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

January 2020

About This Presentation
These slides were developed using the Guidelines updated in December 2019
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the field of HIV care is rapidly changing, users are cautioned that the information in this presentation may become out of date quickly.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.
January 2020

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)
January 2020

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
January 2020

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
January 2020

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)
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)

January 2020

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)
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)

January 2020

Initial Treatment: Recommended Regimens
2 regimen 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 c/w recommended regimens (e.g., more toxicity, more pills, less clinical trial data)
January 2020

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
January 2020

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
DTG + (TAF or TDF) + (FTC or 3TC) (AI)
RAL + (TAF or TDF) + (FTC or 3TC) (BI for TDF + FTC or 3TC, BII for TAF/FTC)

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.
January 2020

Recommended Initial Regimens in Certain Clinical Situations (1)
INSTI + 2 NRTIs
EVG/COBI/TAF/FTC or EVG/COBI/TDF/FTC (B1)
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 use of INSTIs in those of childbearing potential – see slide 15.
January 2020

Recommended Initial Regimens in Certain Clinical Situations (2)
INSTI + 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 or RPV/TAF/FTC; if HIV RNA <100,000 copies/mL and CD4 >200 cells/µL (BI)

Note: TAF: fewer bone and kidney toxicities; TDF: lower lipids.
January 2020

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/µL (CI)
DRV/r (once daily) + 3TC (CI)

Notes:
Special considerations re use of INSTIs in those of childbearing potential – see slide 15.
January 2020

Persons of Childbearing Potential: Considerations before Starting INSTIs
Perform pregnancy test before ART start
DTG:
Preliminary data show small (0.3%) but increased risk of neural tube defects (NTDs) in women who were receiving DTG at time of conception
Discuss benefits and risks (incl. possible risk of NTD)
Other INSTIs: unclear risk of NTDs; discuss possibility of class effect
BIC: no data; similar considerations as for DTG; BIC and DTG have similar chemical structures
EVG/c: not recommended in pregnancy: low EVG levels in 2nd and 3rd trimesters
RAL: no evidence of increased fetal malformations, but limited data
January 2020

ART for Persons of Childbearing Potential: Selecting ARVs
Preferred ART if trying to conceive:
RAL, ATV/r, or DRV/r + TDF/FTC, TDF/3TC, or ABC/3TC
(DTG = alternative option)
If using effective contraception:
DTG = recommended option; discuss risks/benefits
Consult Perinatal Guidelines
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.
(DTG = alternative option)
January 2020

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

January 2020

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
January 2020

Selecting Initial ART Regimen: Specific Clinical Scenarios (2)
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)

January 2020

Selecting Initial ART Regimen: Specific Clinical Scenarios (3)
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/µL)

January 2020

Selecting Initial ART Regimen: Specific Clinical Scenarios (4)
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

January 2020

Selecting Initial ART Regimen: Specific Clinical Scenarios (5)
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)

January 2020

Selecting Initial ART Regimen: Specific Clinical Scenarios (6)
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

January 2020

Selecting Initial ART Regimen: Specific Clinical Scenarios (7)
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

January 2020

Selecting Initial ART Regimen: Specific Clinical Scenarios (8)
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)

January 2020

Selecting Initial ART Regimen: Specific Clinical Scenarios (9)
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

January 2020

Selecting Initial ART Regimen: Specific Clinical Scenarios (10)
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

January 2020

ARV Medications: What Not to Use
ARVs
ddI, d4T, DLV, IDV, NFV

ARV regimens
Monotherapy
Dual-NRTI therapy
3-NRTI regimen

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

January 2020

Websites to Access the Guidelines
AETC National Coordinating Resource Centerhttps://aidsetc.org
AIDSInfohttps://aidsinfo.nih.gov
January 2020

About This Slide Set
This presentation was prepared by Susa Coffey, MD, for the AETC National Resource Center in March 2020.
See the AETC NCRC website for the most current version:
https://aidsetc.org