Didactic Series International AIDS Society Paris, France July 2017 - - PowerPoint PPT Presentation

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Didactic Series

International AIDS Society Paris, France July 2017

Geeta Gupta, MD UC Irvine Medical Center October 26, 2017

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Learning Objectives

1) Review recent studies on antivirals presented at the IAS Conference 2) Discuss how the results of these antiviral studies may affect practice

ANTIVIRAL STUDIES

New Antivirals

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POLLING QUESTION

In recent Phase III trials, when compared to Dolutegravir, Bictegravir showed virologic suppression that was: A) Superior B) Non- inferior (similar) C) Inferior D) Could not be assessed

POLLING QUESTION

When compared to Dolutegravir, Bictegravir’s adverse event (AE) profile was: A) Superior B) Non- inferior (similar) C) Inferior D) Could not be assessed

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Bictegravir

INSTI – Integrase Inhibitor

• unboosted INSTI
• long half-life
• high barrier to resistance
• low drug–drug interaction potential

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Study 1489: Bictegravir/FTC/TAF Versus Dolutegravir/ABC/3TC

Gallant J, et al. J Int AIDS Soc. 2017;20(suppl 5):103-104. Abstract MOAB0105LB.

Phase 3

Double-blind Treatment-naïve HIV RNA ≥500 copies/mL eGFR: ≥50 mL/min HLA B*5701 negative No HBV Week 0 48 96 144

Bictegravir: unboosted integrase inhibitor with high in vitro barrier to resistance and low potential for drug interactions. Primary outcome: HIV RNA <50 copies/mL. Non-inferiority margin: 12% (FDA snapshot algorithm). Stratified by HIV RNA level, CD4 count, geographic region. Baseline demographics: Male: 91%. Age: 31-32 years. Black: 36%. HCV RNA: 4.4-4.5 log10 copies/mL. CD4: 443-450 cells/µL. Asymptomatic HIV infection: 91%. eGFR: 123-126 mL/min.

Bictegravir/Emtricitabine/Tenofovir AF (n=314) Dolutegravir/Abacavir/Lamivudine (n=315)

Current Analysis

Study 1489: Bictegravir/FTC/TAF Versus Dolutegravir/ABC/3TC at Week 48

• Bictegravir group met non-

inferiority criteria

– Treatment difference: -0.6% (95%

CI: -4.8, 3.6)

• No INSTI or NRTI resistance

detected in either treatment arm

• CD4 cell increase was similar

between the treatment arms (~230 cells/µL)

Gallant J, et al. J Int AIDS Soc. 2017;20(suppl 5):103-104. Abstract MOAB0105LB.

20 40 60 80 100 Bictegravir/ FTC/TAF (n=314) Dolutegravir/ ABC/3TC (n=315)

92%

HIV RNA <50 Copies/mL

Patients (%) 93%

Study 1489: Safety Outcomes

Bic/FTC/TAF Versus Dol/ABC/3TC

• Both regimens were well tolerated
• No deaths
• No discontinuations due to adverse

events in the bictegravir/C/F/TAF arm

• Nausea was more common in the

dolutegravir arm

• No discontinuations due to renal

adverse events

• Similar changes in eGFR: -11

mL/min

• Both treatment arms had similar

changes in BMD and lipid parameters

Gallant J, et al. J Int AIDS Soc. 2017;20(suppl 5):103-104. Abstract MOAB0105LB.

Safety Results

Bictegravir/ FTC/TAF (n=314) Dolutegravir/ ABC/3TC (n=315) Discontinuations due to adverse events (%) 1.3 Adverse events (%) Diarrhea Headache Nausea 13 12 10 13 14 23* Change in BMD (%) Spine Hip

• 0.8
• 0.8
• 0.6
• 1.0

Lipid changes (mg/dL) Total cholesterol LDL-C HDL-C Triglycerides 13 7 5 9 11 4 5 3

*P<0.001 versus bictegravir/FTC/TAF.

Study 1489: Safety Outcomes Bic/FTC/TAF Versus Dol/ABC/3TC

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Study 1490: Bictegravir/FTC/TAF Versus Dolutegravir + FTC/TAF

Sax PE, et al. J Int AIDS Soc. 2017;20(suppl 5):121-122. Abstract TUPDB0201LB.

Phase 3

Double-blind Treatment-naïve HIV RNA ≥500 copies/mL eGFR: ≥30 mL/min HBV or HCV allowed Week 0 48 96 144

Primary outcome: HIV RNA <50 copies/mL. Non-inferiority margin: 12% (FDA snapshot algorithm). Stratified by HIV RNA level, CD4 count, geographic region. Baseline demographics: Male: 89%. Age: 33-34 years. Black: 31%. HCV RNA: 4.4 log10 copies/mL. CD4: 441 cells/µL. HBV/HCV infection: 2%/2%. eGFR: 120 mL/min.

Bictegravir/Emtricitabine/Tenofovir AF (n=320) Dolutegravir + Emtricitabine/Tenofovir AF (n=325)

Primary Endpoint HIV RNA <50 copies/mL

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Study 1490: Safety Outcomes With Bictegravir/FTC/TAF Versus Dolutegravir/FTC/TAF

• Overall, both treatment arms were

well tolerated

• Deaths (n=3, none related to study

drugs)

• Low rate of discontinuations due to

adverse events

• Less decrease in eGFR in the

bictegravir versus the dolutegravir arm

• No discontinuations due to renal

adverse events and no cases of renal tubulopathy

• Similar changes in lipid parameters

in the bictegravir and dolutegravir arms

Sax PE, et al. J Int AIDS Soc. 2017;20(suppl 5):121-122. Abstract TUPDB0201LB.

Safety Results

Bic/FTC/TAF (n=320) Dolutegravir/ FTC/TAF (n=325) Discontinuations due to adverse events (%) 2 <1 Adverse events (%) Headache Diarrhea Nausea 13 12 8 12 12 9 Change in eGFR (mL/min)

• 7
• 11*

Lipid changes (mg/dL) Total cholesterol LDL-C HDL-C Triglycerides 12 9 5 3 15 12 5 7

*P=0.02 versus bictegravir/FTC/TAF.

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Study 1490: Treatment Outcomes With Bictegravir/FTC/TAF Versus Dolutegravir + FTC/TAF at Week 48

• Bictegravir group met non-inferiority

criteria

– Treatment difference: -3.5% (95% CI: -

7.9, 1.0)

• Similar increases in CD4 in the

bictegravir and dolutegravir arms (180 versus 201 cells/µL)

• No resistance occurred in either

treatment group

• No discontinuations due to lack of

efficacy

Sax PE, et al. J Int AIDS Soc. 2017;20(suppl 5):121-122. Abstract TUPDB0201LB.

20 40 60 80 100 Bictegravir/ FTC/TAF (n=320) Dolutegravir/ FTC/TAF (n=325)

89%

HIV RNA <50 Copies/mL

Patients (%) 93%

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DORAVIRINE: next generation NNRTI

Doravirine: novel, next-generation NNRTI

• Unique resistance profile confers activity against most prevalent NNRTI

resistance mutations (K103N, Y181C, G190A, K103N/Y181C, E138K)

• Dosed once daily with no food requirements
• Low potential for drug–drug interactions, including with gastric acid–

reducing agents

• Demonstrated favorable efficacy and superior neuropsychiatric profile vs

EFV in phase IIb trial

• Demonstrated noninferior efficacy and more favorable lipid profile vs

ritonavir-boosted darunavir in phase III DRIVE-FORWARD trial

• Now under investigation as a fixed-dose combination with 3TC and TDF

DRIVE-AHEAD Study:

Doravirine/Lamivudine/Tenofovir DF vs EFV/TDF/FTC in Treatment-Naïve Patients

Squires KE, et al. J Int AIDS Soc. 2017;20(suppl 5):110-111. Abstract TUAB0104LB.

Phase 3

Double-blind Treatment-naïve HIV RNA ≥1000 copies/mL Stratified by HIV RNA HCV or HBV allowed Week 0 48 96

Primary outcome: HIV RNA <50 copies/mL (FDA snapshot algorithm). Non-inferiority: -10%. Baseline demographics: Male: 85%., Age: 30-32 years. White: 48%. History of AIDS: 14%. HIV RNA: 4.4-4.5 log10 copies/mL. CD4: 416-435 cells/mm3.

Doravirine/Lamivudine/Tenofovir DF (n=364) Efavirenz/Emtricitabine/Tenofovir DF (n=364)

Primary Endpoint HIV RNA <50 copies/mL

DRIVE-AHEAD Study: Treatment Outcomes With Doravirine/Lamivudine/Tenofovir DF vs Efavirenz/TDF/FTC in Treatment-Naïve Patients

• Doravirine/3TC/TDF was non-inferior to

efavirenz/FTC/TDF at Week 48

• HIV RNA >50 copies/mL: ~10% in each

arm

• Virologic failures in doravirine arm (6%)
• Primary NNRTI resistance: 1.6%
• Primary NRTI resistance: 1.4%
• Doravirine arm was superior to efavirenz

– Lower incidence of neuropsychiatric

adverse events

• Sleep disturbances (12% versus 26%) and

dizziness (9% versus 37%) (both P<0.001) – More favorable change from baseline in

lipids [LDL-C (-2% versus 9%), non-HDL-C (-4%

versus 13%) (both P<0.001)]

Squires KE, et al. J Int AIDS Soc. 2017;20(suppl 5):110-111. Abstract TUAB0104LB.

HIV RNA <50 Copies/mL

Patients (%)

20 40 60 80 100

91% 91% 84% 81%

Overall ITT

(n=364/364)

≤100K

(n=277/258) Difference (%): 3.5 (-2.0, 9.0)

Doravirine/3TC/TDF Efavirenz/FTC/TDF 81% 81%

>100K

(n=69/73)

HIV RNA (copies/mL) (Observed Failure Approach)

EMERALD Study: Switch to Darunavir/Cobicistat/Emtricitabine/Tenofovir AF

Molina JM, et al. J Int AIDS Soc. 2017;20(suppl 5):28. Abstract TUAB0101.

Phase 3 (n=1149)

Open-label, non- inferiority HIV RNA <50 copies/mL for >2 months Previous ART virologic failure allowed eGFR: ≥50 mL/min Absence of darunavir RAMs

C/F/TAF: cobicistat/emtricitabine/tenofovir AF. bPI: boosted PI. Non-inferiority margin: 4% (FDA snapshot algorithm). Baseline demographics: Male: 82%. Age: 45-46 years. CD4: 624-630 cells/mm3. Prior virologic failure: 15%.

Darunavir/C/F/TAF Continue bPI + F/TDF

Current Analysis

Primary Endpoint HIV RNA >50 copies/mL (cumulative)

Darunavir/C/F/TAF

Extension Phase Treatment Phase

Week 0 24 48 96

EMERALD Study: Virologic Outcomes After

Switching to Darunavir/Cobicistat/Emtricitabine/Tenofovir AF

• Treatment difference

(darunavir/C/F/TAF versus boosted PI + F/TDF)

• Virologic rebound: 0.3% (-2.0, 1.5)
• Most were resuppressed by week 24
• No confirmed rebounds (HIV RNA

>200 copies/mL)

• HIV RNA <50 copies/mL: 0.8% (-1.7,

3.3)

• No discontinuations for virologic

failure

• No darunavir, primary PI, or NRTI

RAMs were observed (2 patients genotyped in each group)

Molina JM, et al. J Int AIDS Soc. 2017;20(suppl 5):28. Abstract TUAB0101.

Patients (%)

Virologic Outcomes at Week 24

20 40 60 80 100 Virologic Rebound

(n=763/378)

2% 2% 0.8% 96% 96% 0.5% HIV RNA <50 Copies/mL

(n=735/361)

Virologic Failure

(n=735/361)

Darunavir/C/F/TAF (n=735) bPI + F/TDF (n=378)

EMERALD Study: Safety Outcomes After Switching to Darunavir/Cobicistat/Emtricitabine/Tenofovir AF at Week 24

• Both treatment arms were well tolerated
• No deaths and a few discontinuations due to

adverse events

• Few serious adverse events (3% in each

arm)

• Safety changes of note in the darunavir

arm

• Minimal decrease in eGFR (consistent with

the known effect of cobicistat on inhibition of tubular secretion of creatine)

• Significant improvement in hip and spine

BMD

• Slight increase in LDL-C levels, but no

difference between the 2 arms in the change to total cholesterol/HDL-C ratio

• Ongoing trial of darunavir/C/F/TAF in

treatment-naïve patients (AMBER)

Molina JM, et al. J Int AIDS Soc. 2017;20(suppl 5):28. Abstract TUAB0101.

Safety Outcomes

DRV/ C/F/TAF (n=763) bPI + F/TDF (n=378) Discontinuations due to adverse events (%) 3 3 Most common adverse events % Nasopharyngitis URI Vitamin D deficiency 8 6 6 7 6 5 Creatinine clearance <60 mL/min (%) 4 3 Lipids (%) LDL-C ≥4.9 mmol/L(190mg/dL) Change in total cholesterol/HDL-C ratio 3 0.2 0.5 0.1 Change in BMD (%) Hip (n=209/108) Spine (n=209/108) 0.6 1.2

• 0.3*
• 0.3*

*P<0.001 versus darunavir/C/F/TAF.

STUDIES ON SWITCHING ARV’S

NEAT 022 Study: Switching From a Boosted PI- to Dolutegravir-Based Regimen in Patients With High CVD Risk

Gatell JM, et al. J Int AIDS Soc. 2017;20(suppl 5):28-29. Abstract TUAB0102.

Randomized trial (6 European Countries)

Open-label Treatment-naïve HIV RNA <50 copies/mL on

• PI/r-based regimen
• >50 years of age and/or

Framingham risk score >10% at 10 years

• No resistance or previous

virologic failure

Week 0 48 96

Primary outcome: HIV RNA <50 copies/mL. Non-inferiority: -10%. Baseline demographics: Male: 89%. Framingham score >10% at 10 years: 74%. Age >50 years: 88%. CD4: 617 cells/mm3. Receiving lipid-lowering agents: 30%. Baseline boosted PI: darunavir (51%); atazanavir (37%).

Dolutegravir + 2 NRTIs (n=205) PI/r + 2 NRTIs (n=210)

Current Analysis: Primary Endpoint HIV RNA <50 copies/mL

Dolutegravir + 2 NRTIs (n=205)

Immediate Switch Delayed Switch

NEAT 022 Study: Switch from a Boosted PI- to Dolutegravir-Based Regimen in Patients With High CVD Risk

• Maintaining HIV RNA <50 copies/mL

– Switching to a dolutegravir-based

regimen was non-inferior to remaining

• n a boosted PI-based regimen

– Similar results seen regardless of

baseline strata of Framingham 10-year risk score

• Virologic non-response was slightly

higher in the dolutegravir arm (2.0% versus 0.5%)

• No resistance selected in either

treatment arm

• Both arms had similar gains in CD4

cell counts

Gatell JM, et al. J Int AIDS Soc. 2017;20(suppl 5):28-29. Abstract TUAB0102.

HIV RNA <50 Copies/mL (ITT)

Patients (%)

20 40 60 80 100

94% 97% 93% 95%

Overall

(n=205/210)

<15%

Difference (%):

• 2.1 (-6.6, 2.4)

Switch to dolutegravir(n=205) Continue boostedPI(n=210

93% 93%

≥15% Framingham 10-Year CVD Risk

NEAT 022 Study: Safety After Switching From a Boosted PI- to Dolutegravir-Based Regimen in Patients With High CVD Risk

• After switch to DOL-

based regimen

– Improved total cholesterol

and other lipid parameters

– Similar results regardless

• f baseline Framingham

CVD risk score ± age group or PI used in the boosted PI arm

• Both arms were well

tolerated

– Similar rates of

discontinuations due to adverse events

– Similar rates of serious

and grade 3/4 adverse events

Gatell JM, et al. J Int AIDS Soc. 2017;20(suppl 5):28-29. Abstract TUAB0102.

• 20
• 15
• 10
• 5

5 10

Change in Lipids (Week 48)

Change (%)

Total Cholesterol

Switch to dolutegravir (n=205) Continue boosted PI (n=210)

• 8.7%

Non- HDL-C Triglycerides LDL-C HDL-C TC/HDL-C Ratio

• 0.7%
• 11.3%

0.5%

• 18.4%

4.2%

• 7.7%

2.0% 1.1% 2.5%

• 7.0%

0.4%

P<0.001 P<0.001

P<0.001

P<0.001 P=0.3 P<0.001

POLLING QUESTION

In patients failing an initial NNRTI based regimen: A) A Lopinavir/r based regimen was superior to a Dolutegravir based regimen. B) A Dolutegravir based regimen was superior to a Lopinavir/r based regimen C) Lopinavir/r and Dolutegravir performed equally well

DAWNING Study: Dolutegravir + 2 NRTIs for Patients Failing NNRTI + 2 NRTIs

Aboud M, et al. J Int AIDS Soc. 2017;20(suppl 5):111-112. Abstract TUAB0105LB.

Phase 3b (ongoing)

Open-label, non-inferiority Virologic failure of NNRTI + 2 NRTIs (HIV RNA ≥400 copies/mL for >6 months) No primary resistance to PIs or INSTIs Investigator-selected NRTIs (≥1 fully active) Week 0 24 48 52

Non-inferiority margin: 12% (FDA snapshot algorithm). Baseline demographics: Male: 65%. Age: 37 years. HIV RNA >100K copies/mL: 21%. CD4 <200 cells/mm3: 50%. AIDS: 32%. Duration of 1st line ART: 36 months. Prior therapy agent: Efavirenz (78%), tenofovir DF (59%), zidovudine (29%), abacavir (2%).

Dolutegravir + 2 NRTIs (n=312) Lopinavir/r + 2 NRTIs (n=312)

Current Interim Analysis

Primary Analysis

Dolutegravir + 2 NRTIs

Continuation Phase

IDMC recommended discontinuation

• f lopinavir/r arm following post-hoc

review of week-24 results

DAWNING Study: Treatment Outcomes With Dolutegravir +2 NRTIs for Patients Failing NNRTI + 2 NRTIs at Week 24

• Dolutegravir + 2 NRTIs was superior to

lopinavir/r + 2 NRTIs with respect to achieving HIV RNA <50 copies/mL at week 24 (P<0.001)

– Similar results at weeks 36 and 48 – Similar week-24 results in key baseline subgroups

(HIV RNA ≤ or >100K copies/mL, 2 or <2 active NRTIs, and CD4 < or ≥200 cells/mm3)

• Virologic non-response

– Dolutegravir versus lopinavir/r: 12% versus 25%

• No emergent INSTI or NRTI resistance in the

dolutegravir arm

– NRTI resistance in the lopinavir/r arm (n=3, 2 with

K70R and M184V, 1 with K70R and K219E)

• Dolutegravir arm had fewer drug-related

adverse events (15% versus 36%) and less grade 2-4 diarrhea (<1% versus 7%)

Aboud M, et al. J Int AIDS Soc. 2017;20(suppl 5):111-112. Abstract TUAB0105LB.

HIV RNA <50 Copies/mL (ITT)

Patients (%)

20 40 60 80 100

74% 55% 82% 69%

Overall

(n=312/312)

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(n=61/64) Difference (%):

• 13.8 (7.3, 20.3)

Dolutegravir Lopinavir/r 84% 73%

<2

(n=251/ 248)

Number of Fully Active NRTIs

Both arms received 2 NRTIs.

ANTIVIRALS IN PREGNANCY

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Current DHHS Recommendations: Initial ART in Pregnant Women

Guideline Status NRTIs PIs INSTIs NNRTIs Preferred 3TC/ABC FTC/TDF 3TC + TDF ATV/RTV* DRV/RTV*† RAL*‡§ Alternative 3TC/ZDV LPV/RTV*† EFV* RPV*§ Insufficient data to recommend FTC/TAF FPV DTG EVG/COBI

*In addition to preferred 2-NRTI backbone. †Must be used twice daily in pregnancy. ‡ If adherence concerns or potential for ART discontinuation postpartum, a PI is preferred

• ver INSTI to reduce resistance risk.§Only if pretreatment HIV-1 RNA ≤ 100,000

copies/mL and CD4+ cell count ≥ 200 cells/mm3.

DHHS Perinatal Guidelines. October 2016. Slide credit: clinicaloptions.c

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Tsepamo: Safety of Dolutegravir/FTC/TDF Started in Pregnancy in Botswana

• Botswana

– In May 2016, switched from efavirenz- to dolutegravir-based

regimens for 1st line ART, including pregnancy

– Analyzed birth outcomes among pregnant women who delivered

(similar maternal characteristics)

• Efavirenz/FTC//TDF (8/2014-8/2016; n=4593)
• Dolutegravir/FTC/TDF (11/2016-4/2017; n=845)

Zash R, et al. J Int AIDS Soc. 2017;20(suppl 5):105-106. Abstract MOAX0202LB.

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Tsepamo: Birth Outcomes When Initiating First- line DTG vs EFV in Pregnancy

Slide credit: clinicaloptions.com Zash R, et al. IAS 2017. Abstract MOAX0202LB.

Adverse Birth Outcomes, n (%) DTG (n = 845) EFV (n = 4593) aRR* (95% CI) Any

• Severe

291 (34.4) 92 (10.9) 1606 (35.0) 519 (11.3) 1.0 (0.9-1.1) 1.0 (0.8-1.2) Stillbirth 18 (2.1) 105 (2.3) 0.9 (0.6-1.5) Neonatal death (< 28 days) 11 (1.3) 60 (1.3) 1.0 (0.5-1.9) Preterm birth (< 37 wks)

• Very preterm (< 32

wks) 149 (17.8) 35 (4.2) 844 (18.5) 160 (3.5) 1.0 (0.8-1.1) 1.2 (0.8-1.7) SGA (< 10th percentile weight)

• Very SGA (< 3rd

percentile weight) 156 (18.7) 51 (6.1) 838 (18.5) 302 (6.7) 1.0 (0.9-1.2) 0.9 (0.7-1.2)

*For DTG vs EFV; adjusted for maternal age, education, gravida.

• Few first-trimester ART

exposures (DTG, n = 116; EFV, n = 396); most second/third trimester

• Only 1 major congenital

abnormality observed (skeletal dysplasia in EFV-exposed group)

• ABO risks similar when

initiating first-line DTG vs EFV in pregnancy

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Safety of Dolutegravir/FTC/TDF Started in Pregnancy in Nationwide Birth Outcomes Surveillance in Botswana

CONCLUSION: The risks of adverse birth outcomes were similar among HIV-infected women who initiated dolutegravir or efavirenz plus FTC/TDF in pregnancy ONGOING ANALYSIS

• Birth outcomes with dolutegravir exposure from conception
• Congenital abnormalities and other rare outcomes
• Combination with other backbones
• Maternal viral load at delivery

Zash R, et al. J Int AIDS Soc. 2017;20(suppl 5):105-106. Abstract MOAX0202LB.

POLLING QUESTION

Dual Therapy regimens are a recommended initial antiviral regimen, based on new studies presented at the International AIDS Society Conference.

• True
• False

Selected Previous Trials of Dual Therapy Regimens for Initial Therapy

Study N Regimen Results PI-Based Dual Therapy NEAT001[1] 805 DRV/RTV + RAL Similar efficacy as DRV/RTV + FTC/TDF; poor efficacy in pts with high HIV-1 RNA, low CD4+ cell counts GARDEL[2] 426 LPV/RTV + 3TC Similar efficacy as LPV/RTV + 2 NRTIs DTG-Based Dual Therapy PADDLE[3] 20 DTG + 3TC 18/20 pts achieved virologic suppression; n = 1 experienced PDVF (BL HIV-1 RNA > 100,000 c/ml); resuppressed HIV-1 RNA without ART change by discontinuation visit

• 1. Raffi F, et al. Lancet. 2014;384:1942-1951. 2. Cahn P, et al.

EACS 2015. Abstract 961. 3. Cahn P, et al. IAC 2016. Abstract FRAB0104LB. Slide credit: clinicaloptions.com

ANDES Study: Darunavir/r + Lamivudine in Treatment-Naïve Patients

Sued O, et al. J Int AIDS Soc. 2017;20(suppl 5):104. Abstract MOAB0106LB.

Phase 4 study (Argentina)

Treatment-naïve Open-label, non-inferiority HIV RNA >1000 copies/mL No major IAS-USA resistance mutations No HBV Stratified by baseline HIV RNA <100K, ≥100K copies/mL

Randomization 1:1

Darunavir/r (800/100 mg) + Lamivudine (300 mg) + Tenofovir DF (300 mg) qd (n=70) Darunavir/r (800/100 mg) + Lamivudine (300 mg) qd (n=75)

Primary endpoint: proportion of patients with HIV RNA <50 copies/mL at week 48. Baseline characteristics: Age: 30 years. Male: 91%. MSM/bisexual: 73%. CDC stage B: 8%. HIV RNA: 4.5 log10 copies/mL. HIV RNA >100K copies/mL: 24%. Median CD4 count: 383 cells/mm3.

Week 0 24 48

Current Interim Analysis HIV RNA <400 copies/mL Primary Endpoint

ANDES Study: Treatment Outcomes With Darunavir/r + Lamivudine in Treatment-Naïve Patients at Week 24

• Dual therapy arm met non-inferiority

criteria at week 24

– Treatment difference: -2.5% (95% CI: -7.9,

2.9)

– Similar results between overall group and

patients with baseline HIV RNA >100K copies/mL

• Overall, both regimens were well

tolerated

– No deaths nor drug-related serious adverse

events

– Most common adverse events

– Gastrointestinal (10%) – Rash (8%) – Neurologic (4%)

Sued O, et al. J Int AIDS Soc. 2017;20(suppl 5):104. Abstract MOAB0106LB.

HIV RNA <400 Copies/mL (ITT)

Darunavir/r +: Lamivudine Lamivudine + Tenofovir DF

Patients (%)

20 40 60 80 100

100% 100% 95% 97%

Overall

(n=75/70)

Baseline HIV RNA >100K Copies/mL

(n=20/15) Difference (%):

• 2.5 (-7.9, 2.9)

ACTG A5353: Pilot Study of Dolutegravir + Lamivudine in Treatment-Naïve Patients

• Phase 2 single-arm, 52-week study (n=120)

– HIV RNA ≥1000 to <500,000 copies/mL; no NRTI,

integrase, or PI resistance; no HBV

– Age (30 years), male (87%), CD4 count (350-413

cells/mm3), HIV RNA (4.2-5.2 log10 copies/mL)

• Primary efficacy outcome

– 90% achieved HIV RNA <50 copies/mL at week 24

(FDA snapshot algorithm), regardless of baseline HIV RNA level

– Virologic failure (n=3) was uncommon and

associated with suboptimal adherence

• 1 virologic failure had emergent R263RK and M184V
• No discontinuations due to adverse events
• GEMINI-1 and -2 are underway and should

provide more data on the resistance barrier to dolutegravir + lamivudine

Taiwo BO, et al. J Int AIDS Soc. 2017;20(suppl 5). Abstract MOAB0107LB.

>100K (n=37) ≤100K (n=83) HIV RNA <50 copies/mL (%) 89 90 Virologic non-success (%) HIV RNA >50 copies/mL Other reasons 8 2

Week 24 Virologic Outcomes

Baseline HIV RNA (copies/mL)

QUESTIONS?

Geeta Gupta, MD ggupta@uci.edu