2/16/2017. Management and Prevention of HIV Infection: Case Discussion. Case 1. Case 1

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1 Management and Prevention of HIV Infection: Case Discussion Eric S. Daar, M.D. Chief, Division of HIV Medicine Harbor-UCLA Medical Center Professor of Medicine David Geffen School of Medicine at UCLA Grant support: Consultant: DISCLOSURES Gilead, Merck, ViiV Bristol Myers Squibb, Gilead, Janssen, Merck, Teva, ViiV Case 1 34 year old man presents to clinic after having a routine HIV Ab screening test that was positive in a local testing site. He also had a CD4 count sent and was told it was 570 cells/ul The patient was immediately referred to you and is upset but understands that there are good treatments available and he has insurance to cover costs of care, but is nonetheless not completely sure he wants to start treatment He has no past medical history, is asymptomatic, has had 5 different partners of unknown HIV status during the past year, 2 in the last month with inconsistent use of condoms for several years Case 1 Which of the following is closest to what you would recommend to this patient with regards to starting ART? A. Strongly encourage to start B. Recommend he start C. Support him in his wishes to defer D. Other 34 yo asymptomatic man CD4= 570 cells/ul 1

2 START Study Outcomes: Composite Primary Endpoint and its Components Immediate ART superior to deferred ART Serious and non serious AIDS events 68% of the primary endpoints with CD4 >500 cells/mm 3 Similar reductions in events across all subgroups No increase in AEs associated with immediate ART Number of Events Composite Endpoint Number of Serious Events 57% Reduction (P<0.001) AIDS- Related 72% Reduction (P<0.001) Deferred ART (n=2359) Immediate ART (n=2326) 47 Components (Serious Events) 29 Non-AIDS Related 39% Reduction (P=0.04) Lundgren J, et al. 8 th IAS Conference. Vancouver, Abstract MOSY0301. The INSIGHT START Study Group. N Engl J Med. 2015;July 20. [Epub ahead of print]. When to Start ARVs AIDS or HIV-Related CD4 Count (cells/mm 3 ) Symptoms < >500 United States DHHS (2016) Yes Yes Yes Yes Yes IAS-USA (2016) Yes Yes Yes Yes Yes British HIV Association (2016) Yes Yes Yes Yes Yes European AIDS Clinical Society Yes Yes Yes Yes Yes (2016) WHO (2015) Yes Yes Yes Yes Yes DHHS. Revision July 14, Günthard HF, et al. JAMA. 2016;316: EACS. Revision October BHIVA. Revision August WHO. Revision September Case 1 If you and patient decide that starting is the right thing to do, what would you recommend next? A. Send routine laboratory studies, HIV genotype and schedule for f/u appointment when results return B. Send routine laboratory studies without a HIV genotype and start ARVs immediately C. Send routine laboratory studies with a HIV genotype and start ARVs immediately D. Something else 34 yo asymptomatic man CD4= 570 cells/ul 2

3 State-transition Markov process model to assess mortality risk associated with ART delays Patient level data from 3 South African cohorts Estimated increase in mortality from 11 to 14.7% (relative increase of 34%) with a 10- week delay in ART Relative risk similar across CD4 counts but differ for absolute risks Contour Plot 11% 19.7% 24.2% Hoffmann CJ, et al. JAIDS 2013; 63: RCT in South Africa clinics (n=377) SOC had 3 5 additional clinic visits over 2 4 wks prior to ARVs Primary outcome was VL <400 c/ml within 10 months 64 vs. 51%; RR 1.26 (1.05, 1.50) Secondary outcome was initiation ART within 90 days 97 vs. 72%; HR 1.36 (95% CI 1.24, 1.49) New SFGH patients, RAPID era: Indicator RAPID Cohort (n=39) Sociodemographics Universal ART (n=47) P- value Age: mean(range) 32 (21-47) 35 (19-68) NS Male: n (%) % 43 92% NS Non-white ethnicity 23 59% 34 71% NS Homeless 11 28% 13 25% NS Uninsured % % NS Staging Acute (Ab- <6m) 21/30 70% 8/31 26% Log 10 VL 4.9 ( ) 4.5 ( ) NS CD4 mean (range) 474 (3-1391) 417 ( ) NS 3

4 Uptake of same-day ART RAPID era : transmitted resistance and drug regimens Indicator RAPID (n=39) Universal ART (n=47) P Genotype obtained 32/39 (82.1%) 43/47 (91.5%) 0.21 Any 4 8/32 (25.0%) 18/43 (41.9%) 0.13 Major NNRTI-R 4 7/32 (21.9%) 11/43 (25.6%) 0.71 Major PI-R 1/32 (3.1%) 2/43 (4.7%) 0.99 Major NRTI-R 0 (0%) 1/43 (2.3%) 0.99 ART initiated 5,6 39/39 (100%) 38/47 (80.9%) INSTI use 6 35/394 (89.7%) 32/38 (84.2%) 0.47 RAPID Antiretroviral Regimens TDF/FTC + DTG 26 (67%) EVG/COBI/FTC/TDF 7 (18%) TDF/FTC + DRV + RTV 4 (10%) TDF/FTC + RAL 1 ( 2%) ABC/3TC/DTG 1 ( 2%) 4

5 Time to VL suppression by ART initiation strategy: SFGH RAPID Universal ART CD4 guided ART Proportion <200 copies RAPID vs. universal ART P<0.001 Case 1 You encourage him to start on the same day and he agrees. He states that he has no specific concerns regarding adherence, side effects or dosing schedule. Which of the following would you recommend? A. Two NRTIs + boosted PI B. Two NRTIs + RAL C. TDF/FTC/EFV D. TDF (or TAF)/FTC/RPV E. TDF (or TAF)/FTC/COBI/EVG F. TDF (or TAF)/FTC + DTG G. ABC/3TC/DTG H. Something else 34 yo asymptomatic man CD4= 570 cells/ul All laboratory studies are pending Must treat before HIV drug resistance results available Avoid NNRTI based regimens Recommended ART Regimens: DRV/r plus TAF/FTC or TDF/FTC DTG plus TAF/FTC or TDF/FTC Transmitted mutations conferring NNRTI resistance are more likely than mutations with PI or INSTI resistance Resistance to DRV/r and DTG emerges slowly; transmitted resistance to DRV is rare and has not been reported to DTG 5

6 Case 1 You decide to defer therapy pending labs and he now returns: VL 23,000 copies/ml; HBsAb+, HCV Ab-, HLA-B5701 neg, chemistries WNL, Genotype is WT. He is ready to start ARVs and has no specific concerns regarding adherence, side effects or dosing schedule. Which of the following would you recommend? A. Two NRTIs + boosted PI B. Two NRTIs + RAL C. TDF/FTC/FTC/EFV D. TDF (or TAF)/FTC/RPV E. TDF (or TAF)/FTC/COBI/EVG F. TDF (or TAF)/FTC + DTG G. ABC/3TC/DTG H. Other 34 yo asymptomatic man CD4= 570 cells/ul; VL= 23,000 c/ml HLA-B5701-negative CrCl= 90 ml/min HCV-neg; HBsAb+ HIV Genotype- wild type If you chose a tenofovir-based regimen, which would you use? A. TAF B. TDF Case 1 34 yo asymptomatic man CD4= 570 cells/ul; VL= 23,000 c/ml HLA-B5701-negative CrCl= 90 ml/min HCV-neg; HBsAb+ HIV Genotype- wild type Tenofovir Alafenamide (TAF) 90% Lower TFV Levels in Plasma Minimizes Renal and Bone Effects While Maintaining High Potency for Suppressing HIV GI Tract PLASMA HIV TARGET CELL TVF TFV TDF 300 mg TAF 25 mg TFV HIV TFV 6

7 Case 1 (v 2.0) Same patient that you sent off awaiting labs only in this case CD4=145 cells/ul, VL= 180,000 c/ml and he missed several clinic appointments after initial visit. He admits to using alcohol and experiencing mild depression. He has met with psychologist a few times and is relatively stable and drinking some what less. Which of the following would you recommend? A. Two NRTIs + boosted PI B. Two NRTIs + RAL C. TDF (or TAF)/FTC/COBI/EVG D. TDF (or TAF)/FTC + DTG E. ABC/3TC/DTG F. Other 34 yo asymptomatic man using alcohol, depressed and missed visits CD4= 145 cells/ul; VL= 180,000 c/ml HLA-B5701-negative CrCl= 90 ml/min HCV-neg; HBsAb+ HIV Genotype- wild type 7

8 Low Virologic Failure and Treatment- Emergent Resistance With Boosted PIs Trial Name F/u, Wks CASTLE [1] 96 ACTG 5202 [2] 96 Study 103 [3] 144 ARTEMIS [4] 96 FLAMINGO [5] 96 ACTG 5257 [6] 96 Treatment Arm Virologic Failure, n (%) Treatment Emergent Primary Mutations, n ATV/RTV + TDF/FTC (n = 440) 28 (6) 1 (PI), 7 (NRTI) LPV/RTV + TDF/FTC (n = 443) 29 (7) 10 (NRTI) ATV/RTV + NRTIs (n = 928) 140 (15) 1 (PI), 16 (NRTI) EFV + NRTIs (n = 929) 129 (14) 68 (NNRTI), 36 (NRTI) ATV/RTV + TDF/FTC (n = 355) NR (7) 2 (NRTI) EVG/COBI/TDF/FTC (n = 353) NR (8) 8 (INSTI), 8(NRTI) DRV/RTV + TDF/FTC (n = 343) NR (12) 2 (NRTI) LPV/RTV + TDF/FTC (n = 346) NR (17) 5 (NRTI) DRV/RTV + 2 NRTI (n = 242) 4 (2) 0 DTG + 2 NRTI (n = 242) 2 (< 1) 0 ATV/RTV + TDF/FTC (n = 605) 95 (16) 1 (INSTI), 8 (NRTI) DRV/RTV + TDF/FTC (n = 601) 115 (19) 11 (INSTI), 3 (NRTI) RAL + TDF/FTC (n = 603) 85 (14) 1 (INSTI), 7 (NRTI) 1. Molina JM, et al. J Acquir Immune Defic Syndr. 2010;53: Daar ES, et al. Ann Intern Med. 2011;154: Clumeck N, et al. J Acquir Immune Defic Syndr. 2014;65:e121-e Mills A, et al. AIDS. 2009;23: Molina JM, et al. Glasgow HIV Abstract O Lennox JL, et al. Ann Intern Med. 2014;161: Dolutegravir + NRTIs in Treatment- Naive Patients HIV-1 RNA < 50 c/ml by Snapshot Analysis: 95% CI for Treatment Difference SINGLE [1] Favors Favors EFV/TDF/FTC DTG + ABC/3TC FLAMINGO [2] Favors Favors DRV/RTV DTG SPRING-2 [3,4] Favors Favors RAL DTG ARIA [5] Favors Favors ATV+TDF/FTC DTG/ABC/3TC Wk % 7.4% 12.3% 7.1% 0.9% 13.2% 2.5% -2.2% 7.1% 10.5% 3.1% 17.8% Wk % 8.0% 13.8% 12.4% 4.7% 20.2% -1.1% 4.5% 10% Wk % 2% 14.6% -5% 0 15% -12% 0 25% -12% 0 12% -5% 0 20% No resistance selected for in any DTG-containing regimen 1. Walmsley S, et al. J Acquir Immune Defic Syndr. 2015;[Epub ahead of print]. 2. Molina JM, et al. Glasgow HIV Abstract O Raffi F, et al. Lancet. 2013;381: Raffi F, et al. Lancet Infect Dis. 2013;13: Orrell C, et al. IAS Low Virologic Failure and Lack of Treatment-Emergent Resistance With DTG Trial Name F/u, Wks SPRING 2 [1] 96 SINGLE [2] 144 FLAMINGO [3] 96 Study 102 [4] 144 Study 103 [5] 144 Treatment Arm Virologic Failure, n (%) Treatment Emergent Primary Mutations, n DTG + 2 NRTI (n = 411) 22 (5) 0 RAL + 2 NRTIs (n = 411) 29 (7) 1 (INSTI), 4 (NRTI) DTG + ABC/3TC (n = 414) 39 (9) 0 EFV/TDF/FTC (n = 419) 33 (8) 1 (NRTI), 6 (NNRTI) DTG + 2 NRTI (n = 242) 2 (< 1) 0 DRV/RTV + 2 NRTI (n = 242) 4 (2) 0 EVG/COBI/TDF/FTC (n = 348) NR (7) 9 (INSTI), 10 (NRTI) EFV/TDF/FTC (n = 352) NR (10) 4 (NRTI), 14 (NNRTI) EVG/COBI/TDF/FTC (n = 353) NR (8) 8 (INSTI), 8(NRTI) ATV/RTV + TDF/FTC (n = 355) NR (7) 2 (NRTI) 1. Raffi F, et al. Lancet Infect Dis. 2013;13: Pappa K, et al. ICAAC Abstract H-647a. 3. Molina JM, et al. Glasgow HIV Abstract O Wohl DA, et al. J Acquir Immune Defic Syndr. 2014;65:e118-e Clumeck N, et al. J Acquir Immune Defic Syndr. 2014;65:e121-e124. 8

9 Cohort study of all patient starting DTG in two centers in Netherlands N=556; 102 (18.4% naïve); median f/u 225 days 85 (15.3%) stopped DTG; 76 (13.7%) for intolerability De Boer MGJ, et al. AIDS 2016; Case 2 49 year old man with stable DM who had been HIVnegative presents to you for advice regarding how to best avoid HIV infection in his new relationship with an HIV-infected man He states that his partner has been on ARVs for nearly two years with good viral suppression Although they mostly use condoms he had heard that they may not be necessary if his partner is suppressed on ARVs He would rather not use condoms but wants to know what his risks would be without Case 2 Which of the below would be closest to what you would tell him with regards to his risks of acquiring HIV from his current partner if they choose to not use condoms? A. You would be at some risk and should ideally use condoms B. The risk would be very low but can t tell you that it is completely safe C. Your risk under these circumstances is essentially zero 9

10 HPTN 052: Final Results of HIV Prevention in Stable Heterosexual Couples Linked HIV transmission to HIVnegative partner (n=46) Overall 93% reduction in risk of transmission with early therapy Linked partner infections diagnosed after index partner started ART (n=8)* Recently initiated ART (n=4) Virologic failure (n=4) No HIV transmission among people who were suppressed Timing of the linked transmission events supports the model that HIV transmission is very unlikely in the setting of viral suppression Linked Partner Infections (number) Overall *Phylogenetic methods compared HIV pol sequences from index partner pairs and controls. Linkage probability was further assessed by comparing the genetic distances between pol sequences (Bayesian analysis). Cohen M, et al. J Int AIDS Soc. 2015;18(suppl 4):15. Abstract MOAC0101LB. Eshleman SH, et al. J Int AIDS Soc. 2015;18(suppl 4):18. Abstract MOAC0106LB Linked HIV Transmission 36 Delayed ART Early ART Contribution to HPTN 052 Condomless sex MSM Limitatons Power, especially for highest risk MSM Cohort of serodiscordant couples Median duration of condomless sex at entry ~2 years Median duration on suppressive ARVs at entry >7 years Adherence rates >90% Counseled to use condoms Additional lessons High rate of STIs Transmissions from non-regular partners JAMA 2016; 316:

11 Case 2 He and his partner decide, based upon the information you provided him that they would not use condoms as long as the infected partners viral load is undetectable. Then your patient asks you if you would recommend he use PrEP. Which of below would be closest to what you would recommend? A. With an HIV-infected partner it would be appropriate for you to be on PrEP B. Your risk with your current partner on ARVs is too low to justify PrEP C. I would totally leave it up to you D. Something else Case 2 He decides that he wants to use PrEP. He is 4 th generation HIV-negative, HBsAb+, has CrCl- 70 ml/min. Which would be closest to what you would recommend: A. TDF/FTC once daily B. TDF/FTC around sex C. TDF/FTC four times per week D. TDF once daily E. Strongly encourage him not to take PrEP since risk is low and renal function impaired F. Something else Table of Recommendations CDC 1 WHO 2 IAS 3 Population for PrEP MSM or Heterosexual Men and MSM >2% background HIV incidence Women with: Serodiscordant Couples Recent incident STI diagnosis HIV(+) sex partner* Transgender women who Especially syphilis, gonorrhea, or Inconsistent condom use, or have sex with men chlamydia recent STI, or high number of IDU (unless negative partner PEP use >2x in past year sexual partners in serodiscordant IDU who Commercial sex work relationship) Share injection equipment In high prevalence area or Inject 1 times/day network (for heterosexual men Inject cocaine or and women only) methamphetamines IDU HIV(+) injecting partner Sharing injection equipment Recent drug treatment (but currently injecting) Regimen suggested TDF 300 mg + TDF 300 mg + TDF 300 mg + FTC 200 mg FTC 200 mg FTC 200 mg Or Or TDF 300 mg (IDU only) TDF 300 mg (serodiscordant couples only) Timing and Frequency Once Daily Once Daily Once Daily *For any regular sex partner should consider if they are on ARVs with undetectable VL IDU: Injection Drug Users, STI: Sexually Transmitted Infections, MSM: Men Who Have Sex With Men, TDF: Tenofovir, FTC: Emtricitabine, PEP: Post Exposure Prophylaxis, PrEP: Pre Exposure 1 Prophylaxis, CDC: Centers for Disease Control Updated and Prevention, May WHO: 14, World Health Accessed Organization, May 21, IAS: International AIDS Society 2 WHO. Consolidated Guidelines on HIV prevention. Switzerland. July HIV Prevention in Clinical Care Settings Recommendations of the International Antiviral Society USA Panel. July

12 Case 2 Your patient starts TDF/FTC once daily He returns several times over the next 12 months with STIs and ultimately admits that he has sex with multiple men without condoms outside of his current relationship You counsel him to use condoms and he continues to return with frequent STIs but to be repeatedly HIV-negative He is noted during the past year to have a progressive decline in CrCl to approximately 50 ml/min Case 2 The patient is having continued high risk sex despite counseling and has progressive decline in renal function. Which of the below is closest to what you would recommend? A. Continue daily TDF/FTC with close monitoring or renal function B. Tell him it is no longer safe for him to take TDF/FTC so he needs to be more consistent with condom use and PrEP is no longer an option C. Switch to four days per week TDF/FTC D. Switch to TAF/FTC E. Switch to non-tenofovir-based PrEP F. Something else iprex Open Label Extension: HIV Incidence and Drug Concentrations Follow up % 26% 12% 21% 12% Risk Reduction 44% 84% 100% 100% 95% CI 31 to 77% 21 to 99% 86 to 100% (combined) Grant R, et al. 20th IAC; Melbourne, Australia; July 20-25, 2014; Abst. TUAC0105LB; Grant R, et al. Lancet ID. [Epub ahead of print July 22, 2014] iprex Open-Label Extension (iprex OLE). 12

13 Molina JM, et al. 21 st IAC 2016, Abst. WEAC

14 Phase 2 study of safety and tolerability of maraviroc-containing regimens to prevent HIV infection in MSM (HPTN 069/ACTG A5305) 5 incident infections (4 MVC alone, 1 MVC + TDF); no sig difference by regimen. 2 with undetectable drug levels at every visit, 2 low levels at seroconversion visit and 1 variable concentrations Gulick RM, et al. JID 2016 Case 3 56 year old man with long history of HIV, DM, and CAD. He has been followed off ARV for several years and now finally agrees to start. No symptoms and negative exam with bp- 125/75 CD4 335 cells/ul; VL 120,000 copies/ml HLA-B5701-negative HgbA1C 7.1% on metformin 1000 mg bid HBVsAb+, HCV Ab- UA with 2+ protein, CrCl 47 ml/min HIV genotype is WT Case 3 Which of the following would you recommend? A. TAF/FTC/EVG/COBI B. TAF/FTC + RAL C. TAF/FTC + boosted PI D. TAF/FTC + DTG E. ABC/3TC/DTG F. ABC/3TC + boosted PI G. ABC and TAF-sparing regimen H. Something else 56 yo man with chronic HIV, DM, CAD CD4 335 cells/ul; VL- 120,000 c/ml HLA-B5701-negative CrCl= 47 ml/min, UA 2+ proteinuria HgbA1C- 7.1% on metformin 1000 mg bid HCV-neg; HBsAb+ Genotype- WT 14

15 Case 3 Which of the following would you recommend if the same patient started out with relatively normal renal function but experienced a decline while on a stable suppressive regimen of TDF/FTC + RAL? A. Monitor without change B. TAF/FTC-based regimen C. ABC/3TC-based regimen D. ABC and TAF-sparing regimen E. Something else 56 yo man with chronic HIV, DM, CAD VL suppressed on TDF/FTC + RAL HLA-B5701-negative CrCl= 47 ml/min, UA 2+ proteinuria Baseline Genotype- WT Abacavir and Cardiovascular Events Study Association Description D:A:D [1] + Cohort collaboration (prospective) Danish HIV Cohort [2] + Cohort (linked with registries) Montreal study [3] + Nested case-control study SMART [4] + Post hoc subgroup analysis of RCT (use of ABC not randomized) STEAL [5] + Preplanned secondary analysis of RCT (use of ABC randomized) Swiss HIV Cohort [6] + Cohort (retrospective) FHDH ANRS CO4 [7] Equivocal Nested case-control study NA-ACCORD [8] Equivocal Cohort (retrospective) VA Clinical Case - Cohort (retrospective) Registry [9] Brothers et al analysis [10] - Post hoc meta-analysis of RCTs ACTG A5001/ALLRT [11] - Post hoc meta-analysis of RCTs FDA meta-analysis [12] - Post hoc meta-analysis of RCTs 1. Friis-Møller N, et al. N Engl J Med. 2003;349: Obel N, et al. HIV Med. 2010;11: Durand M, et al. J Acquir Immune Defic Syndr. 2011;57: Phillips AN, et al. Antiviral Ther. 2008;13: Martin A, et al. AIDS. 2010;24: Young J, et al. J Acquir Immune Defic Syndr. 2015;[Epub ahead of print]. 7. Lang S, et al. AIDS. 2010;24: Palella F, et al. CROI Abstract 749LB. 9. Bedimo RJ, et al. Clin Infect Dis. 2011;53: Brothers CH, et al. J Acquir Immune Defic Syndr. 2009;51: Ribaudo HJ, et al. Clin Infect Dis. 2011;52: Ding X, et al. J Acquir Immune Defic Syndr. 2012;61: GS-112: Switching to a TAF-Based Regimen in Pts With Renal Impairment Virologically suppressed, HIVpositive pts with mildmoderate renal impairment (stable egfr CG [30-69 ml/min]) (N = 242) Multicenter, open-label phase III trial TDF-Based ART (n = 158) Non-TDF Based ART (n = 84) Wk 24 Wk 48 EVG/COBI/FTC/TAF (N = 242) Wk 96 ART use,% PI NNRTI INSTI CCR5 Antag. TDF ABC Other NRTI No NRTI Gupta S, et al. IAS Abstract TUAB

16 GS-112: Key Results Change in egfr From Baseline to Wk 48 Median Change From Baseline 10 0 TDF Non-TDF * -10 Baseline: *P <.05 egfr CG ml/min egfr CKD-EPI Cr ml/min/1.73 m 2 Actual GFR by Iohexol Clearance From Baseline to Wk 24 Iohexol Clearance (ml/min) 80 TDF Non-TDF GLSM Ratio vs BL (% [90% CI]): BL Wk 2/4/8 Wk (94-102)(96-105) BL Wk 2/4/8 96 (86-108) Wk (87-111) Gupta S, et al. IAS Abstract TUAB0103. Case 3 If you were going to go with ABC and TAF-sparing regimen, which of the following would you recommend? A. Boosted PI alone B. Boosted PI + 3TC C. Boosted PI + INSTI D. Boosted PI + NNRTI E. DTG alone F. DTG + 3TC G. DTG + RPV H. Something else 56 yo man with chronic HIV, DM, CAD CD4 335 cells/ul; VL- 120,000 c/ml HLA-B5701-negative CrCl= 47 ml/min, UA 2+ proteinuria HgbA1C- 7.1% on metformin 1000 mg bid HCV-neg; HBsAb+ Genotype- WT NEAT: RAL + DRV/RTV vs. TDF/FTC + DRV/RTV in Naive Pts at 96 Wks Randomized, open-label phase III study of DRV/RTV + RAL vs DRV/RTV + TDF/FTC in ART-naive pts Primary Endpoint at Wk 96: Adjusted Difference Estimate (95% CI) RAL - TDF/FTC RAL TDF/FTC Overall N = BL HIV-1 RNA < 100,000 c/ml n = ,000 c/ml n = 275 BL CD4+ cell count < 200/mm n = /mm n = Raffi F, et al. Lancet 2014; 384: (P =.09) (P =.02) 16

17 Simplification to RTV-Sparing and/or NRTI-Sparing or NRTI-Limiting Regimens (partial list) Study N Switch Regimen Results ASSURE [1] 296 ATV + ABC/3TC Similar efficacy as continued standard ART; decline in urine β 2 -microglobulin creatinine ratio OLE [2] 250 LPV/RTV + 3TC Similar efficacy as continued standard ART or FTC NA [3] 48 DRV/RTV + 3TC Small study; encouraging efficacy ATLAS-M [4] 266 ATV/RTV + 3TC Improved efficacy vs ATV/RTV + 2 NRTIs SALT [5] 286 ATV/RTV + 3TC Similar efficacy as continued standard ART KITE [6] 60 LPV/RTV + RAL Small study; encouraging efficacy 1. Wohl DA, et al. HIV Med. 2016;17: Arribas JR, et al. Lancet Infect Dis. 2015;15: Casado JL, et al. J Antimicrob Chemother. 2015;70: Di Giambenedetto S, et al. EACS Abstract Perez-Molina JA, et al. Lancet Infect Dis. 2015;15: Ofotokun I, et al. AIDS Res Hum Retroviruses. 2012;28:

18 Thank You!! 18