Elliot DeHaan, MD Clinical Assistant Professor Division of Infectious Diseases/S.T.A.R. Program SUNY Downstate Medical Center October 24, 2014

 Introduce 5 classes of ARVs & origins of HAART  Review ARV regimens for naïve patients  Review “switch” regimens  Review ARV combinations in experienced patients  Cases of treatment in primary care settings

Attachment fusion Budding Reverse transcription Maturation Integration Uncoating Transcription, translation Assembly

 NRTIs  Chain terminators, active site of the RT enzyme  NNRTIs  Confers allosteric change of the RT enzyme  PIs  Inhibits viral protease from cleaving polypeptide  INSTIs  Inhibits integration of proviral DNA into cell genome  Entry inhibitors  Enfuvirtide-fusion inhibitor  Maraviroc- CCR5 antagonist

 Decreased disease progression; improved CD4 on HAART Hammer SM et al. N Eng J Med 1997; 337:

 28/31 patients (90%) suppressed to <500 copies/mL Gulick RM et al. N Eng J Med 1997; 337:

 Introduce 5 classes of ARVs & origins of HAART  Review ARV regimens for naïve patients  Review “switch” regimens (CAUTION!)  Review ARV combinations in experienced patients  Cases of treatment in primary care settings

 ABC-3TC arms showed increased risk of virologic failure after early unblinding in patients with viral loads >100K Daar ES et al. Ann Int Med 2011; 154:

Sax PE et al. N Eng J Med 2009; 361:

HIV-1 RNA < 50 copies/mL (%) By Baseline CD4+ Count (cells/mm 3 ) ≤ 100K Rilpivirine Efavirenz Cohen CJ, et al. AIDS. 2013;27: > 100K < 50 Rilpivirine Efavirenz < < 350≥ 350 By Baseline HIV-1 RNA (copies/mL) n = n = n =

 Randomized, double-blind (through 5 yrs), placebo-controlled, phase III trial  Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48 HIV-infected, treatment-naive patients with HIV-1 RNA > 5000 copies/mL and no resistance to EFV, TDF, or FTC (N = 563) Efavirenz 600 mg QHS + TDF/FTC (n = 282) Raltegravir 400 mg BID + TDF/FTC (n = 281) Lennox J, et al. Lancet. 2009;374: Stratified by HIV-1 RNA (> vs ≤ 50,000 copies/mL) and viral hepatitis status

 RAL noninferior to EFV in HIV-1 RNA < 50 c/mL at Wk 48 (primary endpoint; ITT, NC = F analysis); superior from Wk 192 Rockstroh J, et al. J Acquir Immune Defic Syndr. 2013;63: HIV-1 RNA < 50 c/mL (%) Wks RAL EFV Pts at Risk, n ∆: +9.5% (95% CI: 1.7% to 17.3%; noninferiority P <.001)

 Efficacy as good as or better than EFV in all baseline subgroups tested  CD4+ cell count at Wk 240: +374 (RAL) vs +312 (EFV)  RAL associated with – Fewer CNS adverse events (39.1% vs 64.2%; P <.001) – Fewer drug-related clinical adverse events (52.0% vs 80.1%; P <.001) – Fewer discontinuations due to adverse events (5% vs 9%) Rockstroh J, et al. J Acquir Immune Defic Syndr. 2013;63:77-85 plus Supplemental Digital Content. VF and Resistance at Wk 240 RAL (n = 281) EFV (n = 282) VF, n (%)55 (19.6)59 (20.9) Resistance data available, n 2320 INSTI or NNRTI mutations only, n 17 NRTI mutations only, n 32 NRTI + (RAL or EFV) resistance mutations, n 33

 Primary endpoints – Virologic failure: time to HIV-1 RNA > 1000 c/mL (at Wk 16 or before Wk 24) or > 200 c/mL (at or after Wk 24) – Tolerability failure: time to discontinuation of randomized component for toxicity  Composite endpoint: the earlier occurrence of either VF or TF in a given participant  Switch of regimens allowed for tolerability Landovitz R, et al. CROI Abstract 85. ART-naive patients with HIV-1 RNA ≥ 1000 c/mL (N = 1809) ATV/RTV 300/100 mg QD + TDF/FTC (n = 605) RAL 400 mg BID + TDF/FTC (n = 603) Stratified by HIV-1 RNA < or ≥ 100,000 c/mL, participation in metabolic substudy, CV risk DRV/RTV 800/100 mg QD + TDF/FTC (n = 601) Wk 96 after last patient enrolled

 Regimens equivalent in time to VF Landovitz R, et al. CROI Abstract 85. Reproduced with permission.  Significantly greater incidence of treatment failure with ATV/RTV vs RAL or DRV/RTV –In part due to high proportion of pts with hyperbilirubinemia  Considering both efficacy and tolerability, RAL superior to either boosted PI  DRV/RTV superior to ATV/RTV Virologic Failure Tolerability FailureComposite Endpoint Difference in 96-Wk Cumulative Incidence (97.5% CI) ATV/RTV vs RAL 3.4% (-0.7 to 7.4) DRV/RTV vs RAL 5.6% ( ) ATV/RTV vs DRV/RTV -2.2% (-6.7 to 2.3) ATVRTV vs RAL 15% (10-20) DRV/RTV vs RAL 7.5% ( ) ATV/RTV vs DRV/RTV 7.5% ( ) Favors RAL Favors DRV/RTV Favors RAL ATV/RTV vs RAL 13% ( ) DRV/RTV vs RAL 3.6% ( ) ATV/RTV vs DRV/RTV 9.2% ( ) Favors RAL Favors DRV/RTV

89% In ITT analysis with ART changes allowed (per protocol), regimens similar in virologic efficacy at Wk 96 and through Wk 144 In ITT analysis when change = failure (Snapshot), RAL superior to both boosted PIs at Wk 96 and DRV/RTV superior to ATV/RTV at Wks 96 and 144 Similar mean change in CD4+ count across arms ATV/RTV (+284); RAL (+288) DRV/RTV (+256) cells/mm 3 Landovitz R, et al. CROI Abstract 85. Reproduced with permission. 1.0 Proportion With HIV-1 RNA ≤ 50 c/mL ITT, Regardless of ART Change ITT, NC = Failure (Snapshot) RAL DRV/RTV ATV/RTV Study Wk % 94% 63% 73% 80% RAL DRV/RTV ATV/RTV

 Randomized, noninferiority phase III trial of RAL 800 mg QD (n = 382) vs RAL 400 mg BID (n = 389), both with TDF/FTC [1]  RAL QD inferior to RAL BID at Wk 48 in ITT (NC = F) analysis  Lower RAL trough levels associated with higher risk of failure in QD arm but not in BID arm  More resistance at failure in QD arm  PK studies of 2 new RAL formulations administered as 1200-mg once daily showed promise in healthy patients [2] 1. Eron J, et al. Lancet Infect Dis. 2011;11: Krishna R, et al. EACS 2013, Abstract PE10/17. HIV-1 RNA < 50 c/mL (NC = F) *Failure included both failure to suppress and rebounders. Most patients with VF and RAL resistance had ≥ 2 mutations associated with resistance to RAL. Parameter, nRAL QD (n = 382) RAL BID (n = 388) Pts with VF* and HIV-1 RNA > 400 c/mL 3016 Resistance data available2711 FTC resistance only112 Integrase inhibitor and FTC resistance 92 No evidence of resistance RAL 800 mg QD (n = 382) RAL 400 mg BID (n = 389) 318/ / 389 ∆: -5.7 (95% CI: to -0.83; P for noninferiority =.044) Wk 48

 Randomized, double-blind, active-controlled phase III studies  Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk Sax P, et al. Lancet. 2012;379: DeJesus E, et al. Lancet. 2012;379: Treatment naive; HIV-1 RNA ≥ 5000 copies/mL; any CD4+ cell count; susceptible to TDF, FTC, and EFV, or ATV; eGFR ≥ 70 mL/min Study 102 [1] (N = 700) Study 103 [2] (N = 708) EVG/COBI/TDF/FTC QD (n = 348) EFV/FTC/TDF QD (n = 352) EVG/COBI/TDF/FTC QD (n = 353) ATV/RTV + TDF/FTC QD (n = 355)

 EVG/COBI arm noninferior to EFV arm at Wk 48 primary endpoint [1] and through Wk 144 [2,3] – Results consistent across subgroups: BL HIV-1 RNA, CD4+ cell count, age, sex, race – Treatment-related study d/c: 6% in EVG/COBI arm vs 7% in EFV arm at Wk 144  VF: 7% in EVG/COBI arm and 10% in EFV arm at Wk 144  Similar CD4+ cell count increase at Wk 144: – +321 cells/mm 3 (EVG/COBI) vs +300 cells/mm 3 (EFV) 1. Sax PE, et al. Lancet. 2012;379: Zolopa A, et al. J Acquir Immune Defic Syndr. 2013;63: Wohl D, et al. ICAAC Abstract H-672a. Wk 48 Wk 144 EVG/COBI/TDF/FTC (n = 348) EFV/TDF/FTC (n = 352) HIV-1 RNA < 50 copies/mL (%) Δ: 3.6% (-1.6 to 8.8) Δ: 4.9% (1.3 to 11.1) Wk 96 Δ: 2.7% (-2.9 to 8.3)

 EVG/COBI arm noninferior to ATV/RTV arm at Wk 48 primary endpoint [1] and through Wk 144 [2,3] – Results consistent across subgroups: BL HIV-1 RNA, CD4+ count, adherence, age, sex, race  Treatment-related study d/c: 6% in EVG/COBI arm vs 9% in ATV/RTV arm at Wk 144  VF: 8% in EVG/COBI arm vs 7% in ATV/RTV arm at Wk 144  Similar CD4+ cell count increase at Wk 144: cells/mm 3 (EVG/COBI) vs +293 cells/mm 3 (ATV/RTV ) 1. De Jesus E, et al. Lancet. 2012;379: Rockstroh J, et al. J Acquir Immune Defic Syndr. 2013;62: Clumeck N, et al. EACS Abstract LBPS7/2. EVG/COBI/TDF/FTC (n = 353) ATV/RTV + TDF/FTC (n = 355) Δ: 3.0% (-1.9 to 7.8) Δ: 1.1% (-4.5 to 6.7) Wk 48 Wk HIV-1 RNA < 50 copies/mL (%) Δ: 3.1% (-3.2 to 9.4) Wk 96

 Randomized, noninferiority phase III studies  Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48 ART-naive pts VL ≥ 1000 c/mL (N = 822) DTG 50 mg QD + 2 NRTIs* (n = 411) RAL 400 mg BID + 2 NRTIs* (n = 411) *Investigator-selected NRTI backbone: either TDF/FTC or ABC/3TC. ART-naive pts VL ≥ 1000 c/mL HLA-B*5701-neg CrCL > 50 mL/min (N = 833) DTG 50 mg QD + ABC/3TC QD (n = 414) EFV/TDF/FTC QD (n = 419) SPRING-2 [1] (active controlled) SINGLE [2] (placebo controlled) DTG 50 mg QD + 2 NRTIs* (n = 242) DRV/RTV 800/100 mg QD + 2 NRTIs* (n = 242) ART-naive pts VL ≥ 1000 c/mL (N = 484) FLAMINGO [3] (open label) 1. Raffi F, et al. Lancet. 2013;381: Walmsley S, et al. N Engl J Med. 2013;369: Feinberg J, et al. ICAAC Abstract H1464a.

 DTG noninferior to RAL at both Wk 48 primary endpoint [1] and Wk 96 [2]  Treatment-related study d/c: 2% in each arm at Wk 96  VF at Wk 96 [2] : 5% (22/411) in DTG arm and 7% (29/411) in RAL arm  Similar CD4+ cell count increase at Wk 96: – +276 cells/mm 3 (DTG) vs +264 cells/mm 3 (RAL) HIV-1 RNA < 50 copies/mL (%) DTG 50 mg QD (n = 411) RAL 400 mg BID (n = 411) Wk 48 Wk Raffi F, et al. Lancet. 2013;381: Raffi F, et al. IAS Abstract TULBPE / / / / 411 Δ: 4.4% (-1.1% to 10.0%) Δ: 2.5% (-2.2% to 7.1%)

 DTG superior to EFV at Wk 48 primary efficacy endpoint  Treatment-related study d/c: 2% in DTG arm vs 10% in EFV arm  VF at Wk 48: 4% (18/414) in DTG arm and 4% (17/419) in EFV arm  CD4+ cell count increase at Wk 48 greater with DTG: – +267 cells/mm 3 (DTG) vs +208 cells/mm 3 (EFV) (P <.001) HIV-1 RNA < 50 c/mL at Wk 48 (%) Δ +7.4% (95% CI +2.5% to +12.3%; P =.003) Walmsley S, et al. N Engl J Med. 2013;369: DTG 50 mg + ABC/3TC QD EFV/TDF/ FTC QD / / 419

 DTG superior to DRV/RTV at Wk 48 primary efficacy endpoint – Treatment-related study d/c: 2% in DTG arm vs 4% in DRV/RTV arm  VF at Wk 48: < 1% (n = 2) in each arm  Similar CD4+ cell count increase at Wk 48: – +210 cells/mm³ in each arm HIV-1 RNA < 50 c/mL at Wk 48 (%) Δ +7.1% (95% CI: +0.9% to +13.2%; P =.025) Feinberg J, et al. ICAAC Abstract H1464a. DTG 50 mg QD + NRTIs DRV/RTV 800/100 mg QD + NRTIs 217/ /

 Introduce 5 classes of ARVs and origins of HAART  Review ARV regimens for naïve patients  Review “switch” regimens (CAUTION!)  Review ARV combinations in experienced patients  Cases of treatment in primary care settings

 SWITCHMRK-1 and -2 [1] – Switching to RAL inferior to remaining on LPV/RTV-based regimen in pts with HIV-1 RNA 3 mos, particularly among those with previous VF – TC, non–HDL-C, and TG improved in switch pts  SPIRAL [2] – Switching from to RAL noninferior to remaining on boosted PI-based regimens through Wk 48 in pts with HIV-1 RNA < 50 c/mL for ≥ 6 mos  Switching to RAL significantly improved lipids and TC:HDL-C ratio  EASIER/ANRS 138 [3] – Switch from ENF to RAL regimens maintained virologic suppression through Wk 48 in patients with multidrug resistance and HIV-1 RNA < 400 c/mL for ≥ 3 mos 1. Eron J, et al. Lancet. 2010;375: Martinez E, et al. AIDS. 2010;24: Gallien S, et al. J Antimicrob Chemother. 2011;66:

 Open-label, multicenter, 48-wk pilot study of switch from RAL + TDF/FTC to EVG/COBI/TDF/FTC in pts with HIV-1 RNA < 50 c/mL for 6 mos (N = 48)  Primary endpoint: HIV-1 RNA < 50 c/mL at Wk 12 postswitch  Secondary endpoints: Safety and tolerability by Wk 24 and Wk 48 HIV-1 RNA < 50 c/mL at Wk 24 and Wk 48 postswitch  All subjects maintained virologic suppression at Wks 12 and 24 – 38/38 subjects who reached Wk 48 at time of report also suppressed  TC and LDL-C improved; no renal AEs Crofoot G, et al. IAS Abstract TUPE283. HIV-1 RNA < 50 c/mL (%) Wk 12 48/48 38/38* Wk 24Wk 48

 Randomized, open-label switch studies in pts virologically suppressed on an NNRTI- or boosted PI–based regimen (both with TDF/FTC) for ≥ 6 mos  Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48 HIV-1 RNA < 50 c/mL,  2 previous regimens, no resistance to FTC or TDF and CrCl ≥ 70 mL/min STRATEGY-NNRTI [1] (N = 434) STRATEGY-PI [2]* (N = 433) Switch to EVG/COBI/TDF/FTC QD (n = 291) Remain on NNRTI + TDF/FTC (n = 143) Switch to EVG/COBI/TDF/FTC QD (n = 293) Remain on Boosted PI + TDF/FTC (n = 140) *Pts with previous VF ineligible. 1. Pozniak A, et al. CROI Abstract 553LB. 2. Arribas J, et al. CROI Abstract 551LB.

 Regimens: EFV, 78%; NVP, 17%; RPV, 4%; ETR, < 1%; 74% on EFV/TDF/FTC; 91% on first regimen  Results similar across all baseline virologic and demographic subgroups  3 pts with VF in EVG/COBI arm and 1 in NNRTI arm – No pts with resistance in either arm  5 in the switch arm and 1 in the NNRTI arm discontinued due to adverse event Patients (%) Δ +5.3% (95% CI: -0.5 to +12) EVG/COBI/TDF/FTC (n = 290) Stable NNRTIs (n = 143) < Virologic Success* Virologic Nonresponse No Data  n = *HIV-1 RNA < 50 c/mL as defined by FDA Snapshot algorithm  Discontinued for AE, death, or missing data. Pozniak A, et al. CROI Abstract 553LB. Reproduced with permission

 Regimens: ATV, 40%; DRV, 40%; LPV, 17%; FPV, 3%; SQV, < 1%; 79% on first regimen  Results similar across all baseline virologic and demographic subgroups  2 pts with VF in each arm but no pts with resistance in either arm  5 in the switch arm and 2 in the boosted PI arm discontinued due to adverse event  Lipids in switch pts –  TGs vs all bPIs –  TC, TG, HDL-C vs LPV/RTV –  HDL-C vs DRV/RTV Patients, % Δ +6.7% (95% CI: ) EVG/COBI/TDF/FTC (n = 290) Stable boosted PIs (n = 139) < Virologic Success* Virologic Nonresponse No Data  n = *HIV-1 RNA < 50 c/mL as defined by FDA Snapshot algorithm  Discontinued for AE, death, or missing data. Arribas J, et al. CROI Abstract 551LB

 Multicenter, randomized, open-label switch study – Primary endpoint: maintenance of VL < 50 c/mL at Wk 24 (FDA snapshot analysis) Pts with VL < 50 c/mL on stable ritonavir- boosted PI + 2 NRTIs for ≥ 6 mos, no previous NNRTI use (N = 476) Rilpivirine/Tenofovir/Emtricitabine (n = 317) Ritonavir-Boosted PI* + 2 NRTIs (n = 159) Wk 48 Randomized 2:1 Wk 24 Primary endpoint Rilpivirine/ Tenofovir/Emtricitabine (n = 159) Palella F, et al. AIDS Abstract TUAB0104. *PIs: ATV/RTV, 37%; LPV/RTV, 33%; DRV/RTV, 20%; FPV/RTV, 8%; SQV/RTV, 2%.

 Switch to RPV/TDF/FTC noninferior to maintaining boosted- PI regimen at Wk 24 – 93.7% vs 89.9% with VL < 50 c/mL – Noninferiority observed regardless of pretreatment (naive) VL stratum  All 17 pts with baseline K103N who switched to RPV/TDF/FTC maintained virologic suppression  Significant reductions in TC, LDL, TG, HDL, TC:HDL ratio (P <.001) and in 10-yr Framingham score (P =.001) at Wk 24 among RPV/TDF/FTC switch pts HIV-1 RNA < 50 copies/mL at Wk 24 RPV/TDF/FTCBoosted PI / / 160 n = ≥ 100K Pts With VL < 50 c/mL (%) / / 52 < 100K Overall Δ 3.8% (-1.6 to 9.1) Δ 3.2% (-4.8 to 11.3) Δ 5.9% (-1.4 to 12.9) *Excludes 23 RPV and 14 boosted PI pts lacking baseline VL while ARV naive. Palella F, et al. AIDS Abstract TUAB0104. Graphic reproduced with permission Baseline VL (When Naive)*

 Introduce 5 classes of ARVs and origins of HAART  Review ARV regimens for naïve patients  Review “switch” regimens (CAUTION!)  Review ARV combinations in experienced patients  Cases of treatment in primary care settings

 ALWAYS GET THE TREATMENT HISTORY!!!  Try to predict the genotype YOU’D expect from the treatment history  Ask yourself: why did the provider switch from this regimen to the other?  TRY TO GET EVERY POSSIBLE RESISTANCE TEST DONE  Cannot rely on a wildtype genotype result in a highly treatment experienced patient  Archived resistant strains may exist  Mutations come at a cost! Example: M184V mutations makes HIV-1 less replicatively fit

 Never switch from a high genetic barrier to a low. Examples of what NOT to do include:  Blind switch of PI-based to 1 st gen NNRTI  Switch from DRVr or LPVr to ATVr or FAMPr  The only 2 nd gen NNRTI studied in experienced patients is etravirine  INSTIs have been studied in experienced patients  MVC studied in experienced patients; remember it requires dosing adjustments depending on other drugs  Last resort: there’s always enfuvirtide!

 Rate of viral suppression correlates with number of active background agents in salvage regimen Katlama C et al. AIDS 2009; 23:

 Patients suppressed at week 48 generally stayed suppressed on maraviroc combined with optimized backbone Hardy WD et al. J AIDS 2010; 55:

 Multicenter phase II study of DRV/RTV + ETR + RAL (N = 103); addition of NRTIs, ENF at discretion of physician – Inclusion criteria: susceptibility to DRV and ETR based on ≤ 3 DRV and ≤ 3 ETR RAMs, respectively – 59% of pts had < 1 active agent in OBR, as assessed by GSS  86% of pts reached HIV-1 RNA < 50 c/mL at Wk 48 (95% CI: 79% to 93%) [1]  Of 100 pts entering extension trial through Wk 96, 88% achieved HIV-1 RNA < 50 c/mL (95% CI: 82% to 94%) [2]  Median CD4+ cell count change: +150 cells/mm 3  4 tx-related grade 3/4 AEs reported before Wk 48: recurrent epidermal necrolysis (n = 1) (study d/c); nephrolithiasis (n = 1); lipodystrophia (n = 1); muscle spasm (n = 1)  No further events between Wks 48 and Yazdanpanah Y, et al Clin Infect Dis. 2009;49: Fagard C, et al. Acquir Immune Defic Syndr. 2012;59:

 Randomized, double-blind, noninferiority, phase III study Treatment-experienced, integrase inhibitor–naive patients with HIV-1 RNA > 400 copies/mL and ≥ 2 class resistance (N = 715) Dolutegravir 50 mg QD + Raltegravir placebo + OBR* (n = 354) Raltegravir 400 mg BID + Dolutegravir placebo + OBR* (n = 361) Stratified by number of fully active background agents, use of DRV, screening HIV-1 RNA (≤ vs > 50,000 copies/mL) Wk 48 *OBR comprising at least 1 and no more than 2 active agents. Cahn P, et al. Lancet. 2013;382:

 Lower incidence of resistance at VF with DTG vs RAL – Integrase resistance: 1% (4/354) vs 5% (17/361); P =.003 – OBR resistance: 1% (4/354) vs 3% (12/361)  Both regimens well tolerated with similar AE profiles – Grades 2-4: 8% vs 9% – Discontinuations: 3% vs 4%  No difference in outcome between study arms when combined with fully active DRV/RTV Cahn P, et al. Lancet. 2013;382: Subjects (%) Virologic Success Virologic Nonresponse No Wk 48 Data DTG + OBR (n = 354) RAL + OBR (n = 361) Δ: 7.4% (95% CI: ; P =.03)

 Phase III single-arm trial  Mean HIV-1 RNA change from baseline to Day 8 – Overall: -1.4 log 10 copies/mL (P <.001) – No primary integrase resistance mutations at BL: -1.6 log 10 copies/mL – Q148 + ≤ 1 secondary integrase resistance mutation: -1.1 log 10 copies/mL – Q148 + ≥ 2 secondary integrase resistance mutations: -1.0 log 10 copies/mL Nichols G, et al. Glasgow Abstract O232. Pts with HIV-1 RNA ≥ 500 c/mL, RAL and/or EVG resistance, and resistance to ≥ 2 other antiretroviral classes* (N = 183) Dolutegravir 50 mg BID + Continue Failing Regimen Dolutegravir 50 mg BID + Optimized Background Regimen With Overall Susceptibility Score ≥ 1 (ie, ≥ 1 active drug) Day 8Wk 24Wk 48 *Detected at screening or based on historical evidence. Functional Monotherapy Optimized Therapy

 24-wk data on full cohort (N = 183) and 48-wk data on first 114 pts  Response rates affected by baseline INSTI resistance but not overall susceptibility score of background regimen HIV-1 RNA < 50 c/mL at Wk 24 by INSTI Mutation(s), n/N (%) Overall Susceptibility Score 01≥ 2Total No Q1484/4 (100)35/40 (83)57/70 (76)96/114 (79) Q /2 (100)8/12 (67)10/17 (59)20/31 (65) Q148 + ≥ 21/2 (50)2/11 (18)1/3 (33)4/16 (25) Outcome, n (%)Wk 24 (n = 183) Wk 48 (n = 114) HIV-1 RNA < 50 c/mL at Wk 24 (snapshot, ITT-E) 126 (69)64 (56) Virologic nonresponse50 (27)44 (39) d/c due to AE or death5 (3)5 (4) Nichols G, et al. IAS Abstract TULBPE19.

 Introduce 5 classes of ARVs and origins of HAART  Review ARV regimens for naïve patients  Review “switch” regimens (CAUTION!)  Review ARV combinations in experienced patients  Cases of treatment in primary care settings

 Evidence-based guidelines exist for selecting ARV regimens in treatment naïve patients. Adhere to these recs!  Reasons to switch a regimen (CAUTION!) when virologically suppressed include simplification, avoidance of adverse effects, and patient request when appropriate  Selecting second or third line regimens after virologic failure can be complicated and requires understanding of acquired resistance, drug combinations, and sometimes additional resistance/tropism testing