HIV Antiretroviral Adverse Effects
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Direct answer
Antiretroviral adverse effects in HIV are largely class-specific, and knowing them guides the choice of regimen. NRTIs carry renal, marrow and mitochondrial risks, NNRTIs cause rash, liver and central nervous system effects, protease inhibitors cause metabolic and gastrointestinal problems, and integrase inhibitors cause weight gain. A few hazards are drug-specific, such as abacavir hypersensitivity and nevirapine skin and liver toxicity.
What you must remember
- Tenofovir: nephrotoxicity with proximal tubular injury and reduced GFR, along with bone mineral loss, so creatinine and phosphate are monitored.
- Zidovudine: bone marrow suppression causing anaemia and neutropenia, and myopathy with prolonged use.
- Stavudine and didanosine: peripheral neuropathy, pancreatitis and lactic acidosis, and both are largely phased out of current practice.
- Abacavir: hypersensitivity reaction linked to HLA-B*5701, so the allele is tested before starting the drug.
- Nevirapine: severe skin reactions including Stevens-Johnson syndrome, and hepatotoxicity, with higher risk in women and in those starting with higher CD4 counts.
- Efavirenz: central nervous system effects such as vivid dreams, insomnia and dizziness, which often settle over weeks.
- Protease inhibitors: lipodystrophy, dyslipidaemia and diarrhoea, while atazanavir causes indirect hyperbilirubinaemia and kidney stones.
- Dolutegravir: weight gain and insomnia, along with a creatinine rise that does not reflect a true fall in GFR.
Matching the drug to its hazard
Each class has a predictable toxicity profile, so the table below pairs a representative drug with its hallmark effect and the check that follows from it. The list is a teaching set, and the national guidance sets the actual regimen.
| Drug (class) | Key toxicity | Practical check |
|---|---|---|
| Tenofovir (NRTI) | Proximal tubulopathy, bone loss | Creatinine and phosphate |
| Zidovudine (NRTI) | Anaemia, neutropenia, myopathy | Full blood count |
| Abacavir (NRTI) | Hypersensitivity | HLA-B*5701 test before use |
| Efavirenz (NNRTI) | Vivid dreams, insomnia, dizziness | Ask about mood and sleep |
| Nevirapine (NNRTI) | Stevens-Johnson syndrome, hepatotoxicity | Lead-in dose and early review |
| Lopinavir-ritonavir (PI) | Diarrhoea, hyperlipidaemia, PR prolongation | Lipid profile |
| Atazanavir (PI) | Indirect hyperbilirubinaemia, kidney stones | Bilirubin and urine |
| Dolutegravir (INSTI) | Weight gain, insomnia | Weight and sleep review |
Most toxicities can be predicted from the class, so the clinician can plan monitoring before the drug is started. A drug-specific hazard such as the HLA-B*5701 link for abacavir, or the rash risk with nevirapine, needs its own test or early review. Indian national guidance has moved towards dolutegravir-based regimens, which are generally well tolerated, although weight gain must be discussed with the patient.
Where the exam tries to catch you
Examiners test whether the student recognises a benign laboratory artefact and does not stop a useful drug by mistake. The traps below are the errors that cost marks most often here.
- Trap: a creatinine rise on dolutegravir means true kidney injury Correct: dolutegravir blocks tubular creatinine secretion, so creatinine rises without a true fall in GFR.
- Trap: abacavir hypersensitivity can be ignored in a patient with no prior reaction Correct: HLA-B*5701 testing is done before starting abacavir, because the reaction can be severe on re-exposure.
- Trap: stopping lamivudine or tenofovir in a patient with hepatitis B is harmless Correct: these drugs also suppress hepatitis B, so stopping them can cause a severe flare.
Frequently asked questions
Which antiretroviral drug causes hypersensitivity linked to HLA-B*5701?
Abacavir causes the hypersensitivity reaction, and the risk is linked to the HLA-B*5701 allele. Patients are tested for this allele before abacavir is started, and a positive result means the drug is avoided.
Which antiretroviral drug is most associated with nephrotoxicity in HIV therapy?
Tenofovir disoproxil fumarate is the antiretroviral most associated with nephrotoxicity, causing proximal tubular injury and reduced GFR. Renal function and phosphate are monitored during treatment, and tenofovir alafenamide has a lower renal toxicity profile.
Why does dolutegravir raise serum creatinine without true kidney damage?
Dolutegravir raises serum creatinine by inhibiting tubular secretion of creatinine through the OCT2 transporter, without reducing the true glomerular filtration rate. Clinicians interpret a creatinine rise on dolutegravir with care and do not stop the drug for that reason alone.
What are the most serious toxicities of nevirapine in HIV therapy?
Nevirapine causes severe skin reactions, including Stevens-Johnson syndrome, and hepatotoxicity. A lead-in dose and early monitoring reduce the risk, and the drug is stopped for severe rash or liver injury.
Which protease inhibitor causes indirect hyperbilirubinaemia?
Atazanavir causes indirect hyperbilirubinaemia by inhibiting UGT1A1, so jaundice can appear without true hepatitis or raised transaminases. Atazanavir can also cause kidney stones through crystal deposition in the urinary tract.