ARV TOXICITY

ARV drugs can cause a wide range of toxicities, from mild to life threatening.

Active monitoring and management of toxicities and side effects is important not only to avoid negative medical outcome but also to ensure that they do not negatively affect adherence.

CATEGORY ACTION
Severe Life-
Threatening
Reactions
(e.g. SJS/TEN,
severe hepatitis
Immediately discontinue all ARV
drugs (possibly all drugs in general),
manage the medical event and
substitute the offending drug when the
patient is stabilised
Severe
Reactions
(e.g. Hepatitis,
anaemia)
Stop the offending drug and substitute
it without stopping the ART (if
clinically possible)
Moderate
Reactionsy
(Gynaecomastia,
lipodystrophy)
Substitute with a drug in the same
ARV class but with a different toxicity
profile, or with a drug in a different
class.Do not discontinue ART. Continuation
of ART as long as feasible. If
the patient does not improve on
symptomatic therapy, consider singledrug
substitution
Mild Reactions
(Headache,
minor rash,
nausea)
Do not discontinue or substitute ART.
Reassure the patient or caregiver that
while the reaction may be bothersome,
it does not require a change in therapy
and often it subsides in few weeks.
Provide support to mitigate the
adverse reactions as well as counseling
about the events
DRUG AND SIDE EFFECTS MANAGEMENT
Zidovudine (AZT)

Mild toxicities
Blue to black discoloration
of nails, nausea, and
headache.

Major toxicities

  • Anaemia, neutropenia
  • Lactic acidosis, fatty liver
  • Myopathy, liposystrophy
  • ? Severe vomiting
  • Diabetes mellitus
  • Avoid if Hb < 7.5 g/dL
  • Transfuse if needed
  • Replace with TDF or ABC
Nevirapine (NVP)

Mild toxicities

  • Skin rash

Major toxicities

  • Acute symptomatic
    hepatitis
  • Severe hypersensitivity
    (SJS, TEN)
  • Use loading dose (1/2
    dose for 2 weeks)
  • If mild: continue
    cautiously, give antihistamine
  • If severe: substitute with
    DTG
Dolutegravir (DTG)

Major toxicities

  • Hepatitis,
    hypersensitivity
  • Replace with ATV/r
Abacavir (ABC)

Major toxicities

  • Hypersensitivity reaction
  • Lactic acidosis and
    hepatosteatosis
  • Replace with TDF or AZT
Tenofovir (TDF)

Mild toxicity

  • Sleep disturbances,
    headache, dizziness,
    stomach upset

Major reaction

  • Renal dysfunction (weeks
    to months)
  • Reduced mineral density
  • Lactic acidosis, fatty liver
  • Subsitute with ABC
Efavirenz (EFV)

Mild toxicities
Dizziness, headache, sleep
disturbances, rash

Major toxicities

  • Pesistent CNS symptoms,
    confusion, psychosis,
    convulsions
  • Hepatitis, gynaecomastia
  • If mild rash and CNS
    disturbances, reassure
    and wait
  • If severe, replace with
    NVP/DTG.
Lopinavir/ritonavir (LPV/r)

Mild reaction

  • Gastrointestinal upset

Major reaction

  • Hepatotoxicity
  • Pancreatitis,
    dyslipidemia
  • ECG abnormalities
  • Patient unable to tolerate
    taste
  • Substitute with NVP
  • If dyslipidemia switch to
    ATV/r
  • Avoid in patients with
    ECG abnormalities.
Atazanavir/ritonavir
(ATV/r)
Mild toxicity

  • Benign unconjugated
    hyperbilirubinemia
  • Nephrolithiasis

Major toxicity

  • Dyslipidemia
  • ECG abnormalities
    (prolonged PR/QRS)
  • If hyperbilirubinemia,
    reassure
  • If dyslipidemia: treat with
    atorvastatin 10 mg
  • Use with caution in
    patient with ECG
    abnormalities
  • Increase hydration if
    history of kidney stones
Raltegravir (RAL)
Major reactions

  • Rhabdomyolisis,
    myopathy
Management

  • Switch to PI or etravirine