9.7. Antiretroviral therapy:

The use of a combination ARVs or highly active antiretroviral therapy (HAART) has been a major advance in the treatment of HIV infection. These drugs are classified into four classes according to the mechanisms of inhibition of viral replication (Table 9.2): reverse transcriptase enzyme inhibitors, protease enzyme inhibitors, integrase inhibitors and entry inhibitors.

9.7.1 Adverse effects:

Many adverse side effects are associated with ARVs and should be looked for during preoperative assessment. They can be divided broadly into four groups:

Mitochondrial dysfunction: lactic acidosis, hepatic toxicity, pancreatitis, peripheral neuropathy
Metabolic abnormalities: fat maldistribution and change in body habitus, dyslipidemia, hyperglycemia and insulin resistance, bone disorders e.g. osteoporosis and osteonecrosis
Bone marrow suppression: anemia, neutropenia and thrombocytopenia
Allergic reactions: skin rashes and hypersensitivity responses.

9.7.2 Antiretroviral drugs and their side effects

Class Sub class Drugs Side effects

Reverse transcriptase inhibitors Nucleoside/nucleotide analogues (NRTIs) Abacavir (ABC) Gastrointestinal disturbances, skin rash, myalgia

Didanosine (ddI) Peripheral neuropathy, pancreatitis, gastrointestinal disturbances

Lamivudine (3TC) Peripheral neuropathy, skin rash, gastrointestinal disturbances

Stavudine (d4T) Peripheral neuropathy, pancreatitis

Zidovudine (AZT, ZDV) Anemia, neutropenia, pancytopenia, headache, neuropathy, myopathy

Non-nucleotide reverse transcriptase Inhibitors (NNRTIs)

Efavirenz (EFV) Skin rash, GI disturbances, increased liver enzymes

Nevirapine (NVP) GI disturbances, increased liver enzymes, skin rash, P-450 enzyme induction

Protease inhibitors (PIs) Atazanavir GI disturbances, renal failure, hyperglycemia, skin rash, nephrolithiasis, unusual distribution of fat, inhibits cytochrome P-450

Lopinavir

Nelfinavir (NFV) GI disturbances, hyper-glycemia, lipodystrophy, inhibits cytochrome P-450

Ritonavir (RTV) GI disturbances, hyperglycemia, increased liver enzymes, lipo-dystrophy, inhibits cytochrome P-450

Saquinavir (SQV) GI disturbances, hyper- glycemia, lipodystrophy, inhibits cytochrome P-450

Amprenavir (APV) Skin rash, inhibits cytochrome P-450

Table 9:2 anti retroviral drugs and their side effects

Class	Sub class	Drugs	Side effects
Reverse transcriptase inhibitors	Nucleoside/nucleotide analogues (NRTIs)	Abacavir (ABC)	Gastrointestinal disturbances, skin rash, myalgia
		Didanosine (ddI)	Peripheral neuropathy, pancreatitis, gastrointestinal disturbances
		Lamivudine (3TC)	Peripheral neuropathy, skin rash, gastrointestinal disturbances
		Stavudine (d4T)	Peripheral neuropathy, pancreatitis
		Zidovudine (AZT, ZDV)	Anemia, neutropenia, pancytopenia, headache, neuropathy, myopathy
	Non-nucleotide reverse transcriptase Inhibitors (NNRTIs)
		Efavirenz (EFV)	Skin rash, GI disturbances, increased liver enzymes
		Nevirapine (NVP)	GI disturbances, increased liver enzymes, skin rash, P-450 enzyme induction
Protease inhibitors (PIs)		Atazanavir	GI disturbances, renal failure, hyperglycemia, skin rash, nephrolithiasis, unusual distribution of fat, inhibits cytochrome P-450
		Lopinavir
		Nelfinavir (NFV)	GI disturbances, hyper-glycemia, lipodystrophy, inhibits cytochrome P-450
		Ritonavir (RTV)	GI disturbances, hyperglycemia, increased liver enzymes, lipo-dystrophy, inhibits cytochrome P-450
		Saquinavir (SQV)	GI disturbances, hyper- glycemia, lipodystrophy, inhibits cytochrome P-450
		Amprenavir (APV)	Skin rash, inhibits cytochrome P-450

Adherence to antiretroviral therapy is of paramount importance, with adherence levels of below 95% being associated with increases in viral load and drug resistance. This naturally has implications for interruption of ARV therapy due to perioperative fasting. Fasting times should be kept to an absolute minimum.