Note: drugs that are more strongly associated with the listed toxicities appear in bold lettering.
Eto/Pto, PAS, Cfz, FQs, H, Lzd, E, Z
Abdominal pain is common and often benign; however, it may be an early symptom of severe adverse effects such as pancreatitis, hepatitis or lactic acidosis.
Central nervous system (CNS) toxicity
Cs, H, Eto/Pto, FQs
EFV has a high rate of CNS adverse effects (dizziness, impaired concentration, depersonalization, abnormal dreams, insomnia and confusion) in the first 2-3 weeks of use, but they typically resolve on their own. If they do not resolve, consider substitution of the agent. There are limited data on the use of EFV with Cs; concurrent use is accepted practice as long as there is frequent monitoring for CNS toxicity.
Cs, FQ, Eto/Pto
Severe depression can be seen in 2.4% of patients receiving EFV. Consider substitution of EFV if severe depression develops.
All protease inhibitors, ddI (buffered formulation)
Eto/Pto, PAS, FQs Amx/Clv, Ipm/Cln
Diarrhoea is common. Also consider opportunistic infections as a cause of diarrhoea, or Clostridium difficile (pseudomembranous colitis).
PI tend to cause insulin resistance and hyperglycaemia. Eto/Pto may cause hypoglycaemia and poor glucose regulation in diabetics.
Rule out more serious causes of headache such as bacterial or cryptococcal meningitis, toxo- plasmosis, etc. Use of analgesics (ibuprofen, paracetamol) and good hydration may help. Headaches secondary to AZT, EFV and Cs are usually self-limited.
|Hepatitis||NVP, EFV, all protease inhibitors (RTV)||Z, H, R, E, PAS, Eto/ Pto|
When severe, stop both the ART and TB medications, and restart the TB medications first.
|Hypothyroidism||d4T||Eto/Pto, PAS||Several studies show subclinical hypothyroidism associated with d4T.|
|Lactic acidosis||d4T, ddI, AZT, 3TC||Lzd||Early detection and management of hyperlactatemia in order to prevent development of lactic acidosis.|
Monitor blood counts regularly. Replace AZT if bone marrow suppression develops. Consider suspension of Lzd.
|Nausea and vomiting||RTV, d4T, NVP, and most others||Eto/Pto, PAS, Z, Amx/Clv, Cfz, Lzd, Ipm/Cln||Persistent vomiting may be a result of developing lactic acidosis (especially common with long-term d4T use) and/or hepatitis secondary to medications.|
TDF may cause renal injury with the characteristic features of Fanconi syndrome, hypophosphataemia, hypo-uricaemia, proteinuria, normoglycaemic glycosuria and, in some cases, acute renal failure.
|Optic neuritis||ddI||E, Eto/Pto, Lzd||Suspend agent responsible for optic neuritis permanently and replace with an agent that does not cause optic neuritis.|
|Pancreatitis||d4T, ddI||Lzd||Avoid concomitant use of these agents. If an agent causes pancreatitis, suspend it permanently and do not use any of the potentially pancreatitis-producing ARVs (d4T or ddI) in the future.|
|Peripheral neuropathy||d4T, ddI||Lzd, Cs, H, Eto/Pto, S, Km, Amk, Cm, E, FQs||Avoid use of d4T or ddI in combination with Cs or Lzd (increased risk of peripheral neuropathy).|
|QT prolongation||RTV boosted PI||Bdq, Cfz, Mfx, other FQs|
ABC, NVP, EFV, d4T and others
|All anti-TB drugs|
Do not re-challenge with ABC (risk of life-threatening anaphylaxis). Do not re-challenge with any agent that may have caused Stevens-Johnson syndrome.
Adapted from WHO Guidelines for the programmatic management of drug-resistant tuberculosis8.