HIV Treatment Optimization: 2018 In this downloadable slideset, Eric S. Daar, MD, provides a comprehensive update on ART management. Format: Microsoft PowerPoint (.ppt) File Size: 723 KB Released: April 26, 2018

1. Supported by educational grants from AbbVie; Gilead Sciences;
Janssen Therapeutics; Merck & Co., Inc; and ViiV Healthcare.
HIV Treatment Optimization: 2018
Eric S. Daar, MD
Chief, Division of HIV Medicine
Harbor-UCLA Medical Center
Professor of Medicine
David Geffen School of Medicine at UCLA
Los Angeles, California

2. About These Slides
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Slide credit: clinicaloptions.com

3. Disclosures
Eric S. Daar, MD, has disclosed that he has received consulting
fees from Gilead Sciences, Merck, and Theratechnologies and
funds for research support from Gilead Sciences, Merck, and ViiV.

4. Outline
 Treatment-Naive Patients
– When and What to Start, Now and in the Future
 Patients With Virologic Suppression
– Newer Options for Switching
 Patients With Virologic Failure
– New Data
Slide credit: clinicaloptions.com

5. Improved Clinical Outcomes With Rapid ART
Initiation
 START and HPTN Study resulted in universal recommendations for treating all
HIV-infected persons
 Systematic review of 22 studies of rapid ART initiation (including 4 RCTs)
– In the 4 RCTs, compared with standard care, same day ART increased likelihood of
ART initiation in first 90 days, patient retention and viral suppression at 12 mos
Characteristic
ART start within 90 days
Retained in care at 12 mos
Viral suppression at 12 mos
LTFU at 12 mos
Died by 12 mos
.2 1 3
Standard Care Same Day ART
2
RR (95% CI)
1.35 (1.13-1.62)
1.11 (0.99-1.26)
1.17 (1.07-1.27)
0.66 (0.42-1.04)
0.53 (0.28-1.00)
Ford N, et al. AIDS. 2018;32:17-23. Slide credit: clinicaloptions.com

6. RAPID ART Program for HIV Diagnoses (RAPID)
in San Francisco
 Linkage to care within 5 working
days
 Labs, counseling, medical/
psychosocial assessment, ART
start at first care visit
– (INSTI or DRV/RTV) + FTC/TDF*
 HIV clinics identified using HIV
surveillance data, RAPID Provider
Directory identified best clinic for
each patient
 Time to first virologic suppression
decreased > 50% from 134 days
to 61 days and time from care
linkage to ART start decreased
96% from 27 days to 1 day
 Time to ART start and first viral
suppression decreased in
vulnerable populations, including
racial/ethnic minorities and
homeless patients
– Disparities still exist for some
outcomes
Bacon O, et al. CROI 2018. Abstract O93. Slide credit: clinicaloptions.com
*4-drug regimen optional if HIV infection suspected to
have occurred while on PrEP.

7. What to Start?

8. Boosted PIs in Clinical Practice
 ACTG A5257[1]
– Similar efficacy between
RAL, DRV/RTV, and
ATV/RTV
– Better tolerability for RAL or
DRV/RTV than ATV/RTV
 DRV/COBI and ATV/COBI
available for simplification[2,3]
 Consider boosted PIs when
high barrier to resistance is
needed[4]
– If starting ART prior to
availability of resistance
data, if high risk of poor
adherence
 Boosted PIs more widely
used in those with
transmitted or acquired
drug resistance
1. Lennox JL, et al. Ann Intern Med. 2014;161:461-471. 2. Gallant JE, et al. J Infect Dis.
2013;208:32-39. 3. Tashima K, et al. AIDS Res Ther. 2014;11:39. 4. DHHS guidelines. March 2018. Slide credit: clinicaloptions.com

9. Novel Darunavir-Containing First-line Therapy:
Efficacy at Wk 48
1. Gallant J, et al. EACS 2017. Abstract PS8/2. 2. Figueroa MI, et al. CROI 2018. Abstract 489. Slide credit: clinicaloptions.com
*Primary endpoint: HIV-1 RNA < 50 c/mL by FDA snapshot.
AMBER: Virologic Outcomes[1]
DRV/COBI/FTC/TAF (n = 362)
DRV/COBI + FTC/TDF (n = 363)
Treatment difference: 2.7%
(95% CI: -1.6% to 7.1%)
91.4 88.4
3.3
(n = 12)
4.4
(n = 16)
Patients(%)
100
80
60
40
20
0
Virologic
Success*
HIV-1 RNA
≥ 50 c/mL
93 9194 92
0
20
40
60
80
100
All Patients Patients With BL HIV-1
RNA > 100,000 c/mL
(n = 35)
Patients(%)
ANDES: HIV-1 RNA < 50 copies/mL (ITT)[2]
Treatment difference: -1.0%
(95% CI: -7.5% to 5.6%)
Treatment difference: -1.4%
(95% CI: -17.2% to 14.4%)
No Virologic
Data
4
8
DRV/RTV + 3TC DRV/RTV + 3TC/TDF
70/
145
66/
145
n/N =
20/
35
12/
35

10. INSTIs

11. ONCEMRK: RAL 1200 mg QD vs 400 mg BID
With TDF/FTC at 96 Wks
Cahn P, et al. IAS 2017. Abstract TULBPEB20. Slide credit: clinicaloptions.com
Wk
PatientsWithHIV-1RNA
<40c/mL(FDASnapshot)(%)
RAL 1200 mg QD + TDF/FTC
RAL 400 mg BID + TDF/FTC
Wk 48 treatment
difference: 0.5%
(95% CI: -4.2% to 5.2%)
Wk 96 treatment
difference: 1.4%
(95% CI: -4.4% to 7.3%)
0
20
40
60
80
100
0 4 8 16 3624 6048 72 9684
89
88
82
80

12. BIC/FTC/TAF vs DTG-Containing Regimens
for Treatment-Naive Patients
Slide credit: clinicaloptions.com
GS-1489: Wk 48 Virologic Efficacy[1] GS-1490: Wk 48 Virologic Efficacy[2]
Patients(%)
Patients(%)
100
80
60
40
20
0
HIV-1 RNA
< 50 c/mL
HIV-1 RNA
≥ 50 c/mL
No Virologic
Data
BIC/FTC/TAF (n = 314)
DTG/ABC/3TC (n = 315)
92 93
1 3 7 4
100
80
60
40
20
0
HIV-1 RNA
< 50 c/mL
No Virologic
Data
BIC/FTC/TAF (n = 320)
DTG + FTC/TAF (n = 325)
89 93
4 1
66
Treatment difference: -0.6%
(95% CI: -4.8% to 3.6%)
Treatment difference: -3.5%
(95% CI: -7.9% to 1.0%)
1. Gallant J, et al. Lancet. 2017;390:2063-2072. 2. Sax PE, et al. Lancet. 2017;390:2073-2082.
No resistance selected for in any DTG- or BIC-containing regimen
HIV-1 RNA
≥ 50 c/mL

13. BIC/FTC/TAF FDA Approved: March 2018
 Once-daily single-tablet regimen with novel, unboosted INSTI
BIC/FTC/TAF [package insert]. 2018.
Key US Label Information
Indications
 For treatment-naive patients
 For patients with HIV-1 RNA < 50 copies/mL for ≥ 3 mos, no history of
treatment failure, and no resistance to regimen components
Key DDIs
 Contraindicated with rifampin, dofetilide
 May increase metformin concentrations
 Polyvalent cation–containing supplements/medications (including antacids)
may decrease BIC concentration
Special
populations
 Not recommended for patients with estimated CrCl < 30 mL/min
 BIC only available in combination STR; not approved for use with other ARVs
Slide credit: clinicaloptions.com

14. Class DHHS[1] IAS-USA*[2]
INSTI  BIC/TAF/FTC
 DTG/ABC/3TC
 DTG + (TAF or TDF)/FTC
 EVG/COBI/(TAF or TDF)/FTC
 RAL + (TAF or TDF)/FTC
 DTG/ABC/3TC
 DTG + TAF/FTC
 EVG/COBI/TAF/FTC
 RAL + TAF/FTC
DHHS, IAS-USA Guidelines:
Recommended Regimens for First-line ART
 Recommendations may differ based on BL HIV-1 RNA, CD4+ cell count,
CrCl, eGFR, HLA-B*5701 status, HBsAg status, and osteoporosis status
 With FDA approval of 1200-mg RAL,[3] all options now available QD (except
in pregnancy)
1. DHHS guidelines. March 2018. 2. Günthard HF, et al.
JAMA. 2016;316:191-210. 3. Raltegravir [package insert]. 2018.
Bold text identifies single-tablet regimens. *IAS-USA guidelines not updated since the approval of BIC/TAF/FTC.
Slide credit: clinicaloptions.com

15. Choosing Integrase Inhibitors
Agent Advantages Disadvantages
Bictegravir
 STR once daily
 Available with TAF
 Few drug or food interactions
 Potentially high barrier to resistance
 Least amount of data
 Only available as STR with TAF/FTC
Dolutegravir
 Only non-TFV QD STR
 High barrier to resistance
 Few drug or food interactions
 Active against some RAL- and
EVG-resistant viruses
 STR only with ABC/3TC
 Increases metformin levels
Elvitegravir
 STR once daily
 Available with TAF and TDF
 Requires COBI boosting
 COBI drug interactions
Raltegravir
 Longest experience
 Few drug or food interactions
 Multiple pills
 No STR
DHHS guidelines. March 2018. Dolutegravir [package insert]. 2017. Slide credit: clinicaloptions.com

16. Novel NNRTI

17. Doravirine for Treatment-Naive Patients:
Efficacy at Wk 48
 n = 1 noncompliant patient d/c at Wk 24,
developed DOR and FTC resistance
1. Molina JM, et al. Lancet HIV. 2018;[Epub ahead of print].
2. Squires KE, et al. IAS 2017. Abstract TUAB0104LB.
0
HIV-1 RNA
< 50 c/mL
HIV-1 RNA
≥ 50 c/mL
No Data in
Window
Patients(%)
100
80
60
40
20
84 81
DOR/3TC/TDF (n = 364)
EFV/FTC/TDF (n = 364)
11 10
5
9
Treatment difference: 3.5%
(95% CI: -2.0% to 9.0%)
DRIVE-AHEAD[2]
Virologic
Nonresponse
HIV-1 RNA
< 50 c/mL
No Data
100
80
60
40
20
0
Patients(%)
84 80
11 13
5 7
Treatment difference: 3.9%
(95% CI: -1.6% to 9.4%)
DOR + 2 NRTIs (n = 383)
DRV + RTV + 2 NRTIs (n = 383)
DRIVE-FORWARD[1]
 1° NNRTI resistance, n (%): DOR, 6 (1.6);
EFV, 12 (3.3); no unanticipated mutations
observed
Slide credit: clinicaloptions.com

18. Novel First-line Regimens

19. Dual Therapy With Boosted PIs in ART-Naive
Patients
 Randomized, open-label phase III
noninferiority trial (N = 805)
 Randomized, open-label phase III
noninferiority trial (N = 416)
Overall
BL HIV-1 RNA < 100,000 c/mL
BL HIV-1 RNA ≥ 100,000 c/mL
CD4+ cell count < 200 cells/mm3*
CD4+ cell count ≥ 200 cells/mm3*
Adjusted Difference in Proportions of Failure at Wk 96, % (95% CI)
RAL +
DRV/RTV
TDF/FTC +
DRV/RTV
*Interaction test P = .010
NEAT: DRV/RTV + RAL
vs DRV/RTV + TDF/FTC[1]
GARDEL: LPV/RTV + 3TC
vs LPV/RTV + 2 NRTIs[2]
Wks
Patients(%)
Difference: 4.6%
(95% CI: -2.2% to 11.8%;
P = .171)
1. Raffi F, et al. Lancet. 2014;384:1942-1951. 2. Cahn P, et al. Lancet Infect Dis. 2014;14:572-580. Slide credit: clinicaloptions.com
HIV-1 RNA < 50 copies/mL
17.8
7.4
36.8
43.2
13.7
13.8
7.3
27.3
20.9
12.3
-5 0 5 1015 20253035 40
Dual therapy
Triple therapy
0
100
80
60
40
20
0 4 8 12 24 36 48

20. ACTG A5353: Pilot Study of Dolutegravir +
Lamivudine in Treatment-Naive Patients
 Single-arm, 52-wk phase II study
(N = 120)[1]
– HIV-1 RNA ≥ 1000 to < 500,000 c/mL;
no PI, INSTI, or reverse transcriptase
resistance; no active HBV infection
– Median age, 30 yrs; male, 87%; median
CD4+ cell count, 387 cells/mm3; median
HIV-1 RNA, 4.61 log10 copies/mL
 Primary efficacy outcome
– 90% achieved HIV RNA-1 < 50 copies/mL
at Wk 24 (FDA Snapshot)
 No discontinuations due to AEs
1. Taiwo BO, et al. Clin Infect Dis. 2017;[Epub ahead of print].
2. ClinicalTrials.gov. NCT02831673. 3. ClinicalTrials.gov. NCT02831673. Slide credit: clinicaloptions.com
Outcome, %
BL HIV-1 RNA, c/mL
> 100,000
(n = 37)
≤ 100,000
(n = 83)
HIV-1 RNA < 50 c/mL 89 90
Virologic nonsuccess
 HIV-1 RNA ≥ 50 c/mL
 D/c for other reasons* while
HIV-1 RNA ≥ 50 c/mL
8
0
0
2
Virologic Outcomes at Wk 24[1]
Fully powered phase III
GEMINI-1[2] and -2[3] under way

21. Switching Patients With
Virologic Suppression

22. The Why and How of Switching in Virologic
Suppression
Why
 Simplify regimen (pill number
and frequency)
 Tolerability
 Comorbidity
 Drug–drug and drug–food
interactions
 Pregnancy
 Cost
How
 Maintain viral suppression to
avoid resistance
 Need to consider
– Previous ART
– Previous resistance
– Likelihood of adherence
– Drug–drug or drug–food
interactions
– Comorbid conditions
DHHS guidelines. March 2018. Slide credit: clinicaloptions.com

23. Within Class
 EFV RPV[1]
 RAL EVG[2] or DTG[3]
 DTG BIC[4]
 Boosted DRV, DRV/C/FTC/TAF[5]
boosted ATV,
or LPV/RTV
 TDF or ABC TAF[6,7]
Switch Studies With Evidence of Sustained
Efficacy
Between Class
 Boosted PI RPV[8]
 Boosted PI EVG,[9] DTG,[10] or
BIC[11]
 NNRTI EVG[12] or DTG[3]
References in slidenotes Slide credit: clinicaloptions.com

24. Study 380-1844: Switch From Suppressive
DTG/ABC/3TC to BIC/FTC/TAF
 Randomized, double-blind, international, active-controlled phase III trial (N = 563)
Molina JM, et al. CROI 2018. Abstract 22. Slide credit: clinicaloptions.com
Outcome at Wk 48
Switch to
BIC/FTC/TAF
(n = 282)
Continued
DTG/ABC/3TC
(n = 281)
Treatment
Difference, %
(95.002% CI)
P Value
HIV-1 RNA ≥ 50 c/mL, n (%) 3 (1.1) 1 (0.4) 0.7 (-1.0 to 2.8) .62
HIV-1 RNA < 50 c/mL, n (%) 264 (93.6) 267 (95.0) NR .59
No virologic data, n (%) 15 (5.3) 13 (4.6) NR NR
Median eGFRCG change from BL, mL/min 1.0 -1.8 NR < .001
Median change for triglycerides, mg/dL -5 +3 NR .028
 No treatment-emergent resistance
detected in any patient
 No significance differences between arms
in changes from BL for proteinuria levels,
spine and hip BMD
 Difference in eGFR attributable to greater
inhibition of tubular secretion of creatinine
by DTG
 No significant differences in changes for
fasting lipids, except triglycerides

25. BIC/FTC/TAF for Initial/Maintenance Therapy
 Once-daily single-tablet regimen with novel, unboosted INSTI
BIC/FTC/TAF [package insert]. 2018.
Key US Label Information
Indications
 For treatment-naive patients
 For patients with HIV-1 RNA < 50 copies/mL for ≥ 3 mos, no history of
treatment failure, and no resistance to regimen components
Key DDIs
 Contraindicated with rifampin, dofetilide
 May increase metformin concentrations
 Polyvalent cation–containing supplements/medications (including antacids)
may decrease BIC concentration
Special
populations
 Not recommended for patients with estimated CrCl < 30 mL/min
 BIC only available in combination STR; not approved for use with other ARVs
Slide credit: clinicaloptions.com

26. SWORD 1 & 2: Switch From Suppressive ART to
DTG + RPV in Patients With No Previous VF
 Randomized, open-label phase III trials of virologically suppressed patients with no previous
virologic failure switched to DTG + RPV or continued baseline ART (N = 1024; 70% to 73%
of patients receiving TDF at baseline)
Llibre JM, et al. Lancet. 2018;391:839-849.
Virologic
Nonresponse
HIV-1 RNA
< 50 c/mL
No Data
100
80
60
40
20
0
Patients(%)
95 95
< 1 1
5 4
DTG + RPV (n = 513)
Baseline ART (n = 511)
Virologic Efficacy, Wk 48 Treatment Difference (95% CI)
Favors
Baseline ART
Favors
DTG + RPV
-4% 0 4%
-3.0 2.5
-0.2
Slide credit: clinicaloptions.com

27. DTG/RPV FDA Approved for Maintenance
Therapy: November 2017
 Once-daily single-tablet regimen of DTG/RPV
– First 2-drug STR approved by FDA for use as a complete regimen in the US
DTG/RPV [package insert]. 2018. DHHS guidelines. March 2018.
Key US Label Information
Indication
 For patients who have been virologically suppressed for ≥ 6 mos
 Patients must have no history of treatment failure and no resistance to DTG or RPV
Administration
requirements
 Must be taken with a meal
Key DDIs
 Separate dose of DTG/RPV and antacid/polyvalent cation–containing medications
 Avoid PPIs (eg, omeprazole, pantoprazole)
Dose
adjustments
 None required for patients with mild/moderate renal impairment; in patients with CrCl
< 30 mL/min, increase monitoring for AEs
DHHS  Consider when NRTIs not desirable
Slide credit: clinicaloptions.com

28. DHHS: Guidance for Switching to Dual Therapy
in Virologically Suppressed Patients
With Evidence
 DTG + RPV a reasonable option
when use of NRTIs not
desirable and when no expected
resistance to regimen
components
 PI/RTV + 3TC may be a
reasonable option when use of
TDF, TAF, or ABC is
contraindicated or not desirable
Without Evidence
 Insufficient evidence to
recommend: DTG + 3TC,
DRV/RTV + RAL
 Not recommended: DTG
or PI/RTV monotherapy,
ATV/RTV + RAL
DHHS guidelines. March 2018. Slide credit: clinicaloptions.com

29. DUAL-GESIDA 8014: Switching to DRV/RTV +
3TC From Triple Therapy
 Open-label, randomized, noninferiority trial of virologically suppressed patients
switched to DRV/RTV + 3TC or continued DRV/RTV + ABC/3TC or FTC/TDF
 DRV/RTV + 3TC noninferior to triple therapy for maintenance of virologic
suppression through 48 wks (noninferiority margin: 12%)
Outcome at Wk 48
Switch to Dual Therapy
(n = 126)
Continue Triple Therapy
(n = 123)
HIV RNA < 50 c/mL (ITT FDA Snapshot),* % 89 93
HIV RNA < 50 c/mL in all study visits, % 83 83
Genotypic resistance, n
 PI
 NRTI
0
0
0
1
D/c due to AEs, % 0.8 1.6
*Treatment difference: -3.8 (95% CI: -11 to 3.4).
Pulido F, et al. Clin Infect Dis. 2017;65:2112-2118. Slide credit: clinicaloptions.com

30. ASPIRE: DTG + 3TC Maintenance Therapy
 DTG + 3TC as effective as
standard 3-drug therapy
(blips, n = 1)
– Virologic failure, n = 1 in each arm
– No emergence of resistance
 CD4+ cell count gain was similar
 Both regimens well tolerated
– D/c due to AE: dual therapy, n = 1
– Similar changes in lipids and CrCl
Fully powered phase III TANGO enrolling
Taiwo BO, et al. Clin Infect Dis. 2017;[Epub ahead of print]. Slide credit: clinicaloptions.com
Wk 48Wk 24 Wk 24
100
80
60
40
20
0
Patients(%)
1 0
93 91 91 89
Wk 48 treatment
difference: 2.0%
(95% CI: -12.6%
to 16.5%)
DTG + 3TC (n = 44)
Continue triple therapy (n = 45)
Virologic Outcomes (FDA Snapshot)
Wk 48
Virologic Failure HIV-1 RNA < 50 c/mL
0 0

31. 1. Margolis DA, et al. Lancet 2017;390:1499-1510. 2. ClinicalTrials.gov. NCT02951052.
3. Clinical Trials.gov. NCT02938520. 4. Clinical Trials.gov. NCT03299049.
Fully powered phase III
ATLAS, FLAIR (every
month)[2,3] and ATLAS-2M
(every 2 months)[4] enrolling
LATTE-2: Maintenance Therapy With
Cabotegravir IM + RPV IM
 Multicenter, open-label phase IIb study comparing continuation of oral CAB +
ABC/3TC vs switching to IM CAB + RPV Q4W or Q8W (after induction with oral
CAB + ABC/3TC)[1]
Virologic Outcomes
94
HIV-1RNA<50c/mL(%)
Virologic
Success
Virologic
Nonresponse
No Virologic
Data
87
100
80
60
40
20
0
Q8W IM CAB + RPV (n = 115)
Q4W IM CAB + RPV (n = 115)
Oral CAB + ABC/3TC (n = 56)
84
4
0 2
13
2
14
Slide credit: clinicaloptions.com

32. Switching After Virologic Failure

33. EARNEST: Second-line LPV/RTV in Patients With
Virologic Failure
 Randomized, controlled, open-label phase III study of patients with virologic failure after
first-line NNRTI-based ART in resource-limited settings (N = 1277)
Wks From Switch to Second Line
HIV-1RNA<400c/mL(%)
Hakim JG, et al. Lancet Infect Dis. 2018;18:47-57. Paton NI, et al. Lancet HIV. 2017;4:e341-e348. Slide credit: clinicaloptions.com
100
80
60
40
20
0
0 4 12 24 36 48 64 80 96 112 128 144
LPV/RTV + 2-3 NRTIs
LPV/RTV + RAL
LPV/RTV monotherapy
Wks From Switch to Second Line
100
80
60
40
20
0
04 12 24 36 48 64 80 96 112 128 144
LPV/RTV + 0 NRTIs (n > 188)
LPV/RTV + 2-3 NRTIs (n > 23)
LPV/RTV monotherapy (n > 374)
LPV/RTV + 1 NRTI (n > 104)
LPV/RTV + RAL (n > 351)

34. DAWNING: Second-line DTG vs LPV/RTV +
2 NRTIs in Patients With Virologic Failure
 Interim results of an international, randomized, open-label phase IIIb study of patients with
virologic failure after first-line NNRTI + 2 NRTIs in resource-limited settings (N = 627)
Aboud M, et al. IAS 2017. Abstract TUAB0105LB. Slide credit: clinicaloptions.com
Virologic Efficacy, Wk 24
HIV-1 RNA < 50 c/mL
Patients(%)
100
80
60
40
20
0
82
69
LPV/RTV + 2 NRTIs*
(ITT-E, n = 312)
Treatment Difference (95.002% CI)
-12
7.3 20.3
13.8DTG + 2 NRTIs*
(PP, n = 282)
LPV/RTV + 2 NRTIs*
(PP, n = 275)
DTG + 2 NRTIs*
(ITT-E, n = 312)86
72
ITT-E
8.1 21.0
14.5
PP
0 12 24
Favors
LPV/RTV
Favors
DTG
P < .001
*Including at least 1 active NRTI.

35. Management of ARV Failure
First-line regimen failure
Boosted PI + NRTIs
Boosted PI + active INSTI
Yes
2 (preferably 3)
fully active drugs
(or partially active drug if
no other options)
No‡
Second-line regimen failure
and beyond
PI susceptibleFailing regimen (+ NRTI)
Boosted PI
NNRTI
INSTI
Reinforce adherence
Modify for convenience or toxicity
Boosted PI + NRTIs
Boosted PI + INSTI
DTG + NRTIs (if 1 fully active)
Boosted PI + NRTIs
Boosted PI + active INSTI*
DTG + NRTIs (≥ 1 fully active)†
DHHS guidelines. March 2018. Slide credit: clinicaloptions.com
*If RAL or EVG resistance detected, DTG + boosted PI can be used if DTG susceptible.
†In setting of no INSTI resistance.
‡Rare in patients never exposed to unboosted PI.

36. BENCHMRK: Efficacy of Raltegravir + OBR
Through Wk 156
Placebo + OBRRAL + OBR
59
45 43
60
24
8 5
20
233/
396
51/
209 2/437/93
26/
61
68/
152
13/
64
76/
126
69
38
156/
226
43/
112
66
29
17/
58
81/
123
0
20
40
60
80
100
0 ≥ 1
PatientsWithHIV-1RNA
<50c/mL(%)
n/N =
Overall
Active PIs in OBR
0 1
Agents in OBR for Which
Phenotypic Sensitivity Demonstrated
2
61
43
16/
37
39/
64
≥ 3
Eron JJ, et al. Lancet Infect Dis. 2013;13:587-596. Slide credit: clinicaloptions.com
 Randomized studies of INSTI-naive patients with VF, HIV resistant to 3 ARV classes

37. TMB-311: Ibalizumab in Pretreated Patients
Infected With Multidrug-Resistant HIV
 Ibalizumab: humanized mAb to CD4 receptor that blocks HIV entry into
CD4+ T-cells[1]
– FDA approved March 2018 as IV injection for heavily treatment–experienced adults with
multidrug-resistant HIV infection and virologic failure
 Single-arm, open-label phase III trial in patients on a failing regimen (N = 40)[2,3]
Patients with HIV-1 RNA
> 1000 c/mL; on ART ≥ 6 mos,
on stable ART ≥ 8 wks;
resistant to ≥ 1 ARV from
3 classes, sensitive to
≥ 1 ARV for OBR
(N = 40)
Wk 25
Ibalizumab
2000 mg IV Day 7
(loading dose)
Continue Failing ART
Days 0-14
Ibalizumab
800 mg IV Day 21, Q2W
(maintenance dose)
Switch to OBR
Day 14
Primary Endpoint:
Day 14Control Period:
Day 0-7
1. Ibalizumab [package insert]. 2018. 2. Emu B, et al.
IDWeek 2017. Abstract 1686. 3. ClinicalTrials.gov. NCT02475629. Slide credit: clinicaloptions.com

38. TMB-301: Ibalizumab Efficacy at Wk 24
 Deaths, n = 4 (all unrelated to study drug); discontinuations due to drug-
related AE, n = 1 (IRIS); no infusion-related AEs
Virologic Outcome
Ibalizumab +
Optimized Background Regimen
≥ 1.0 log10 HIV-1 RNA decrease, % 55
≥ 2.0 log10 HIV-1 RNA decrease, % 48
HIV-1 RNA < 50 copies/mL, % 43
HIV-1 RNA < 200 copies/mL, % 50
Mean HIV-1 RNA decrease from BL, log10 1.6
Emu B, et al. IDWeek 2017. Abstract 1686. Slide credit: clinicaloptions.com

39. Summary
 Treatment-Naive Patients
– Increasingly simple to take, well tolerated, and highly effective options
– Novel regimens, including 2-drug regimens, in advanced stages of
development
 Patients With Virologic Suppression
– Increasing options for switching, including 2-drug regimens
 Patients With Virologic Failure
– Increasing data, and even a few new drugs, to guide and facilitate
management
Slide credit: clinicaloptions.com

40. clinicaloptions.com/hiv
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