II. Precautions

  1. Obtain Genotypic Antiretroviral Resistance Testing (GART) before starting therapy (and if failing therapy)
    1. See Genotypic Antiretroviral Resistance Testing
    2. Consider repeating resistance testing if failure to reach or maintain HIV RNA <200 copies/ml
  2. Despite HIV Antiretroviral therapy high efficacy (see below), it is underutilized
    1. Only half of the 1.2 million patients with HIV in U.S. (2015) were adequately treated with Antiretrovirals
    2. Woodring (2015) Natl Health Stat Report (83):1-13 [PubMed]
  3. Compliance is critical to suppress viral load (<500 c/ml)
    1. Adherence of 95% to drug regimen: 81% success rate
    2. Adherence of 90-95% to drug regimen: 64% success rate
    3. Adherence of 80-90% to drug regimen: 50% success rate
    4. Adherence of 70-80% to drug regimen: 24% success rate
    5. Adherence of <70% to drug regimen: 6% success rate
  4. Hospitalizations are high risk for Antiretroviral medication errors (85% of HIV patients)
    1. HIV Patients should be encouraged to bring their Antiretrovirals to hospital
    2. Many Antiretrovirals are substituted during admission for formulary options
    3. Consider infectious disease Consultation
    4. Adjust adntiretroviral doses for reduced Renal Function (esp. GFR <50 ml/min)
    5. On hospital discharge, arrange phone follow-up at 2 days, and clinic visit at 7-14 days
    6. Be aware of antiretroviral Drug Interactions
      1. Azole Antifungals
      2. Anticoagulants
      3. Anticonvulsants
      4. Antacids
      5. Calcium, Magnesium or Zinc
    7. References
      1. (2017) Presc Lett 24(5): 26-7

III. Pearls: Better compliance

  1. Compliance is critical to prevent drug resistance
    1. Set up reminders to take medications
      1. Alarm clock
      2. Pill box
      3. Place medication on night stand
    2. Anticipatory guidance that adverse effects are common
    3. Emphasize risks of nonadherence (drug resistance, fewer treatment options later)
  2. Patient forgets to take dose
    1. Take dose as soon as remembered
    2. Take next dose if time (do not double dose)
  3. Patient experiences adverse effects
    1. Call primary doctor or pharmacist
    2. Do not stop just one Anti-retroviral medication
      1. Stop all Anti-retrovirals, or stop none
      2. Prevents developing resistance to Antiretrovirals
    3. Antiretrovirals may taste awful
      1. Pediatric HIV patients may require Gastrostomy Tubes to stay on regimen
  4. Patient traveling
    1. Gradually adjust dosing to the next time zone
    2. Ritonavir may be un-refrigerated for 30 days
  5. Understand that cost is very expensive: $1000/month
  6. Consider combination pills that reduce number per day
    1. See combinations listed below
    2. Truvada or Descovy (Tenofovir-TDF or TAF 300 mg AND Emtricitabine-Emtriva-FTC 200 mg) once daily
    3. Combivir (AZT/3TC) bid with Efavirenz qhs
    4. Trizavir (AZT/3TC/Abacavir) one orally twice daily
  7. Consider monthly injection in those achieving stable viral suppression
    1. Cabenuva (Cabotegravir and Rilpivirine) IM monthly

IV. Preparations

  1. Nucleotide-Nucleoside Reverse Transcriptase Inhibitor (nRTI)
    1. Abacavir (Ziagen, ABC)
      1. Contraindicated in HLA-B*5701 positive patient
      2. Relatively contraindicated if high cardiovascular risk or HIV RNA >100,000 copies/ml pre-treatment
    2. Didanosine (Videx EC, ddI)
    3. Emtricitabine (FTC)
    4. Lamivudine (Epivir, 3TC)
    5. Stavudine (Zerit, d4T)
    6. Zalcitabine (Hivid, ddC)
    7. Zidovudine (Retrovir, ZDV or AZT)
    8. Tenofovir (Viread, TDF or TAF)
  2. Nonnucleoside Reverse Transcriptase Inhibitor (NNRTI)
    1. Delavirdine (Rescriptor)
    2. Efavirenz (Sustiva, EFV)
      1. Efavirenz (EFV) is absolutely contraindicated in first trimester pregnancy (or if unreliable Contraception)
    3. Etravirine (Intelence)
    4. Nevirapine (Viramune, NVP)
    5. Rilpivirine (Endurant)
  3. Protease Inhibitor (PI) - suffix '/r' added when combined with Ritonavir
    1. Amprenavir (Agenerase)
    2. Atazanavir (Reyataz, ATV or ATV/r)
      1. Contraindicated in high dose Proton Pump Inhibitor (e.g. Omeprazole >20 mg daily)
    3. Darunavir (DRV or DRV/r)
    4. Fosamprenavir (FPV or FPV/r)
    5. Indinavir (Crixivan)
    6. Lopinavir with Ritonavir (Kaletra, LPV/r)
    7. Nelfinavir (Viracept)
    8. Ritonavir (Norvir, r)
    9. Saquinavir (Fortovase)
    10. Saquinavir mesylate (Invirase)
    11. Tiprinavir (Aptivus)
  4. Entry Inhibitor (Coreceptor Antagonist)
    1. Maraviroc (Selzentry)
  5. Fusion Inhibitor
    1. Enfuvirtide (Fuzeon)
  6. Integrase Strand Transfer Inhibitor (InSTI)
    1. Raltegravir (Isentress, RAL)
    2. Elvitegravir (EVG) used with Cobicistat (Ritonavir-like booster)
    3. Dolutegravir (Trivicay, DTG)
    4. Bictegravir (BIC)

V. Preparations: Combination

  1. Atripla
    1. Efavirenz (EFV), Emtricitabine (FTC) and Tenofovir (TDF)
  2. Combivir
    1. Lamivudine (3TC) and Zidovudine (ZDV)
  3. Epzicom
    1. Abacavir (ABC) and Lamivudine (3TC)
  4. Trizivir
    1. Abacavir (ABC), Lamivudine (3TC), and Zidovudine (ZDV)
  5. Triumeq
    1. Dolutegravir (Trivicay) AND Epzicom (Abacavir and Lamivudine)
  6. Dovato
    1. Dolutegravir (Trivicay) and Lamivudine (3TC)
  7. Descovy (or Truvada)
    1. Emtricitabine (FTC) and Tenofovir (TAF in Descovy, or TDF in Truvada)
    2. TAF formulation in Descovy is preferred due to less renal and BMD toxicity
  8. Genvoya (or Stribild)
    1. Elvitegravir/Cobicistat (EVG) and Emtricitabine (FTC) and Tenofovir (TAF in Genvoya, or TDF in Stribild)
    2. Creatinine Clearance must be >70 ml/min/1.73m2 (especially due to Cobicistat which increase Serum Creatinine)
    3. TAF formulation in Genvoya is preferred due to less renal and BMD toxicity
  9. Biktarvy
    1. Emtricitabine (FTC), Bictegravir (BIC) and Tenofovir (TAF)
    2. Fewer Drug Interactions than Genoya and no Genetic Testing needed before use
    3. Contraindicated for Creatinine Clearance <30 ml/min
    4. Avoid with high dose NSAIDS (Nephrotoxicity Risk), and within 2 hours of Antacid salts (Mg, Ca, Al)
  10. Juluca
    1. Combines the InSTI, Dolutegravir (Tivicay) with the NNRTI, Rilpivirine (Endurant) taken once daily

VI. Indications: Initiation of Antiretroviral therapy (Combination Antiretroviral Therapy or CART)

  1. Indications: Early Therapy
    1. Combination Antiretroviral Therapy (CART) is now recommended at initial diagnosis
      1. Regardless of CD4 Count, age, comorbidity or HIV Viral Load
      2. Based on International Antiviral Society (2012, U.S.) Guidelines
    2. Benefits of early therapy
      1. Lowers HIV Viral Loads to nearly undetectable levels
      2. Community-based prevention (decreased transmission rates)
    3. Risks of early initiation of therapy
      1. Increased Antiretroviral drug resistance due to noncompliance
      2. Greater risk of longterm Antiretroviral therapy adverse effects and Drug Interactions
    4. Thompson (2012) JAMA 308(4): 387-402 [PubMed]
  2. Other indications based on labs
    1. CD4 Count < 350 (<500 per prior IAS guidelines)
    2. Rapid decline in CD4 Count >100/year
    3. Viral load >100,000 copies/ml
  3. Other indications based on comorbidity
    1. AIDS Defining Illness (start within 2 weeks)
      1. Exception: Tuberculosis and Cryptococcal Meningitis require a delayed start and tailored CART therapy
        1. Increased risk of Immune Reconstitution Inflammatory Syndrome
        2. Severe inflammatory response to infection when immune response is Restored to HIV patients
    2. Pregnancy
    3. HIV Associated Nephropathy
    4. Hepatitis B coninfection (also for Hepatitis C per IAS )
    5. Symptomatic HIV
    6. Age over 60 years
    7. Cardiovascular disease
    8. High risk for HIV Transmission

VII. Labs: Before starting treatment

  1. HIV Viral Load (HIV-1 RNA)
  2. CD4 Cell Count
  3. Pregnancy Test
  4. HIV Genotype for NRTI, non-NRTI, Protease Inhibitors
  5. Screening for active Viral Hepatitis (Hepatitis A, Hepatitis B, Hepatitis C)
    1. Many of the Combination Medications when stopped, risk a flare of coinfected Hepatitis B or Hepatitis C
  6. Screening for Sexually Transmitted Infection (e.g. Gonorrhea PCR, Chlamydia PCR, Syphilis)
  7. Tuberculosis Screening (and repeat annually depending on risk)
  8. Adverse effects of HIV Medications
    1. Lipid Profile
    2. Compled blood count
    3. Comprehensive metabolic panel
      1. Serum Glucose (or Hemoglobin A1C)
      2. Hepatic profile
      3. Serum Creatinine
  9. Other labs
    1. HLA-B*5701 Allele (if prescribing Abacavir)

VIII. Approach: Preferred agents for therapy-naive non-pregnant patients

  1. Based on strong quality data from randomized controlled trials (A-I as of 2018)
    1. Many other protocols supported by non-AI level evidence are available (see resources below)
    2. Preferred agent if baseline Genotypic Antiretroviral Resistance Testing not yet available
      1. Bictegravir AND Tenofovir Alafenamide AND Emtricitabine (Biktarvy)
      2. Dolutegravir (Tivicay) based regimens
    3. Each agent has specific GFR-related containdications below which they should not be used (30-60 ml/min)
  2. First-Line regimens: Integrase Strand Transfer Inhibitor Based Therapy
    1. Bictegravir AND Tenofovir Alafenamide AND Emtricitabine (Biktarvy)
      1. Avoid if Creatinine Clearance <30 ml/min
    2. Dolutegravir AND Abacavir AND Lamivudine (Triumeq)
      1. Avoid if HLA-B*5701 positive (due to Abacavir)
      2. Avoid if Creatinine Clearance <50 ml/min
    3. Dolutegravir (Tivicay) AND one of the following
      1. Tenofovir alefenamide/Emtricitabine (Descovy) or
      2. Emtricitabine/Tenofovir disopoxil fumarate (Truvada) or
      3. Lamivudine/Tenofovir disopoxil fumarate (Cimduo)
  3. Alternative regimens: Integrase Strand Transfer Inhibitor Based Therapy with two medication combinations
    1. Dolutegravir and Lamivudine (Dovato)
      1. Contraindications
        1. Hepatitis B coninfection
        2. Genotypic Antiretroviral Resistance Testing not yet available
        3. HIV RNA >500k copies on initial viral load
        4. GFR <50 ml/min
  4. Alternative regimens: Integrase Strand Transfer Inhibitor Based Therapy
    1. Elvitegravir AND cobicistat AND Tenofovir alefenamide AND Emtricitabine (Genvoya)
      1. Genvoya is preferred over Stribild
      2. Less renal and Bone Mineral Density (BMD) toxicity (see above)
    2. Elvitegravir AND cobicistat AND Tenofovir disopoxil fumarate AND Emtricitabine (Stribild)
    3. Raltegravir (Isentress) AND one of the following
      1. Emcitrabine AND Tenofovir disopoxil fumarate or
      2. Emcitrabine AND Tenofovir Alafenamide or
      3. Lamivudine AND Tenofovir disopoxil fumarate
  5. Alternative regimens: Protease Inhibitor-Based
    1. Darunavir/cobicistat (Prezcobiz) AND
      1. Tenofovir alefenamide/Emtricitabine (Descovy) OR
      2. Tenofovir disopoxil fumarate/Emtricitabine (Truvada)
    2. Darunavir (Prezista) AND Ritonavir (Norvir or /r) AND
      1. Tenofovir alefenamide/Emtricitabine (Descovy) OR
      2. Tenofovir disopoxil fumarate/Emtricitabine (Truvada)
  6. Alternative regimens: NNRTI-Based
    1. Efavirenz AND Tenofovir disopoxil fumarate AND Emtricitabine (Atripla)
      1. NNRTI based therapy with Atripla was previously first-line therapy prior to 2015
  7. Other NNRTI-Based Alternative Regimens (if HIV RNA <100,000 and CD4 Count >200 cells/ul)
    1. Rilpivirine AND Tenofovir Alafenamide AND Emtricitabine (Odefsey)
    2. Rilpivirine AND Tenofovir disopoxil fumarate AND Emtricitabine (Complera)

IX. Approach: Preferred agents for therapy-naive pregnant patients

  1. Consult perinatal specialist (also see resources below)
  2. Antiretroviral therapy should be used in pregnancy for benefit of both the mother and the fetus
  3. Based on strong quality data from randomized controlled trials (A-I, as of 2014)
  4. Agent 1: Nucleoside-Nucleotide Reverse Transcriptase Inhibitor (NRTI)
    1. Lamivudine (3TC)
  5. Agent 2: Nucleoside-Nucleotide Reverse Transcriptase Inhibitor (NRTI)
    1. Zidovudine (ZDV)
  6. Agent 3: Protease Inhibitor (see precautions below)
    1. Lopinavir with Ritonavir (LPV/r)
  7. Precautions
    1. Efavirenz (EFV) is contraindicated in first trimester pregnancy or in women with unreliable Contraception
    2. Dolutegravir
      1. Risk of Neural Tube Defects (avoid in preconception and first trimester)
      2. Preferred Integrase Strand Transfer Inhibitor AFTER first trimester due to safety, efficacy
    3. Darunavir/cobicistat and atazanavir/cobicistat are NOT recommended for use in pregnancy (high failure rates)
    4. Many older Protease Inhibitors are not recommended in pregnancy (lower efficacy, toxicity risk)

X. Monitoring

  1. Obtain viral load 1 month (2-8 weeks) after initiating therapy and after any treatment change
    1. Repeat every 4-8 weeks until viral load undetectable
    2. When on stable therapy, repeat every 3-4 months for 2 years, then every 6 months
  2. Obtain CD4 Count 3 months after initiating Antiretroviral therapy
    1. Then obtain CD4 Count every 3-6 months for 2 years, and then every 12 months if CD4>300 cells/uL
    2. CD4 Count is optional if CD4 Count is consistently >500 cell/uL for 2 years, and suppressed viral load
  3. Other lab monitoring
    1. Comprehensive metabolic panel (renal profile, hepatic profile, Serum Glucose, Serum Albumin)
      1. Obtain at baseline, at 2-8 weeks and then at 3-6 months
      2. Consider Hemoglobin A1C yearly
    2. Complete Blood Count with differential
      1. Obtain at baseline, 3-6 months, then every 12 months (if not monitoring CD4 Counts)
    3. Fasting Lipid Profile
      1. Obtain at baseline and then yearly
  4. Goal optimal viral suppression
    1. Viral load falls by >0.5 log copies/ml OR falls below detectable level (20-75 copies/ml)
    2. Typically achieved by 8-24 weeks
    3. Brief rises in viral load may occur, but consider resistance or noncompliance if sustained
  5. Failure to decrease viral load to undetectable levels by 8-24 weeks
    1. Address compliance (see above)
    2. Consider change in therapy
    3. Consult HIV specialist
    4. See Genotypic Antiretroviral Resistance Testing
    5. Consider repeat Genotypic Antiretroviral Resistance Testing if unable to maintain HIV RNA <200 copies/ml
  6. Predictors of decreased HIV progression
    1. Viral load decreases by >0.5 log copies/ml or becomes undetectable
    2. CD4 Count increases >200 cells/mm3
      1. CD4 Count lags viral load in response to therapy
      2. Expect CD4 Count increases of 50 to 150 cells/mm3 per year until reaching steady state
  7. Reference
    1. Kitchen (2001) Clin Infect Dis 33:466-72 [PubMed]

XI. Efficacy: Retroviral therapy payoff is excellent

  1. Antiretroviral therapy results in excellent key clinical outcomes
    1. Near normal Life Expectancy
    2. Prevents clinical progression to advanced HIV disease or AIDS
    3. Reduces transmission risk
  2. Dollars denote cost per life saved
    1. Antiretroviral therapy: $10,000 to $18,000
    2. HMG CoA Reductase Inhibitors: $21,000
    3. Mammogram: $30,000
    4. Flexible Sigmoidoscopy and FOBT: $43,000
    5. Hemodialysis: $50,000
    6. Warfarin for Atrial Fibrillation: $110,000
    7. Prostate Cancer Screening: $113,000
    8. Coronary Artery Bypass Graft: $113,000

XII. Drug Interactions

  1. Antiretroviral Drug Interactions are common (a few examples listed below)
    1. Protease Inhibitors and Simvastatin, Lovastatin, apixiban, Rivaroxaban
    2. OTC medication interactions (e.g. iron, Antacids, Proton Pump Inhibitors)
  2. Interactions often lower Antiretroviral concentrations
  3. Drug Interactions frequently cause viral resistance
  4. Address potential interactions when starting new agent

XIII. Adverse Effects

  1. See Immune Reconstitution Inflammatory Syndrome
  2. See specific agents for contraindications, adverse effects and required monitoring

XIV. Resources

  1. Guidelines for use of Antiretroviral agents in HIV-1 Infected Adults and Adolescents
    1. http://www.aidsinfo.nih.gov/ContentFiles/AdultandAdolescentGL.pdf
    2. Updated 1/10/11 and accessed 10/8/2011
  2. HIV-AIDS Treatment Information Service Website
    1. http://www.hivatis.org
  3. Stanford HIV Drug Resistance Database
    1. http://hivdb.stanford.edu/pages/links.html
  4. UCSF National HIV/AIDS Clinicians Consultation Center
    1. http://www.nccc.ucsf.edu/about_nccc/warmline/
    2. Phone (warmline): 800-933-3413
  5. NIH AIDS Info Site
    1. http://www.aidsinfo.nih.gov/
  6. Perinatal HIV/AIDS
    1. http://nccc.ucsf.edu/clinician-consultation/perinatal-hiv-aids/

Images: Related links to external sites (from Bing)

Related Studies

Cost: Medications

cart (on 5/17/2017 at Medicaid.Gov Survey of pharmacy drug pricing)
CARTEOLOL HCL 1% EYE DROPS Generic $1.24 per ml
CARTIA XT 120 MG CAPSULE Generic $0.30 each
CARTIA XT 180 MG CAPSULE Generic $0.30 each
CARTIA XT 240 MG CAPSULE Generic $0.39 each
CARTIA XT 300 MG CAPSULE Generic $0.70 each

Ontology: Anti-Retroviral Agents (C0599685)

Definition (MSH) Agents used to treat RETROVIRIDAE INFECTIONS.
Concepts Pharmacologic Substance (T121)
MSH D044966
French Agents antirétroviraux, Médicaments antirétroviraux, Antirétroviraux, ARV (Antirétroviraux), Anti-rétroviral, Anti-rétroviraux, Agent antirétroviral, Antirétroviral
Swedish Antiretovirala medel
English ANTIRETROVIRAL AGENTS, antiretroviral agent, agents antiretroviral, anti retroviral agents, antiretroviral agents, Antiretroviral agents, Agents, Anti-Retroviral, Anti Retroviral Agents, Antiretroviral Agents, Agents, Antiretroviral, Anti-Retroviral Agents
Czech antiretrovirové látky
Finnish Retroviruslääkkeet
Japanese 抗レトロウイルス剤
Polish Leki przeciwretrowirusowe
Spanish Antirretrovirales, ARV, Antirretrovíricos, Fármacos Antirretrovirales, Fármacos Antirretrovíricos, Agentes Antirretrovirales, Agentes Antirretrovíricos, Agentes Anti Retrovirales
Portuguese Antirretrovirais, ARV, Agentes Antirretrovirais, Medicamentos Antirretrovirais, Fármacos Antirretrovirais
German Antiretrovirale Mittel
Italian Agenti antiretrovirali

Ontology: Antiretroviral Therapy, Highly Active (C0887947)

Definition (NCI_NCI-GLOSS) Treatment for human immunodeficiency virus (HIV) infection that uses a combination of several antiretroviral drugs. The drugs inhibit the ability of the virus to multiply in the body, and they slow down the development of AIDS.
Definition (NCI) Drug therapy which targets retrovirus function by multiple mechanisms.
Definition (MSH) Drug regimens, for patients with HIV INFECTIONS, that aggressively suppress HIV replication. The regimens usually involve administration of three or more different drugs including a protease inhibitor.
Definition (CSP) drug regimens, for patients with HIV infection, that aggressively suppress HIV replication; regimens usually involve administration of three or more different drugs including a protease inhibitor.
Concepts Therapeutic or Preventive Procedure (T061)
MSH D023241
SnomedCT 416234007
Swedish Antiretrovirusterapi, aggressiv
English HIGHLY ACTIVE ANTIRETROVIRAL THER, ANTIRETROVIRAL THER HIGHLY ACTIVE, haart, Antiretroviral Therapy, Highly Active, Highly Active Antiretroviral Therapy, HAART, highly active antiretroviral therapy, HAART-Highly active anti-retroviral therapy, Highly active anti-retroviral therapy (procedure), Highly active anti-retroviral therapy, highly active retroviral therapy, HAART (highly active antiretroviral therapy)
Czech HAART, vysoce aktivní antiretrovirová terapie
Finnish Hyvin aktiiviset antiretroviraaliset hoidot
Italian HAART, Terapia aggressiva antiretrovirus
Japanese 高活性抗レトロウイルス療法, 抗レトロウイルス療法-高活性
French TARHA, HAART (Highly Active Antiretroviral Therapy), Thérapie antirétrovirale hautement active, Traitement antirétroviral hautement actif
Polish Leczenie przeciwretrowirusowe wysokoaktywne, HAART, Terapia antyretrowirusowa wysokoaktywna
Norwegian Høyaktiv antiretroviral terapi, Antiretroviral terapi, høyaktiv, HAART
Portuguese Terapia Antirretroviral de Alta Atividade, Terapia de Alta Atividade Antirretroviral, HAART
German Antiretrovirale Therapie, hochaktive, HAART, Hochaktive antiretrovirale Therapie
Dutch 'Antiretroviral therapy, highly active', 'Highly active antiretroviral therapy', HAART
Spanish TARAA, HAART, terapia antirretroviral altamente activa (procedimiento), terapia antirretroviral altamente activa, terapia antirretroviral muy activa, tratamiento antirretroviral de gran actividad (TARGA), Terapia Antirretroviral Altamente Activa, Terapia de Alta Actividad Antirretroviral

Ontology: Antiretroviral therapy (C1963724)

Definition (NCI_NCI-GLOSS) Treatment with drugs that inhibit the ability of the human immunodeficiency virus (HIV) or other types of retroviruses to multiply in the body.
Concepts Therapeutic or Preventive Procedure (T061)
LNC LP66375-4, MTHU000163
Spanish Tratamiento antirretroviral
French Traitement antirétroviral
Dutch amtiretrovirale therapie
Portuguese Terapia antiretroviral
German antiretrovirale Therapie
Italian Terapia antiretrovirale
Japanese コウレトロウイルスリョウホウ, 抗レトロウイルス療法
Czech Antiretrovirová terapie
English ART, Antiretroviral therapy, Antiretroviral Therapy, antiretroviral therapy
Hungarian Antiretrovírusos terápia

Ontology: Antiretroviral/Anti HIV (C1979629)

Concepts Pharmacologic Substance (T121)
LNC LP31472-1
English Antiretroviral/Anti HIV

Ontology: antiretroviral combinations (C2193864)

Concepts Pharmacologic Substance (T121)
English antiretroviral combinations, antiretroviral combinations (medication)