Initiating Antiretroviral Therapy (ART)

ART is recommended for all individuals with HIV to reduce the morbidity and mortality associated with HIV infection and to prevent HIV transmission to sexual partners and infants.  ART should be initiated as soon as possible after HIV diagnosis. When initiating ART, it is important to educate patients about the goals and benefits of ART and to identify and address barriers to care engagement and treatment adherence. Patients should also understand that currently available ART does not cure HIV. To improve and maintain immunologic function and maintain viral suppression, ART should be continued indefinitely without interruption. Initiating ART early is particularly important for patients with AIDS-defining conditions, those with acute or recent HIV infection, and individuals who are pregnant; delaying therapy in these subpopulations has been associated with high risks of morbidity, mortality, and HIV transmission.

The Panel on Antiretroviral Guidelines for Adults and Adolescents (the Panel) classifies the following regimens as Recommended Initial Regimens for:

Most People with HIV (in alphabetical order):

Acute and Recent (Early) HIV Infection

Antiretroviral Regimen Considerations for Initial Therapy Based on Specific Clinical Scenarios

Patient or Regimen Characteristics

Clinical Scenario

Consideration(s)

Rationale/Comments
Update 12/18/2019 
The older ARV drugs ddI, d4T, FPV, IDV, NFV, SQV, and TPV are no longer commonly used in clinical practice.

Pre-ART Characteristics

CD4 count <200 cells/mm3

Do Not Use the Following Regimens:

  • RPV-based regimens
  • DRV/r plus RAL

A higher rate of virologic failure has been observed in those with low pretreatment CD4 counts.

HIV RNA >100,000 copies/mL (also see next row if HIV RNA >500,000 copies/mL)

Do Not Use the Following Regimens:

  • RPV-based regimens
  • ABC/3TC with EFV or ATV/r
  • DRV/r plus RAL

Higher rates of virologic failure have been observed in those with high pretreatment HIV RNA levels

HIV RNA >500,000 copies/mL

Do Not Use the Following Regimens:

  • RPV-based regimens
  • ABC/3TC with EFV or ATV/r
  • DRV/r plus RAL
  • DTG/3TC

For DTG/3TC, limited data are available in patients above this viral load threshold.

HLA-B*5701 positive or result unknown

Do not use ABC-containing regimens.

ABC hypersensitivity, a potentially fatal reaction, is highly associated with the presence of the HLA-B*5701 allele.

ARV should be started before HIV drug resistance results are available (e.g., in a person with acute HIV) or when ART is being initiated rapidly.

Avoid NNRTI-based regimens and DTG/3TC.

Avoid ABC.

Recommended ART Regimens:

  • BIC/TAF/FTC
  • DTG plus (TAF or TDF)a plus (3TC or FTC)
  • (DRV/r or DRV/c) plus (TAF or TDF)a plus (3TC or FTC)

Transmitted mutations conferring NNRTI and NRTI resistance are more likely than mutations associated with PI or INSTI resistance.

HLA-B*5701 results may not be available rapidly.

Transmitted resistance to DRV, BIC, and DTG is rare, and these drugs have high barriers to resistance.

ART-Specific Characteristics

A one-pill, once-daily regimen is desired

STR Options as Initial ART Include:

  • BIC/TAF/FTC
  • DOR/TDF/3TC
  • DRV/c/TAF/FTC
  • DTG/ABC/3TC
  • DTG/3TC
  • EFV/TDF/FTC
  • EFV/TDF/3TC
  • EVG/c/TAF/FTC
  • EVG/c/TDF/FTC
  • RPV/TAF/FTC
  • RPV/TDF/FTC

Do not use DTG/ABC/3TC if patient is HLA-B*5701 positive.

DTG/3TC is not recommended if HIV RNA is >500,000 copies/mL.

Do not use DTG/ABC/3TC or DTG/3TC in the setting of HBV coinfection or unknown HBV status.

Do not use RPV-based regimens if HIV RNA is >100,000 copies/mL and CD4 count is <200/mm3.

See Appendix B, Table 10 for ARV dose recommendations in the setting of renal impairment.

Food effects

Regimens that Can be Taken Without Regard to Food:

  • BIC-, DOR-, DTG-, or RAL-based regimens

Oral bioavailability of these regimens is not significantly affected by food.

Regimens that Should be Taken with Food:

  • ATV/r- or ATV/c-based regimens
  • DRV/r- or DRV/c-based regimens
  • EVG/c/TAF/FTCa
  • EVG/c/TDF/FTCa
  • RPV-based regimens

Food improves absorption of these regimens. RPV-containing regimens should be taken with ≥390 calories of food.

Regimens that Should be Taken on an Empty Stomach:

  • EFV-based regimen

Food increases EFV absorption and may increase CNS side effects.

Presence of Other Conditions

Chronic kidney disease (defined as CrCl <60 mL/min)

In general, avoid TDF.

ABC may be used if patient is HLA-B*5701 negative. If HIV RNA is >100,000 copies/mL, do not use ABC/3TC plus (EFV or ATV/r).

TAF may be used if CrCl >30 mL/min or if patient is on chronic hemodialysis (only studied with EVG/c/TAF/FTC).

Consider avoiding ATV.

ART Options When ABC, TAF, or TDF Cannot be Used:

  • DTG/3TC (if HIV RNA <500,000 copies/mL and without HBV coinfection)
  • DRV/r plus 3TC
  • DRV/r plus RAL (if CD4 count >200 cells/mm3 and HIV RNA <100,000 copies/mL)

TDF has been associated with proximal renal tubulopathy. Higher rates of renal dysfunction have been reported in patients using TDF in conjunction with RTV-containing regimens.

An adjusted dose of TDF can be used in patients with ESRD or in those who are on hemodialysis. Refer to Appendix B, Table 10 for specific dosing recommendations.

TAF has less impact on renal function and lower rates of proteinuria than TDF.

ATV has been associated with chronic kidney disease in some observational studies.

ABC has not been associated with renal dysfunction.

Liver disease with cirrhosis

Some ARVs are contraindicated or may require dosage modification in patients with Child-Pugh class B or C disease.

Refer to Appendix B, Table 10 for specific dosing recommendations.

Patients with cirrhosis should be carefully evaluated by an expert in advanced liver disease.

Osteoporosis

Avoid TDF.a 

ABC may be used if patient is HLA-B*5701 negative. If HIV RNA is >100,000 copies/mL, do not use ABC/3TC plus (EFV or ATV/r).

TDF is associated with decreases in BMD along with renal tubulopathy, urine phosphate wasting, and resultant osteomalacia. TAFa and ABC are associated with smaller declines in BMD than TDF.

Psychiatric illnesses

Consider avoiding EFV- and RPV-based regimens.

Patients on INSTI-based regimens who have pre-existing psychiatric conditions should be closely monitored.

Some ARVs are contraindicated, and some psychiatric medications need dose adjustments when coadministered with certain ARVs.

EFV and RPV can exacerbate psychiatric symptoms and may be associated with suicidality.

INSTIs have been associated with adverse neuropsychiatric effects in some retrospective cohort studies and case series.

 

HIV-associated dementia (HAD)

Avoid EFV-based regimens if possible.

The beneficial effects of ART on HAD-symptoms may be confounded by EFV-related neuropsychiatric effects.

Medication-assisted treatment for opioid use disorder

Opioid withdrawal may occur when EFV is initiated in patients who are on a stable dose of methadone.

Clinical monitoring is recommended, as medications used to treat opioid dependence may need to be adjusted in some patients.

EFV reduces methadone concentrations and may lead to withdrawal symptoms.

 

Cardiac QTc interval prolongation

Consider avoiding EFV- or RPV-based regimens if patient is taking other medications with known risk of Torsades de Pointes, or in patients at higher risk of Torsades de Pointes.

High EFV or RPV concentrations may cause QT prolongation.

High cardiac risk

Consider avoiding ABC- and LPV/r -based regimens.

If a boosted PI is the desired option, an ATV-based regimen may have advantages over a DRV-based regimen.

Refer to Hyperlipidemia below for regimens associated with more favorable lipid profiles.

An increased risk of CV events with ABC has been observed in some studies.

Observational cohort studies reported an association between some PIs (DRV, IDV, FPV, and LPV/r) and an increased risk of CV events; this risk has not been seen with ATV (see text). Further study is needed.

Certain ART regimens are associated with more favorable lipid profiles than other regimens, although evidence on whether this improves CV outcomes is lacking.

Hyperlipidemia

The Following ARV Drugs Have Been Associated with Dyslipidemia:

  • PI/r or PI/c
  • EFV
  • EVG/c

BIC, DOR, DTG, RAL, and RPV have fewer lipid effects.

TDF lowers lipids; therefore, switching from TDF to TAF is associated with increased lipids.

TDF has been associated with lower lipid levels than ABC or TAF.

Patients with history of poor adherence to non-ARV medications or inconsistent engagement in care

Consider using regimens with a boosted PI or BIC or DTG.

These regimens have a high genetic barrier to resistance.

Pregnancy
Panel's Recommendations for the Use of Antiretroviral Drugs During Pregnancy
  • When choosing an antiretroviral (ARV) drug regimen for a pregnant woman, providers and patients should consider multiple factors, including adverse effects, drug interactions, pharmacokinetics (PKs), convenience of the individual drugs and drug combinations in the regimen, available pregnancy safety and outcome data, and the patient’s resistance test results and comorbidities.
  • The same regimens that are recommended for the treatment of nonpregnant adults should be used in pregnant women when sufficient data suggest that appropriate drug exposure is achieved during pregnancy; clinicians should weigh the risks of adverse effects for women, fetuses, or infants against the benefits of these regimens and recognize that there are often incomplete data on the safety of ARV drugs in pregnancy. For more information, see Tables 4 and 5.
  • In most cases, women who present for obstetric care on fully suppressive ARV regimens should continue their current regimens.
  • PK changes in pregnancy may lead to lower plasma levels of some ARV drugs and necessitate increased doses, more frequent dosing, boosting, more frequent viral load monitoring, or a change in ARV regimen; see Pregnant Women with HIV Who Are Currently Receiving Antiretroviral Therapy.
  • The Panel emphasizes the importance of counseling and informed decision-making regarding all ARV regimens for people with HIV. For additional information, see Preconception Counseling and Care for Women of Childbearing Age with HIV, Teratogenicity, Appendix C: Antiretroviral Counseling Guide for Health Care Providers, and Tables 4 and 5.
  • After delivery, clinicians should discuss reproductive desires, the risks and benefits of conceiving on the current ARV regimen, and contraceptive options. See Preconception Counseling and Postpartum Care for more information.
  • Folic acid is known to prevent neural tube defects in the general population. All pregnant women and women who might conceive should take at least 400 mcg of folic acid daily ). 
Preferred Dual-NRTI Backbones
ABC/3TC Available as an FDC. Can be administered once daily. ABC should not be used in patients who test positive for HLA-B*5701 because of the risk of developing a hypersensitivity reaction. ABC/3TC administered with ATV/r or EFV is not recommended if pretreatment HIV RNA is >100,000 copies/mL.
TDF/FTC
or
TDF/3TC		 TDF/FTC is available as an FDC. Either coformulated TDF/FTC or separate doses of TDF and 3TC can be administered once daily. TDF has potential renal toxicity; thus, TDF-based, dual-NRTI combinations should be used with caution in patients with renal insufficiency.
Preferred INSTI Regimens
DTG/ABC/3TC (FDC)
or
DTG plus a Preferred Dual-NRTI Backbonea		 Administered once daily. The use of DTG/ABC/3TC requires HLA-B*5701 testing, because this FDC contains ABC. INSTI-based regimens may be particularly useful when drug interactions or the potential for preterm delivery with a PI-based regimen are a concern. In nonpregnant adults, DTG is associated with lower rates of INSTI resistance than RAL; like RAL, DTG has been shown to rapidly decrease viral load in ARV-naive pregnant women who present to care later in pregnancy. DTG is Preferred for the treatment of pregnant women with acute HIV infection and for women who present to care late in pregnancy. There are specific timing and/or fasting recommendations if DTG is taken with calcium or iron (e.g., in prenatal vitamins; see Table 10). The use of DTG at conception and in very early pregnancy has been associated with a small, but statistically significant, increase in the risk of NTDs; this information should be discussed with patients to ensure informed decision-making. For more information, see Recommendations for Use of Antiretroviral Drugs During Pregnancy, Table 5, Teratogenicity, and Appendix C: Antiretroviral Counseling Guide for Health Care Providers. 
RAL plus a Preferred Dual-NRTI Backbone PK data are available for RAL in pregnancy when using the twice-daily formulation (400 mg twice daily), but data are not available for the once-daily 1,200 mg (2 x 600 mg) extended-release formulation “raltegravir HD”. Twice-daily dosing is required in pregnancy. RAL has been shown to produce rapid viral load decline to undetectable levels in women who present for initial therapy late in pregnancy. INSTI-based regimens may be particularly useful when drug interactions or the potential for preterm delivery with PI-based regimens are a concern. There are specific timing and/or fasting recommendations if RAL is taken with calcium or iron (e.g., in prenatal vitamins; see Table 10).
Preferred PI Regimens
ATV/r plus a Preferred Dual-NRTI Backbone Once-daily administration. Extensive experience with use in pregnancy. Maternal hyperbilirubinemia; no clinically significant neonatal hyperbilirubinemia or kernicterus reported, but neonatal bilirubin monitoring is recommended. Cannot be administered with PPIs. Specific timing recommended for dosing with H2 blockers (see Table 10).
DRV/r plus a Preferred Dual-NRTI Backbone Better tolerated than LPV/r. Experience with use in pregnancy is increasing. Must be used twice daily in pregnancy.
Source: Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. Available at https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/what-start-initial-combination-regimens-antiretroviral-naive 
 

Reference

Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents with HIV. Department of Health and Human Services. Available at https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/what-start-initial-combination-regimens-antiretroviral-naive 

Centers for Disease Control and Prevention: US Public Health Service: Preexposure prophylaxis for the prevention of HIV infection in the United States—2017 Update: a clinical practice guideline. https://www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2017.pdf. Published March 2018.