Top 10 stories in HIV Medicine Disclosures n Receive funding for research from NIH n Gilead sciences provides antiretroviral therapy for NIH funded SEARCH research study Diane Havlir, MD Professor of Medicine University of California, San Francisco Story 1: United States Epidemic: The “Big Picture” in the U.S. Spotlight on the Real News n What is the big n Number of new HIV diagnosis: 37,600 picture? n Number of persons living with HIV: 1.2 million n Are new HIV n Percent of persons infected with HIV who do not infections going up know it: 13% or down? n Percent of people diagnosed with HIV who are n Who and where are virally suppressed: 55% the newly infected? n Who is living with HIV? n What is happening in San Francisco? 1
44% new infections in Blacks vs 12% of U.S. population AR1: >50% of new infections are Answer: the South in what region of the U.S.? n Northeast n Southeast n South n Central n West n Islands/District 2
States with the most cases and HIV: Spanning life stages the highest rates of infection n New Infections: 17% of new HIV infections in the U.S. among persons 50 years and older • Among these 43% black 36% white and 17% latino n Presentation: 40% are persons 55 and older and had AIDS at time of diagnosis n Living with HIV: 45% living with HIV are aged 50 and older • San Francisco 63% over 50 years of age New HIV diagnoses, deaths, Disparities in achieving viral prevalence in San Francisco 2006-2016 suppression in San Francisco 2013:Getting To Zero: Expand PREP,RAPID,LINCS 2012: PREP/ RAPID Lower rates of 2010:Universal ART viral suppression among: • Females • African Americans • Youth 16% decline • PWID new infections • Homeless in one year SFDPH HIV Epidemiology Annual Report 2016 3
Conclusions: Real News calls for Story 2: ART – a new framework for Real Action initial therapy in DHSS Guidelines n Nationally, there was a very modest decline in rates of HIV over the last 6 years (18%) n Recommended for n Overall viral suppression rates are suboptimal “most people with (55%) HIV” n Disparities must be addressed for prevention and n Recommended for treatment approaches “certain clinical Youth, women, PWID, homeless, foreign born, others situations” n We need to find persons early in disease--Late presentations can be lethal n We need resources and investment for our aging population Answer: DRV/c + TDF/FTC is Not AR2: First line therapy– which is Not recommended for most people recommended for “most people with HIV”? n DTG + ABC/3TC n DTG+ TDF*/FTC n EVG+ TDF*/FTC n RAL+ TDF*/FTC n DRV/C + TDF/FTC * Or TAF DHSS guidelines, October 2017 4
Recommended “in certain situations”– what kind of situations? n Patient virus or genetics– drug resistance, HLAB5701+ n Patient preference Recommended “in certain clinical • Fewer pills situations” (e.g. DRV/c+ TDF/FTC ), • Taking pills with food we will discuss these during the • Smaller pills n Co-morbidities conference • Renal disease • Cardiovascular disease • Hepatitis B • TB Story 3: INSTIs: The “First Line” 2 studies with DTG monotherapy: … but never alone High virologic failure and resistance Dolumono Study N=104 Retrospective review DTG monotherapy N=122 n Adults, suppressed on ART x 6 months n RESULTS: 11 Virologic failures n DTG 50 mg qd vs continue ART n 9/11 INSTI resistance n All switch to DTG at 24 weeks n RESULTS: 8 Virologic failures by week 72 Blanco JL, et al. CROI 2017. Abstract 5
Summary Story 4: Switch Mania n Old thinking– Dolutegravir has a very high genetic barrier and resistance unlikely to happen in patients with no prior INSTI n New thinking- Dolutegravir resistance can happen: • Never use DTG monotherapy • Make sure combination therapy has potency to protect DTG n Under study/new data • DTG+ 3TC for treatment naïve and for switch • DTC+ rilpivirine for switch Switching ART in patients with SWITCH: Boosted PI/TDF/FTC to viral load suppression Single tablet Darunavir/cobi/FTC/TAF n Why? – toxicity, potency, simplicity, drug EMERALD STUDY interactions, pregnancy n Why not? Patients like current regimen, unknown drug resistant mutations, lack of data on such a • N=1141 switch for patient with a complicated history • Endpoint: Virologic Failure n Why is this such an issue now? New data, new • 48 weeks co-formulated drugs, new drug combinations • Findings: Single tablet PI combination suited for specific situations effective and safe Orkin, Lancet HIV, 2017 6
SWITCH: ART to 2 Drug SWITCH: ART to 2 Drug Dolutegravir+Rilpivirine Dolutegravir + 3TC Virologic outcomes SWORD (1 and 2) POOLED 95 95 LAMIDOL • N=104 entered phase II • Endpoint: Virologic • N=1024 suppression at 48 weeks • Endpoint: Virologic • Findings: 97% viral suppression suppression at week 48, • 48 weeks no INSTI resistance; • Findings: DTG/RPV 1 NRTI resistance effective and safe Percentage-point difference 5 4 1 <1 DTG + RPV is non-inferior to CAR with respect to snapshot in the ITT- E population (<50 c/mL) at Week Libre, CROI, 2017 Joly, CROI, 2017 48 a Adjusted for age and baseline 3 rd agent. SWITCH: ART to 2 drug injection Summary: Switch for patients with Cabotegravir + Rilpivirine viral load suppression n “Switch” ART is major and complicated element of LATTE-2 HIV medicine – but it can help our patients! q8 q4 Oral • N=309 n New options with robust data (examples) • Oral cabotegravir + • Single pill protease inhibitor combination: Darunavir, cobicistat, ABC/3TC FTC, TAF (Prezcobix) • Randomize to injection (Q4 or 8 • 2 drug: Dolutegravir + Rilpivirine weeks) cabotegravir+ 2 drug options under study in Phase III trials rilpivirine vs continue n (examples) oral • Endpoint: Virologic • INSTI: Dolutegravir + 3TC suppression • Injection: Cabotegravir+ Rilpivirine • Findings: Injection( q4 or 8 weeks) effective and safe Margolis, Lancet, 2017 7
Story 5: 2 New antiretroviral Doravirine Agents* n NNRTI, once-daily dosing (100 mg), active in vitro against common NNRTI resistance mutations (including K103N, Y181C, E138K) n No food or PPI restrictions n Phase 2: Doravirine + TDF/FTC: HIV RNA suppression matches efavirenz, fewer adverse events Pipeline and innovation *among many LAI M-T. CROI 2016. Abs 506 Bictegravir Doravirine vs Darunavir/r DOR + 2 NRTIs (n = 383) 100 DRIVE FORWARD study DRV + RTV + 2 NRTIs (n = 383)) n INSTI, once daily 50 mg, unboosted 84 80 n Active against many INSTI resistance mutations ( in 80 vitro ) Treatment • N=766, ART naïve 60 difference: 3.9% Pts (%) n Phase 2: performed comparably to dolutegravir • Endpoint: Virologic (95% CI: -1.6% to suppression n CYP3A4 metabolized 9.4%) 40 • 48 weeks • Findings: Viral suppression 20 13 11 Doravirine similar to 7 5 darunavir regimen 0 • NNRTI resistance HIV-1 RNA Virologic No Data seen in failure < 50 c/mL Nonresponse Wk 48 Molina, CROI, 2017 Tsiang M, Antimicro Agents Chemother, Molina JM, et al. CROI 2017. Abstract 45LB. 2016 8
Bictegravir/TAF/FTC (single pill) Story 6: Intermittent PrEP – is it combination vs Dolutegravir + TAF/FTC time ? GS- 1490 study • N=657, ART naïve • Endpoint: Virologic suppression • 48 weeks • Findings: Viral suppression Bictegarvir similar to dolutegravir regimen • No INSTI resistance Sax, Lancet, HIV 2017 AR3: New data suggest intermittent Answer: MSM (vs daily) PrEP is promising option for n IPERGAY extension study • 361 participants • On demand PrEP n MSM • Median 18 pills/month n Women • Compare HIV incidence to prior n Both control arm of IPERGAY n Neither n Results: • 97% reduction in new HIV infections with intermittent PrEP • Condomless sex increased 77% to 86% -- high, but no increase in STI’s Molina, Lancet HIV, 2017 9
Story 7: Steroids—any role in TB Where are we in PrEP? IRIS for prevention? n CDC recommends daily PrEP for MSM • Recommendation based on IPrEX and Partners PrEP • IPERGAY study not considered sufficient to change recommendation n CDC recommends daily PrEP for women • Pharmacokinetic data support this recommendation n What is happening in communities? • Persons are already using intermittent PrEP • Communities are in discussion on policy • Providers are faced with a variety of new situations regarding PrEP, PEP and seroconversion AR4: In what situation does AR4: In what situation does addition of steroids have positive addition of steroids have positive effect on outcomes? effect on outcomes? n Cryptococcal meningitis (reduce mortality) n Cryptococcal meningitis (reduce mortality) n TB (reduce IRIS) n TB (reduce IRIS) n Both Cryptococcal meningitis and TB n Both Cryptococcal meningitis and TB 10
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