Treatment Guideline Chart
Antiretroviral therapy is recommended for all HIV-infected individuals regardless of CD4 count to decrease morbidity and mortality associated with HIV infection.
Goals of antiretroviral treatment are suppression of viral load for maximum possible duration, restore and preserve immunologic function, reduce HIV-related morbidity and mortality and prevent HIV transmission.
Urgent initiation of antiretroviral treatment is recommended in the following individuals: Pregnant women, patients with HIV with coinfections (HBV, HCV, active tuberculosis), AIDS-defining illness, HIV-associated nephropathy, low CD4 counts, acute opportunistic infections and HIV HBV with evidence of chronic liver disease.

Antiretroviral%20therapy%20for%20hiv-infected%20adults Treatment

Principles of Therapy

Indications and Recommendations for Starting Antiretroviral Therapy (ART)

  • Regardless of CD4 cell count or WHO clinical stage, initiation of ART is strongly recommended for individuals with the following conditions:
    • Pregnancy
      • All pregnant and breastfeeding women with acute or recent HIV infection should start a combination ART as soon as possible to prevent mother-to-child transmission of HIV
    • History of an AIDS-defining illness
    • HIV-associated nephropathy
    • HIV/hepatitis B virus (HBV) and IV/Hepatitis C (HCV) coinfections
    • HIV/Active tuberculosis disease coinfection
      • TB treatment should also be started immediately
    • Advanced HIV disease (clinical stage 3 or 4)
    • HIV-positive partners in serodiscordant couples
  • Treat all patients including asymptomatic individuals with CD4 T-cell count of 350-500 cells/mm3 regardless of the clinical stage but prioritize patients with CD4 cell count of  ≤350 cells/mm3 and those with advanced HIV disease
  • ART should be offered to patients who are at risk of transmitting HIV to sexual partners
    • Effective ART has been shown to prevent transmission of HIV from an infected individual to a sexual partner
  • ART is recommended in patients >50 years of age, regardless of CD4 cell count
    •  Immunologic response to ART may be reduced and risk of non-AIDS complications may increase in older HIV-infected patients
  • ART is recommended for all HIV-infected individuals to reduce the risk of disease progression and prevent its transmission
  • Patients starting ART should be willing, able to commit, understand the risks and benefits of therapy and the importance of adherence
  • All patients who are HIV-positive should be counseled on how the infection is being transmitted, how can it be prevented & the responsibility of notifying their partners about the infection

Goals of Antiretroviral Treatment

  • Suppression of viral load for maximum possible duration
  • Restore and preserve immunologic function
  • Reduce HIV-related morbidity and mortality
  • Improve quality of life
  • Prevent HIV transmission

Initiating Antiretroviral Therapy in Treatment-Naive Patients

  • ART is recommended for all HIV infected individuals regardless of CD4 count to decrease morbidity and mortality associated with HIV infection
    • In patients with much lower CD4 count, ART must be started immediately
  • Urgent initiation of ART is recommended in the following individuals:
    • Patients age ≥50 years 
    • Pregnant women
    • HIV with coinfections (HBV, HCV, active tuberculosis)
    • AIDS-defining illness, including HIV-associated dementia (HAD) and AIDS-associated malignancies
    • HIV-associated nephropathy (HIVAN)
    • Low CD4 counts (eg <200 cells/mm3)
    • Acute opportunistic infections (eg cryptosporidiosis, microsporidiosis and progressive multifocal leukoencephalopathy), as well as in patients with early/acute infections
    • HIV HBV with evidence of chronic liver disease
  • ART is also recommended for serodiscordant couples
  • When initiating ART, it is important to educate patients about its benefits and considerations in order to optimize compliance to therapy

ART in Special Populations

  • All pregnant and breastfeeding women with acute or recent HIV infection should start ART regimen as soon as possible to prevent mother-to-child transmission and protect their own health
  • Principles of active TB treatment in HIV-infected patients are the same as those for HIV-uninfected patients
    • All HIV patients coinfected with active TB should be immediately started on TB treatment
    • CD4 counts <50 cells/mm3: Start ART within 2 weeks of TB treatment
    • CD4 counts ≥50 cells/mm3 with severe clinical disease: Start within 2-4 weeks of TB treatment
    • CD4 counts ≥50 cells/mm3 without severe clinical disease: ART may be started within 8-12 weeks of TB treatment
  • In patients with HBV coinfection, ART drugs active against HBV should be continued even in the setting of HIV virologic failure
  • The drug active against HBV should be continued and combined with other suitable ART agents to achieve HIV suppression
  • Concurrent treatment of HIV and hepatitis C (HCV) infection may be complicated by overlapping drug toxicities and high pill burden
    • Decision to start HCV treatment should consider medical need for such treatment based on HCV stage
  • ART is recommended in patients >50 years of age regardless of CD4 count because immunologic response to ART may be reduced in older HIV-infected patients and the risk of non-AIDS complications may increase
  • ART is recommended for all individuals with  HIV-1 infection and to those with early HIV-1 infection (p I-1)
  • If treatment is initiated in a patient with early HIV-1 infection, the goal is to suppress plasma HIV-1 RNA to undetectable levels
  • In patients with early HIV-1 infection in whom therapy is initiated, testing for plasma HIV-1 RNA levels, CD4 T lymphocyte counts, and toxicity monitoring should be performed as described for patients with chronic HIV-1 infection
  • Genotypic drug resistance testing should be performed before initiation of ART to guide the selection of the regimen
  • In patients without transmitted drug resistant virus, therapy should be initiated with one of the combination regimens for patients with chronic HIV-1 infection
  • ART can be initiated before drug resistance test results are available
  • Patients starting ART should be willing and able to commit to treatment and should understand the possible benefits and risks of therapy and the importance of adherence

Regimen Selection

  • Selection of treatment regimen should be individualized based on virologic efficacy, toxicity, potential drug-drug interaction, dosing frequency, pill burden, resistance testing results, comorbidities, patient characteristics (eg pregnancy potential, adherence potential) and needs
  • Initial treatment for treatment-naive patients consists of 2 NRTIs (eg Abacavir, Didanosine, Emtricitabine, Lamivudine, Stavudine, Tenofovir, Zalcitabine, Zidovudine) plus either INSTI, NNRTI, or PK-enhanced PI
    • First-line agents should include 2 NRTIs plus an NNRTI
    • Second-line agents should include 2 NRTIs plus a Ritonavir-boosted PI (eg ATV/r and LPV/r)
    • Third-line agents should include new drugs with minimal potential for cross-resistance with prior regimens (eg integrase inhibitors, 2nd-generation NNRTIs and PIs)


Recommended Antiretroviral Drug Regimens for Treatment-Naive Patients

Preferred boosted PI-based Regimens + 2 NRTIs

Ritonavir-boosted Darunavir + either Tenofovir disoproxil fumarate/Emtricitabine or Tenofovir alafenamide/Emtricitabine

Preferred INSTI-based Regimens + 2 NRTIs

Dolutegravir + either Tenofovir disoproxil fumarate/Emtricitabine or Tenofovir alafenamide/Emtricitabine
Cobicistat-boosted Elvitegravir/Tenofovir alafenamide/Emtricitabine or Cobicistat-boosted Elvitegravir/Tenofovir disoproxil fumarate/Emtricitabine
Raltegravir + either Tenofovir disoproxil fumarate/Emtricitabine or Tenofovir alafenamide/Emtricitabine

Alternative NNRTI-based Regimens + 2 NRTIs

Efavirenz/Tenofovir disoproxil fumarate/Emtricitabine6
Efavirenz/Tenofovir alafenamide/Emtricitabine
Rilpivirine/Tenofovir disoproxil fumarate/Emtricitabine5 or Rilpivirine/Tenofovir alafenamide/Emtricitabine4,5

Alternative boosted PI-based Regimens + 2 NRTIs

(Cobicistat-boosted Atazanavir or Ritonavir-boosted Atazanavir) + either Tenofovir disoproxil fumarate/Emtricitabine or Tenofovir alafenamide/Emtricitabine
Cobicistat-boosted Darunavir or Ritonavir-boosted Darunavir + Abacavir/Lamivudine1,3
Cobicistat-boosted Darunavir + either Tenofovir disoproxil fumarate/Emtricitabine or Tenofovir alafenamide/Emtricitabine
Ritonavir-boosted Lopinavir + either Tenofovir disoproxil fumarate/Emtricitabine or Tenofovir alafenamide/Emtricitabine5

If HIV RNA <100,000 copies/mL & HLA-B*5701 Negative

Cobicistat-boosted Atazanavir or Ritonavir-boosted Atazanavir + Abacavir/Lamivudine
Efavirenz + Abacavir/Lamivudine1
Raltegravir + Abacavir/Lamivudine1

Other Regimens When TAF, TDF or ABC Cannot be Used

Ritonavir-boosted Darunavir + Raltegravir4 (twice daily)
Ritonavir-boosted Lopinavir + Lamivudine1 (twice daily)

Adapted from: Department of Health & Human Services Panel on Antiretroviral Guidelines for Adults and Adolescents. Guidelines for the use of antiretroviral agents in HIV-1-infected adults and adolescents 2017, and the 2017 European AIDS Clinical Society (EACS) guidelines for the clinical management and treatment of HIV-infected adults.
¹3TC may be substituted for FTC & vice-versa
²Once daily LPV/r is not recommended in pregnant patients
³If HLA-B*5701 is negative
⁴If HIV RNA is <100,000 copies/mL and CD4 is >200 cells/mm³ 
5A recommended regimen by the EACS 2017 guidelines 
6To be used only if with HIV viral load of <100,000 copies/mL based on the EACS 2017 guidelines 

Non-Nucleoside Reverse Transcriptase Inhibitor (NNRTI)-based Regimens

  • Advantage: Have demonstrated virologic potency and durability
  • Disadvantage: Prevalence of NNRTI-resistant viral strains in ART-naive patients and the low genetic barrier of these agents for the development of resistance
    • All NNRTIs except for Etravirine (ETV) require only a single gene mutation to confer resistance; cross resistance among these NNRTIs are common
    • Partial resistance to Efavirenz (EFV), Nevirapine (NVP), or Rilpivirine (RPV) is conferred by a single mutation in the reverse transcriptase gene, hi and it may develop rapidly after virologic failure
  • A single tablet formulation consisting of EFV, Tenofovir (TDF) and Emtricitabine (FTC) allows one-tablet, once-daily dosing and is currently the preferred NNRTI-based regimen
    • Regimen consisting of RPV/TDF/FTC is only an alternative due to the limited data on durability to response lower virologic response to RPV

Delavirdine (DLV)

  • Requires 3-times daily dosing and has the least supporting data in clinical trials
  • Appears to have the least antiviral activity and as such is not recommended as part of an initial ART regimen

Efavirenz (EFV)

  • EFV with ABC/3TC is now recommended as other regimen
  • It is coformulated with TDF/FTC
  • Transmitted resistance is commonly reported than PIs and INSTIs
  • Only for patients with pre-ART viral load <100,00 copies/mL and negative HLA B*5701 status
  • Advantage: To date, no regimen has proven superior to EFV-based regimens with respect to virologic response; aside from potency, it is also preferred due to its tolerability
  • Disadvantages: Contraindicated in the 1st trimester of pregnancy or in women of childbearing potential who are trying to conceive, or in those not using effective and consistent contraception
    • Also, EFV-based regimens are associated with skin rash and neuropsychiatric adverse effects (eg depression and increase rate of suicidality)

Etravirine (ETV)

  • Advantage: Has in-vitro activity against some viruses with mutations that confer resistance to DLV, EFV, and Nevirapine (NVP)
  • Disadvantage: In RPV-treated patients, presence of RPV-resistant mutations at virologic failure is common and may confer cross-resistance to ETV

Nevirapine (NVP)

  • Advantage: May be used as an acceptable NNRTI option in women with aseline CD4 counts of ≤250 cells/mm3 or in men with pretreatment CD4 counts ≤400 cells/mm3
  • Disadvantage: Serious hepatic events have been observed when started in ART-naive patients
    • However, patients who experience increases in CD4 count to levels above the aforementioned thresholds can safely continue without an increased risk for hepatic events
    • Monitoring of serum transaminases at baseline, 2 weeks after dose increase and then monthly for the first 18 weeks are recommended by some experts

Rilpivirine (RPV)

  • May be used in combination with NRTIs for ART-naive patients with pre-treatment viral load <100,000 copies/mL
  • Use of RPV with TDF/FTC should be limited to ART-naive patients with pre-treatment viral load copies of <100,000 and  CD4 count >200 cells/mm3
  • Advantage: A once daily dosing and is coformulated with TDF/TFC; compared with FV, drug discontinuations with RPV due to adverse effects (eg dizziness, abnormal dreams, hyperlipidemia and rash) were less frequent
    • Frequency of depressive disorders and discontinuations secondary to depression are similar between RPV and EFV
  • Disadvantage: Lower virologic response compared with EFV in patients with high baseline viral loads and requires acid to have an adequate absorption

Protease inhibitor (PI)-based Regimens

  • Have demonstrated durability and virologic potency in ART-naive patients
  • Resistance mutations are seldom detected at virologic failure, unlike NNRTI- and Integrase Strand Transfer Inhibitor (INSTI)-based regimens

Boosted PI Regimens

  • Ritonavir (RTV)-boosted PI-based regimens have demonstrated good immunologic and virologic responses
  • Advantage: Drug resistance to most PIs require multiple mutations in the HIV protease gene and seldom develops after early virologic failure, especially when RTV boosting is used
  • Disadvantage: Are often associated with more gastrointestinal (GI) symptoms than EFV-based regimens; like EFV-based regimens, are also associated with hepatic transaminase elevations
    • Other disadvantages include higher pill burden and more clinically significant drug interactions are seen with RTV-boosted PI regimens than with NNRTI-based regimens

Atazanavir + Ritonavir (ATV/r) or Atazanavir + Cobicistat (ATV/c)

  • ATV/r and ATV/c combined with TDF/FTC are recommended as alternative regimens for ART-naive patients regardless of pre-treatment HIV RNA
  • ATV/c + TDF/FTC is not recommended for patients with CrCl <70 mL/minute
  • ATV/r or ATV/c + ABC/3TC is recommended as other regimen
    • Its use is limited to patients with pre-ART HIV RNA <100,000 copies/mL
  • Advantage: A clinical trial has shown RTV-boosting of ATZ enhances ATV concentration, improving virologic activity as compared with ATV alone
  • Disadvantage: Main adverse effect is indirect hyperbilirubinemia that is not associated with hepatic transaminase elevation; also requires acidic gastric pH for dissolution; thus, antacids, H2 agonists and proton pump inhibitors (PPI) may impair its absorption

Darunavir + Cobicistat (DRV/c)

  • Regimens consisting of DRC/c + TDF/FTC and DRV/c + ABC/3tc is recommended as alternative regimens for ART-naive patients
  • DRV/c + TDF/FTC is not recommended:
    • For patients with CrCl <70 mL/minutes

Darunavir + Ritonavir (DRV/r)

  • Regimen consisting of DRV/r + TDF/FTC is also a preferred PI-based regimen
    • ARTEMIS study has shown DRV/r, compared with LPV/r (both in combination with TDF/FTC), to have a superior virologic response

Fosamprenavir + Ritonavir (FPV/r)

  • Recommended as an alternative PI-based regimen, with once- or twice-daily dosing
  • Studies have shown similar CD4 and virologic benefits when compared with ATV/r, both in combination with TDF/FTC

Indinavir + Ritonavir (IDV/r)

  • Associated with high incidence of nephrolithiasis
  • Indinavir requires high fluid intake

Lopinavir + Ritonavir (LPV/r)

  • Is the only available coformulated boosted PI with RTV
  • LPV/r + TDF/FTC or LPV/r + ABC/3TC is recommended as other regimen
  • Compared with other PIs boosted with 100 mg/daily of RTV, LPV/r should be boosted with 200 mg/day of RTV
  • Associated with higher rates of GI side effects and hyperlipidemia
  • Once-daily LPV/r should not be given to patients who have HIV mutations associated with PI resistance
  • Twice-daily dosing is preferred for pregnant women, especially during 3rd trimester, when LPV levels are expected to decline

Saquinavir + Ritonavir (SQV/r)

  • Has a high pill burden and requires twice-daily dosing and 200 mg of RTV
  • At recommended dose, this regimen is associated with increases in both PR and QT prolongation
    • Degree of QT prolongation is greater than that seen with some other boosted PI
    • ECG is recommended prior to its initiation
  • May be an acceptable regimen but should be used with caution against certain ART-naive patients (contraindicated in patients with QT prolongation, complete AV block, refractory hypokalemia or hypomagnesemia)

Unboosted PI-based Component


  • Given once daily and has fewer effects on lipid profiles compared with other PIs
  • May be an acceptable initial therapy when a once-daily regimen is desired and then there is concern for hyperlipidemia
  • Studies have shown it to have similar virologic efficacy to ATV-based combination regimens with either EFV- or NVP-based regimens
  • RTV boosting is needed when given with TDF or EFV since the latter can lower ATV concentration

Integrase Strand Transfer Inhibitor (INSTI)-based Regimens

Dolutegravir (DTG)

  • Inhibitor of HIV integrase
  • Treatment of HIV-1 infection in adults and children
  • Licensed for both treatment-naive and treatment-experienced patients
  • DTG/ABC/3TC is only given in patients who are HLA-B*5701 negative
  • DTG plus TDF/FTC or TAF/FTC are now recommended for ART-naive patients

Elvitegravir (EVG)

  • Potent, CYP3A inhibitor that has no activity against HIV
  • Non-inferior to a combination of ATC + TDF/TC
  • EVG/c/TAF/FTC is only given in patients with pre-ART CrCl of > 30 mL/minute
  • EVG/c/TDF/FTC is only given in patients with pre-ART CrCl of >70 mL/minute

Elvitegravir/Cobicistat (EVG/c)

  • Advantage: Coformulated with TDF/FTC as a single tablet regimen and once daily dosing; causes a smaller increase in the total and LDL cholesterol as comparted with ARTV/r
  • Disadvantage: Oral administration can be reduced by simultaneous administration with antacid that contains polyvalent cations (eg Al, Ca or Mg)
  • Cobicistat inhibits active tubular secretion of Cr and an increase serum Cr without affecting renal glomerular function
  • Since Cobicistat is a potent CYP3A4 inhibitor, it may have interactions with the substrates of CYP3A

Raltegravir (RAL)

  • Approved for use in ART-naive patients
  • Use has been associated with increase in creatine kinase, myopathy and rhabdomyolysis
  • A potential disadvantage when comparing with other regimens is its twice-daily dosing
  • Like EFV, has a low genetic barrier to resistance
  • The combination of TDF/FTC and RAL demonstrated similar virologic efficacy as that of EFV/TDF/FTC up to 156 weeks and is generally well tolerated
  • Co-administration of antacids containing Al or Mg is not recommended, as it significantly impairs the oral absorption of RAL
  • Combination with Ritonavir-based DRV should be avoided in patients with CD4 count of <200 cells/mm3

Raltegravir + 2 Nucleoside Reverse Transcriptase Inhibitors (NRTIs)

  • RAL + TDF/FTC is the preferred INSTI-based regimen for ART-naive patients, with immunologic and virologic responses similar to EFV + TDF/FTC and no safety concerns identified based on studies
  • RAL + Abacavir (ABC)/Lamivudine (3TC) is the preferred alternative INSTI-based regimen

Nucleoside Reverse Transcriptase Inhibitors (NRTI)Triple NRTI Regimens

  • Currently, three of the approved NRTIs have activity against hepatitis virus (HBV): 3TC, FTC and TDF
  • Single- and dual-NRTI therapy are not recommended as these have not demonstrated sustained and potent virologic activity
    • Stavudine (d4T) should not be used as 1st-line agent due to its metabolic toxicities
  • Dual NRTIs are commonly used in combination with an NNRTI, a PI, an INSTI or a CCR5 antagonist
    • In clinical practice, most dual NRTI combinations consist of a primary NRTI plus 3TC or FTC

Preferred Dual NRTI

Tenofovir (TDF)/Emtricitabine (FTC) [coformulated]

  • Tenofovir is a nucleotide analog with potent activity against both HIV and hepatitis B virus (HBV)
    • Has a long intracellular half-life which allows for once-daily dosing
    • Demonstrated potent virologic activity when used with either 3TC or FTC as part of an EFV-based regimen in ART-naive patients
    • Renal impairment with TDF use has been reported; greater risk of renal dysfunction when used in PI-based regimens
  • TDF plus either 3TC or FTC is the preferred NRTI combination, especially for patients coinfected with both HIV and HBV
    • Use of a single HBV-active NRTI (either 3TC or FTC) is not recommended as it can lead to HBV resistance
  • Superior to ZDV/3TC in virologic efficacy up to 144 weeks

Alternative Dual NRTI

Abacavir (ABC)/Lamivudine (3TC) [coformulated]

  • Remains a good alternative dual-NRTI option for some ART-naive patients
  • Should only be given to patients who tested negative for HLA-B*5701
  • Abacavir has the potential for serious hypersensitivity reactions
  • The fixed dose combination allows for once-daily dosing
  • Should be used with caution in patients at higher risk for cardiovascular disease and whose plasma HIV RNA levels are at ≥100,000 copies/mL


Tenofovir disoproxil fumarate (TDF)/Emtricitabine (FTC) [coformulated]

  • It is coformulated with  EFV, EVG/c and RPV as a STR
  • The recommended dual-NRTI in patients co-infected with HIV/HBV
  • Gives a better virologic response than ABC/3TC in patients with a baseline viral load of >100,000 copies/mL when combined with ATV/r or EFV
  • Causes renal toxicity, including proximal tubulopathy and acute or chronic renal insufficiency
  • It also decreases BMD more than other NRTI combinations

Zidovudine (ZDV)/Lamivudine (3TC) [coformulated]

  • Has extensive durability, tolerability and safety experience
  • Recommended only as an acceptable regimen due to its greater toxicity than other dual NRTIs and its requirement for twice-daily dosing

Triple NRTI

  • Triple NRTI regimens have been shown to have suboptimal virologic activity based on several controlled trials

ABC/3TC/ZDV (coformulated)

  • The only triple NRTI combination with available supporting randomized clinical trial data
  • With comparable virologic activity to IDV- and NFV-based regimens but was inferior to EFV-based regimen
  • Generally not recommended and should only be used when a preferred alternative or an acceptable NNRTI-, PI-, or INSTI-based regimen is less desirable due to toxicities, complexity of regimen or drug interactions

CCR5 Antagonist-based Regimens

CCR5-Antagonist (eg Maraviroc) + 2 NRTIs (Zidovudine/Lamivudine)

  • Maraviroc (MVC) is recommended only as an acceptable regimen for ART-naive patients due to its limited experience with regimens other than ZDV/3TC, its cost (requires tropism assay prior to use), and requirement for twice-daily dosing

Fusion Inhibitor-based Regimens

Enfuvirtide (T20)

  • An HIV-1 fusion inhibitor, is a treatment option for inclusion in a regimen when drug resistance to a previously given ART regimen is confirmed

Other Antiretroviral Regimens for Initial Therapy When Abacavir or Tenofovir Cannot Be Used

Darunavir/Ritonavir + Raltegravir (DRV/r + RAL)

  • Considered in patients with HIV RNA <100,000 copies/mL, CD4 cell counts >200 cells/mm3 and those who cannot take either TAF or ABC

Lopinavir/Ritonavir + Lamivudine (LPV/r + 3TC)

  • Recommended as initial therapy when both TDF and ABC are contraindicated
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