Table. Classes of antiretroviral therapy.
| Antiretroviral class | Comments |
|---|---|
| Entry inhibitors | |
| Maraviroc (CCR5 antagonist) | • Not routinely used. • Only indicated for CCR5-tropic strains of HIV. |
| Fusion inhibitors | |
| Enfuviritide | • Not routinely used. • Twice daily subcutaneous injections, high rate of injection-site reactions. |
| Nucleoside and nucleotide reverse transcriptase inhibitors | |
| Abacavir | • Hypersensitivity reaction, check for HLA-B*5701 allele before prescribing. • Potential increased cardiovascular risk, avoid if cardiovascular risk factors. |
| Lamivudine Emtricitabine |
• Also used to treat hepatitis B in combination with tenofovir to avoid the development of hepatitis B virus resistance. • Generally well tolerated. |
| Tenofovir alafenamide | • Can cause renal toxicity – avoid if eGFR <30 mL/min. • Potential weight gain and raised lipids. • Drug interactions with rifampicin, rifabutin, phenytoin and phenobarbital (may reduce exposure to tenofovir). • Used with another drug to treat hepatitis B co-infection. |
| Tenofovir disoproxil fumarate | • Reduced renal function – avoid if eGFR <60 mL/min. Associated with renal tubulopathy and urine phosphate wasting. Monitor renal function. • Avoid nephrotoxic drugs e.g. NSAIDs. • Associated with decreases in bone mineral density and osteomalacia. Avoid in osteoporosis. • Used with another drug to treat hepatitis B co-infection. |
| Zidovudine | • Rarely used now. • Can cause anaemia. |
| Non-nucleoside reverse transcriptase inhibitors | |
| • Rilpivirine | • Take with a meal for optimal absorption. • Contraindicated with proton pump inhibitors (cause virological failure), H2-receptor antagonists and antacids. Should be dosed separately to rilpivirine. • Adverse effects include raised serum creatinine concentration without an effect on renal function, skin rash, QT prolongation on the ECG, exacerbation of psychiatric symptoms. • Drug interactions with carbamazepine, rifampicin, dexamethasone and St John’s wort. Avoid with other drugs that can increase risk of torsades de pointes. |
| Efavirenz | • Rarely used now. • Neuropsychiatric adverse effects are common, e.g. vivid dreams. Avoid if the patient has a history of psychiatric illness. Take on an empty stomach to reduce adverse effects. • Causes raised lipids. • Drug interactions with oral contraception, direct-acting oral anticoagulants (apixiban and rivaroxaban), rendering them ineffective. Avoid with other drugs that can increase risk of torsades de pointes. Reduces methadone concentrations, so may lead to withdrawal symptoms. |
| Nevirapine Etravirine |
• Rarely used now. • Nevirapine causes serious and potentially fatal toxicity (hepatotoxicity, Stevens-Johnson syndrome, toxic epidermal necrolysis). Reduces plasma concentrations of direct-acting oral anticoagulants (apixiban and rivaroxaban), rendering them ineffective. |
| Integrase strand inhibitors | |
| Bictegravir | • Raised serum creatinine concentration, nil effect on renal function. • Raised creatine kinase. • Concentration decreased by products containing polyvalent cations.* • CYP3A4 and UGT1A1 substrate, potential for drug–drug interactions e.g. with rifampicin. |
| Dolutegravir | • Raised serum creatinine concentration, nil effect on renal function. Hepatotoxicity, raised creatine kinase. • Neuropsychiatric adverse effects. • Concentration decreased by products containing polyvalent cations.* • Interaction with metformin – do not exceed metformin 1 g daily. • Interactions with phenytoin, phenobarbital, rifampicin, St John’s wort, carbamazepine. |
| Elvitegravir/cobicistat | • Take with food. • Lots of potential drug interactions due to cobicistat. • Raised lipids. • Raised serum creatine kinase concentration, monitor for myopathy and rhabdomyolysis. |
| Raltegravir | • Depression, suicidal ideation (rare – usually if pre-existing psychiatric conditions). Concentration decreased by products containing polyvalent cations.* • Statins – increased risk of rhabdomyolysis. • Rare cases of severe hypersensitivity reactions (Stevens-Johnson syndrome, toxic epidermal necrolysis). |
| Protease inhibitors† | |
| Darunavir | • Absorption is improved with food. • Skin rash, raised serum transaminases, raised lipids, potential cardiovascular risk. |
| Atazanavir | • Absorption depends on food and a low gastric pH. Absorption reduced with proton pump inhibitors which should be avoided. H2-receptor antagonists and antacids should be avoided or dosed apart. Adverse effects include jaundice, indirect hyperbilirubinaemia, cholethiasis, nephrolithiasis and prolongation of the PR interval on the ECG. |
| Indinavir | • Raised lipids. |
| Lopinovir | • Raised lipids. |
* Polyvalent cations include aluminium, calcium, iron, magnesium and zinc.
† All protease inhibitors are ‘boosted’ with either cobicistat or ritonavir which are inhibitors of CYP3A, increasing the concentrations of drugs metabolised through the same pathway. This interaction is seen with statins, phosphodiesterase 5 inhibitors, direct-acting oral anticoagulants, calcium channel blockers, beta blockers and some antiarrhythmic drugs (amiodarone and flecainide). Cushing’s syndrome has been reported in patients taking cobicistat or ritonavir with fluticasone, budesonide or mometasone, which are predominantly metabolised by CYP3A enzymes (inhaled, intranasal, intra-articular, topical, and intraocular corticosteroids). Beclomethasone is not metabolised by CYP3A4 and so is suitable to use.
eGFR estimated glomerular filtration rate
NSAIDs non-steroidal anti-inflammatory drugs
CYP cytochrome P450