5/2/2016. Antiretroviral Therapy (ART) Strategies: A Case-Based, Panel Discussion

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1 Antiretroviral Therapy (ART) Strategies: A Case-Based, Panel Discussion Joseph J. Eron, Jr, MD Professor of Medicine University of North Carolina at Chapel Hill Chapel Hill, North Carolina FORMATTED: 4/13/216 Los Angeles, California: April 25, 216 Financial Relationships With Commercial Entities Dr Eron has received research grants awarded to the University of North Carolina from Bristol-Myers Squibb, GlaxoSmithKline/ViiV Healthcare, Merck & Co, Inc, Janssen and Abbvie. He has served as an ad hoc consultant to Bristol-Myers Squibb, Gilead Sciences, Inc, GlaxoSmithKline/ViiV Healthcare, Merck & Co, Inc, Tibotec Therapeutics/Janssen Therapeutics. Slide 2 of 5 Learning Objectives After attending this presentation, participants will be able to: List the reasons for initiating antiretroviral therapy in all patients regardless of CD4 cell count Describe potential drug-drug interactions with first-line recommended antiretroviral therapy Discuss options for second-line therapy in patients who have NRTI and NNRTI resistance Slide 3 of 5 1

2 Case Presentation #1 24 year old man, recently diagnosed with HIV infection on routine screening. He is in good health, takes no medication, had a severe case of mono about 4 years ago after coming out as gay while a sophomore in college. He is a dance/art major at a local university. He has one partner for the last 8 months who is HIV negative. They practice safer sex and are monogamous but have been talking about having other partners. He has no h/o STI His CD4 cell count is 1,1 and his HIV RNA is 2,65, HBV sab +, HCV Ab - and baseline RT/PR genotype shows K13N. HLA B571 negative, ALT and Cr are WNL He has told that his adherence counselor is worried he would be bad at taking pills Slide 4 of 5 Would you get an integrase resistance genotype? 35% 1. Yes 53% 2. No 11% 3. Not sure 24 yo, no other med, HBsAb+, HCV Ab -, B571 -, HIV RNA 265, CD4 11 BL genotype K13N Slide 5 of 5 Would you begin antiretroviral therapy at this point? 82% 1. Yes 11% 7% 2. No 3. Not sure 24 yo, no other med, HBsAb+, HCV Ab -, B571 -, HIV RNA 265, CD4 11 BL genotype K13N Slide 6 of 5 2

3 Published July 2, 215 at NEJM.org Primary Endpoint Immediate ART Deferred ART No. with event (%) 42 (1.8) 96 (4.1) Rate/1 PY HR (immediate/deferred).43 (95% P <.1) CI:.3-.62; Slide 7 of 5 START: Reduced Risk of Cancers With Immediate ART Cancer Event Immediate ART Deferred ART Kaposi s sarcoma 1 11 Lymphoma, NHL + HL 3 1 Prostate cancer 2 3 Lung cancer 2 2 Anal cancer 1 2 Cervical or testis cancer 1 2 Other types* 4 9 Total Slide 8 of 5 *Immediate ART: squamous cell carcinoma, plasma cell myeloma, bladder cancer, fibrosarcoma. Deferred ART: gastric adenocarcinoma, breast cancer, ureteric cancer, malignant melanoma, myeloid leukemia, thyroid cancer, leiomyosarcoma, liver cancer, squamous cell carcinoma of head and neck. INSIGHT START Study Group. N Engl J Med. 215;373: Lundgren J, et al. IAS 215. Abstract MOSY32. You opt for follow-up appointments with his adherence counselor and with you. He attends all of them and understands the benefits of ART. Which ART regimen will you recommend 44% 1. Dolutegravir/abacavir/3TC 15% 19% 7% 4% 7% 4% % % 2. Dolutegravir plus TDF or TAF/FTC 3. Elvitegravir/cobi/TAF/FTC 4. Elvitegravir/cobi/TDF/FTC 5. Raltegravir plus TDF or TAF/FTC 6. Darunavir/cobi plus TDF or TAF/FTC 7. Rilpivirine/TAF/FTC 8. Rilpivirine/TDF/FTC 9. Something else Slide 9 of 5 24 yo, no other med, HBsAb+, HCV Ab -, B571 -, HIV RNA 265, CD4 11 BL genotype K13N 3

4 HIV-1 RNA <5 c/ml, % 5/2/216 DHHS Guidelines: Recommended Regimens (Rating: A-I) Regardless of Baseline HIV RNA Level or CD4 Count INSTI-Based Regimens: DTG/ABC/3TCa if HLA-B*571 negative (AI) DTG plus TDF/FTCa (AI) EVG/c/TAF/FTC only for patients with estimated CrCl 3 ml/min EVG/c/TDF/FTC only for patients with estimated CrCl 7 ml/min RAL plus TDF/FTCa (AI) PI-Based Regimens: DRV/r plus TDF/FTCa (AI) DHHS. Downloaded DHHS Guidelines: Alternative Regimens May Be the Preferred Regimen for Some Patients NNRTI PI Efavirenz/emtricitabine/tenofovir DF* (B-I) Rilpivirine/emtricitabine/tenofovir DF* (B-I) Atazanavir/cobicistat + emtricitabine/tenofovir DF (B-I) Atazanavir + ritonavir + emtricitabine/tenofovir DF (B-I) Darunavir/cobicistat + emtricitabine/tenofovir DF (B-II) Darunavir/cobicistat + abacavir/lamivudine (B-III) Darunavir + ritonavir + abacavir/lamivudine (B-II) *Available as a once-daily, single-tablet regimen. Notes: Efavirenz: avoid use in women trying to conceive or are sexually active and not using contraception. Lamivudine may substitute for emtricitabine or visa versa. Tenofovir DF: use with caution in patients with renal insufficiency. Rilpivirine/emtricitabine/TDF: only for patients with pre-art HIV RNA <1K c/ml and CD4 >2 c/mm 3. Atazanavir/cobicistat or darunavir/cobicistat + emtricitabine/tdf: only for patients with pre-art creatinine clearance >7 ml/min. Atazanavir + RTV: absorption depends on food and low gastric ph. Dolutegravir/cobicistat or darunavir/ritonavir + abacavir/3tc: patients who are HLA-B*571 negative. DHHS. Revision April 8, 215. Elvitegravir/cobi/TAF/FTC vs. Elvitegravir/cobi/TDF/FTC Phase III treatment naïve study: 48 week results Virologic Outcome Treatment Difference (95% CI) E/C/F/TAF (n=866) E/C/F/TDF (n=867) Favors E/C/F/TDF Favors E/C/F/TAF %.7% 4.7% Success Failure No Data 12% +12% Slide 12 of 5 E/C/F/TAF was non-inferior to E/C/F/TDF at Week 48 in each study 93% E/C/F/TAF vs 92% E/C/F/TDF (Study 14) 92% E/C/F/TAF vs 89% E/C/F/TDF (Study 111) Sax P, Wohl D, et al Lancet 215 4

5 Virologic Success (%) Mean (SD) % Change from Baseline 5/2/216 Efficacy in Select Subgroups Studies 14 and 111: Week 48 Combined Analysis E/C/F/TAF (n=866) E/C/F/TDF (n=867) Overall Age Sex Race <5 years 5 years Male Female Non-Black Black Slide 13 of 5 Changes in Spine and Hip BMD Through Week 48 Studies 14 and 111: Week 48 Combined Analysis Spine Hip 2 p <.1 2 p < Week Week E/C/F/TAF, n E/C/F/TDF, n Slide 14 of 5 If available would you consider oral therapy for 3-5 months then long-acting therapy for this patient (intramuscular injections every 2 months)? 58% 24% 18% 1. Yes 2. No 3. Not sure 24 yo, no other med, HBsAb+, HCV Ab -, B571 -, HIV RNA 265, CD4 11 BL genotype K13N Slide 15 of 5 5

6 LATTE-2: Cabotegravir IM + Rilpivirine IM for Long- Acting Maintenance ART Multicenter, open-label phase IIb study Primary endpoints: HIV-1 RNA < 5 c/ml by FDA snapshot, PDVF, and safety at maintenance Wk 32 Induction Phase* Maintenance Phase Wk 32 Wk 16: RPV primary analysis; Wk 1 dose selection Wk 96 PO Added Wk 2 CAB 4 mg IM + RPV 6 mg IM Q4W ART-naive HIVinfected pts with (n = 115) CAB 3 mg PO QD + CAB 6 mg IM + RPV 9 mg IM Q8W CD4+ cell count ABC/3TC (n = 115) > 2 cells/mm 3 (N = 39) CAB 3 mg PO + ABC/3TC PO QD (n = 56) *Pts with HIV-1 RNA < 5 c/ml from Wk 16 to Wk 2 continued to maintenance phase. In snapshot induction analysis, 14 pts had virologic nonresponse and 13 pts had no virologic data in window, including 6 pts who discontinued for AEs or death and 7 pts who discontinued for other reasons. Slide 16 of 5 Margolis DA, et al. CROI 216. Abstract 31LB. Slide credit: clinicaloptions.com LATTE-2 Week 32 Primary Endpoint: HIV-1 RNA <5 c/ml by Snapshot (ITT-ME) Virologic outcomes Treatment differences (95% CI) * Oral IM * Q8W Q4W Both Q8W and Q4W comparable/non-inferior to oral CAB at Week 32 Slide 17 of 5 *Met pre-specified threshold for concluding IM regimen is comparable to oral regimen (Bayesian posterior probability >9% that true IM response rate is no worse than -1% compared with the oral regimen). Margolis et al. CROI 216; Boston, MA. Abstract 31LB. Snapshot Outcomes: HIV-1 RNA <5 c/ml at Week 32 (ITT-ME) Week 32 outcome Q8W IM (n=115) Q4W IM (n=115) Oral CAB (n=56) Virologic success 19 (95%) 18 (94%) 51 (91%) Virologic non-response 5 (4%) 1 (<1%) 2 (4%) Data in window not <5 c/ml 3 (3%) 1 (<1%) 1 (2%) Discontinued for lack of efficacy 1 (<1%) 1 (2%) Discontinued for other reason while not <5 c/ml 1 (<1%) No virologic data in window 1 (<1%) 6 (5%) 3 (5%) Discontinued due to adverse event or death a 4 (3%) 1 (2%) Discontinued for other reasons b 1 (<1%) 2 (2%) 2 (4%) a Q4W: hepatitis C, rash, depression, and psychosis; oral CAB: hepatitis C. b Q8W: ISR; Q4W: pregnancy and prohibited medication; oral CAB: lost to follow-up, relocation. Slide 18 of 5 Margolis et al. CROI 216; Boston, MA. Abstract 31LB. 6

7 Linked Partner Infections (number) 5/2/216 If you were the clinician for the above patient s HIV negative partner would you recommend preexposure prophylaxis (PrEP)? 93% 1. Yes 2% 2. No 5% 3. Not sure Slide 19 of 5 HPTN 52 (Final Results): Stable Heterosexual Couples Slide 2 of 5 Randomization Phase 3 study 1:1 Americas, African, Asian sites Stable, healthy, sexually active, serodiscordant couples Delayed ART CD4 <25 cells/mm 3 CD cells/mm 3 Early ART CD4 35 to 55 cells/mm 3 Similar baseline demographic characteristics and sexual Primary Endpoints history/behavior both arms Transmission - Virologically linked transmission Status of Participants events Enrolled (21; n=1763 enrolled) Clinical Remained in trial - WHO stage 4 clinical events 211 (n=1642) 215 (n=1535) - Pulmonary TB - Severe bacterial infection and/or Cohen M, et al. J Int AIDS Soc. 215;18(suppl 4):15. Abstract MOAC11LB. death Cohen MS, et al. N Engl J Med. 211;365: HPTN 52: 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 HIV Transmission Delayed ART 43 Early ART Overall *Early arm (n=3) and delayed arm (n=5). 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). Slide 21 of 5 Cohen M, et al. J Int AIDS Soc. 215;18(suppl 4):15. Abstract MOAC11LB. Eshleman SH, et al. J Int AIDS Soc. 215;18(suppl 4):18. Abstract MOAC16LB. 7

8 Case Presentation #2 You are working in an STD clinic in San Diego. A 35 yo MSM is seen for a rash and is diagnosed with syphilis. GC/chlamydia screens of pharynx, urine and rectum are negative. He asks you about PrEP He states he works as an accountant, has no medical history, is on no medications and has no steady sex partner 2 or 3 weekends a month he meets partners on-line and likes top put will also be a bottom depending on the partner. He almost always uses condoms but is embarrassed to admit he has does not always and would like to have sex without them if he could. Slide 22 of 5 He is HIV negative and cr is normal. Would you prescribe PrEP for him? 1% 1. Yes % 2. No % 3. Not sure Slide 23 of 5 Would you prescribe TAF/FTC now that it is available? 46% 1. Yes 34% 2. No 2% 3. Not sure Slide 24 of 5 8

9 He has never taken pills in his life. And asks can he only take the medication on weekends? You will: 73% 1. Tell him he has to take daily TDF/FTC 25% 2. Prescribe the Ipergay regimen 2 TDF/FTC 24-2 hours prior to having sex and then one pill 24 and 48 hours later 1% 3. Something else Slide 25 of 5 Case Presentation #3 54 year old woman, recently diagnosed HIV positive Test done after her partner was diagnosed with HIV after an hospital admission for pneumonia She has never been tested previously Medical history includes obesity, GERD, type 2 diabetes diagnosed 5 years ago, hypertension and osteopenia by DEXA SHx: One male partner, smokes 1 PPD, no alcohol or other substances, unemployed Medications include esomeprazole 2 mg QD, amlodipine 1 mg QD (cough on lisinopril), metformin 1 mg BID, CaCarbonate and Vit D, fluticasone/salmeterol inhaler Slide 26 of 5 Case Presentation #3 Physical exam: BMI 36, 138/88, mild peripheral neuropathy Baseline labs: cr 1.3, ALT 26, CBC diff NL egfr = 48 cc/min Hepatitis A, B immune; HCV negative, HLAB571 negative, Hgb A1C = 7.2 CD4 15 (18%), HIV RNA 354,4 RT/PR genotype no resistance She is very anxious to start therapy Slide 27 of 5 9

10 Which ART regimen will you recommend 49% 1. Dolutegravir/abacavir/3TC 19% 2. Dolutegravir plus TDF or TAF/FTC 6% 3. Elvitegravir/cobi/TAF/FTC 2% 4. Elvitegravir/cobi/TDF/FTC 8% 5. Raltegravir plus TDF or TAF/FTC 6% 6. Darunavir/cobi plus TDF or TAF/FTC 6% 7. Rilpivirine/TAF/FTC % 8. Rilpivirine/TDF/FTC 3% 9. Something else 54 yo F, DM, GERD, HTN, smokes, PPI, amlodipine, metformin, Ca++, fluticasone/salmeterol Slide 28 of 5 egfr = 48, CD4 =15, RNA = 35,, wild-type genotype Potential Drug-Drug Interactions Metformin dolutegravir Esomeprazole rilpivirine Ca++ - co-administration with dolutegravir or elvitegravir Fluticasone cobicistat and ritonavir Salmeterol cobicistat and ritonavir - all PI Amlodipine cobicistat and ritonavir all PI Slide 29 of 5 You decide to use dolutegravir- based therapy. What will you do with her metformin dose 3% 1. Stop metformin 2. Continue on the current dose of metformin and monitor 42% carefully 5% 3. Reduce the daily dose of metformin to 1 mg. 5% 4. Something else Slide 3 of 5 1

11 Case Presentation #4 48 yo fair skinned man on ATV/r and TDF/FTC who presents asking if his therapy can be simplified. HIV RNA < 4 c/ml, CD4 45 No other medical problems, on no other medications Cr 1.9 (was 1. 3 years ago), egrf = 55 cc/min, total bilirubin 3.9, AST/ALT normal. HbSAb +, HCV Ab -, HLAB571 negative Excellent adherence to care Followed in your clinic for 6 yrs; all HIV RNA BLD Slide 31 of 5 Case Presentation #4 Additional Treatment history Diagnosis in 21 CD4 168 HIV RNA 537, Enrolled in ACTG study at nearby site Knows he got efavirenz and other medications Doesn t remember treatment response and stopped all ART at the end of the study in approximately 24 In 27 began treatment with ATV/r and TDF/FTC thinks his HIV RNA was over 1, and CD4 was 4 He can tell you the 6 times he missed his ARV dose in the last 8 years. Slide 32 of 5 Will you get an HIV DNA archival resistance genotype? 37% 1. Yes 47% 2. No 16% 3. Not sure Slide 33 of 5 Porter DP, et al HIV Clin Trials. 216 Jan;17(1):

12 Insurance refused to pay for archive HIV DNA genotype testing. You decide to switch therapy anyway. What ART will you recommend? 57% 1. Dolutegravir/abacavir/3TC 15% 2. Elvitegravir/cobi/TAF/FTC 2% 3. Rilpivirine/TAF/FTC 9% 4. Darunavir/c or ritonavir TAF/FTC % 5. Atazanavir/c or ritonavir TAF/FTC 4% 6. Dolutegravir/rilpivirine 2% 7. Boosted PI plus 3TC or FTC only % 8. Something else 11% 9. I would not switch Slide 34 of 5 48 yo, ATV/r TDF/FTC, RNA < 4, egfr = 55, bili = 3.9, HbSAb -, B571 -, no resistance tests Switch to Elvitegravir/cobi/TAF/FTC from several regimens in patients with suppressed plasma HIV RNA Improvements in proximal renal tubular function Slide 35 of 5 Mills et al, Lancet Infect Dis 216; 16: see Abstract 29 Gallant et al STRIIVING: Switch From Suppressive ART to Fixed-Dose DTG/ABC/3TC Ongoing randomized, open-label phase IIIB study Primary endpoint: HIV-1 RNA < 5 copies/ml at Wk 24 Wk 24 Wk 48 HIV-1 RNA < 5 copies/ml on stable ART 6 mos; no previous virologic failure; HLA-B*571 negative (N = 551) DTG/ABC/3TC (n = 274) Baseline ART* DTG/ABC/3TC (n = 277) (n = 277) *Containing 2 NRTIs plus NNRTI, PI, or INSTI. PI NNRTI INSTI TDF/FTC BL ART use, % Slide 36 of 5 Trottier B, et al. ICAAC

13 HIV-1 RNA < 5 c/ml (%) 5/2/216 STRIIVING: Virologic Outcomes at Wk 24 Switch to DTG/ABC/3TC noninferior to maintaining baseline ART No cases of protocol-defined virologic failure 3 pts in DTG/ABC/3TC arm (1%) and 4 pts in BL ART arm (1%) had HIV-1 RNA > 5 but < 1 copies/ml through Wk 24 1 pts in DTG/ABC/3TC (4%) withdrew due to AE vs. in BL ART Primary Efficacy Analysis: ITT-Exposed and Per Protocol Populations DTG/ABC/3TC (ITT-E, n = 274) Baseline ART (ITT-E, n = 277) DTG/ABC/3TC (PP, n = 22) Baseline ART (PP, n = 215) Baseline ART DTG/ABC/3TC ITT-E Population PP Population < 1 Virologic Virologic No Virologic Success Nonresponse Data Slide 37 of 5 Trottier B, et al. ICAAC 215. Slide created by Clinical Care Options Two Drug ART Maintains Suppression Latte: Cabotegravir (InSTI) + rilpivirine maintenance vs. EFV-based therapy Slide 38 of 5 Margolis DA, et al Lancet Infect Dis 15; Case Presentation #4 The patient is switching to FDC elvitegravir/cobi/ftc/taf He returns 1 month later and thanks you! HIV RNA < 4 c/ml undetected and CD4 56 Total bilirubin 1.1, cr = 1.4 At 3 months HIV RNA < 4 detected At 6 months HIV RNA 1,7 and CD4 487 You call him for repeat and HIV RNA 11, Slide 39 of 5 13

14 Case Presentation #4 RT/PR genotype shows: K13N, M184V and codon 69 insertion (OMG) Integrase Genotype shows 155H mutation What happened? Call to nearby site shows patient received efavirenz plus d4t/ddi Intermittent adherence, multiple HIV RNA levels above limit of detection no resistance testing available to the study site What will you do next? Slide 4 of 5 48 yo, ATV/r TDF/FTC, RNA < 4, egfr = 55, bili = 3.9, HbSAb -, B571 -, no resistance tests Case Presentation #5 35 yo AA MSM diagnosed in 29 with CD4 25 and HIV RNA 127,, wild type genotype, HCV negative, HBV DNA + at 8.9 million. PMHx essentially negative otherwise, used meth amphetamine in his late 2s Started on EFV/TDF/FTC with excellent response and follow-up CD4 increase to 547 and HIV RNA consistently < 4 c/ml Slide 41 of 5 Case Presentation #5 Missed his last appointment in 213 and he finally returns in June 214 He states at New Year s he started using methamphetamine again for several months. Was able to stop when his partner threatened to leave. During much of early 214 he was intermittently adherent He restarted consistently taking ART 2 months ago. His HIV RNA is 1,5 and CD4 45. PT/PR genotype shows K13N and 184V. Cr =.98 and ALT 93, HBV DNA = 57, Slide 42 of 5 14

15 Pts (%) 5/2/216 He states he is in therapy and in recovery and has been adherent to ART for last 2 months. What NRTI therapy will you recommend? 2% 1. TDF/FTC 2% 2. TAF/FTC 2% 3. ABC/3TC 2% 4. TDF or TAF but no FTC or 3TC 2% 5. I would not recommend NRTI-based therapy Slide 43 of 5 35 yo M, rebound on EFV/TDF/FTC RNA = 1,5, CD4 = 45, K13N, M184V, HBV co-infection, HBV DNA 57, 1 Switching Pts With HIV/HBV Coinfection to a TAF-Based Regimen International, multicenter, single-arm, open-label phase IIIb trial (N = 72) Pts with HIV RNA BDL on any regimen, chronic HBV coinfection, and egfr > 5 ml/min switched to EVG/COBI/FTC/TAF for 48 Wks HIV-1 RNA < 5 c/ml HBV DNA < 29 IU/mL Wk 24 Wk 48 By Wk 48, 2/7 (3%) pts lost HBsAg/gained HBsAb; 2/3 (7%) pts had lost HBeAg; 1/3 (3%) pts gained HBeAb Slide 44 of 5 Gallant J, et al. IAS 215. Abstract WELBPE13. TAF vs. TDF in HBV Mono-infection Two phase III studies. TAF 25 mg daily vs. TDF 3 mg daily In Study 18, evaluating HBeAg-negative patients, 94. percent (n=268/285) of patients receiving TAF and 92.9 percent (n=13/14; CI -3.6 percent to +7.2 percent, p=.47) of patients receiving TDF achieved HBV DNA below 29 IU/mL at week 48. In Study 11, evaluating HBeAg-positive patients, 63.9 percent (n=371/581) of TAF patients and 66.8 percent (n=195/292; CI percent to +2.6 percent, p=.25) of TDF patients achieved HBV DNA below 29 IU/mL at week 48. Slide 45 of 5 Press release January 5,

16 Patients (%) 5/2/216 Given his HBV history you choose TAF/FTC therapy. What additional ART will you recommend? 14% 1. Elvitegravir/cobi (TAF/FTC) FDC 14% 2. Dolutegravir 14% 3. Raltegravir 14% 4. Rilpivirine (TAF/FTC) FDC 14% 5. DRV/c or ritonavir 14% 6. Recommend one of the above plus an additional fully active agent 14% 7. Something else Slide 46 of 5 35 yo M, rebound on EFV/TDF/FTC RNA = 1,5, CD4 = 45, K13N, M184V, HBV co-infection, HBV DNA 57, 1 Management of First-line NNRTI Failure Boost Protease Plus Re-cycled NRTI Are Enough SECOND LINE 1 EARNEST 2 1 Lopinavir/r + NRTIs (n=426) Lopinavir/r + raltegravir (n=433) Lopinavir/r monotherapy (n=418) 8 74%* 73%* 6 6% 64% 56% 4 44% 2 Good HIV Disease Control HIV RNA <5 copies/ml *P<.1 versus lopinavir/r monotherapy. Patients with HIGHER levels of baseline resistance had better treatment responses Slide 47 of 5 1. Boyd M, et al. Lancet. 213;381: Paton NI, et al. N Engl J Med. 214; 371: Summary of ODIN Data Slide 48 of 5 Number of PIs previously DRV/r once-daily DRV/r twice-daily used (82.2) (79.6) (64.9) (63.6) (62.4) (63.4) M184V/I mutation at DRV/r once-daily DRV/r twice-daily baseline Absent (6.6) (55.2) Present (78.4) (79.6) Cahn P, et al. AIDS. 211;25(7):929-39; Sension M, et al. HIV Med. 213;14(7):

17 Management of First Line ARV Failure DHHS Guidelines Failing an NNRTI plus NRTI regimen Even patients with NRTI resistance can often be treated with a bpi plus NRTI or RAL Failing a bpi plus NRTI regimen A systematic review of multiple randomized studies of first line bpi therapy showed that maintaining the same regimen, presumably with measure to enhance adherence is as effective as changing to new regimens Failing an InSTI plus NRTI regimen Patients should respond to a bpi plus NRTI A bpi plus InSTI may also be a viable option if there is no InSTI resistance If RAL or EVG resistance DTG plus a boosted PI can be used Slide 49 of 5 Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents. Department of Health and Human Services. Last Updated: April 8, 215. Available at Accessed April 3, 216. Günthard HF, et al. JAMA. 214;312: Slide 5 of 5 17