Antiretroviral Therapy Update 2016

Joseph J. Eron, Jr., MD
Professor of Medicine and Epidemiology
University of North Carolina School of
Medicine
Director, AIDS Clinical Trials Unit
University of North Carolina
Chapel Hill, North Carolina
Antiretroviral Therapy Update 2016
Supported by educational grants from AbbVie, Bristol-Myers Squibb,
Gilead Sciences, Janssen Therapeutics, Merck, and ViiV Healthcare.

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Disclosures
Joseph J. Eron, Jr., MD, has disclosed that he has
received consulting fees from AbbVie, Bristol-Myers
Squibb, Gilead Sciences, Merck, Roche Molecular
Systems, Tibotec/Janssen, and ViiV and funds for
research support (paid to the University of North
Carolina) from AbbVie, Bristol-Myers Squibb, Gilead
Sciences, Janssen, and ViiV.

START: Immediate vs Deferred Therapy
for Asymptomatic, ART-Naive Pts
 International, randomized phase IV study involving 215 sites in 35
countries
Serious AIDS and
Non-AIDS Events, n
42
96
Lundgren JD, et al. N Engl J Med. 2015;373:795-807.
Immediate ART
(n = 2326)
Delayed ART
(until CD4+ ≤ 350 cells/mm³)
(n = 2359)
Treatment-naive
pts with CD4+ count
> 500 cells/mm³
(N = 4685)
 Study stopped by DSMB following results of interim analysis
– Overall HR: 0.43 (P < .001)
– HR for serious AIDS-related events: 0.28 (P < .001)
HR for non-AIDS–related events: 0.61 (P = .04)
 Similar HIV-1 RNA suppression rates 12 mos after starting ART in both
arms (immediate: 98%; delayed: 97%)

START: Primary Endpoint Events by
Latest CD4+ Cell Count
Latest CD4+ count > 500 cells/mm3
Immediate
ART
Deferred
ART
Primary
events,
% (n/N)
88
(37/42)
59
(57/96)
Rate/100 PY 0.6 1.1
Latest CD4+ Cell Count (cells/mm3
)
<350350-499
500-649
650-799
≥800
<350
350-499
500-649
650-799
≥800
Immediate ART Deferred ART
%ofFollow-upTime
60
50
40
30
20
10
0
2
(4.7)
Pts With Events
(Rates/100 PY)
Pts With Events
(Rates/100 PY)
3
(0.8)
6
(0.4)
11
(0.6)
20
(0.6)
5
(1.8)
34
(2.0)
34
(1.5)
9
(0.6)
14
(1.1)
Lundgren JD, et al. N Engl J Med. 2015;373:795-807. Slide credit: clinicaloptions.com

START: Cancer Events With Immediate vs
Deferred ART
Cancer Event, n
Immediate
ART
(n = 2326)
Deferred
ART
(n = 2359)
Total 14 39
Kaposi’s sarcoma 1 11
Lymphoma, NHL + HL 3 10
Prostate cancer 2 3
Lung cancer 2 2
Anal cancer 1 2
Cervical or testis
cancer
1 2
Other types* 4 9
Time to Cancer Event
10
8
6
4
2
0
Cumulative%WithEvent
0 12 24 36 48 60
Mos
*Immediate ART: squamous cell carcinoma, plasma cell myeloma, bladder cancer, fibrosarcoma.
Deferred ART: gastric adenocarcinoma, breast cancer, ureteric cancer, malignant melanoma, myeloid
leukemia, thyroid cancer, leiomyosarcoma, liver cancer, squamous cell carcinoma of head and neck.
Lundgren JD, et al. N Engl J Med. 2015;373:795-807.
Lundgren J, et al. IAS 2015. Abstract MOSY0302.
Deferred ART
Immediate ART
Rate/100 PY: immediate, 0.20; deferred, 0.56
(HR: 0.36; 95% CI: 0.19-0.66; P = .001)

HPTN 052: ART for Prevention of HIV
Transmission in Serodiscordant Couples
 International, randomized, controlled trial
Stable, healthy, sexually
active, HIV-discordant
couples with CD4+ cell
count 350-550 cells/mm3
(N = 1763 couples)
Early ART Arm
Initiate ART immediately
(n = 886 couples)
Delayed ART Arm
Initiate ART at CD4+ cell count
≤ 250 cells/mm3
or at development of
AIDS-defining illness
(n = 877 couples)
Grinsztejn B, et al. Lancet Infect Dis. 2014;14:281-290. Slide credit: clinicaloptions.com

HPTN 052: Reduced Risk of Partner
Infection
 ART offered to all index pts in
delayed ART arm from May
2011 after interim results
 8 linked HIV infections
diagnosed after seropositive
patient started ART
– All occurred before or soon
after initiation or after virologic
failure
 No linked HIV transmissions
observed when index
participant stably suppressed
on ART
Partner
Infections, n (rate
per 100 PY)
Overall
(April 2005 - May 2015)
Early
(4314 PY F/U)
Delayed
(4180 PY F/U)
All 19 (0.44) 59 (1.41)
Linked 3 (0.07) 43 (1.03)
Risk Reduction
With Early ART,
%
All infections 69 --
Linked infections 93 --
Cohen MS, et al. IAS 2015. Abstract MOAC0101LB. Slide credit: clinicaloptions.com

Comparison of Current International
Guidelines for Treatment-Naive Pts
Regimen DHHS[1]
EACS[2]
BHIVA[3]
IAS-USA[4]
GeSIDA[5]
DTG/3TC/ABC*
DTG + FTC/TDF
EVG/COBI/FTC/TDF†
EVG/COBI/FTC/TAF‡
RAL + FTC/TDF
ATV/RTV + FTC/TDF
DRV/RTV + FTC/TDF
EFV/FTC/TDF
RPV/FTC/TDF§
1. DHHS Guidelines. January 2016.
2. EACS HIV Guidelines. V 8.0. October 2015.
3. BHIVA Guidelines. 2015.
4. Günthard H, et al. JAMA. 2014;312:410-425.
5. GeSIDA. Enferm Infecc Microbiol Clin. 2013;31:602.e1-602.e98.
Recommended Alternative Not included
*Only if HLA-B*5701 negative. †
Only if CrCl ≥ 70 mL/min. ‡
Only if CrCl ≥ 30 mL/min. §
Only if baseline
HIV-1 RNA < 100,000 copies/mL and CD4+ cell count > 200 cells/mm3
.

Continued Improvement in Currently
Available ART Classes
 Dolutegravir
– Once-daily, unboosted integrase inhibitor
– Limited drug interactions, high barrier to resistance
– Use in renal dysfunction (CrCl down to 50 mL/min for
DTG/3TC/ABC)
 Tenofovir alafenamide
– Equal efficacy with TDF-containing therapies, less bone toxicity
and renal tubular effects
– Smaller mg dosing (10 mg to 25 mg)
– Use in renal dysfunction (CrCl down to 30 mL/min)
 2-drug therapy
– Less expensive, fewer toxicities?

Studies 104/111: Tenofovir Alafenamide
vs TDF in Treatment-Naive Pts
 Parallel, randomized, double-blind, active-controlled phase III studies
– Primary endpoint: HIV-1 RNA at Wk 48
EVG/COBI/FTC/TAF*
single-tablet regimen
(n = 866)
EVG/COBI/FTC/TDF†
single-tablet regimen
(n = 867)
Treatment-naive pts with
HIV-1 RNA ≥ 1000 c/mL,
eGFR ≥ 50 mL/min
(N = 1733)
Stratified by HIV-1 RNA,
CD4+ cell count,
geographic region
Wk 48
1º endpoint Wk 144
*150/150/200/10 mg QD.
†
150/150/200/300 mg QD.
1. Sax PE, et al. Lancet. 2015;385:2606-2615.
2. Wohl D, et al. J Acquir Immune Defic Syndr. 2016;72:58-64.
HIV-1 RNA < 50 c/mL
by FDA Snapshot
92%
90%
Difference
(95% CI):
Wk 48[1]
Wk 96[2]
+2.0%
(-0.7 to +4.7)
+1.5%
(-1.8 to +4.8)
86.6%
85.2%

TAF vs TDF: Change in Spine and Hip
BMD Through Wk 96 by Age
 More favorable proteinuria effects, smaller eGFR decline with TAF
 Higher lipid levels with TAF due to absence of TDF lipid protective effect, but TC:HDL-C
ratio same as TDF
Hip
All Ages Difference
E/C/F/TAF
E/C/F/TDF
MeanChangesFromBaselineBMD(%)
DifferenceinLSM(%)
18-25 Yrs 18-25 Yrs
Wk Wk
Wohl D, et al. EACS 2016. Abstract LBBPD1/1.
Spine
All Ages
0
-1
-2
-3
-4
0
-1
-2
-3
-4
0
-1
-2
-3
-4
0
-1
-2
-3
-4
4
3
2
1
0
4
3
2
1
0
4
3
2
1
0
4
3
2
1
0
0 24 48 72 96 0 24 48 72 96

PADDLE: Dolutegravir + Lamivudine in
Treatment-Naive Pts
 Open-label, single-arm phase IV exploratory trial
– Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48
(ITT-e, FDA snapshot analysis)
Figueroa MI, et al. EACS 2015. Abstract 1066.
Treatment-naive pts
with HIV-1 RNA
5000-100,000 copies/mL;
CD4+ cell count
≥ 200 cells/mm3
;
HBsAg negative
(N = 20)
Second Cohort
Dolutegravir 50 mg QD +
Lamivudine 300 mg QD
(n = 10)
Dolutegravir 50 mg QD +
Lamivudine 300 mg QD
(n = 10)
First Cohort
Second cohort to be enrolled
following confirmation of
first cohort success at Wk 8

PADDLE: All Pts Virologically Suppressed
by Wk 8 of Dolutegravir + Lamivudine
 Included 4 pts with HIV-1 RNA > 100,000 copies/mL at BL[1]
 ACTG A5353: ph II (N = 120), single-arm, now enrolling (HIV-1 RNA < 500,000 c/mL)[2]
1. Figueroa MI, et al. EACS 2015. Abstract 1066.
2. Clinicaltrials.gov. NCT02582684.
Pt #
HIV-1 RNA, copies/mL
Screen BL Day 2 Day 4 Day 7 Day 10 Wk 2 Wk 3 Wk 4 Wk 6 Wk 8 Wk 12 Wk 24
1 5584 10,909 3701 383 101 71 < 50 < 50 < 50 < 50 < 50 < 50 < 50
2 8887 10,233 5671 318 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50
3 67,335 151,569 37,604 1565 1178 266 97 53 < 50 < 50 < 50 < 50 < 50
4 99,291 148,370 11,797 3303 432 179 178 55 < 50 < 50 < 50 < 50 < 50
5 34,362 20,544 4680 1292 570 168 107 < 50 < 50 < 50 < 50 < 50 < 50
6 16,024 14,499 3754 1634 162 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50
7 37,604 18,597 2948 819 61 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50
8 25,071 24,368 6264 1377 Not done 268 105 < 50 < 50 < 50 < 50 < 50 < 50
9 14,707 10,832 Not done 516 202 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50
10 10,679 7978 5671 318 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50
11 50,089 273,676 160,974 68,129 3880 2247 784 290 288 147 < 50 < 50 < 50
12 13,508 64,103 3496 3296 135 351 351 84 67 < 50 < 50 < 50 < 50
13 28,093 33,829 37,350 26,343 539 268 61 < 50 < 50 < 50 < 50 < 50 < 50
14 15,348 15,151 3994 791 198 98 < 50 61 64 < 50 < 50 < 50 < 50
15 23,185 23,500 15,830 4217 192 69 < 50 < 50 < 50 Not done < 50 < 50 < 50
16 11,377 3910 370 97 143 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50
17 39,100 25,828 11,879 1970 460 147 52 < 50 < 50 < 50 < 50 < 50 < 50
18 60,771 73,069 31,170 2174 692 358 156 < 50 < 50 < 50 < 50 < 50 < 50
19 82,803 106,320 35,517 2902 897 352 168 76 < 50 < 50 < 50 < 50 < 50
20 5190 7368 3433 147 56 < 50 < 50 < 50 < 50 < 50 < 50 < 50 < 50

Dolutegravir Monotherapy in Treatment-
Naive Pts
 N = 9 pts who refused NRTIs and initiated DTG monotherapy
– All pts had baseline HIV-1 RNA < 100,000 copies/mL
– No baseline NRTI, NNRTI, PI, or INSTI resistance
Lanzafame M, et al. J Acquir Immune Defic Syndr. 2016;72:e12-e14.
Pt
HIV-1 RNA, copies/mL CD4+ Cell Count, cells/mm3
Mos on DTG
Baseline After 4 Wks’ DTG At Last Visit Baseline At Last Visit
1 20,400 Undetectable Undetectable 248 600 10
2 18,400 Undetectable < 20 335 471 9
3 90,500 31 Undetectable 356 527 7
4 39,000 35 Undetectable 350 623 7
5 43,300 < 20 Undetectable 329 613 7
6 17,500 45 < 20 229 404 6
7 18,200 < 20 Undetectable 785 879 6
8 16,900 Undetectable Undetectable 214 309 8
9 52,000 < 20 Undetectable 345 484 6

Reasons to Switch ART in Suppressed Pts
 Simplification of complex therapies
 Improve tolerability and ease of administration
 Avoid or minimize drug–drug interactions
 Reduce toxicity or avoid future toxicity
 Change in clinical status
– Pregnancy or planned pregnancy, chemotherapy,
organ transplant
 Reduce costs or decrease copayments

Principles of Switching Therapy in
Suppressed Patients
 Essential to get a complete ARV treatment history and resistance
tests results
– Archival HIV DNA resistance testing may be helpful
 Maintain viral load suppression
– Complex history, missing information, and previous resistance increase
risk
 Within class switching likely has lowest risk
– TDF → TAF, EFV → RPV, RAL → DTG, RTV → COBI
 Cross-class switching or from high to low barrier agents has greater
risk
– b-PI → RPV, DTG → EVG, ETR → RPV (?)

STRIIVING: Switch From Suppressive ART
to Fixed-Dose DTG/ABC/3TC
 Randomized, open-label phase IIIB study
– Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 24
– 12% to 13% of pts withdrew after randomization; ~ one half of withdrawals
were for protocol deviations
HIV-1 RNA < 50 copies/mL
on stable ART ≥ 6 mos;
no previous virologic failure;
HLA-B*5701 negative
(N = 551)
DTG/3TC/ABC
(n = 274)
Wk 48Wk 24
Trottier B, et al. ICAAC 2015.
*Containing 2 NRTIs plus NNRTI, PI, or INSTI.
Baseline ART*
(n = 277)
DTG/3TC/ABC
PI NNRTI INSTI FTC/TDF
BL ART use, % 42 31 26 77

STRIIVING: Outcomes at Wk 24
 Switch to DTG/3TC/ABC
noninferior to continued BL ART
 Treatment difference (95% CI):
– ITT-exposed (E): -3.4 (-9.1 to 2.3)
– Per protocol (PP): -0.3 (-4.9 to 4.4)
 No cases of protocol-defined
virologic failure
– 3 pts in DTG/3TC/ABC arm (1%)
and 4 pts in BL ART arm (1%) had
HIV-1 RNA > 50 but < 100
copies/mL through Wk 24
 10 pts discontinued for AEs in
DTG/3TC/ABC arm vs 0 in baseline
ART arm
 However, significantly greater
increase in treatment satisfaction
score from baseline to Wk 24 in
DTG/3TC/ABC arm vs baseline
ART arm (P < .001)
Trottier B, et al. ICAAC 2015.
52
100
80
60
40
20
0
Virologic
Success
Virologic
Nonresponse
No Virologic
Data
HIV-1RNA<50c/mL(%)
DTG/3TC/ABC (n = 274)
Baseline ART (n = 277)
:
DTG/3TC/ABC (n = 220)
Baseline ART (n = 215)
85 88
93 93
14
10
61 1 < 1
ITT-E:
PP

GS-1089: Switch From Suppressive TDF-
to TAF-Containing ART: Wk 48 Efficacy
 Randomized, double-blind, active-controlled phase III trial
– Primary endpoint: HIV-1 RNA < 50 c/mL at Wk 48 by ITT
FDA snapshot; noninferiority margin 10%
*FTC/TAF dosing: 200/10 mg with boosted PIs;
200/25 mg with unboosted third drug.
HIV-1 RNA < 50 c/mL
at Wk 48, %
Gallant JE, et al. Lancet HIV. 2016;3:e158-e165.
Treatment difference:
1.3% (95% CI:
-2.5% to 5.1%)
Switch FTC/TDF to FTC/TAF*
Continue third ARV
(n = 333)
Continue FTC/TDF
Continue third ARV
(n = 330)
HIV-infected pts with
HIV-1 RNA < 50 c/mL,
eGFR ≥ 50 mL/min
while receiving
FTC/TDF + third ARV
(N = 663)
Wk 48 Wk 96
94.3
93.0

GS-1089: Renal and Bone Outcomes With
Switch From TDF- to TAF-Containing ART
 Significant improvement in BMD and proteinuria
TAF
40
20
0
-20
-40
Median%ChangeatWk48
Protein Albumin RBP β2-M
Urine Protein-to-Creatinine
Ratio
7.7
-14.6
-7.7
-16.3
-39.6
12.3
18.2
22.0
TDF
P < .001
P < .001
P < .001
P < .001
Hip
4
2
0
1.1
-0.2
BL 24 48
Wks
321
317
309
305
300
303
P < .001
FTC/TAF, n
FTC/TDF, n
No proximal renal tubulopathy or Fanconi syndrome in either arm
Mean%Change
inBMD(95%CI)
Gallant JE, et al. CROI 2016. Abstract 29.
Gallant JE, et al. Lancet HIV. 2016;3:e158-e165. Slide credit: clinicaloptions.com

LATTE-2: Cabotegravir IM + Rilpivirine IM
for Long-Acting Maintenance ART
 Multicenter, open-label phase IIb study
– Primary endpoints: HIV-1 RNA < 50 c/mL by FDA snapshot at
maintenance Wk 32, PDVF, and safety
Margolis DA, et al. CROI 2016. Abstract 31LB.
CAB 400 mg IM + RPV 600 mg IM Q4W
(n = 115)
CAB 600 mg IM + RPV 900 mg IM Q8W
(n = 115)
*Pts with HIV-1 RNA < 50 c/mL from Wk 16 to Wk 20 continued to maintenance phase.
6 pts discontinued for AEs or death in induction analysis.
ART-naive HIV-
infected pts with
CD4+ cell count
> 200 cells/mm3
(N = 309) CAB 30 mg PO + ABC/3TC PO QD
(n = 56)
CAB 30 mg PO QD
+ ABC/3TC
Wk 32
primary analysis;
dose selection
Wk 20
Induction Phase* Maintenance Phase
Wk 1 Wk 96
Wk 16: RPV
PO added

LATTE-2: Maintenance Wk 32 Efficacy
(ITT-Maintenance Exposed) and Safety
 No INSTI, NNRTI, or NRTI
resistance mutations detected
 Most frequent ISRs were pain
(67%), swelling (7%), and
nodules (6%)
– ISR events/injection: 0.53
– 99% of ISRs grade 1/2; none
grade 4
– 1% of pts withdrew for ISRs
Margolis DA, et al. CROI 2016. Abstract 31LB.
9594 91
4< 1 4 < 15 5
Virologic
Success
Virologic
Non-
response
No
Virologic
Data
HIV-1RNA<50c/mL(%)
100
80
60
40
20
0
IM CAB + RPV Q4W (n = 115)
IM CAB + RPV Q8W (n = 115)
Oral CAB + ABC/3TC (n = 56)
Treatment Differences (95% CI):
Q8W IM vs Oral: 3.7 (-4.8 to 12.2)
Q4W IM vs Oral: 2.8 (-5.8 to 11.5)
AEs, % Pooled IM
Arms
(n = 230)
Oral Arm
(n = 56)
Drug-related
grade 3/4 AEs
(excluding ISRs)
3 0
Serious AEs 6 5
AEs leading to
withdrawal 3 2

LATTE-2: Wk 32 Pt Satisfaction With
Maintenance Therapy vs Oral Induction
Pts(%)
How satisfied are you with your
current treatment?
100
80
60
40
20
0
Q8W
(n = 106)
Q4W
(n = 100)
Oral CAB
(n = 49)
More Neutral Less
100
80
60
40
20
0
Q8W
(n = 106)
Q4W
(n = 100)
Oral CAB
(n = 49)
More Neutral Less
How satisfied would you be to continue
with your present form of treatment?
97 96 71
29
3 1
3
98 98 71
29
2 1
1
Margolis DA, et al. CROI 2016. Abstract 31LB. Slide credit: clinicaloptions.com

Doravirine + FTC/TDF vs EFV + FTC/TDF
In Treatment-Naive Pts
 Doravirine: investigational NNRTI
with potent activity against common
NNRTI RAMs, QD dosing, no PPI
interactions, improved CNS safety
vs EFV in early studies
 Part 2 of 2-part randomized,
double-blind phase II study in which
ART-naive pts randomized to:
– Doravirine 100 mg QD + FTC/TDF
(n = 66) or
– Efavirenz 600 mg QD + FTC/TDF
(n = 66)
 Current analysis also includes 85
pts who received these regimens in
Part 1 of study
Gatell JM, et al. CROI 2016. Abstract 470.
78.7
77.877.8
81.5
73.1
72.9
57.5
63.0
42.1
26.9
47.2
27.8
12.0
15.7
100
80
60
40
20
0
Doravirine 100 mg
Efavirenz 600 mg
0 4 8 12 16 20 24 28 32 36 40 44 48
Treatment Wk
Primary Endpoint:
HIV-1 RNA < 40 c/mL (NC = F)
Wk 48 Difference (95% CI):
-1.1 (-12.2 to 10.0)Pts,%(95%CI)

Doravirine vs Efavirenz: Clinical AEs
Gatell JM, et al. CROI 2016. Abstract 470.
Clinical AEs, % DOR + FTC/TDF
(n = 108)
EFV + FTC/TDF
(n = 108)
Difference,
DOR–EFV (95% CI)
≥ 1 AE 87.0 88.9 -1.9 (-10.9 to 7.1)
Serious AEs 6.5 8.3 -1.9 (-9.5 to 5.6)
Death 0 0
D/c for AEs 2.8 5.6 -2.8 (-9.2 to 3.0)
Drug-related AEs* 31.5 56.5 -25.0 (-37.3 to 11.8)
 Diarrhea 0.9 6.5
 Nausea 7.4 5.6
 Dizziness 6.5 25.9
 Headache 2.8 5.6
 Abnormal dreams 5.6 14.8
 Insomnia 6.5 2.8
 Nightmares 5.6 8.3
 Sleep disorder 4.6 6.5
*Specific AEs occurring in > 5% of pts included.

Attachment Inhibitor Clinical
Development: BMS-663068
 BMS-663068: prodrug of attachment inhibitor BMS-626529
 HIV-1 variants have a range of susceptibility: in phase IIb study,
6% had BMS-626529 IC50 > 100 nM at screening
 Phase IIb study in participants with limited resistance[1]
– BMS-663068 (over range of doses) + RAL + TDF had similar
activity over 48 wks vs ATV/RTV + RAL + TDF
 Phase III study in highly ARV-experienced pts with MDR HIV[2]
– If at least 1 fully active ARV available, then
– BMS-663068 600 mg or placebo BID for 8 days with no change in
background ART followed by BMS-663068 600 mg BID + OBR for
≥ 48 wks
– If no fully active ARV available, then
– BMS-663068 600 mg BID + OBR for ≥ 48 wks
1. Feinberg J, et al. IDWeek 2015. Abstract 1075.
2. Clinicaltrials.gov. NCT02362503. Slide credit: clinicaloptions.com

Short-term Activity of a Maturation
Inhibitor in Combination With a PI
 Randomized, multipart phase IIa trial
– BMS-955176: blocks viral maturation by inhib. cleavage between p24 and Gag SP1
HIV, subtype B–infected
PI- and MI-naive pts
with HIV-1 RNA
≥ 5000 c/mL and
CD4+ cell count
≥ 200 cells/mm3
(N = 28)
BMS-955176 40 mg QD + ATV 300 mg QD +
RTV 100 mg QD
(n = 8)
BMS-955176 40 mg QD + ATV 400 mg QD
(n = 8)
BMS-955176 80 mg QD + ATV 400 mg QD
(n = 8)
Day 28*
ATV 300 mg QD + RTV 100 mg QD +
FTC 200 mg QD/TDF 300 mg QD
(n = 4)
Max. Median Decline
in HIV-1 RNA Through
Day 42 (log10 c/mL)
-2.02
-1.86
-2.23
-2.39
*Followed through Day 42.
 No serious AEs or discontinuations for AEs; 1 grade 3/4 Tx-related AE in
BMS-955176 80 mg + ATV 400 mg arm (transient neutropenia)
Hwang C, et al. IAS 2015. Abstract TUAB0106LB. Slide credit: clinicaloptions.com

MK-8591: Investigational NRTI With Potent
Monotherapy Activity
 MK-8591: 4'-ethynyl-2-fluoro-2'-
deoxyadenosine[1]
– Active triphosphate exhibits
prolonged intracellular half-life
in vitro (> 72 hrs in PBMCs)
 Open-label dose-ranging study
in ART-naive pts[2]
– Single 10-mg MK-8591 dose
(n = 6) suppressed HIV
replication for at least 10 days
– AEs: headache (n = 6) and no
other AE was seen in more
than 1 participant
1. Stoddart CA, et al. Antimicrob Agents Chemother. 2015;59:4190-4198.
2. Friedman E, et al. CROI 2016. Abstract 437LB.
HIV-1 RNA Decrease
Least-Squares
Mean (95% CI)
Placebo (n = 20) -0.03 (-0.13 to 0.08)
MK-8591 10 mg (n = 6) -1.67 (-1.88 to -1.46)
-2.5
-2.0
-1.5
-1.0
-0.5
0
0.5
LogHIV-1RNADecrease
Hrs
0 50 100 150 200 250
Change in HIV-1 RNA Following Single
10-mg Dose of MK-8591

Conclusions
 When to start
– Pts should be started on ART regardless of CD4+ cell count
– HIV-related serious events including malignancy are more frequent in
untreated vs treated pts with CD4+ cell counts > 500 cells/mm3
 What to start
– Simple, effective, well-tolerated regimens exist for initial therapy
including some for pts with moderate chronic kidney disease
 Switching ART in suppressed patients
– Many pts suppressed on older regimens can have therapy
simplified
– Careful history taking and review of resistance testing are critical
 New therapies
– Long-acting ART and agents with new mechanisms of action are
in late-stage clinical development

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Editor's Notes