11. Managing Antiretrovirals in a Hospitalized Patient

Overview

The use of antiretrovirals (ARVs) in the hospitalized patient can be complex. It is always appropriate to ask for help from an HIV specialist or ID pharmacist. Hivinsite.ucsf.edu and www.AIDSmeds.com are excellent resources for dosing and checking drug interactions. If you are at ZSFG, the inpatient HIV/AIDS Consult Service (443-4601) is always on call to assist you. If you are at Parnassus or the VA, the ID consult service or ID pharmacist can help with questions related to ARVs in the inpatient setting.

General Principles

  • Most ARV regimens have a combination of 2 nucleoside reverse transcriptase inhibitors (NRTIs) plus either a:
  1. Protease-inhibitor (PI), or
  2. Non-nucleoside reverse transcriptase inhibitor (NNRTI), or
  3. Integrase strand transfer inhibitor (INSTI)
  • The most recent DHHS guidelines in 2019 recommend an INSTI-based regimen as first line for treatment-naïve patients
  • The most common ARVs used are (see table for abbreviations):
    • NRTI combinations: TDF/FTC, TAF/FTC, or ABC/3TC
    • Boosted PIs: DRV/r or ATV/r
    • INSTI: RAL, DTG, or BIC
  • In almost all instances, ARVs should be continued when a patient is admitted to the hospital
  • In the setting of acute renal failure or significant hepatic dysfunction, consult ID, HIV/AIDS Service, or ID pharmacy for appropriate dose adjustments
  • If the patient is intubated or unable to swallow pills, ARVs can usually be delivered via feeding tube or sometimes crushed or given as a liquid. Consult with HIV, ID, or ID pharmacy for assistance
  • Only one ARV (atazanavir; brand name Reyataz®) is contraindicated with concomitant administration of PPIs. H2 blockers can be used with atazanavir in the hospital, but should be spaced out from the atazanavir administration by at least 2 hours (preferably 12)

Toxic Effects of ARVs

  • Abacavir (NRTI) can be associated with systemic hypersensitivity syndrome (HSR)
    • Presents with fever, rash, nausea, headache, dyspnea, or SIRS
    • Hypersensitivity syndrome is now rare as all patients should be tested for the HLA-B5701 polymorphism (associated with HSR) prior to starting abacavir
  • All ARVs can be hepatotoxic, but darunavir (PI, Prezista®) and nevirapine (NNRTI, Viramune®) are of particular concern for this toxicity
  • Some NRTIs can cause lactic acidosis, hepatoxicity, and hepatic steatosis, but this syndrome is very rare in the current setting where “d-drugs” (d4T, ddI and even AZT) are rarely used
  • Tenofovir (NRTI, Viread®) can cause proximal tubular wasting (manifested initially by phosphaturia and hypophosphatemia) or creatinine elevations
  • Raltegravir (INSTI, Isentress®), is generally well tolerated, but patients can develop CK elevations (and even frank myositis)

Drug

Adverse Events

Comments

NRTIs

    

Abacavir (ABC)

Hypersensitivity syndrome (fever, myalgia, malaise, nausea, vomiting, symptoms suggestive of upper respiratory tract infection, anorexia). Can also cause GI upset, rashes.

Risk of hypersensitivity related to certain genetic factors, particularly HLA B*5701. In case of hypersensitivity syndrome, abacavir must be discontinued permanently, re-challenge can be fatal.

Emtricitabine (FTC)

Headache, nausea, insomnia. Hyperpigmentation of palms and soles (occurs most frequently in dark-skinned people). All of these side effects are rare.

Adjust dosage for renal insufficiency.

Lamivudine (3TC)

Well tolerated but can cause headache, dry mouth.

Adjust dosage for renal insufficiency.

Tenofovir disoproxil fumarate (TDF)

Acute/chronic renal insufficiency, Fanconi syndrome, proximal tubular wasting (without Fanconi), bone density loss.

Adjust dosage for renal insufficiency. Consider checking serum phosphate levels on this medication.

Tenofovir alafenamide (TAF)

Acute/chronic renal insufficiency, Fanconi syndrome, proximal tubular wasting (without Fanconi), bone density loss (less common than with TDF).

Not recommended with CrCl < 15.

Zidovudine (AZT)

Anemia, neutropenia, fatigue, malaise, headache, GI upset, myalgia, myopathy, hyperpigmentation of skin and nails.

Fatigue, nausea, headache, and myalgia usually resolve 2-4 weeks after initiation. Adjust dosage for renal insufficiency or failure.

NNRTIs

    

Efavirenz (EFV)

Abnormal dreams, drowsiness, dizziness, confusion, hyperlipidemia, elevations in LFTs.

Central nervous system symptoms are common; severity usually decreases within 2-4 weeks. Contraindicated during pregnancy and for use by women who may become pregnant.

Etravirine (ETR)

Elevations in LFTs, rash (more common in women).

Tablets may be dissolved in water. Has significant interactions with many other drugs.

Nevirapine (NVP)

Elevations in LFTs, can progress to liver failure, rash which can be severe (SJS).

Most rash develops within first 6 weeks of therapy so dose is increased slowly; rash is most common in women; hepatotoxicity may be life threatening.

PIs

    

Atazanavir (ATV)

Indirect hyperbilirubinemia (benign), jaundice, elevations in LFTs, PR interval prolongation.

Proton pump inhibitors interfere with atazanavir absorption and are contraindicated. Asymptomatic hyperbilirubinemia does not require discontinuation. May have less effect than other PIs on lipid levels.

Darunavir (DRV)

Rash, elevations in LFTs.

Increases pravastatin (and other statin) levels; no significant interaction with atorvastatin; sulfa moiety so don’t use in patients with SJS in past to sulfa drugs.

Lopinavir/ritonavir (LPV/r)

Diarrhea, nausea, vomiting, dyslipidemia, elevations in LFTs, taste alteration.

Available in tablets or oral solution (oral solution contains 42% alcohol); contraindicated with lovastatin and simvastatin; raises cholesterol levels more than other PIs.

Integrase Inhibitors

    

Raltegravir (RAL)

Nausea, diarrhea, flatulence, transaminitis, headache, dizziness, abnormal dreams, pruritus, rash, fatigue, muscle pain.

Do not co-administer with cations (space administration by at least 2 hours).

Dolutegravir (DTG)

Transaminitis, myositis, leukopenia.

Do not co-administer with cations.

Elvitegravir-Cobicistat

(EVG/c)

Increased serum creatinine, proteinuria, nausea, diarrhea, headache.

Avoid use if CrCl <70mL/min, multiple drug-drug interactions, do not co-administer with cations (space administration by at least 4 hours).

 

Bictegravir (BIC)

Nausea/diarrhea, headache, increased serum creatinine, rash, weight gain.

Substrate of CYP3A4 + UGT1A1 mediated glucuronidation. Rifampin/rifapentine may substantially decrease bictegravir plasma levels and are contraindicated.

Chart adapted from McNicholl, hivinsite.ucsf.edu

Key Points

  • ARVs should be continued in most hospitalized patients
  • Changes in ARVs or discontinuation should be done in consultation with HIV/ID specialists

Huang L, Quartin A, Jones D, et al. Intensive care of patients with HIV infection. N Engl J Med 2006;355:173-181

Mandell GL, Bennett JE, Dolin R. Principles and Practice of Infectious Diseases, Sixth Edition. Churchill Livingstone;2005.

Commers, T., Swindells, S., Sayles, H., Gross, A., Devetten, M., Sandkovsky, U., Antiretroviral and Medication Errors in Hospitalized HIV-Positive Patients. Ann Pharmacother (2014) 48 (8): 998-1010

DHHS Panel on Antiretroviral Guidelines for Adults and Adolescents — A Working Group of the Office of AIDS Research Advisory Council (OARAC). Guidelines for the use of antiretroviral agents in adults and adolescents with HIV. AIDSinfo. 2019 Dec 18. (https://www.aidsinfo.nih.gov/contentfiles/lvguidelines/adultandadolescentgl.pdf)

Key words: ARVs, HIV, HAART, antiretroviral, AIDS