12/7/17 Disclosures Antiretroviral Therapy Management: • Brad Hare: • None • Annie Luetkemeyer: Panel Discussion & Debate • Research support from ViiV • Susa Coffey: Medical Management of AIDS & Hepatitis • None December 8, 2017 • Vivek Jain: • Research grant support from Gilead Sciences for work Brad Hare, MD, 1 Annie Luetkemeyer, MD 2 in East Africa related to methods of ART care delivery Susa Coffey, MD, 2 Vivek Jain, MD 2 • Research grant support from NIH, CDC, PEPFAR 1 Kaiser Permanente, San Francisco & 2 Division of HIV, Infectious Diseases & Global Medicine San Francisco General Hospital, University of California, San Francisco Goals/Format Patient 1 • Explore three cases in ART management • 38 year old man, no medical history • Being routinely tested for HIV every three months; • Elicit audience opinions last negative test 3 months ago, August 2017 • Expert panel reflections • In November 2017, HIV test is positive • CD4=640 cells/uL, HIV-1 RNA = 31,000 c/mL • HIV-1 genotype is sent, and still pending • Patient expresses desire to initiate ART immediately (and you agree) 1
12/7/17 Audience Preliminary Vote • Given the many options for ART, would you Case 1: initiate TAF/FTC (Descovy) + dolutegravir Susa Coffey (Tivicay)? Yes, comfortable initiating TAF/FTC + dolutegravir – (A) YES, I would give TAF/FTC + DTG. – (B) NO, I would recommend something else. Case 1: Starting DTG + TAF/FTC is appropriate Case 1: Starting DTG + TAF/FTC is appropriate . . Pt with early HIV, CD4=640, VL=31,000; genotype is pending. Pt Pt with early HIV, CD4=640, VL=31,000; genotype is pending. Pt • Mountains of data and experience with DTG + 2 NRTIs in • Assuming resistance to 1 NRTI, should still be initial ART; preferred regimen effective • If concern for transmitted resistance (R) • Data for DTG + 1 fully- active NRTI • How likely? • How likely to impact this regimen in NEXT 2-3 WEEKS? • Naives: • DTG + 3TC: • TDR present in ~15%, NRTI mutation ~7% • PADDLE, wk 48 VF in 1/20, no mutations DAWNING Study • K65R rare, M184V ~4-5% • ACTG 5353: wk 24 VL <50 in 90%; 89% if BL VL • Major INSTI mutations RARE >100,000. VF with R in 1/120 (adherence issues) • Treatment-experienced: • DTG + 2NRTIs • SAILING: subset on DTG + 2 NRTIs with resistance to 1-2 NRTIs-> Wk 48 NO VF if 0 or 1 fully-active NRTI (0/13) • DAWNING: DTG + 2NRTIs (vs LPV/r + 2NRTIs) after VF • Almost certainly has fully-active DTG and TAF, fully Mean BL VL 4.21 log; >100K with 1 st ART regimen-> 251 pts w/ 1 fully active NRTI, in 22% or perhaps partially effective FTC; this should be sufficient 84% w/ VL <50 at w k 48 (vs 73% of LPV/r ); no IN or new RT mutations Cahn et al. J IAS 2017. Taiwo BO, IAS 2017. Demaest J, IAS 2014. Aboud M, et al. IAS 2017. Abstract Menza TW et al, AIDS 2017. TUAB0105LB. 2
12/7/17 Real-World Risk of Virologic Failure in Pts Starting DTG-Based vs DRV-Based ART • Patients who initiated DHHS • DTG + TAF/FTC is a Case 1: Counterpoint: Recommended ART from 8/13- potent, simple, tolerable 3/17 at 8 CNICS sites (N = 5177) Brad Hare regimen • 1229 on DTG or DRV/r with ABC/3TC, TDF/FTC, or TAF/FTC • Likelihood of No, not comfortable initiating transmitted resistance is aHR* for VF † of DTG vs Pts TAF/FTC + dolutegravir… very low, and risk of VF DRV (95% CI) All pts Would initiate another regimen from transmitted § DRV § DTG 0.41 (0.30-0.55) resistance is even lower, Tx-naive pts (1229) esp. in next 2-3 weeks § DRV • Much clinical experience § DTG 0.32 (0.14-0.75) from SFGH RAPID ART † Virologic failure: HIV-1 RNA > 400 c/mL at ≥ 6 mos after initiating ART. *Cox models adjusted for age, CD4+ cell count, days from last HIV-1 RNA, CNICS site, sex, HBV, HCV, HIV risk factor, and race . Nance R, et al. IDWeek 2017. Abstract 1688. Modified from clinicaloptions.com Case 1 (BH) Case 1 (BH) Pa Patient diagnosed w/HIV in acute care setting, last tested negative 3 months ago, CD4=640, Patient diagnosed w/HIV in acute care setting, last tested negative 3 months ago, CD4=640, Pa VL VL=31, 31,000, 000, b but g genotype i is s sent a and p pending—do do no not ha have da data. VL VL=31, 31,000, 000, b but g genotype i is s sent a and p pending—do do no not ha have da data. Wo Would you start De Descovy DT DTG or something else Wo Would you start De Descovy DT DTG or something else • Transmitted drug resistance still • Transmitted drug resistance still occurs occurs • Clinical trials: ARV Drug % with Major Most Common Mutations • Participants always have Class IAS-USA baseline genotypes to enter Mutations • Reasonable clinical strategy: NRTI 8.9 A62V, M41L, M184V, K70R, • Start broad (still simple), wait for D67N the data, and refine NNRTI 7.8 K103N, K101E, L100I, V108I, Y188C/L • What’s worse: 2-4 weeks of one PI 3.2 M46I/L, V321, L90M, I84V, extra drug, or a lifetime of D30N generated resistance? Buchacz (CROI 2013, #615). HOPS Cohort 1999-2011 3
12/7/17 Final Audience Vote • Given the many options for ART, would you initiate TAF/FTC (Descovy) + dolutegravir (Tivicay)? – (A) YES, I would TAF/FTC + DTG. – (B) NO, I would recommend something else. Patient 2 Audience Preliminary Vote • 56 year old man, no medical co-morbidities • Would you recommend switching off the • Diagnosed with HIV in 2012; initially started protease inhibitor and switching to an TDF/FTC (Truvada) + ritonavir/darunavir and integrase inhibitor? Or stay with current achieved virologic suppression. protease inhibitor? • Switched Truvada to TAF/FTC (Descovy) in 2016; maintained RTV/DRV – (A) I would switch the PI to an INSTI. • Continuous virologic suppression – (B) I would continue the PI. 4
12/7/17 NO Protease inhibitors in Preferred initial ART DHHS guidelines 10/17 https://aidsinfo.nih.gov/guidelines Case 2: Annie Luetkemeyer NEAT-022: ≥ 50 yrs old or Framingham >10%, PI’s associated with: on PI/r + NRTI, suppressed x ≥ 6 months, no Would switch to integrase-based regimen Increase CVD (53% increase in D:A:D • documented resistance/virologic failure with DRV/r!) • Dyslipidemia Non-inferior to PI/r • • Metabolic derangement • Improved lipid AND NO current single pill formulation, profile to boot! • Improved Framingham score Ryom L, et al. CROI 2017. Abstract 128LB. (both ATZ and DRV) Gatell TUAB1012 IAS 2017 Ryom L, et al. CROI 2017. Abstract 128LB. Wha What if f pr preexi xisting ng resi sistanc nce? ? Ge Genosure Ar Archive: e: Us Usefu ful a application on • SPIRAL study: 282 patients suppressed on PI/r x > 24 weeks, 40% with prior virologic failure • RAL-based regimen equivalent to PI/r, virologic failure rare (1 vs. 3) • DTG more potent than RAL • DTG/3TC dual therapy thus far effective in several pilot switch studies and several pilot treatment initiation studies, thus: ü TAF should have efficacy with DTG even if M184 and 1-2 TAMs present ü Transmitted INSTI resistance still very rare. • Can get an Genosure Archive if worried Martinez AIDS 2010;24:1697, DOLAM Blanco EACS 2017, Taiwo EACS 2017, Figueroa IAS 2017, ACTG 5353 Taiwo IAS 2017 5
12/7/17 Co Concordance of f Ar Archive with GT Genos Ge osure Arch chive: Cautionary tale Genosure showed • RT T369 A/I/V • PR L10/I, D60E, 162V, L63 S/C/T Singh ID Week 2016 Abstract 1507 Historic genotype: • 48 paired samples, % concordance with historical GT was 92% for • RT M41L, D67N, Protease Inhibitor resistance and 88% for reverse transciptase. L210W, T215Y, V106I, Y181V Toma ICAAC 2015 • PR: L10I, M36I/M, M46L, I54V, L63S, I64V, V82A. Case 2 (BH) TAF/FTC + DRV/RTV, suppressed, and you don’t have any GT info TA 56y 56yo m man n no c co m morbidities, o on A ART x x7 y 7 years, g good a adherence à sw switch off PI PI to integr grase or stay on PI PI? • If it’s not broken, don’t fix it • Where are the data for DTG/TDF with M184V? ArchiveDNA test? • Want convenience? Symtuza is on the way Case 2: Counterpoint: Brad Hare Would stay with PI-based regimen 6
Recommend
More recommend
