HIV Clinical Update: Treatment in 2017 and Beyond Shobha - PDF document

5/25/17 HIV Clinical Update: Treatment in 2017 and Beyond Shobha Swaminathan, MD Associate Professor of Medicine Rutgers New Jersey Medical School Overview • Whats new in the guidelines • Starting antiretroviral therapy • Switching antiretroviral therapy • New medications • Hope for the future Case Presentation-1 • A 23 year old male comes to your clinic after going to the ER for a urethral discharge and was diagnosed with gonorrhea and at the same time had an HIV test that was reactive. He was then referred to you. • States that he feels fine and does he need meds • If he needs meds then he wants as few pills as possible • CD4-467, HIV VL- 27,000 copies/ml • RPR- negative, HCV neg 7 2017 HIV Clinical Update 1

5/25/17 DHHS Guidelines for Initial HIV Treatment (Preferred) • Integrase Strand Transfer Inhibitor-Based (INSTI) Regimens: • Dolutegravir (DTG)/abacavir (ABC)/lamivudine (3TC)— only for patients who are HLA-B*5701 negative • DTG plus either tenofovir disoproxil fumarate (TDF)/emtricitabine(FTC) or tenofovir alafenamide (TAF)/FTC • Elvitegravir (EVG)/cobicistat (c) /TAF/FTC • EVG/c/TDF/FTC • Raltegravir (RAL) plus either TDF/FTC or TAF/FTC • Protease Inhibitor-Based Regimens: • Darunavir(DRV)/ritonavir (r) plus either TDF/FTC or TAF/FTC DHHS Guidelines, updated July 2016 DHHS Guidelines for Initial HIV Treatment (Alternate) • NNRTI plus 2 NRTIs: • EFV/TDF/FTC • EFV plus TAF/FTC • RPV/TDF/FTCor RPV/TAF/FTC —if HIV RNA <100,000 copies/mL and CD4 >200 cells/mm 3 • Boosted PI plus 2 NRTIs: • ATV/c or ATV/r plus either TDF/FTCor TAF/FTC • DRV/c or DRV/r plus ABC/3TC— if HLA-B*5701 negative • DRV/c plus either TDF/FTC or TAF/FTC DHHS Guidelines, updated July 2016 Case Presentation-1 • A 23 year old male comes to your clinic after going to the ER for a urethral discharge and was diagnosed with gonorrhea and at the same time had an HIV test that was reactive. He was then referred to you. • States that he feels fine and does he need meds • If he needs meds then he wants as few pills as possible • CD4-467, HIV VL- 27,000 copies/ml • RPR- negative, HCV neg 8 2017 HIV Clinical Update 2

5/25/17 What would you recommend for him 1. EFV/TDF/FTC 2. RPV/TDF/FTC 3. TDF/FTC/RAL 4. TDF/FTC/DRV/r 5. EVG/c/TDF/FTC Case Presentation-2 • A 32 year old woman diagnosed with HIV in 2011 • Baseline CD4- 145 cells/cu mm, HIV VL 250,000 copies/ml • HIV genotype- wild type • HLA B 5701 negative • Has been on EFV/TDF/FTC • Usually well controlled, has rare blips • Current CD4- 564 cells/cu mm, HIV VL < 50 copies/ml • Feels grateful to her current regimen for saving her life Would you advise her to change her regimen • Yes • No 9 2017 HIV Clinical Update 3

5/25/17 What would you switch to 1. EFV/TDF/FTC 2. RPV/TDF/FTC 3. TDF/FTC/RAL 4. TDF/FTC/DRV/r 5. EVG/c/TDF/FTC Switching From Suppressive ART: Study Results • Trial Switch From Switch To Findings • Pts switched due to CNS toxicity (N = 40) UK EFV/TDF/ RPV/TDF/ • 100% maintained virologic suppression following switch Multicenter FTC FTC • Grade 2-4 CNS AEs significantly decreased at Wks 4, 12, including Study [1] dizziness, depression, insomnia, aggressive mood, abnormal dreams • Phase IIIb randomized study; pts switched (n = 291) or remained on original regimen (n = 143) • Switch to EVG/COBI/TDF/FTC noninferior to remaining on stable NNRTIs STRATEG NNRTI + EVG/COBI/T at Wk 48 (93% vs 88% HIV-1 RNA < 50 c/mL) Y-NNRTI [2] TDF/FTC DF/FTC • Dizziness, insomnia, anxiety, vivid dreams significantly decreased from BL at Wk 48 in switch group; no changes noted for pts who remained on EFV + TDF/FTC 1. Nelson M, et al. ICAAC 2013. Abstract H-672b. 2. Pozniak A, et al. Lancet Infect Dis. 2014;14:590-599. Slide credit: clinicaloptions.com Switching From Suppressive ART: Study Results • Trial Switch From Switch To Findings • Phase IIIb randomized study; pts switched (n = 275) or remained on original regimen (n = 278) 2 NRTIs + STRIIVING [1 DTG/ABC/3T • Switch to DTG/ABC/3TC noninferior to maintaining baseline ART (Wk 24 NNRTI, PI, or ] C HIV-1 INSTI RNA < 50 c/mL 85% vs 88%, respectively) • For pts initially switched to DTG/ABC/3TC, 83% maintained suppression through Wk 48 • Pts randomized to switch regimen (n = 959) or remaining on previous regimen (n = 477) • Switch to TAF regimen noninferior to maintaining TDF-based ART (97% TDF-based EVG/COBI/T GS-109 [2] vs 93% regimen AF/FTC HIV-1 RNA < 50 c/mL; P = .0002) • Prior EFV/TDF/FTC, HIV-1 RNA < 50 c/mL 96% with switch vs 90% with remaining on EFV/TDF/FTC 1. Lake JE, et al. IAC 2016. Abstract THAB0203. 2. Mills A, et al. Lancet Infect Dis. 2016;16:43-52. Slide credit: clinicaloptions.com 10 2017 HIV Clinical Update 4

5/25/17 Drugs That Should Not Be Used With Antiretroviral Agents • ARV Drugs That Should Not Be Used Concomitantly DTG [1] Dofetilide, rifapentine, St John’s wort EFV [1] St John’s wort, dasabuvir, ombitasvir, paritaprevir, simeprevir, elbasvir/grazoprevir EVG/COBI [1] Ranolazine, eplerenone, ivabradine, lovastatin, simvastatin, rifampin, rifapentine, carbamazepine, phenobarbital, phenytoin, lurasidone, pimozide, midazolam, triazolam, St John’s wort, dasabuvir, elbasvir/grazoprevir, ledipasvir, ombitasvir, paritaprevir, simeprevir, alfuzosin, cisapride, ergot derivatives, flibanserin, salmeterol , sildenafil for PAH RPV [1] Rifampin, rifapentine, carbamazepine, oxcarbazepine, phenobarbital, phenytoin, St John’s wort, dasabuvir, ombitasvir, paritaprevir, PPIs (eg, omeprazole) TDF/FTC [2] Nephrotoxic drugs 1. DHHS guidelines. July 2016. 2. TAF/FTC [package insert]. 2016. 3. TDF/FTC [package insert]. 2016. Slide credit: clinicaloptions.com If the pt wished to become pregnant via sperm donation, what regimen would you recommend? A. RAL + TAF/FTC B. EVG/COBI/TDF/FTC C. EVG/COBI/TAF/FTC D. RPV/TDF/FTC or RPV/TAF/FTC E. DRV + RTV + TDF/FTC F. Maintain current regimen DHHS Recommendations: ART in Pregnant Women DHHS Guidelines [1] PIs NNRTIs NRTIs Entry Inhibitors Integrase Inhibitors ABC/3TC Atazanavir/RTV* TDF/FTC Recommended Efavirenz* † Raltegravir* Darunavir/RTV* TDF + 3TC ZDV/3TC Alternative Lopinavir/RTV* Rilpivirine* Dolutegravir Insufficient data to RPV/TAF/ TAF/FTC [3] Fosamprenavir Maraviroc EVG/COBI/TDF/ FTC recommend FTC [2] EVG/COBI/TAF/FTC [2] Indinavir/RTV Nelfinavir Etravirine ABC/3TC/ZDV Not recommended Ritonavir Nevirapine d4T Enfuvirtide ddI Saquinavir/RTV Tipranavir/RTV *In addition to 2-NRTI backbone. † May be initiated after first 8 wks of pregnancy. 1. DHHS Perinatal Guidelines. August 2015. 2. EVG/COBI/TAF/FTC [package insert]. 2015. 3. RPV/TAF/FTC [package insert]. 2016. 4. TAF/FTC [package insert]. 2016. Slide credit: clinicaloptions.com 11 2017 HIV Clinical Update 5

5/25/17 HIV Coinfection • TAF/FTC OR TDF/FTC recommended for patients with HIV/HBV • HCV infection • All patients should be treated • Use Direct acting agents • Monitor for DDI AASLD Guidance on HCV/HIV DDIs Grazo/ElbXa SMV SOF LDV VEL DCV PrOD s C Ö » » » Ö Atazanavir/r X C Ö » » Ö » Darunavir/r X Lopinavir/r C Ö » » Ö C X Tipranavir/r C C C No data C C No data Efavirenz C Ö Ö X » C X Rilpivirine Ö Ö Ö Ö Ö C Ö Etravirine » Ö No data No data » No data No data Ö Ö Ö Ö Ö Ö Ö Raltegravir C » » » » Elvitegravir/c No data X Dolutegravir Ö Ö Ö Ö Ö Ö Ö Maraviroc Ö Ö Ö Ö Ö » No data TDF Ö Ö » » Ö Ö Ö TAF Ö Ö Ö Ö Ö Ö Ö No clinically significant interaction expected Do not coadminister Potential interaction may require dose adjustment , timing, or monitoring DHHS Guidelines, updated July 2016 AASLD/IDSA. HCV guidelines. July 2016. Why Do We Need New Options for Pts With HIV • Short-term and long-term safety • Tolerability • Convenience • Cost • Activity against panresistant virus • Still no available cure 12 2017 HIV Clinical Update 6