young (age 16-29 yrs)
black MSM in Atlanta
 Participants followed for 24 mos with services at each 3-monthly study visit:
‒ STI testing, risk reduction counseling, urine drug testing, HIV rapid test, HIV/HBV/HCV
nucleic acid test, substance use and sexual behavior surveys
 Included optional PrEP program, with enrollment offered at each study visit
‒ Study to provide clinician visits and labs, PrEP navigator to facilitate medication access
and lab scheduling, and medication prescription
‒ Medication provided via commercial pharmacy and funded by insurance or patient
assistance program
 PrEP discontinuation defined as ≥ 14 days off PrEP after initiation (considered final
if never restarted before end of study or interim censoring)
Slide credit: clinicaloptions.comSerota. CROI 2019. Abstr 963.

14. EleMENt: Rates and Predictors of PrEP Discontinuation
 42% (125/298) initiated PrEP
‒ 63% discontinued at least once
during follow-up, with median time
to first discontinuation of 219 days
‒ 31% had final discontinuation,
with median time to final
discontinuation of 690 days
 Risky alcohol use and illicit drug
use other than marijuana not
significantly associated with PrEP
discontinuation
Slide credit: clinicaloptions.comSerota. CROI 2019. Abstr 963.
Predictor of Discontinuation aHR (95% CI)
First PrEP discontinuation
 < 22 yrs of age
 Marijuana use
 < 3 partners* in last 6 mos
 STI in past 12 mos
4.15 (2.24-7.72)
1.78 (1.07-2.95)
2.12 (1.31-3.42)
1.72 (1.05-2.81)
Final PrEP discontinuation
 < 22 yrs of age
 Marijuana use
 < 3 partners* in last 6 mos
3.72 (1.65-8.37)
2.68 (1.14-6.29)
2.39 (1.13-5.03)
*Anal sex.

15. Women Living With HIV

16. Pooled Efficacy and Safety Analysis of TAF vs TDF in
Women With HIV Infection
 Multiple randomized trials have suggested similar efficacy but more favorable renal
and bone safety profile with TAF vs TDF; however, women are underrepresented in
ART clinical trials
 Current analysis pooled efficacy and safety data from women with HIV infection
enrolled in 7 randomized trials (5 double-blind, 2 open-label) of TAF vs TDF for
antiretroviral initiation or switch
‒ Evaluated ARV activity, overall safety as well as renal and bone safety profiles
‒ Compared outcomes with those seen in men
 N = 779 cis-women (n = 260 treatment naive, n = 519 virologically suppressed)
‒ Received TAF- or TDF-containing regimens (other agents included EVG/COBI/FTC,
BIC/FTC, RPV/FTC, EFV/FTC, boosted PIs, and others)
Thompson. CROI 2019. Abstr 519. Slide credit: clinicaloptions.com

17. TAF vs TDF in Women: Virologic Outcomes at Wk 96
 Rates of
virologic
suppression
similar
between
agents and
vs men
Slide credit: clinicaloptions.com
Treatment Naive Virologically Suppressed % Treatment Difference
(95% CI)
TAF
TDF
Patients(%)
100
80
60
40
20
0
86
3
85
6
11 9
86 85
3 1
11 14
HIV-1 RNA
< 50 c/mL
HIV-1 RNA
≥ 50 c/mL
No Data HIV-1 RNA
< 50 c/mL
HIV-1 RNA
≥ 50 c/mL
No Data
n/N =
115
133
108
127
4
133
7
127
14
133
12
127
222
257
149
175
7
257
1
175
28
257
25
175
Favors TDF Favors TAF
TN
1.5
-7.3 10.4
6.8-6.9
0
VS
-12% -6% 0 6% 12%
Thompson. CROI 2019. Abstr 519. Reproduced with permission.

18. TAF vs TDF in Women: Safety Outcomes at Wk 96
 Significantly improved bone/renal parameters in women receiving TAF vs TDF,
especially in switch setting
‒ Most common AEs, treatment-emergent renal AEs, discontinuations for AE or death
similar between agents and vs men
Slide credit: clinicaloptions.com
Median Change From Baseline at Wk 96
Treatment Naive Virologically Suppressed
TAF TDF P Value TAF TDF P Value
BMD
 Spine
 Hip
-0.3
-1.3
-2.6
-3.9
< .001
< .001
1.7
1.7
-1.1
-0.8
< .001
< .001
eGFRCG -5.8 -8.6 .082 7.8 0 < .001
Renal
biomarker
 Urine albumin:Cr ratio
 Retinol binding protein:Cr
 β2M:Cr ratio
-12
12
-37
5
68
13
.084
< .001
< .001
-3
8
-10
28
51
29
< .001
< .001
< .001
Thompson. CROI 2019. Abstr 519.

19. NICHD P1081: RAL- vs EFV-Based ART Initiated During
Pregnancy
 Multicenter, randomized, open-label phase IV trial
 Primary endpoints: HIV-1 RNA < 200 copies/mL at delivery, discontinuation of RAL
or EFV prior to delivery, grade ≥ 3 AEs (mother and infant)
 Secondary endpoints: rapid/sustained HIV-1 RNA decline with continued use of
study ARV until delivery, stillbirth, preterm birth, infant HIV infection
Mirochnick. CROI 2019. Abstr 39LB. NCT01618305. Slide credit: clinicaloptions.com
ART-naive*, pregnant women
with HIV infection at
20† to < 37 wks of gestation
(N = 408)
Raltegravir + ZDV/3TC‡
(n = 206)
Efavirenz + ZDV/3TC‡
(n = 202)
Patients
followed until 24
wks postpartum
*Short-course ZDV (≤ 8 wks) for prevention of MTCT in previous pregnancies allowed. †Minimum gestational age reduced from
28 to 20 wks after 22% of study population enrolled. ‡Alternative NRTI backbone permitted if clinically indicated.
Stratified by gestational age

20.  Similar proportion on assigned ARV through delivery with RAL vs EFV: 99% vs 97% (P = .05)
P = .001 Interaction P = .04
ProportionWithOutcome(%)
RAL-based ART
Overall*
(n = 307)
20 to < 28 Wks
Gestation†
28 to < 37 Wks
Gestation†
HIV-1 RNA < 200 copies/mL at Delivery
100
40
80
60
20
0
84
94 9796
71
93
NICHD P1081: Primary Endpoints
EFV-based ART
Mirochnick. CROI 2019. Abstr 39LB. Reproduced with permission. Slide credit: clinicaloptions.com
Grade ≥ 3 Adverse Events
ProportionWithOutcome(%)
Infants§
(n = 393)
P = .94
Women‡
(n = 403)
P = .91
3030
100
40
80
60
20
0
2525
*Primary efficacy population: women with HIV-1 RNA ≥ 200 copies/mL and no genotypic resistance to any study ARV at entry; similar trends observed in sensitivity analyses
when restrictions on HIV-1 RNA, resistance lifted. †Time of study entry. ‡Women who received ≥ 1 dose of study ARV and their §live-born infants delivered on-study.

21. NICHD P1081: Kinetics of Virologic Suppression
Mirochnick. CROI 2019. Abstr 39LB. Reproduced with permission. Slide credit: clinicaloptions.com
EstimatedProportionWith
HIV-1RNA<200copies/mL
 Median time to
HIV-1 RNA < 200 copies/mL:
8 days with RAL vs 15 days with EFV
1.0
0.25
0.75
0.50
0
0 147 28 42 56 70 84 98 112
Days From Randomization
Generalized log-rank P < .001
RAL-based ART
EFV-based ART

22. *Includes women in primary efficacy/tolerability analyses with HIV-1 RNA data available at Wk 2 and
≥ 1 subsequent value after Wk 4.
NICHD P1081: Secondary Endpoints
Mirochnick. CROI 2019. Abstr 39LB. Slide credit: clinicaloptions.com
Outcome, n/N (%) RAL-Based ART EFV-Based ART P Value
Rapid, sustained virologic response in women
remaining on study drug through delivery*
 HIV-1 RNA decline ≥ 2 log or < 200 c/mL by Wk 2
 HIV-1 RNA < 1000 c/mL at all visits after Wk 4
 Remained on study drug through delivery
121/132 (92)
123/132 (93)
115/120 (96)
131/132 (99)
84/131 (64)
91/131 (69)
117/123 (95)
129/131 (98)
< .001
Birth outcome
 Stillbirth
 Preterm delivery (< 37 wks of gestation)
 Infant HIV infection
3/200 (2)
24/195 (12)
1/190 (1)
1/194 (1)
20/190 (11)
6/184 (3)
.62
.63
.06

23. DolPHIN-2: DTG- vs EFV-Based ART Initiated During
Pregnancy
 Randomized, open-label, active-controlled phase III trial
 Primary endpoint: HIV-1 RNA < 50 copies/mL at delivery
 Secondary endpoints: HIV-1 RNA < 1000 copies/mL at delivery, MTCT,
maternal and infant safety
Kintu. CROI 2019. Abstr 40LB. NCT03249181. Slide credit: clinicaloptions.com
Adult women with HIV infection at
≥ 28 wks of gestation; no ART
within 12 mos, prior INSTIs, NNRTI
failure, or EFV intolerance
(N = 268)
Treatment and
follow-up continued to
postpartum Wk 72
Dolutegravir + 2 NRTIs
(n = 137)
Efavirenz + 2 NRTIs
(n = 131)

24. DolPHIN-2: Virologic Suppression
Slide credit: clinicaloptions.comKintu. CROI 2019. Abstr 40LB. Reproduced with permission.
*RR: 1.66 (95% CI: 1.32-2.08).
Results unaffected by BL HIV-1 RNA or CD4+ cell count, gestation at entry, maternal age, or country in multivariate analysis.
HIV-1 RNA < 50 copies/mL at Delivery in Evaluable ITT Patients
PatientsWithOutcome(%)
Overall*
(N = 237)
< 100,000
(n = 198)
≥ 100,000
(n = 39)
BL HIV-1 RNA,
copies/mL
≥ 200
(n = 206)
< 200
(n = 31)
BL CD4+ Cell Count,
cells/mm3
< 36
(n = 200)
≥ 36
(n = 37)
Gestation,
Wks
P < .0001 P < .0001
P = .063
P = .124
P < .0001 P < .0001
P = .219
100
80
60
40
20
0
73.8
42.6
78.9
48.9 44.4
14.3
75.9
45.9
57.1
23.5
74.5
44.1
70.8
30.8
DTG-based ART
EFV-based ART

25. DolPHIN-2: Kinetics of Virologic Suppression
Slide credit: clinicaloptions.comKintu. CROI 2019. Abstr 40LB. Reproduced with permission.
Time to HIV-1 RNA < 50 copies/mL
(Primary Endpoint) Time to HIV-1 RNA < 1000 copies/mL
Days Since Randomization
ProportionWithOutcome
HIV-1 RNA < 1000 copies/mL at delivery: 92.6% in DTG arm vs 82.6% in EFV arm (RR: 1.11; 95% CI: 1.00-1.23; P = .05).
Median time on ART at delivery: 55 days (IQR: 33-77).
1.0
0.8
0.6
0.4
0.2
0
0 15 30 45 60 75
HR: 2.73 (95% CI: 1.91-3.89;
log-rank P < .0001)
Days Since Randomization
ProportionWithOutcome
1.0
0.8
0.6
0.4
0.2
0
0 15 30 45 60 75
DTG-based ART
EFV-based ART
HR: 1.49 (95% CI: 1.14-1.95;
log-rank P = .0011)

26. DolPHIN-2: Maternal and Infant Safety
 Infant transmissions: 3 in DTG arm vs 0 in EFV arm
 Maternal Cr Δ from BL: 6.2 μmol/L with DTG vs 1.8 μmol/L with EFV (P < .0001)
 Stillbirths: 4 with DTG vs 0 with EFV; all unrelated/not likely related to ART or IRIS
Safety Outcome in Evaluable Live Births
DTG-Based ART
(n = 123)
EFV-Based ART
(n = 119)
Overall
(N = 242)
Median gestation at delivery, wks (IQR)
 Preterm at < 37 wks, n (%)
 Preterm at < 34 wks, n (%)
39.9 (37.6-41.9)
21 (17.1)
6 (4.9)
39.9 (38.3-41.4)
18 (15.1)
6 (5.0)
39.9 (37.9-41.6)
39 (16.1)
12 (5.0)
≥ 1 serious AE, n (%) 65 (52.8) 55 (46.2) 120 (49.6)
Infant deaths,* n (%) 5 (4.1) 3 (2.5) 8 (3.3)
Slide credit: clinicaloptions.comKintu. CROI 2019. Abstr 40LB.
*All unrelated/not likely related to ART or IRIS.

27. Effects of INSTI Use During Conception/Pregnancy
 Interim analysis of birth defect surveillance study in Botswana raised concerns
about possible increased risk of NTDs with DTG at conception[1]
 Prospective analyses of pregnancy outcomes since that report have not found
any association between NTDs and INSTI use (including DTG or RAL) during
pregnancy, including periconception exposure[2-5]
‒ Hospital-based surveillance program in Uganda found no significant association
between NTDs and maternal HIV status or ART use[4]
‒ Antiretroviral Pregnancy Registry reported no NTDs after INSTI use in pregnancy;
mostly from Europe and North America where NTD incidence is low[5]
 Serum folate levels changed during course of ART (n = 483 women in
ADVANCE); DTG-based therapy associated with higher serum folate than EFV-
based regimens[6]
Slide credit: clinicaloptions.com
1. Zash. N Engl J Med. 2018;379:979. 2. Sibiude. CROI 2019. Abstr 744. 3. Shamsuddin. CROI 2019. Abstr 745.
4. Barlow-Mosha. CROI 2019. Abstr 743. 5. Albano. CROI 2019. Abstr 747. 6. Chandiwana. CROI 2019. Abstr 749.

28. Integrase Inhibitors in the
Switch/Maintenance Setting

29. DAWNING: Study Design
 International, randomized, open-label phase IIIb noninferiority study
 Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48 by FDA
Snapshot algorithm with noninferiority margin of 12%
*Investigator-selected NRTIs; included ≥ 1 fully active NRTI according to HIV genotypic resistance testing at screening.
†Based on recommendation by monitoring committee, protocol amended to allow d/c of LPV/RTV arm and crossover to DTG arm.
DTG + 2 NRTIs*
(n = 312)
LPV/RTV + 2 NRTIs*†
(n = 312)
Stratified by number of fully active NRTIs
(2 vs < 2), HIV-1 RNA (≤ vs > 100,000 c/mL)
Patients with HIV infection and VF (2 instances
of HIV-1 RNA ≥ 400 copies/mL) on first-line
NNRTI + 2 NRTIs; receiving first-line regimen
≥ 6 mos; no primary resistance to INSTIs or PIs
(N = 624)
Primary Endpoint
Wk 48
DTG + 2 NRTIs
continuation phase
Wk 52
Brown. CROI 2019. Abstr 144. Aboud. Lancet Infect Dis. 2019;19:253. Slide credit: clinicaloptions.com

30. DAWNING: Virologic Response by Presence of M184V/I ±
Other NRTI Mutations and Use of 3TC or FTC
HIV-1 RNA < 50 copies/mL at Wk 48
in ITT-E Analysis, % (n/N)
DTG + 2 NRTIs LPV/RTV + 2 NRTIs
Treatment
Difference, %
Overall
 M184V/I* present
• Use of 3TC or FTC
• No use of 3TC or FTC
 No M184V/I
84 (261/312)
84 (220/261)
85 (187/220)
80 (33/41)
80 (41/51)
70 (219/312)
72 (182/252)
72 (152/210)
71 (30/42)
62 (37/60)
13.8
12.1
12.6
9.1
18.7
3TC or FTC use
 M184V/I only
 M184V/I + ≥ 1 NRTI RAM
 M184V/I + ≥ 1 TAM
 M184V/I + K65R
82 (47/57)
86 (140/163)
90 (54/60)
85 (23/27)
68 (44/65)
74 (108/145)
72 (46/64)
68 (15/22)
14.8
11.4
18.1
17.0
Slide credit: clinicaloptions.comBrown. CROI 2019. Abstr 144.
*Alone or with other NRTI mutations.

31. DAWNING: Virologic Response by Use of TDF With K65R
or ZDV With TAMs
Slide credit: clinicaloptions.comBrown. CROI 2019. Abstr 144.
HIV-1 RNA < 50 copies/mL at Wk 48
in ITT-E Analysis, % (n/N)
DTG + 2 NRTIs LPV/RTV + 2 NRTIs
Treatment
Difference, %
Overall 84 (261/312) 70 (219/312) 13.8
K65R present 84 (80/95) 74 (68/92) 10.3
Use of TDF in presence of K65R 86 (6/7) 88 (7/8) -1.8
≥ 1 TAM present 87 (62/71) 75 (61/81) 12.0
Use of ZDV in presence of ≥ 1 TAM 86 (30/35) 78 (40/51) 7.3

32. Study 380-1474: Study Design
 Multicenter, multicohort, open-label, single-arm phase II/III trial
 Assessments: PK, safety, HIV-1 RNA, CD4+ cell count, treatment
palatability and acceptability, adherence by pill count
Gaur. CROI 2019. Abstr 46. Slide credit: clinicaloptions.com
Adolescents (12 to < 18 yrs) weighing ≥ 35 kg*
(n = 50)†
BIC/FTC/TAF 50/200/25 mg PO QD
Children (6 to < 12 yrs) weighing ≥ 25 kg*
(n = 50)†
Current Analysis
Wk 48
Extension phase
Primary Endpoint
Wk 24
*Eligibility: HIV-1 RNA < 50 copies/mL for ≥ 6 mos, CD4+ cell count ≥ 200 cells/mm3, and eGFR ≥ 90 mL/min/1.73 m2.
†At study outset, 25 adolescents enrolled with intensive PK analysis at Wk 2 or 4. After IDMC review, 25 additional adolescents
enrolled, along with 25 children. PK analysis/IDMC review repeated for children’s cohort prior to enrollment of last 25 children.

33. Study 380-1474: Pharmacokinetics
 BIC
‒ AUCtau similar in
adolescents and
children vs adults
‒ Ctau lower in
adolescents (but
> 11-fold above
paEC50), similar in
children vs adults
Gaur. CROI 2019. Abstr 46. Reproduced with permission. Slide credit: clinicaloptions.com
 FTC (noncompartmental analysis) and TAF (population PK analysis)
exposures in line with historical EVG/COBI/FTC/TAF data in adults and
pediatrics
For GMR, adults used as reference.
Adolescents Children
BICGMR,%(90%CI)
200
143
100
70
0
AUCtau Ctau
200
143
100
70
0
AUCtau Ctau

34. Study 380-1474: Safety
 Most common grade 3/4 lab abnormality:
hematuria (11%)
‒ 10/11 were adolescent females with normal
menses, remained on study drug
‒ No other grade 3/4 lab abnormality occurred
in ≥ 5% of patients
 Median decrease in eGFR through Wk 48
(range): -6.0 to -17.0 mL/min/1.73 m2
‒ Changes consistent with known renal effects
of BIC; not clinically relevant per investigators
 Median adherence at Wk 48: 98.8%
 BIC/FTC/TAF considered palatable, of
acceptable shape/size, by 100% of patients
Gaur. CROI 2019. Abstr 46. Slide credit: clinicaloptions.com
Safety Outcome, %
BIC/FTC/TAF
(N = 100)
Any grade AE 69
Any grade AE in ≥ 5% of patients
 Upper RTI
 Diarrhea
 Cough
 Headache
 Nasopharyngitis
 Viral upper RTI
19
9
7
6
6
5
Grade 3/4 AE 1
AE related to study drug 10
Serious AE 2*
AE leading to study drug discontinuation 1†
Death 0
*Both unrelated to study drug. †Grade 2 insomnia and anxiety.

35. Study 380-1474: Efficacy
 No emergent resistance to BIC/FTC/TAF components in any patient
Gaur. CROI 2019. Abstr 46. Reproduced with permission. Slide credit: clinicaloptions.comMeanChangeFromBL,
cells/mm3(SD)
FDA Snapshot Analysis Change in CD4+ Cell Count
Patients(%)
HIV-1 RNA
< 50 copies/mL
Wk 24 (N = 100)
Wk 48 (n = 75)
HIV-1 RNA
≥ 50 copies/mL
100
80
60
40
20
0
100 99
0 1
240
160
80
0
-80
-240
-160
0 24 8 12 16 24 36 48
Wk
Patients at Risk, n 971001009898 75 7599

36. ATLAS: Switch to Long-Acting CAB + RPV vs Continued
3-Drug ART in Virologically Suppressed Adults
 Multicenter, randomized, open-label phase III noninferiority trial
 Primary endpoint: HIV-1 RNA ≥ 50 copies/mL at Wk 48 by FDA Snapshot (6% noninferiority margin)
 Secondary endpoints: HIV-1 RNA < 50 copies/mL at Wk 48 by FDA Snapshot, resistance at confirmed
virologic failure, safety and tolerability, patient-reported outcomes
Swindells. CROI 2019. Abstr 139. NCT02951052. Slide credit: clinicaloptions.com
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)
*Permitted baseline regimens: 2 NRTIs + INSTI (except DTG/ABC/3TC), NNRTI, or boosted PI (or unboosted ATV).
†Loading dose: LA CAB 600 mg IM + LA RPV 900 mg IM; regular dosing begun at Wk 8.
LA CAB 400 mg IM +
LA RPV 600 mg IM Q4W†
(n = 303)
Continue Baseline ART‡
(n = 308)
CAB 30 mg +
RPV 25 mg PO QD
(n = 308)
Primary Endpoint
Wk 48Wk 4
Comparator arm
eligible to receive
LA CAB + LA RPV
in extension
phase after Wk 52

37. ATLAS: Efficacy at Wk 48 in ITT-E Population
Swindells. CROI 2019. Abstr 139. Reproduced with permission. Slide credit: clinicaloptions.com
Patients(%)
Difference (%)
Continued ARTLA CAB + LA RPV
Difference (%)
Continued ART LA CAB + LA RPV
100
80
40
60
20
0
Virologic
Nonresponse
(≥ 50 c/mL)
Virologic
Success
(< 50 c/mL)
No Virologic
Data
1.6 1.0
92.595.5
5.8 3.6
LA CAB + LA RPV
(n = 308)
Continued BL ART
(n = 308)
-6.7
-3.0
-10 -8 -6 -4 -2 0 2 4 6 8 10
0.7
-1.2 2.5
0.6
-10 -8 -6 -4 -2 0 2 4 6 8 10
Virologic Outcomes (FDA Snapshot) Adjusted Treatment Difference (95% CI)*
Key Secondary Endpoint
(HIV-1 RNA < 50 copies/mL)
LA CAB + LA RPV noninferior
to continued BL ART
Primary Endpoint
(HIV-1 RNA ≥ 50 copies/mL)
LA CAB + LA RPV noninferior
to continued BL ART
6% NI
margin
-10% NI
margin
*Adjusted for sex and
BL third agent class.

38. ATLAS: Safety
 99% of ISRs were grade 1/2, 88% resolved
within 7 days
Swindells. CROI 2019. Abstr 139. Slide credit: clinicaloptions.com
AEs, n (%)
LA CAB +
LA RPV
(n = 308)
Continued
BL ART
(n = 308)
AEs in ≥ 10% of patients
 Any event (per patient)
• Nasopharyngitis
• Upper RTI
• Headache
264 (86)
52 (17)
32 (10)
34 (11)
220 (71)
42 (14)
25 (8)
17 (6)
Drug-related AEs in ≥ 3% of patients
 Any event (per patient)
• Fatigue
• Pyrexia
• Headache
• Nausea
88 (29)*
11 (4)
11 (4)
11 (4)
11 (4)
8 (3)
0
0
0
0
AEs leading to d/c 10 (3) 5 (2)
Injection-Site Reactions
LA CAB +
LA RPV
(n = 308)
Patients receiving injections, n 303
Injections given, n 6978
ISR events, n (%)
 Pain
 Nodule
 Induration
 Swelling
 Grade 3 ISR pain
1460 (20.9)
1208 (82.7)
54 (3.7)
54 (3.7)
48 (3.3)
20 (1.7)
Median duration of ISRs, days 3
Patients with ISR leading to d/c, n (%) 4 (1.3)
*95% (84/88) were grade 1/2.

39. FLAIR: Long-Acting CAB + RPV Maintenance After
DTG/ABC/3TC Induction
 Multicenter, randomized, open-label phase III noninferiority trial
Orkin. CROI 2019. Abstr 140LB. NCT02938520. Slide credit: clinicaloptions.com
LA CAB 400 mg IM +
LA 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*
(N = 629)
*K103N permitted. †Patients with HIV-1 RNA < 50 copies/mL from Wk 16 to Wk 20 continued to maintenance phase. ‡Alternative, non-ABC
NRTIs permitted for intolerance or HLA-B*5701 positivity. §Loading dose: LA CAB 600 mg IM + LA RPV 900 mg IM; regular dosing begun at Wk 8.
CAB 30 mg +
RPV 25 mg PO QD
(n = 283)
Current Analysis
Wk 48Wk 4§
DTG/ABC/3TC
PO QD‡
Induction Phase† Maintenance Phase
Wk 96Day 0
Wk 20
 Primary endpoint: HIV-1 RNA ≥ 50 copies/mL at Wk 48 by FDA Snapshot (6% noninferiority margin)
 Secondary endpoints: HIV-1 RNA < 50 copies/mL at Wk 48 by FDA Snapshot, resistance at confirmed
virologic failure, safety and tolerability, patient-reported outcomes

40. Difference (%)
Difference (%)
FLAIR: Efficacy at Wk 48 in ITT-E Population
Orkin. CROI 2019. Abstr 140LB. Reproduced with permission. Slide credit: clinicaloptions.com
Patients(%)
100
80
40
60
20
0
Virologic
Nonresponse
(≥ 50 c/mL)
Virologic
Success
(< 50 c/mL)
No
Virologic
Data
2.1 2.5
93.6 93.3
4.2 4.2
LA CAB + LA RPV
(n = 283)
DTG/ABC/3TC
(n = 283)
-10% NI
margin
Difference (%)
-3.7
0.4
-10 -8 -6 -4 -2 0 2 4 6 8 10
4.5
-2.8 2.1
-0.4
6% NI
margin
-10 -8 -6 -4 -2 0 2 4 6 8 10
Virologic Outcomes (FDA Snapshot) Adjusted Treatment Difference (95% CI)*
DTG/ABC/3TCLA CAB + LA RPV
DTG/ABC/3TC LA CAB + LA RPV
Key Secondary Endpoint
(HIV-1 RNA < 50 copies/mL)
LA CAB + LA RPV noninferior
to DTG/ABC/3TC
Primary Endpoint
(HIV-1 RNA ≥ 50 copies/mL)
LA CAB + LA RPV noninferior
to DTG/ABC/3TC
*Adjusted for sex, BL HIV-1
RNA (< vs ≥ 100,000 c/mL).

41. FLAIR: Safety
 99% of ISRs were grade 1/2, 88% resolved
within 7 days
Orkin. CROI 2019. Abstr 140LB. Slide credit: clinicaloptions.com
AEs, n (%)
LA CAB +
LA RPV
(n = 283)
DTG/ABC/3TC
(n = 283)
AEs in ≥ 10% of patients
 Any event (per patient)
• Nasopharyngitis
• Headache
• Upper RTI
• Diarrhea
246 (87)
56 (20)
39 (14)
38 (13)
32 (11)
225 (80)
48 (17)
21 (7)
28 (10)
25 (9)
Drug-related AEs in ≥ 3% of patients
 Any event (per patient)
• Headache
• Pyrexia
79 (28)*
14 (5)
13 (5)
28 (10)
4 (1)
0
Drug-related serious AEs 1 (< 1)† 0
AEs leading to d/c 9 (3) 4 (1)
Injection-Site Reactions
LA CAB +
LA RPV
(n = 283)
Patients receiving injections, n 278
Injections given, n 7704
ISR events, n (%)
 Pain
 Nodule
 Induration
 Swelling
 Warmth
 Grade 3 ISR pain
2203 (28.6)
1879 (85.3)
86 (3.9)
82 (3.7)
38 (1.7)
38 (1.7)
12 (< 1.0)
Median duration of ISRs, days 3
Patients with ISR leading to d/c, n (%) 2 (< 1.0)
*94% (74/79) were grade 1/2. †Right knee monoarthritis.

42. ATLAS and FLAIR: Treatment-Emergent Resistance With
LA CAB + LA RPV
1. Swindells. CROI 2019. Abstr 139. 2. Orkin. CROI 2019. Abstr 140LB. Slide credit: clinicaloptions.com
Study Sex Country
HIV-1
Subtype
Wk of
Failure
NNRTI RAMs INSTI RAMs
Baseline Failure Baseline Failure
ATLAS[1]
F Russia A/A1 8 E138E/A E138A L74I L74I
F France AG 12 V108V/I, E138K V108I, E138K None None
M Russia A/A1 20 None E138E/K L74I L74I, N155H
FLAIR[2]
F Russia A1 20 None E138E/A/K/T L74I L74I, Q148R
M Russia A1 28 None K101E L74I L74I, G140R
F Russia A1 48 None E138K L74I L74I, Q148R

43. ATLAS and FLAIR: Patient-Reported Preference for Drug
Delivery in Patients Receiving LA CAB + LA RPV
1. Swindells. CROI 2019. Abstr 139. 2. Orkin. CROI 2019. Abstr 140LB. Slide credit: clinicaloptions.com
*Per single question in Wk 48 participant survey.
Study Population
Preferred Regimen,* % (n/N)
Long-Acting IM Daily PO
ATLAS[1]
 ITT-E 86 (266/308) 2 (7/308)
 Responding participants 97 (266/273) --
FLAIR[2]
 ITT-E 91 (257/238) 1 (2/238)
 Responding participants 99 (257/259) --

44. Complications of HIV/ART

45. NA-ACCORD: Weight Gain Among 24,001 ART-Naive
Patients Initiating Treatment
 Multivariate analysis of weight gain following ART initiation
(January 2007 - December 2016)
‒ INSTI-based regimens: n = 4740
‒ EVG: n = 2124; RAL: n = 1681; DTG: n = 935
‒ PI-based regimens: n = 7436
‒ NNRTI-based regimens: n = 11,825
 Higher weight gain with INSTI-based vs NNRTI-based regimens, with
DTG or RAL vs EVG
‒ Weight gain with INSTIs did not vary by sex or race
Slide credit: clinicaloptions.comBourgi. CROI 2019. Abstr 670.

46. NA-ACCORD: Weight Gain by Class or Specific INSTI
Slide credit: clinicaloptions.com
PredictedWeight(kg)
Yrs Since ART Initiation
86
84
82
80
0 1 2 3 4 5
Yr 2
Yr 5
INSTI
PI
NNRTI
+4.9
+4.4
+3.3
+6.0
+5.1
+4.3
PredictedWeight(kg)
86
84
82
80
Yrs Since ART Initiation
0 0.5 1.0 1.5 2.0
Yr 2
DTG
RAL
EVG
+6.0
+4.9
+3.8
PI
NNRTI
Bourgi. CROI 2019. Abstr 670. Reproduced with permission.

47. Weight Gain After Switch to INSTI-Based ART
 Prospective, observational cohort study of weight gain after switch to INSTI-based
ART in patients enrolled on ACTG A5001, A5322 from 2007-2017 (N = 691)
‒ HIV-1 RNA < 200 copies/mL at time of switch required for inclusion
 Annual weight gain increased following switch to INSTI, with greater increases
among women, blacks, and individuals 60 yrs of age or older
Slide credit: clinicaloptions.comLake. CROI 2019. Abstr 669.
Adjusted Annual
Weight Change,*
kg/yr (P Value)
Women Men Women Men Women ≥
30 kg/m2
at SwitchBlack White Black White
40 Yrs or
Younger
60 Yrs or
Older
40 Yrs or
Younger
60 Yrs or
Older
2 yrs pre-INSTI
0.4
(.08)
0.6
(.03)
0.4
(.02)
0.4
(< .0001)
1.5
(.01)
-0.2
(.61)
0.8
(.009)
0.1
(.46)
0.2
(.54)
2 yrs post-INSTI
1.3
(< .0001)
2.0
(< .0001)
1.0
(.002)
0.2
(.09)
-1.0
(.17)
1.8
(.0005)
-0.1
(.88)
0.9
(.0008)
1.9
(< .0001)
Post–pre
difference
0.9
(.04)
1.4
(.02)
0.6
(.11)
-0.2
(.38)
-2.5
(.02)
2.0
(.008)
-0.9
(.20)
0.8
(.04)
1.7
(.002)
Adjusted for age at switch, sex, race/ethnicity, BL BMI and their interactions, nadir CD4+ cell count, smoking history, diabetes, and % time with HIV-1 RNA < 200 c/mL.

48. Weight Gain After Switch to INSTI-Based ART by Agent,
Pre-Switch ART Class, and NRTI Backbone at Switch
 Change in weight gain rate
greater with DTG vs EVG or RAL
 Increases in weight change
per yr from pre- to post-INSTI
periods statistically significant
(P < .05) with:
‒ Switch to DTG from PI or NNRTI
‒ Switch to EVG from NNRTI
‒ Switch to any INSTI + ABC
‒ Switch to EVG + TAF
 However, analysis limited by
small sample sizes in subsets
Slide credit: clinicaloptions.comLake. CROI 2019. Abstr 669.
Adjusted Annual
Weight Change,
kg/yr (P Value)
DTG
(n = 198)
EVG
(n = 204)
RAL
(n = 289)
2 yrs pre-INSTI
0.2
(.11)
0.5
(.008)
0.5
(< .0001)
2 yrs post-INSTI
1.3
(< .0001)
0.9
(< .0001)
0.3
(.045)
Post–pre
difference
1.0
(.0009)
0.5
(.11)
-0.2
(.37)

49. Weight Gain Among ART-Experienced, Virologically
Suppressed Patients
 Retrospective, observational study of treatment-experienced, virologically
suppressed adults with ≥ 3% annual weight gain from 2013-2018
‒ EMR and prescription data
‒ Analysis included patients switched to new ART August 2013 - August 2017,
with viral suppression at time of switch and throughout observation period,
with ≥ 1 BMI measure within -30 to +90 days of ART prescription, and with
≥ 1 BMI measure during treatment (between 365 and 730 days of follow-up)
 N = 3468 patients from 21 states and Washington, DC
‒ 30% had annualized weight gain ≥ 3%
‒ 16% had weight loss ≥ 3%
‒ 54% had weight change < 3%
Slide credit: clinicaloptions.comMcComsey. CROI 2019. Abstr 671.

50. Factors Associated With Weight Gain Among
ART-Experienced, Virologically Suppressed Patients
 In multivariate analysis, weight
gain ≥ 3% significantly associated
with underweight at baseline and
psychiatric disorder
‒ Absence of weight gain associated
with hypogonadism, overweight or
obese at baseline, and PI use
‒ Association between INSTI-based
ART and weight gain was
statistically significant in bivariate
analyses, but not in multivariate
analysis
Slide credit: clinicaloptions.comMcComsey. CROI 2019. Abstr 671.
Factor in
Multivariate
Analysis
OR for Weight
Gain ≥ 3%
(95% CI)
P
Value
Underweight at BL 1.77 (0.9-3.4) .091
Psychiatric disorder 1.28 (1.0-1.6) .020
Female 1.25 (1.0-1.6) .055
Hypogonadism 0.81 (0.6-1.0) .050
Overweight at BL 0.69 (0.6-0.8) < .001
Obese at BL 0.62 (0.5-0.8) < .001
PI use 0.58 (0.4-0.7) < .001

51. HPTN 077: Body Weight Change in Patients Without HIV
Enrolled in Long-Acting Cabotegravir Safety Trial
 Multicenter, randomized, placebo-controlled phase IIa study
Slide credit: clinicaloptions.com
HIV-uninfected
persons at low risk
of HIV infection
(N = 199)
LA CAB 800 mg IM Q12W*
(n = 74)
Placebo 800 mg IM Q12W*
(n = 25)
LA CAB 600 mg IM Q8W†
(n = 60)
Placebo 600 mg IM Q8W†
(n = 18)
CAB 30 mg PO QD
(n = 82)
PBO PO QD
(n = 28)
CAB 30 mg PO QD
(n = 69)
PBO PO QD
(n = 20)
Wk 41 Primary Endpoint
Wk 81
End of Tail Phase
Tail Phase
Tail Phase
Tail Phase
Tail Phase
Cohort1Cohort2
Wk 4
1-wk washout between oral (Wks 1-4) and IM (Wks 5-41) phases. Follow-up continued during tail phase and through Wk 105.
Injections occurred at *Wks 5, 17, 29 in cohort 1 or †Wks 5, 9, 17, 25, 33 in cohort 2.
Landovitz. CROI 2019. Abstr 34LB.
 Primary endpoint: change in body weight; secondary endpoints: BMI change, lipids

52. HPTN 077: Changes in Weight Through Wk 41
(Primary Endpoint)
 No significant weight gain with
LA CAB vs PBO in HIV-uninfected
individuals through Wk 41
‒ ≥ 5% weight gain: 22% with LA
CAB vs 18% with PBO (P = .62)
‒ No differential effects by
BMI category, sex at birth,
race/ethnicity, dosing cohort,
or smoking status
 No statistically significant
differences in fasting glucose or
lipid changes through Wk 41 with
LA CAB vs PBO
Landovitz. CROI 2019. Abstr 34LB. Reproduced with permission. Slide credit: clinicaloptions.com
LA CAB (n = 108) PBO (n = 38)
+0.9 (-1.2, 2.8)
+0.7 (-1.5, 2)
P = .65
+1.1 (-0.9, 3)
+1.0 (-1.2, 3.2)
P = .66
+0.4 (-0.4, 1)
+0.1(-0.6,1)
P = .60
Overall
Wks 0-41
Oral Phase
Wks 0-4
Injection Phase
Wks 5-41
MedianChangeinWeight,kg(IQR)
1.00
0.25
0.75
0.50
0

53. Novel Therapeutic Agents

54. Agent MoA Key Results
Trispecific
anti-HIV
broadly nAbs[1]
Active against 3
independent HIV-1
Env regions
 Mediated antibody-dependent cell cytotoxicity, phagocytosis
 Better cross-protection, less viral escape in vivo vs individual nAbs
 Suppressed viremia in SHIV-infected macaques
PGT121[2]
Human IgG1
mAb against
V3 Env epitope
 Phase I results: safe and well tolerated
 Responses in 5/9 patients with high HIV-1 RNA (3.3-5.0 log copies/mL)
 Rebound at Day 21-28 with PGT121-resistant viruses
GS-6207[3] HIV-1 capsid
inhibitor
 In vitro antiviral activity
 Phase I (interim results) in healthy adults: no deaths, serious AEs
 Shows sustained exposure after injection with predicted dosing
interval ≥ 12 wks
GSK2838232[4] Maturation
inhibitor
 Phase IIa with COBI: well tolerated, no deaths or serious AEs
 Robust antiviral activity at 50-200 mg dose
Investigational Options Under Development for HIV-1
Slide credit: clinicaloptions.com1. Pegu. CROI 2019. Abstr 28LB. 2. Stephenson. CROI 2019. Abstr 145LB. 3. Sager. CROI 2019. Abstr 141. 4. DeJesus. CROI 2019. Abstr 142.

55. Other Issues Affecting HIV Care

56. London Patient: Second Case of Viral Suppression
Without ART After CCR5Δ32 Homozygous Allo-HSCT
 HIV diagnosed in 2003; EFV/FTC/TDF initiated in 2012
 Stage IVb Hodgkin lymphoma diagnosed in December 2012
‒ ART switched to RAL + FTC/TDF to minimize DDI risk with chemotherapy
‒ Multiple lines of chemotherapy and auto-SCT mobilization failed
 Search for allo-HSCT in donor registry found unrelated 9/10 HLA high-
resolution match; donor CCR5Δ32 homozygous
 Based on presence of K65R, M184V, and E157Q, ART was changed to
DTG + RPV + 3TC several mos before allo-HSCT
Slide credit: clinicaloptions.comGupta. Nature. 2019;[Epub]. Gupta. CROI 2019. Abstr 29LB.

57. Second Apparent Case of HIV Cure:
Timeline of Allo-HSCT and Viral Load Measures
 Patient has experienced 18-mos HIV “remission” without ART following allo-HSCT
‒ Adaptive immune responses declining or absent after transplant
Slide credit: clinicaloptions.comGupta. Nature. 2019;[Epub]. Gupta. CROI 2019. Abstr 29LB. Reproduced with permission.
RAL +
FTC/
TDF
10,000
1000
100
10
PlasmaHIV-1RNA
(copies/mL)
< 1.3
Days Post HSCT
CD4+CellCount
(cells/mm3)
0
200
400
600
DTG + RPV + 3TC*
< 0.9 < 0.8 < 0.8
Ultrasensitive VL in copies/mL
May 2016
Allo-HSCT
Sep 2017
Stop ART Dec 2017
PET/CT: HL remission
Feb 2019
18 mos off ART

58. Comparison With First Cure Case From 2009
“The London Patient”
 WT CCR5 homozygous
 R5 tropic HIV infection
 Hodgkin lymphoma
 Single HSCT
 No irradiation
 Reduced intensity conditioning
 T-cell depletion with aCD52
 Mild GvHD
 100% T-cell donor chimerism
“The Berlin Patient”
 CCR5Δ32 heterozygous
 R5 tropic HIV infection
 Acute myeloid leukemia
 2 HSCTs
 Total body irradiation
 Full intensity conditioning
 T-cell depletion with ATG
 Mild GvHD
 100% T-cell donor chimerism
Slide credit: clinicaloptions.comGupta. Nature. 2019;[Epub]. Gupta. CROI 2019. Abstr 29LB.

59. Opioid Overdose Surveillance Study
 Data from National HIV Surveillance System through December 2017
‒ Includes HIV diagnoses for all 50 US states and Washington, DC
‒ Opioid overdose deaths identified using ICD-10 coding
‒ Crude death rates calculated per 100,000 persons with HIV infection
 Objectives
‒ Examine opioid overdose death rates overall and according to
demographics, geography, and HIV transmission risk
‒ Identify change in crude death rates from 2011-2015
Bosh. CROI 2019. Abstr 147. Slide credit: clinicaloptions.com

60. Opioid Overdose Surveillance Study: Overall Deaths
 Between 2011-2015, n = 1363 opioid overdose deaths among persons
with HIV infection
Bosh. CROI 2019. Abstr 147. Slide credit: clinicaloptions.com
Yr
Crude Death Rate per 100,000 Persons With HIV Infection
All Deaths (N = 81,066) Opioid Overdose Deaths (n = 1363)
2011 1869 23
2012 1781 28
2013 1719 31
2014 1696 29
2015 1631 33
Change from 2011-2015 -13% 43%

61. Opioid Overdose Surveillance Study: Deaths by Subgroup
Bosh. CROI 2019. Abstr 147. Slide credit: clinicaloptions.com
Change in Crude Death Rate per
100,000 Persons With HIV Infection
for 2011-2015, %
All
Patients
HIV transmission
risk category
 IDU
 MSM
 MSM and IDU
 Heterosexual
80
18
43
74
Region of
residence at
death
 Northeast
 Midwest
 West
 South
59
32
-2
65
Change in Crude Death Rate per
100,000 Persons With HIV Infection
for 2011-2015, %
All
Patients
Age at death, yrs
 ≥ 60
 50-59
 40-49
 30-39
 20-29
202
21
51
28
113
Sex
 Female
 Male
47
42
Race/ethnicity
 White
 Hispanic/Latino
 Black
 Other
35
26
73
72

62. STREAM: Point-of-Care Viral Load Testing
 Open-label, randomized controlled trial at public clinic in Durban, South Africa
Lab testing + care from NP/MD equivalent
(n = 195)
Adults presenting for
6-mo follow-up and
first HIV-1 RNA test
after initiating ART
(N = 390)
Point-of-care testing* + same-day counseling with RN equivalent
(n = 195)
12 mos†
Drain. CROI 2019. Abstr 53. Slide credit: clinicaloptions.com
Clinic visits every 2 mos; HIV-1 RNA testing at 6 and 12 mos, then annually.
*For HIV-1 RNA, CD4+ cell count, creatinine testing. †Pts considered for community-based ART delivery program at this timepoint.
 Primary endpoint: retention in care with HIV-1 RNA < 200 copies/mL at 12 mos
 Secondary endpoints: Recording/communication of results, referral to community-
based ART delivery programs, healthcare utilization, visit duration, cost analysis

63. STREAM: Patient Care Outcomes
 Median time to enter HIV-1 RNA result into health info system:
0 days with PoC testing vs 2 days with lab testing
 At 12 mos, > 60% of patients receiving PoC testing had been referred to
community-based ART delivery programs vs ~ 25% of those receiving
standard care
*Criteria for noninferiority met.
Drain. CROI 2019. Abstr 53. Slide credit: clinicaloptions.com
Outcome at 12 Mos, %
PoC Test
(n = 195)
Lab Test
(n = 195)
Absolute Risk
Difference (95% CI)
P
Value
HIV-1 RNA < 200 c/mL + retention in care* 89.7 75.9 13.9 (6.4-21.2) < .001
 HIV-1 RNA < 200 c/mL 93.3 83.1 10.3 .003
 Retention in care 92.3 84.6 7.7 .026

64. STREAM: Healthcare System Outcomes
 Total patient visit duration for PoC testing: 2.5-3 hrs
Outcome
PoC Testing
(n = 195)
Lab Testing
(n = 195)
P Value
Clinic visits per patient, n
 Total
 With professional nurse (NP equivalent)
5.2 ± 1.6
4.2 ± 1.8
6.1 ± 1.5
5.6 ± 1.4
< .001
< .001
Cost per HIV-1 RNA test $21.53 $25.98
Total per patient cost for 5 yrs of testing $129.18 $155.88
Drain. CROI 2019. Abstr 53. Slide credit: clinicaloptions.com

65. clinicaloptions.com/hiv
Go Online for More CCO
Coverage of CROI 2019!
Short slideset summaries and additional CME-certified analyses with expert faculty
commentary on all the key studies
Downloadable audio highlighting important take-home messages from this year’s meeting
ClinicalThought™ commentaries providing perspective from
leading US and European clinicians on the practical
impact of the data