Nucleoside analogue reverse transcriptase inhibitors Drug class effects: nausea, vomiting; elevations in liver transaminases/hepatitis; lactic acidosis with hepatic steatosis (potentially life-threatening); lipoatrophy; mitochondrial toxicity (e.g. myopathy, peripheral neuropathy)

Antiretroviral

Category of adverse effects/toxicity

Comments

Haemato- logical

Hepatic

Pancreatic

Skin

Metabolic

Nervous system

Abacavir

+

+++

+

+++

Lactic acidosis

+

Potentially fatal hypersensitivity reaction in 5% (see text); usually occurs in first six weeks of treatment.
Do not restart drug if hypersensitivity has occurred.

Didanosine

+

+++

+++

-

Lactic acidosis

++++

Pancreatitis (possible increase in combination with d4T; can be fatal) and peripheral neuropathy most common.
Nausea, diarrhoea (may be formulation-dependent).
Retinal pigmentation (<5%, asymptomatic, seen in children) and optic neuritis have been reported.
Potential increased risk of lactic acidosis/hepatic steatosis in pregnant women receiving ddI/d4T throughout pregnancy.

Lamivudine

++

++

+++

++

Lactic acidosis

+++

Well tolerated; headache, abdominal pain.
Pancreatitis may be more common in children who have advanced HIV disease.
Peripheral neuropathy, neutropenia, elevated transaminases most common.

Stavudine

+

++++

++++

-

Lactic acidosis(more frequent than with other NsRTIs, especially if given with ddI and/or hydroxyurea)

++++

Peripheral neuropathy, pancreatitis (may be increased with use in combination with ddI, rarely fatal) are the most common serious events.
Gastrointestinal effects: nausea, vomiting, abdominal pain.
Sleep disorders, increased energy/mania.
Rare occurrence of ascending neuromuscular weakness resembling Guillain-Barre syndrome.
Potential increased risk of lactic acidosis/hepatic steatosis in pregnant women receiving ddI/d4T throughout pregnancy.

Nucleoside analogue reverse transcriptase inhibitors Drug class effects: nausea, vomiting; elevations in liver transaminases/hepatitis; lactic acidosis with hepatic steatosis (potentially life-threatening); lipoatrophy; mitochondrial toxicity (e.g. myopathy, peripheral neuropathy)

Antiretroviral drug

Category of adverse effects/toxicity

Comments

Haemato- logical

Hepatic

Pancreatic

Skin

Metabolic

Nervous system

Zidovudine

+++

++

-

-

Lactic acidosis

-

Anaemia, neutropenia, increased transaminases most common. Macrocytosis almost 100%.
Subjective complaints: gastrointestinal intolerance, headache, insomnia (common but self-limited).
Blue to black discoloration of nails may occur. Myopathy 17%; cardiomyopathy rare.

Non-nucleoside reverse transcriptase inhibitors Drug class effects: rash, hepatitis

Antiretroviral drug

Category of adverse effects/toxicity

Comments

Haemato- logical

Hepatic

Pancreatic

Skin

Metabolic

Nervous system

Efavirenz

+

++

-

++++

Lactic acidosis

Modest increases in triglycerides and cholesterol

Rash in ~10% of patients, but rarely severe (<1%), Stevens-Johnson syndrome very rare.
Wide range of central nervous system problems (see text), often resolve in two to four weeks.
Increased risk of liver toxicity if prior hepatitis B or C.
Teratogenic in primates.

Nevirapine

++

+++

-

++++

-

+

Rash occurs in ~16% of patients; rash may may be severe (8%); Stevens-Johnson syndrome or life- threatening rash seen in 0.3%.
Use of two-week low-dose lead-in period(i.e. 200 mg once daily for two weeks, then escalation to 200 mg twice daily) reduces the incidence of rash. If mild to moderate rash occurs during dose escalation, ARVs should be discontinued until rash resolves; when ARVs are restarted, NVP should be restarted in the initial lead-in dosing phase.
If mild to moderate rash occurs after the lead-in phase, NVP can be cautiously continued while rash observed or EFV can be substituted for NVP.
If severe rash, mucosal lesions or systemic symptoms, NVP should be permanently discontinued and use of NNRTIs avoided.
Increased risk of liver toxicity if prior hepatitis B or C; severe hepatitis, sometimes fatal, can occur.
Drug interactions.

Non-nucleoside reverse transcriptase inhibitors Drug class effects: rash, hepatitis

Antiretroviral drug

Category of adverse effects/toxicity

Comments

Haemato- logical

Hepatic

Pancreatic

Skin

Metabolic

Nervous system

Efavirenz

+

++

-

++++

Lactic acidosis

Modest increases in triglycerides and cholesterol

Rash in ~10% of patients, but rarely severe (<1%), Stevens-Johnson syndrome very rare.
Wide range of central nervous system problems (see text), often resolve in two to four weeks. Increased risk of liver toxicity if prior hepatitis B or C.
Teratogenic in primates.

Nevirapine

++

+++

-

++++

-

+

Rash occurs in ~16% of patients; rash may be severe(8%); Stevens-Johnson syndrome or life-threatening rash seen in 0.3%.
Use of two-week low-dose lead-in period(i.e. 200 mg once daily for two weeks, then escalation to 200 mg twice daily) reduces the incidence of rash. If mild to moderate rash occurs during dose escalation, ARVs should be discontinued until rash resolves; when ARVs are restarted, NVP should be restarted in the initial lead-in dosing phase.
If mild to moderate rash occurs after the lead-in phase, NVP can be cautiously continued while rash observed or EFV can be substituted for NVP.
If severe rash, mucosal lesions or systemic symptoms, NVP should be permanently discontinued and use of NNRTIs avoided.
Increased risk of liver toxicity if prior hepatitis B or C; severe hepatitis, sometimes fatal, can occur.
Drug interactions.

Protease inhibitors Drug class effects: insulin resistance, hyperglycaemia, new-onset diabetes mellitus including diabetic ketoacidosis; hyperlipidaemia (elevated triglyceride and cholesterol); fat redistribution (lipodystrophy); possible increased bleeding episodes in haemophiliacs; hepatitis; osteonecrosis, osteopenia/osteoporosis

Antiretroviral drug

Category of adverse effects/toxicity

Comments

Haemato- logical

Hepatic

Pancreatic

Skin

Metabolic

Nervous system

Indinavir

+

+++

-

-

Lipid, glucose abnormalities

-

Nephrolithiasis, 4-10%; adequate hydration must be ensured during therapy.
Gastrointestinal intolerance, nausea 10-15%; oesophageal reflux in 3%.
Indirect hyperbilirubinaemia, 10%.
Subjective complaints: headache, asthenia, blurred vision, dizziness, rash, metallic taste, thrombocytopenia, Retinoid-like effects: alopecia, dry skin/lips, ingrown nails.

Lopinavir/ ritonavir

+

++

+

++

Lipid, glucose abnormalities

++

Gastrointestinal intolerance, nausea, diarrhoea, headache and asthenia most common.
Oral solution contains 42% alcohol.

Nelfinavir

+

++

-

+

Lipid, glucose abnormalities

-

Diarrhoea common (10-30%) at start of therapy, often resolves on its own in a few days to weeks.
Powder contains 11.2 mg phenylalanine per g.

Saquinavir

+

++

-

+

Lipid, glucose abnormalities

-

Gastrointestinal intolerance, nausea, diarrhoea10-20% (more common with soft gel), dyspepsia.
Subjective symptoms: headache.
Elevated transaminase enzymes.

Key:

- not reported or very rare

+

<1%

++

1-4%

+++

5-9%

++++

>10%