File 3 of 8 from HHS Adult ART Guidelines: Initial Therapy

Starting ART Selecting Initial Regimens Guidelines for the Use of Antiretroviral Agentsin Adults and Adolescents June 2021 About This Presentation These slides were developed using the Guidelines updated in June 2021. The intended audience is clinicians involved in the care of patients with HIV. Because the field of HIV care is rapidly changing, users are cautioned that the information in this presentation may become out of date quickly. It is intended that these slides be used as prepared, without changes in either content or attribution. Users are asked to honor this intent. June 2021 Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents Developed by the Department of Health and Human Services (DHHS) Panel on Antiretroviral Guidelines for Adults and Adolescents A Working Group of the Office of AIDS Research Advisory Council (OARAC) June 2021 Starting ART Selecting Initial Regimens: Outline Overview Current ARV medications Recommended regimens ART for persons of childbearing potential ART for specific clinical scenarios ARVs that should not be used June 2021 Selecting Regimen for Initial ART: Overview Most recommended regimens have high efficacy but vary in pill #, possible adverse effects, drug interactions, and risk for resistance mutations Use baseline patient characteristics (incl. VL, CD4, comorbidities) and drug resistance test results to select specific regimen ART adherence is key to virologic suppression (VS) VS to below limits of detection expected with 12-24 weeks Generally, use 3 active drugs: 2 NRTIs + 1 INSTI, boosted PI, or NNRTI Combination of 2 NRTIs + INSTI is preferred for most patients NRTI pairs: ABC/3TC, TAF/FTC, or TDF/FTC June 2021 Available ARV Classes and Medications NRTI Abacavir (ABC) Didanosine (ddI) Emtricitabine (FTC) Lamivudine (3TC) Stavudine (d4T) Tenofovir DF (TDF) Tenofovir alafenamide (TAF) Zidovudine (AZT, ZDV) NNRTI Delavirdine (DLV) Doravirine (DOR) Efavirenz (EFV) Etravirine (ETR) Nevirapine (NVP) Rilpivirine (RPV) Integrase Inhibitor (INSTI) Bictegravir (BIC) Cabotegravr (CAB) Dolutegravir (DTG) Elvitegravir (EVG) Raltegravir (RAL) PI Atazanavir (ATV) Darunavir (DRV) Fosamprenavir (FPV) Indinavir (IDV) Lopinavir (LPV) Nelfinavir (NFV) Saquinavir (SQV) Tipranavir (TPV) Fusion Inhibitor Enfuvirtide (ENF, T-20) CCR5 Antagonist Maraviroc (MVC) Entry Inhibitor Fostemsavir (FOS) Ibalizumab (IBA) Pharmacokinetic (PK) Booster Ritonavir (RTV, /r) Cobicistat (COBI, /c) June 2021 Commonly-used ARV Medications NRTI Abacavir (ABC) Didanosine (ddI) Emtricitabine (FTC) Lamivudine (3TC) Stavudine (d4T) Tenofovir DF (TDF) Tenofovir alafenamide (TAF) Zidovudine (AZT, ZDV) NNRTI Delavirdine (DLV) Doravirine (DOR) Efavirenz (EFV) Etravirine (ETR) Nevirapine (NVP) Rilpivirine (RPV) Integrase Inhibitor (INSTI) Bictegravir (BIC) Cabotegravir (CAB) Dolutegravir (DTG) Elvitegravir (EVG) Raltegravir (RAL) PI Atazanavir (ATV) Darunavir (DRV) Fosamprenavir (FPV) Indinavir (IDV) Lopinavir (LPV) Nelfinavir (NFV) Saquinavir (SQV) Tipranavir (TPV) Fusion Inhibitor Enfuvirtide (ENF, T-20) CCR5 Antagonist Maraviroc (MVC) Entry Inhibitor Fostemsavir (FOS) Ibalizumab (IBA) Pharmacokinetic (PK) Booster Ritonavir (RTV, /r) Cobicistat (COBI, /c) June 2021 Initial Treatment: Recommended Regimens 2 classifications: Recommended Initial Regimens for Most People with HIV Demonstrated durable virologic efficacy, favorable tolerability and toxicity profiles, easy to use Recommended Initial Regimens in Certain Clinical Situations May be preferable for some patients Many other regimens may be effective but have disadvantages compared with recommended regimens (e.g., more toxicity, more pills, less clinical trial data) June 2021 Rating Scheme for Recommendations Strength of recommendation: A: Strong B: Moderate C: Optional Quality of evidence: I: 1 randomized controlled trials II: 1 well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes; also randomized switch studies and bioavailability/bioequivalence studies III: Expert opinion June 2021 Recommended Initial Regimens for Most People with HIV INSTI + 2 NRTIs BIC/TAF/FTC (AI) DTG/ABC/3TC (AI); only if HLA-B*5701 negative, no HBV DTG + (TAF or TDF) + (FTC or 3TC) (AI) INSTI + 1 NRTI DTG/3TC (AI); not if HIV RNA >500,000 copies/mL, HBV coinfection, or ART is started before HIV resistance test results are available Notes: 3TC can be used in place of FTC and vice versa. TAF: fewer bone and kidney toxicities; TDF: lower lipids. Special considerations re use of INSTIs in persons of childbearing potential see slide 15. June 2021 Recommended Initial Regimens in Certain Clinical Situations (1) INSTI + 2 NRTIs EVG/COBI/TAF/FTC or EVG/COBI/TDF/FTC (B1) RAL + (TAF or TDF) + (FTC or 3TC) (BI for TDF + FTC or 3TC, BII for TAF/FTC) Boosted PI + 2 NRTIs (DRV/c or DRV/r) + (TAF or TDF) + (FTC or 3TC) (AI) (ATV/c or ATV/r) + (TAF or TDF) + (FTC or 3TC) (BI) (DRV/c or DRV/r) + ABC/3TC; if HLA-B*5701 negative (BII) Notes: Boosted DRV generally preferred over boosted ATV TAF: fewer bone and kidney toxicities; TDF: lower lipids. Special considerations re persons of childbearing potential see slides 14-15. June 2021 Recommended Initial Regimens in Certain Clinical Situations (2) NNRTI + 2 NRTIs DOR/TDF/3TC (BI) or DOR + TAF/FTC (BIII) EFV + (TAF or TDF) + (FTC or 3TC) EFV 600 mg + TDF + (FTC or 3TC) (BI) EFV 400 mg/TDF/3TC (BI) EFV 600 mg + TAF/FTC (BII) RPV/TDF/FTC (BI) or RPV/TAF/FTC (BII); if HIV RNA <100,000 copies/mL and CD4 >200 cells/L Note: TAF: fewer bone and kidney toxicities; TDF: lower lipids. June 2021 Recommended Initial Regimens in Certain Clinical Situations (3) Regimens to consider when ABC, TAF, and TDF cannot be used or are not optimal DTG/3TC; not for persons with HIV RNA >500,000 copies/mL, HBV coinfection, or in whom ART is started before HIV resistance test results are available (AI) DRV/r + RAL (BID); only if HIV RNA <100,000 copies/mL and CD4 cell count >200 cells/L (CI) DRV/r (once daily) + 3TC (CI) Notes: Special considerations re persons of childbearing potential see slides 14-15. June 2021 Persons of Childbearing Potential: INSTIs Considerations Perform pregnancy test before ART start DTG: DTG-based ART regimens are recommended options, but discuss benefits and risks to inform decision-making Small (0.19%) and not statistically significant increased rate of neural tube defects (NTDs) in infants exposed to DTG at conception Other INSTIs: BIC: should not be used in pregnancy - insufficient data CAB: should not be used in pregnancy no data EVG/c: should not be used in pregnancy: low EVG levels in 2nd and 3rd trimesters RAL: no evidence of increased fetal malformations; included in recommended options in pregnancy June 2021 ART for Persons of Childbearing Potential: Selecting ARVs Preferred ART if trying to conceive (same as Preferred ART during pregnancy): RAL, DTG, ATV/r, or DRV/r + TDF/FTC, TDF/3TC, or ABC/3TC If not planning to conceive but sexually active with men and not using contraception: Choose ARVs after considering available data on potential teratogenicity, and effectiveness, tolerability, pill number, etc. In general, use a regimen that is recommended for initial therapy June 2021 Discuss risks and benefits of DTG with patients to ensure informed decision making. Consult Perinatal Guidelines Selecting Initial ART Regimen: Factors to Consider Patient Characteristics HIV RNA; CD4 count HIV resistance test results HLA-B*5701 status Patient preferences Anticipated adherence Comorbidities or Other Conditions Cardiovascular disease, hyperlipidemia, renal disease, liver disease, osteoporosis, psychiatric illness, others Pregnancy or pregnancy potential Coinfections: HCV, HBV, TB Regimen Characteristics Genetic barrier to resistance Potential adverse effects Drug interactions with other medications Convenience (pill #, dosing frequency, fixed-dose combinations, food requirements) Cost, access June 2021 Choosing Initial ART Regimen: ARVs to Avoid in Specific Clinical Scenarios CD4 <200 Do not use: higher rate of virologic failure RPV-based ART DRV/r + RAL HIV RNA >100,000 Do not use: higher rate of virologic failure RPV-based ART ABC/3TC + EFV or ATV/r DRV/r + RAL HIV RNA >500,000 Do not use: higher rate of virologic failure Regimens listed to left DTG/3TC HLA-B*5701 positive Do not use: risk of abacavir hyper-sensitivity ABC June 2021 Selecting Initial ART Regimen: Specific Clinical Scenarios (1) Starting ART before resistance test results are known Avoid NNRTI-based regimens and DTG/3TC: transmitted resistance more likely to impact regimen Avoid ABC: HLA B*5701 results not available Recommended: BIC/TAF/FTC DTG + (TAF/FTC, TDF/FTC, or TDF/3TC) DRV/r or DRV/c + (TAF/FTC, TDF/FTC or TDF/3TC) June 2021 Selecting Initial ART Regimen: Specific Clinical Scenarios (2) One-pill regimen options BIC/TAF/FTC DOR/TDF/3TC DTG/ABC/3TC (only if HLA-B*5701 negative; not if HBV coinfection) DTG/3TC (not if VL >500,000 copies/mL or if HBV coinfection) EFV/TDF/FTC, EFV/TDF/3TC EVG/c/TAF/FTC, EVG/c/TDF/FTC RPV/TAF/FTC, RPV/TDF/FTC (only if HIV RNA <100,000 copies/mL and CD4 >200 cells/L) June 2021 Selecting Initial ART Regimen: Specific Clinical Scenarios (3) Food effects No food restrictions: BIC-, DOR-, DTG-, RAL-based regimens Should be taken on empty stomach: EFV Should be taken with food: ATV/r, ATV/c DRV/r, DRV/c EVG/c/TAF/FTC, EVG/c/TDF/FTC RPV/TAF/FTC, RPV/TDF/FTC June 2021 Selecting Initial ART Regimen: Specific Clinical Scenarios (4) Chronic kidney disease (CrCl <60 mL/min) Avoid TDF ABC: not associated with renal dysfunction; can use if HLA-B*5701-negative TAF: less impact on renal function and proteinuria than TDF; may be used if eGFR >30 mL/min ATV: associated with CKD in some studies, consider avoiding Options when ABC or TAF cannot be used: DTG/3TC (if VL <500,000 and no HBV) DRV/r + 3TC (if no HBV) DRV/r + RAL (if VL <100,000, CD4 >200, and no HBV) June 2021 Selecting Initial ART Regimen: Specific Clinical Scenarios (5) HCV Consult current recommendations HBV Use TDF or TAF with FTC or 3TC: 2 NRTIs with activity against both HIV and HBV If TDF and TAF are contraindicated: treat HBV with FTC or 3TC + entecavir + suppressive ART regimen Liver disease with cirrhosis Some ARVs contraindicated or require dosage modification Evaluation by expert in advanced liver disease is recommended TB Multiple interactions between some ARVs (including TAF, PIs, INSTIs, and RPV) and rifamycins; check Guidelines or consult pharmacist June 2021 Selecting Initial ART Regimen: Specific Clinical Scenarios (6) High cardiac risk ABC and LPV/r: increased CV risk in some studies; consider avoiding ATV: not associated with increased risk of CV events (unlike other boosted PIs) QTc interval prolongation EFV and RPF: may cause QT prolongation; consider avoiding if taking other medications with known risk for QT prolongation, or risk for Torsades de Pointes Hyperlipidemia Adverse effects on lipids: PI/r or PI/c EFV EVG/c Less effect on lipids: BIC, DOR, DTG, RAL, RPV Lowers lipid levels (modest effect): TDF June 2021 Selecting Initial ART Regimen: Specific Clinical Scenarios (7) Osteoporosis Avoid TDF: associated with greater decrease in BMD, osteomalacia, urine phosphate wasting Use ABC or TAF Associated with smaller decreases in BMD ABC may be used if HLA-B*5701 negative (if HIV RNA >100,000 copies/mL, do not use with EFV or ATV/r) June 2021 Selecting Initial ART Regimen: Specific Clinical Scenarios (8) Medication-assisted treatment for opioid use disorder (OUD) EFV: reduces methadone concentrations, may cause withdrawal if started in patient on stable methadone dose Some ARVs interact with methadone, buprenorphine, and other OUD medications consult pharmacist June 2021 Selecting Initial ART Regimen: Specific Clinical Scenarios (9) History of poor adherence or inconsistent engagement in care Consider boosted PI-, BIC-, or DTG-based regimen: high genetic barrier to resistance Pregnancy or potential for pregnancy See slides 14-15 and Perinatal Guidelines June 2021 Initial ART: What Not to Use ARVs ddI, d4T, DLV, IDV, NFV ARV regimens Monotherapy Dual-NRTI therapy 3-NRTI regimen CAB + RPV (po or IM)* DTG + RPV* ARV combinations FTC + 3TC Ritonavir + cobicistat ETR + unboosted PI ETR + RTV-boosted FPV or TPV 2-NNRTI combinations ATV + IDV ARV components Unboosted DRV, SQV, or TPV NVP initiation in women with CD4 >250 or men with CD4 >400 June 2021 *Approved only for people with viral suppression on another ART regimen. Not studied as an initial ART regimen. Websites to Access the Guidelines AETC National Coordinating Resource Centerhttps://aidsetc.org Clinical Infohttps://clinicalinfo.hiv.gov June 2021 About This Slide Set This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center in June 2021. See the AETC NCRC website for the most current version: https://aidsetc.org