Antiretroviral Therapy: Panel none Discussion Medical Management - PDF document

12/9/17 disclosures Antiretroviral Therapy: Panel • none Discussion Medical Management of HIV December 9, 2017 Panelists: Harry Lampiris, MD; Annie Luetkemeyer, MD; Carina Marquez, MD Moderator: Oliver Bacon, MD Questions • What to start in an ART-naïve, with/without labs Qu Question: : in the era of “Test and Treat,” what • What to start if M184V alone? regimen would you choose for an ARV-na re naïve e • INSTI resistance • New uses for old(er) drugs (rilpivirine, atazanavir)? patien pa ent wi withou out re resistance testing available? • Using fewer than 3 drugs • Initial ART in pregnant women • How will might soon-to-arrive ARVS change your initial management • Treatment modification for (multiple) comorbidities, de- intensification 1

12/9/17 Case 1: panelists, which regimen(s) for ARV- Case 1. naïve patient who wants test-and-treat? • 24, female, newly HIV+ : Lab-based Ag/Ab (+), differentiation Ab(-), 1. Elvitegravir/cobi/FTC/TAF HIV RNA 1.2 million c/mL 2. Darunavir 800mg QD + ritonavir 100mg QD + FTC/(TAF or TDF) • CD4, sCr, HLA-B*5701, genotype, INSTI genotype all pending. 3. Raltegravir 1200mg QD + FTC/(TAF or TDF) • Urine HCG(-); has an IUD 4. Dolutegravir/abacavir/3TC • No comorbidities 5. Dolutegravir + FTC/(TAF or TDF) 6. Rilpivirine/FTC/(TAF or TDF) 7. Dolutegravir + 3TC Recommended initial ART regimens reclassified in Recommended initial ART regimens reclassified in DHHS DHHS OCT2017 OCT2017 II. For certain clinical situations I. For most people with HIV 1. Boosted PI + 2 NRTIs • In general, DRV preferred over ATV INSTI + 2 NRTIs • No distinction between boosting agents (rtv vs cobi) • 2 NRTIs can be (FTC or 3TC) + (tenofovir or ABC) 1. DTG/ABC/3TC if HLA-B*5701 negative • ABC only if HLA-B*5701 negative 2. (DTG or RAL) + FTC/tenofovir • Boosted ATV + ABC/3TC only if HIV RNA<100,000 c/mL 2. NNRTI + 2 NRTIs 3. Elvitegravir/cobicistat/FTC/tenofovir 1. EFV + (FTC or 3TC) + tenofovir 2. RPV/FTC/tenofovir only if HIV RNA<100,000 c/mL and CD4>200 cells/mm3 3. INSTI + 2 NRTIs 1. RAL + ABC + (3TC or FTC) only if HLA-B*5701 negative and HI RNA<100,000 c/mL 4. If TDF, TAF and ABC cannot be used 1. DRV/r + RAL 400mg BID only if HIV RNA<100,000 c/mL and CD4>200 cells/mm3 2. LPV/r BID + 3TC BID 2

12/9/17 Case 2 • 30, MSM, lab-based Ag/Ab(+) differentiation Ab HIV-1(+) at his most recent PrEP visit 3 weeks ago. Question: (How) does presence of M184V V • Had heard about “French study” and was taking Truvada before and after sex, with some of his partners. Stopped altogether after testing affect your choice of initial ART? T? HIV(+) • CD4 550 cells/mm3, HIV RNA 50,000 c/mL, sCr 0.9, Hepatitis B sAg(-), HLA-B*5701(-) • GT: M184M/V DAWNING: DTG Effective Even With Partially Case 2: Panelists, Choice of initial therapy Active Background Regimen with M184V? § Randomized, open-label phase IIIb HIV-1 RNA < 50 copies/mL, Wk 24 (ITT-E) 1. Dolutegravir/abacavir/3TC study in which pts in resource- DTG + 2 NRTIs LPV/RTV + 2 NRTIs limited settings with virologic failure 100 2. Elvitegravir/cobicistat/FTC/(TAF or TDF) on NNRTI + 2 NRTIs treated with 84 82 3. Elvitegravir/cobicistat/FTC/(TAF or TDF) + DRV 80 74 DTG + 2 NRTIs or LPV/RTV + 73 69 2 NRTIs (N = 627) 4. Dolutegravir + FTC/(TAF or TDF) Pts (%) 60 55 – Pts could not have primary 5. Darunavir 800mg QD + ritonavir 100mg QD + FTC/(TAF or TDF) resistance to INSTIs or PIs; pts 40 6. Darunavir/cobi + FTC/(TAF or TDF) required to receive 1 fully active 20 NRTI 257/ 215/ 45/ 35/ 212/ 180/ n/N = 312 312 61 64 251 248 – Baseline NRTIs: ZDV + 3TC, 40%; 0 Overall* 2 < 2 TDF + 3TC or FTC, 42%; TDF + Fully Active NRTIs ZDV, 12%; ABC + 3TC, 2% *Treatment difference: 13.8% (95% CI: 7.3% to 20.3%; P < .001) Aboud M, et al. IAS 2017. Abstract TUAB0105LB. Slide credit: clinicaloptions.com 3

12/9/17 Case 3: Qu Ques estion(s): : Ho How do you inter erpret res esults of the e Ge GenoS oSure • 54 yo man, homeless, heterosexual but no sex in 25 years. Recently moved Arch chive assay when they suggest resistance ce in a to SF from LA patient with an undetect ctable VL? • HCV ab(+) GT1a/1b; TC 153, H29, L62, TG312; sCr 0.8, Sulfa allergy • HIV(+) and on treatment since 1993. Prior regimens unknown, but reports having undetectable VL “ever since since viral loads could be measured,” How comfortable Ho e are e you with do dolut utegravir and CD4 never <200. No h/o OIs. Current VL <20, CD4=816 • Currently on DRV/ABC/3TC x 2 years “I take it as many times a week as I pseudomonotherapy ps py? can;” records from LA clinic state he takes it 3x/week. He says will only take QD regimen. • GenoSure Archive: NRTI: M41L, D67N, M184M/V, L210W T215Y; NNRTI: none; PI: K20R, M36I, I62V Case 3: Virologic suppression on DTG/ABC/3TC with ABC and 3TC resistance mutations by DNA testing Qu Ques estion: : 1. DTG/ABC/3TC (1 QD) 2. DTG + FTC/TAF (2 QD) What ARVs to use in the setting of resistance ce to 3. DRV/Cobi + DTG (2 QD) INS INSTIs Is and and NR NRTIs Is? ? 4. DTG + RPV (2 QD) 5. E/C/F/TAF + DRV (2 QD) 6. Something else GenoSure Archive: NRTI: M41L, D67N, M184M/V, L210W T215Y; NNRTI: none; PI: K20R, M36I, I62V; INSTI: none 4

12/9/17 Audience: if you prescribe ART, have you Case 4: encountered patients who developed INSTI- resistance on Raltegravir or Elvitegravir? • 31, MSM, HIV+ 2007, BL HIV RNA > 100,000; baseline GT= wild-type, HLA-B*5701(-); nadir CD4 189 1. Yes • EFV/FTC/TDF ->rash-> ATV/r + FTC/TDF-> jaundice, total Bili 9.0 2. No • RAL + FTC/TDF with intermittent suppression until persistent viremia in 5/2017: HIV RNA 4136 c/mL, CD4 244 cells/mm3 • GT RT: M184V, K65R; PI: none; INSTI: G140S, Q148H. Trofile = R5 virus Case 4: panelists: which of the following would you include in a regimen for INSTI (G140S, Q148H) and NRTI (K65R, M184V) resistance: 1. dolutegravir 50mg BID 2. darunavir 600 BID + ritonavir 100 BID 3. darunavir 800 QD + ritonavir 100 QD 4. etravirine 200mg BID Question: Qu : What would you use/not use for r 5. etravirine 400mg QD initial ART T in a woman diagnosed with HIV V 6. rilpivirine 25mg QD 7. FTC/TAF 1 tab QD dur during ng pr pregna egnanc ncy? 8. ABC/3TC 1 tab QD Feel free to use coformulations if available 5

12/9/17 Case 5: 1 st line ART for pregnant woman, Case 5: initial ART for pregnant woman rapid start, 3 rd trimester • 32 y.o. woman, B-HCG(+) 6 months ago, LMP 7 months ago 1. Dolutegravir/abacavir/3TC • HIV+ by Ag/Ab and differentiation Ab 4 days ago 2. Dolutegravir + FTC/TAF • Last (-)HIV test: 6 months ago 3. Raltegravir 400mg BID + FTC/TDF • Wants to keep pregnancy 4. Elvitegravir/cobi/FTC/TDF • HIV RNA pending, GT pending, CD4 count 420 cells/mm3, HLA- 5. Efavirenz/FTC/TDF B*5701(-) 6. Atazanavir 300mg QD+ ritonavir 100mg QD + FTC/TDF QD • CrCl>60ml/min 7. Darunavir 600mg BID + ritonavir 100mg BID + FTC/TDF Tsepamo: Birth Outcomes When Initiating First- Antiretroviral Agents and Pregnancy line DTG vs EFV in Pregnancy Entry Integrase § Prospective cohort study in HIV-infected women in Botswana initiating ART with NRTI NNRTI PI Inhibitor Inhibitor EFV/FTC/TDF vs DTG/FTC/TDF while pregnant (N = 5438) Atazanavir/r 3 Preferred Abacavir/lamivudine OR Raltegravir plus Emtricitabine*/tenofovir Darunavir/r plus preferred 2- § Few first-trimester ART Adverse Birth Outcomes, DTG EFV aRR* preferred 2-NRTI NRTI backbone exposures (DTG, n = 116; n (%) (n = 845) (n = 4593) (95% CI) EFV, n = 396); most second/third Alternative Zidovudine/LamivudineZi Efavirenz OR Lopinavir/r plus Dolutegravir Any 291 (34.4) 1606 (35.0) 1.0 (0.9-1.1) trimester Rilpivirine plus preferred 2-NRTI plus preferred § Severe 92 (10.9) 519 (11.3) 1.0 (0.8-1.2) preferred 2- 2-NRTI Stillbirth 18 (2.1) 105 (2.3) 0.9 (0.6-1.5) § Only 1 major congenital NRTI Neonatal death (< 28 days) 11 (1.3) 60 (1.3) 1.0 (0.5-1.9) abnormality observed (skeletal Insufficient data Emtricitabine/tenofovir Preterm birth (< 37 wks) 149 (17.8) 844 (18.5) 1.0 (0.8-1.1) dysplasia in EFV-exposed group) in pregnancy alafenamide (TAF/FTC) § Very preterm (< 32 wks) 35 (4.2) 160 (3.5) 1.2 (0.8-1.7) SGA (< 10th percentile 156 (18.7) 838 (18.5) 1.0 (0.9-1.2) § ABO risks similar when initiating Do not use in ABC/AZT/3TC as complete Etravirine, Tipranavir, Maraviro Elvitegravir/co weight) pregnancy regimen; d4T, ddI Nevirapine Fosamprenavir/ c, T20 bicistat first-line DTG vs EFV in § Very SGA (< 3rd 51 (6.1) 302 (6.7) 0.9 (0.7-1.2) Indinavir/ percentile weight) pregnancy Saquinavir/ *For DTG vs EFV; adjusted for maternal age, education, gravida. *Or lamivudine. Rttonavir alone, 1 May be initiated after the first 8 weeks of pregnancy. Evidence of human fetal risk; Pregnancy Category D. 2 Contraindicated with CD4+ counts >250/mm 3 due to potential for liver toxicity. Nelfinavir 3 Theoretical concern for hyperbilirubinemia. 4 Co-formulated with cobicistat/emtricitabine/tenofovir DF. Note: no data on use of cobicistat in pregnancy and can not be recommended for ART-naïve pregnant women at this time. Zash R, et al. IAS 2017. Abstract MOAX0202LB. Slide credit: clinicaloptions.com 23 DHHS. http://aidsinfo.nih.gov/contentfiles/PerinatalGL.pdf. Revision October 16, 2016. 6