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Managing Treatment-Experienced Patients
With Multidrug Resistance: Emerging Options
and Strategies for Success
This progra...
 Please feel free to use, update, and share some or all of these
slides in your noncommercial presentations to colleagues...
Faculty
Eric S. Daar, MD
Chief, Division of HIV Medicine
Harbor-UCLA Medical Center
Professor of Medicine
David Geffen Sch...
Faculty Disclosures
Eric S. Daar, MD, has disclosed that he has received consulting
fees from Bristol-Myers Squibb, Gilead...
Multidrug-Resistant HIV:
The Scope of the Problem
History of MDR HIV
 In the pre-HAART era, MDR HIV emerged as a result of sequential, partially
suppressive ARV regimens[1...
Decrease in Prevalence of MDR HIV in the US in
Recent Era of HIV Treatment
 Assessment of phenotypic drug resistance patt...
Prevalence of Transmitted MDR HIV in the US:
Selected Studies
 Transmission of HIV resistant to a single class of ARV mor...
Current Status of INSTI Resistance in the US
 Transmitted INSTI resistance remains rare and rates of on-treatment INSTI
r...
MDR Still a Significant Concern in HIV
 Despite modern ARV combination regimens revolutionizing the treatment of HIV,
MDR...
Assessing Virologic Failure and
Potential MDR HIV
Causes of Treatment Failure
DHHS Guidelines.
Poor adherence
Insufficient drug level
Viral replication in the
presence of d...
 Results used to inform design of new ART regimens for pts experiencing VF
DHHS: Recommendations for Resistance
Testing
D...
Principles for Constructing a New Regimen
for a Patient With MDR HIV
 Randomized, open-label, multicenter phase III trial in sub-Saharan Africa
LPV/RTV + RAL
(n = 433)
LPV/RTV + 2-3 NRTIs*
(...
EARNEST: Boosted PI + RAL Comparable to
Boosted PI + NRTIs
 SECOND-LINE[3] and ACTG 5273[4,5] showed similar results
LPV/...
DHHS: Management of First-line Failure
DHHS Guidelines.
*If RAL or EVG resistance detected, DTG + boosted PI can be used i...
 Randomized, double-blind, placebo-controlled, multicenter phase III trials
BENCHMRK: Raltegravir + OBR for MDR HIV
Steig...
BENCHMRK: Efficacy of Raltegravir + OBR
Through Wk 156
Placebo + OBR
Raltegravir + OBR
Eron JJ, et al. Lancet Infect Dis. ...
DHHS: Management of ART Failure Second-line
ARV Failure
 Goal: fully suppressive ARV regimen
 If susceptible to boosted ...
Approved ARV Treatment Options
Mechanism of Action Agent
NRTI 3TC, ABC, FTC, TAF, TDF, ZDV
NNRTI EFV, ETR, NVP, RPV
PI ATV...
DHHS: Treatment of Pts With MDR HIV for Whom
Optimal Virologic Suppression Is Not Possible
 Goals: minimize toxicity, pre...
Emerging Investigational Agents for Pts With
MDR HIV
1. Lalezari JP, et al. Lancet HIV. 2015;2:e427-437. 2. Granados-Reyes...
TMB-301: Ibalizumab in Pretreated Pts Infected
With Multidrug-Resistant HIV
 Ibalizumab: humanized mAb to CD4 receptor th...
TMB-301: Pt Characteristics
Lewis S, et al. CROI 2017. Abstract 449LB.
Baseline Characteristic Pts
(N = 40)
Mean age, yrs ...
TMB-301: Efficacy
Lewis S, et al. CROI 2017. Abstract 449LB.
Virologic Outcome
Ibalizumab
+ OBR
Day 14
≥ 0.5 log10 HIV-1 R...
TMB-301: Safety
 9 pts reported 17 serious AEs[1]
– 1 drug-related serious AE (IRIS) resulted in discontinuation
 9 othe...
AI438011: Fostemsavir + RAL + TDF in
Treatment-Experienced Pts
 Fostemsavir: prodrug; proposed MoA: binding HIV-1 gp120 p...
AI438011: Efficacy, Safety of Fostemsavir + RAL
+ TDF
 At Wk 96, 90% of pts had HIV-1 RNA < 50 copies/mL in both fostemsa...
PRO 140 for Heavily Treatment–Experienced Pts
 PRO 140: humanized IgG4 CCR5 mAb
 Ongoing phase IIb/III study of PRO 140 ...
Options When Limited Information Available for
Tx-Experienced Pt With Suspected Resistance
 If have treatment history, bu...
Take-home Points
 For pts with virologic failure and potential MDR HIV, genotypic and phenotypic
resistance testing resul...
clinicaloptions.com/hiv
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Managing Treatment-Experienced Patients With Multidrug Resistance-Emerging Options and Strategies for Success.2017

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Managing Treatment-Experienced Patients With Multidrug Resistance-Emerging Options and Strategies for Success.2017

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Managing Treatment-Experienced Patients With Multidrug Resistance-Emerging Options and Strategies for Success.2017

  1. 1. Managing Treatment-Experienced Patients With Multidrug Resistance: Emerging Options and Strategies for Success This program is supported by an educational grant from Theratechnologies Inc.
  2. 2.  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 About These Slides
  3. 3. Faculty 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 Daniel R. Kuritzkes, MD Chief, Division of Infectious Diseases Brigham and Women’s Hospital Professor of Medicine Harvard Medical School Boston, Massachusetts
  4. 4. Faculty Disclosures Eric S. Daar, MD, has disclosed that he has received consulting fees from Bristol-Myers Squibb, Gilead Sciences, Merck, Teva, and ViiV and funds for research support from Gilead Sciences, Merck, and ViiV. Daniel R. Kuritzkes, MD, has disclosed that he has received consulting fees from CytoDyn, Gilead Sciences, Janssen, Merck, and ViiV and funds for research support from Gilead Sciences and Merck.
  5. 5. Multidrug-Resistant HIV: The Scope of the Problem
  6. 6. History of MDR HIV  In the pre-HAART era, MDR HIV emerged as a result of sequential, partially suppressive ARV regimens[1,2]  Combination ART transformed HIV into a manageable condition, but early suboptimal 3-drug regimens led to continued selection for resistant HIV[2,3] – Low-potency ARVs with adherence challenges due to toxicity[3] – Cross-resistance within drug classes[3,4]  Improved efficacy of modern ARVs has led to even less resistant HIV[2] – Expansion of ARVs and ARV classes allows for virologic suppression in pts with MDR HIV via informed use of combination regimens[4] 1. Lima VD, et al. Am J Epidemiol. 2010;172:460-468. 2. Richman DD. Clin Infect Dis. 2016;62:1318-1319. 3. Harris M, et al. AIDS Res Treat. 2012;2012:595762. 4. Tang MW, et al. Drugs. 2012;72:e1-e25. Slide credit: clinicaloptions.com
  7. 7. Decrease in Prevalence of MDR HIV in the US in Recent Era of HIV Treatment  Assessment of phenotypic drug resistance patterns in US samples submitted to Monogram Biosciences for HIV resistance testing from 2003-2012 (N = 62,397) Slide credit: clinicaloptions.comPaquet AC, et al. Antivir Ther. 2014;19:435-441. 0 10 20 30 40 50 60 ResistantSamples(%) 1-Class Resistance PI NRTI NNRTI 0 10 20 30 40 50 60 2-Class Resistance PI and NRTI PI and NNRTI NRTI and NNRTI 0 10 20 30 40 50 60 3-Class Resistance
  8. 8. Prevalence of Transmitted MDR HIV in the US: Selected Studies  Transmission of HIV resistant to a single class of ARV more common than HIV resistant to multiple classes[1,3] – 13.6%, 2.1%, and 0.5% of transmitted HIV resistant to 1, 2, and 3 ARV classes, respectively[3] 1. Baxter JD, et al. HIV Med. 2015;16:77-87. 2. INSIGHT START Study Group. N Engl J Med. 2015;373:795-807. 3. Kim D, et al. CROI 2013. Abstract 149. Slide credit: clinicaloptions.com Prevalence of Transmitted Drug-Resistant HIV (2009-2013), %[1-3] Overall  NRTI  NNRTI  PI 12.6-16.2 3.7-6.7 8.1-8.4 2.0-4.5
  9. 9. Current Status of INSTI Resistance in the US  Transmitted INSTI resistance remains rare and rates of on-treatment INSTI resistance continue to be low[1-3] 1. Hernandez AL, et al. CROI 2017. Abstract 478. 2. Davy T, et al. CROI 2017. Abstract 483. 3. Koullias Y, et al. CROI 2017. Abstract 493. Slide credit: clinicaloptions.com Study Key Findings CDC National HIV Surveillance System[1]  Prevalence of INSTI resistance for HIV diagnoses through 2014: 65/14,468 (0.4%)  Pre-ART prevalence of INSTI resistance (ie, transmitted): 2/4631 (0.04%) UNC CFAR HIV Clinical Cohort[2]  2015 INSTI resistance prevalence in 685 pts who began ART in 2007 or later: 1% Modeling study[3]  Assuming 0.1% rate of transmitted INSTI resistance and $250 cost per test: pre-ART INSTI resistance testing correlated with worse outcomes, higher costs vs no test
  10. 10. MDR Still a Significant Concern in HIV  Despite modern ARV combination regimens revolutionizing the treatment of HIV, MDR HIV remains relevant  Contributions to MDR HIV in today’s pts include – Nonadherence – Inadequate past treatment in pre- and early-HAART eras – Transmission of harbored MDR HIV variants – Pharmacokinetic factors  Due to cross-resistance within a drug class, fully active ARV options diminish with each successive viral failure  Pts harboring MDR HIV pose increased risk of drug-resistant virus transmission Tang MW, et al. Drugs. 2012;72:e1-e25. Imaz A, et al. AIDS Rev. 2011;13:180-193. Lima VD, et al. Am J Epidemiol. 2010;172:460-468 Slide credit: clinicaloptions.com
  11. 11. Assessing Virologic Failure and Potential MDR HIV
  12. 12. Causes of Treatment Failure DHHS Guidelines. Poor adherence Insufficient drug level Viral replication in the presence of drug Resistant virus Social/personal issues Regimen issues Toxicities Suboptimal potency Wrong dose Host genetics Poor absorption Rapid clearance Poor activation Drug interactions Virologic failure Transmitted or Acquired Slide credit: clinicaloptions.com
  13. 13.  Results used to inform design of new ART regimens for pts experiencing VF DHHS: Recommendations for Resistance Testing DHHS Guidelines. Question Recommendation Who should receive resistance testing?  Pts with VF and HIV-1 RNA levels > 1000 copies/mL  May be considered for pts with 500-1000 copies/mL When should testing be conducted?  While on failing ART regimen or < 4 wks from treatment end  May still be considered after 4 wks What types of testing should be conducted?  First-/second-line failure: genotypic testing  Suspected MDR: genotypic plus phenotypic testing  When considering CCR5 antagonist: tropism assay  If prior failure on INSTI-containing regimen, test for INSTI resistance Other considerations  Prior treatment history should be obtained Slide credit: clinicaloptions.com
  14. 14. Principles for Constructing a New Regimen for a Patient With MDR HIV
  15. 15.  Randomized, open-label, multicenter phase III trial in sub-Saharan Africa LPV/RTV + RAL (n = 433) LPV/RTV + 2-3 NRTIs* (n = 426) HIV-infected pts > 12 yrs of age with confirmed VF on NNRTI + 2 NRTIs and no prior PIs (N = 1277) Wk 96 LPV/RTV 400/100 mg and RAL 400 mg dosed BID. *New or recycled NRTIs chosen WITHOUT genotype by clinician. EARNEST: Second-line LPV/RTV ± RAL or 2-3 NRTIs in PI-Naive Pts Wk 12 LPV/RTV Monotherapy (n = 418) LPV/RTV + RAL (n = 418) Paton NI, et al. N Engl J Med. 2014;371:234-247. Slide credit: clinicaloptions.com Stratified by study center, CD4+ cell count (< 200 vs ≥ 200 cells/mm3)
  16. 16. EARNEST: Boosted PI + RAL Comparable to Boosted PI + NRTIs  SECOND-LINE[3] and ACTG 5273[4,5] showed similar results LPV/RTV + RAL (n = 433) LPV/RTV + 2/3 NRTIs (n = 426) LPV/RTV monotherapy (n = 418) References in slidenotes. Slide credit: clinicaloptions.com 100 80 60 40 20 0 Pts(%) HIV-1 RNA < 50 copies/mL, Wk 96[1] 7473 44 P < .001 HIV-1 RNA < 400 copies/mL Through Wk 144[2] 0 20 40 60 80 100 LPV/RTV + NRTI (Number of Active NRTIs) Pts(%) 88 0 LPV/ RTV + RAL 77 8185 61 1 2-3 LPV/ RTV
  17. 17. DHHS: Management of First-line Failure DHHS Guidelines. *If RAL or EVG resistance detected, DTG + boosted PI can be used if DTG susceptible. Slide credit: clinicaloptions.com Failing Regimen (+ NRTIs)  Boosted PI: Enforce adherence Modify for convenience or toxicity  NNRTI: Boosted PI + NRTIs Boosted PI + INSTI  INSTI: Boosted PI + NRTIs Boosted PI + active INSTI*
  18. 18.  Randomized, double-blind, placebo-controlled, multicenter phase III trials BENCHMRK: Raltegravir + OBR for MDR HIV Steigbigel RT, et al. N Engl J Med. 2008;359:339-354. Eron JJ, et al. Lancet Infect Dis. 2013;13:587-596. HIV-infected pts ≥ 16 yrs of age with HIV-1 RNA > 1000 copies/mL, no prior INSTIs, and multiclass resistance* (N = 703) Placebo + OBR† (n = 237) Raltegravir 400 mg BID + OBR† (n = 466) Wk 156 *Documented phenotypic or genotypic resistance to ≥ 1 drug in each of 3 oral ARV classes (ie, NRTI, NNRTI, and PI). †Investigator-selected based on ART history, BL resistance, and lab data; DRV and TPV investigational at time of studies but permitted. Wk 48Wk 16Randomized 2:1; stratified by enfuvirtide use and PI resistance (1 vs > 1) All pts offered open-label raltegravir to Wk 240  Baseline: median yrs of ART, 10; median previous drugs, 12; > 95% resistant to > 1 PI Slide credit: clinicaloptions.com
  19. 19. BENCHMRK: Efficacy of Raltegravir + OBR Through Wk 156 Placebo + OBR Raltegravir + OBR Eron JJ, et al. Lancet Infect Dis. 2013;13:587-596. 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 PtsWithHIV-1RNA <50copies/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 Slide credit: clinicaloptions.com
  20. 20. DHHS: Management of ART Failure Second-line ARV Failure  Goal: fully suppressive ARV regimen  If susceptible to boosted PI, regimen can be similar to those for first-line failure  If not susceptible to boosted PI, new regimen should have a minimum of 2 (preferably 3) fully active drugs if possible – Susceptibility to drug predicted from pt treatment history, prior and current resistance and tropism testing, MoA of novel drug class  Not recommended to add single agent to failing regimen due to risk of developing resistance to entire regimen DHHS Guidelines. Boosted PI + NRTIs Boosted PI + active INSTI 2 and preferably 3 fully active drugs Yes No PI Susceptible Slide credit: clinicaloptions.com
  21. 21. Approved ARV Treatment Options Mechanism of Action Agent NRTI 3TC, ABC, FTC, TAF, TDF, ZDV NNRTI EFV, ETR, NVP, RPV PI ATV, DRV, FPV, IDV, LPV, NFV, SQV, TPV INSTI DTG, EVG, RAL Fusion inhibitor T20 CCR5 coreceptor antagonist MVC Slide credit: clinicaloptions.com
  22. 22. DHHS: Treatment of Pts With MDR HIV for Whom Optimal Virologic Suppression Is Not Possible  Goals: minimize toxicity, preserve immunologic function, delay clinical progression, minimize further resistance – Reduction of HIV-1 RNA > 0.5 log10 copies/mL correlated with clinical benefit – If resistant, rarely a reason to continue NNRTIs, ENF, EVG, or RAL: no evidence of clinical benefit; may promote further resistance, limit future treatment options  Consider enrolling pt in clinical study, expanded access program, or FDA single-pt access to investigational agent DHHS Guidelines. Slide credit: clinicaloptions.com
  23. 23. Emerging Investigational Agents for Pts With MDR HIV 1. Lalezari JP, et al. Lancet HIV. 2015;2:e427-437. 2. Granados-Reyes ER, et al. HIV Glasgow 2016. Abstract O335A. 3. ClinicalTrials.gov. NCT02362503. 4. Lewis S, et al. CROI 2017. Abstract 449LB. 5. Lin H-H, et al. CROI 2017. Abstract 438. 6. Lalezari J, et al. CROI 2017. Abstract 437. Slide credit: clinicaloptions.com Investigational Agent Phase MoA Fostemsavir[1-3] III Prodrug; when metabolized binds gp120 to prevent CD4+ cell attachment, entry Ibalizumab[4,5] III Humanized anti-CD4 receptor mAb PRO 140[6] IIb/III Humanized anti-CCR5 mAb
  24. 24. TMB-301: Ibalizumab in Pretreated Pts Infected With Multidrug-Resistant HIV  Ibalizumab: humanized mAb to CD4 receptor that blocks HIV entry into CD4+ T-cells – FDA breakthrough and orphan drug designations  Single-arm, open-label phase III trial – Primary endpoint: ≥ 0.5 log10 HIV-1 RNA decrease at Day 14 Lewis S, et al. CROI 2017. Abstract 449LB. Slide credit: clinicaloptions.com Pts with HIV-1 RNA > 1000 copies/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
  25. 25. TMB-301: Pt Characteristics Lewis S, et al. CROI 2017. Abstract 449LB. Baseline Characteristic Pts (N = 40) Mean age, yrs 51 ± 11 Male, % 85 Mean duration of HIV infection, yrs 21 Mean VL, copies/mL  VL ≥ 100,000 copies/mL, % 100,287 18 Mean CD4+ cell count, cells/mm3 150 Median CD4+ cell count, cells/mm3 73 Previously treated with ≥ 10 ARVs, % 28 Fostemsavir required in OBR, % 43 Slide credit: clinicaloptions.com Characteristic, % Pts (N = 40) Phenotypic/genotypic resistance  NRTI  NNRTI  PI  INSTI 93 93 88 68 Number of exhausted ARV classes  ≥ 1  ≥ 2  ≥ 3  ≥ 4  All 88 73 53 35 15
  26. 26. TMB-301: Efficacy Lewis S, et al. CROI 2017. Abstract 449LB. Virologic Outcome Ibalizumab + OBR Day 14 ≥ 0.5 log10 HIV-1 RNA decrease, % 83* ≥ 1.0 log10 HIV-1 RNA decrease, % 60 Mean HIV-1 RNA decrease, log10 1.1 Wk 24 ≥ 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 *Primary endpoint; P < .0001 vs 3% at end of control period. Slide credit: clinicaloptions.com Outcome, cells/mm3 Baseline CD4+ Cell Count (cells/mm3) < 50 (n = 17) 50-200 (n = 10) > 200 (n = 13) Mean baseline CD4+ cell count 12 109 363 Mean increase in CD4+ cell count at Wk 24  Missing equals failure analysis 9 75 78  Per protocol analysis 15† 75 81‡ †n = 7. ‡n = 10.
  27. 27. TMB-301: Safety  9 pts reported 17 serious AEs[1] – 1 drug-related serious AE (IRIS) resulted in discontinuation  9 other pts discontinued – Death (n = 4; liver failure, Kaposi sarcoma; end-stage AIDS, lymphoma) – Consent withdrawal (n = 3) – Lost to follow-up (n = 2)  No cases of anti-ibalizumab antibodies  Phase III TMB-311 study ongoing; extension for pts from TMB-301; accepting new pts[2]  IM dosing may be viable as administration route as compared with IV dosing[3] 1. Lewis S, et al. CROI 2017. Abstract 449LB. 2. ClinicalTrials.gov. NCT02707861. 3. Lin H, et al. CROI 2017. Abstract 438. Slide credit: clinicaloptions.com
  28. 28. AI438011: Fostemsavir + RAL + TDF in Treatment-Experienced Pts  Fostemsavir: prodrug; proposed MoA: binding HIV-1 gp120 prevents viral attachment and entry into host CD4+ cells  Randomized, active-controlled phase IIb study, blinded to dose – Primary endpoint: HIV-1 RNA < 50 c/mL at Wk 24 Granados-Reyes ER, et al. HIV Glasgow 2016. Abstract O335A. Llamoso C, et al. HIV Glasgow 2016. Abstract O335B. Slide credit: clinicaloptions.com Fostemsavir 600 mg QD* PO + RAL + TDF (n = 51) HIV-infected pts with exposure to ≥ 1 ARV for ≥ 1 wk; HIV-1 RNA ≥ 1000 c/mL; CD4+ ≥ 50 cells/mm3; virus susceptible to RAL, TDF, ATV, and fostemsavir IC50 < 100 nM (N = 254) Wk 48Wk 24: 1̊ endpoint ATV/RTV 300/100 mg QD + RAL + TDF (n = 51) Fostemsavir 1200 mg QD PO + RAL + TDF (n = 50) Fostemsavir 400 mg BID* PO + RAL + TDF (n = 50) Fostemsavir 800 mg BID* PO + RAL + TDF (n = 49) Wk 96 *Fostemsavir dose changed to 1200 mg QD from Wk 48 to Wk 96.
  29. 29. AI438011: Efficacy, Safety of Fostemsavir + RAL + TDF  At Wk 96, 90% of pts had HIV-1 RNA < 50 copies/mL in both fostemsavir and ATV/RTV arms in observed analysis[1] – No significant differences in virologic efficacy regardless of race, sex, age, BL HIV-1 RNA, BL CD4+ cell count, or IC50 subgroups[1] – Fostemsavir generally well tolerated, with higher rates of grade 2-4 treatment-emergent AEs (37% vs 9%) and d/c for AEs (10% vs 3%) for ATV/RTV arm vs fostemsavir arm[2]  Phase III trial of fostemsavir in heavily treatment–experienced pts ongoing[3] 1. Granados-Reyes ER, et al. HIV Glasgow 2016. Abstract O335A. 2. Llamoso C, et al. HIV Glasgow 2016. Abstract O335B. 3. ClinicalTrials.gov. NCT02362503. Slide credit: clinicaloptions.com Wk 49 Placebo Pts with HIV-1 RNA ≥ 400 c/mL on current regimen; ≤ 2 classes of active approved ARVs left to compose OBR due to resistance, intolerance, or contraindications Fostemsavir + OBR Day 8* Fostemsavir Fostemsavir + OBR FostemsavirAs above but with no active approved ARV options remaining *1° endpoint: mean log10 HIV=-1 RNA change from BL.
  30. 30. PRO 140 for Heavily Treatment–Experienced Pts  PRO 140: humanized IgG4 CCR5 mAb  Ongoing phase IIb/III study of PRO 140 plus OBR for heavily treatment– experienced pts (estimated N = 30) – Primary endpoint: proportion with > 0.5 log10 HIV-1 RNA change from BL at Day 7 – PRO 140 dose: 350 mg QW SC ClinicalTrials.gov. NCT02483078. Wk 25 Placebo + Current Regimen Pts with CCR5-tropic virus and HIV-1 RNA ≥ 400 c/mL on current regimen; resistance to ≥ 1 ARV in ≥ 3 classes or ≥ 2 classes plus options limited by intolerance or cross resistance; must have ≥ 1 fully active drug available Day 7 PRO 140 + Current Regimen PRO 140 + OBR Slide credit: clinicaloptions.com
  31. 31. Options When Limited Information Available for Tx-Experienced Pt With Suspected Resistance  If have treatment history, but lack results of resistance testing – Start regimen of 2-3 drugs predicted to be active based on treatment history  In absence of self-reported history, medical records, and resistance testing results – Restart on most recent ARV regimen followed by drug resistance testing at Wk 2 or 4 to guide selection of next regimen DHHS Guidelines. Slide credit: clinicaloptions.com
  32. 32. Take-home Points  For pts with virologic failure and potential MDR HIV, genotypic and phenotypic resistance testing results and treatment history should inform the construction of new ART regimens – When considering CCR5 antagonist, tropism assay should be performed  For pts with confirmed MDR, the goal of a new regimen is a minimum of 2 (preferably 3) active drugs if possible – For pts with resistance to currently available agents, consider enrolling pt in clinical study, expanded access program, or FDA single-pt access to investigational agent  Investigational agents with novel MoAs may provide options for pts with MDR HIV – Fostemsavir (gp120 binder; prevents CD4+ cell attachment), ibalizumab (anti-CD4 receptor mAb), PRO 140 (anti-CCR5 mAb) Slide credit: clinicaloptions.com
  33. 33. clinicaloptions.com/hiv Slidesets on best practices in HIV management with expert faculty commentary Postconference clinical updates available following CROI, the International AIDS Conference, and IDWeek Go Online for More CCO Coverage of HIV!

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