Side-effects

One of the commonest side-effects associated with indinavir (Crixivan) is kidney stones or ‘nephrolithiasis’.1 2 3 4 5 Its symptoms are pain on passing urine, pain along the side of the body and ‘gravel’ in the urine. The pain associated with kidney stones can be severe. About one in 25 people treated with indinavir develop kidney stones. Drinking a large amount of water at the same time as taking the indinavir reduces the risk of this side-effect .

People with high concentrations of indinavir in their blood are more likely to experience kidney and urinary side-effects. Kidney stones have been seen more frequently in people taking indinavir with ritonavir, because indinavir levels are boosted. Drug-level monitoring, if available, can determine indinavir levels and indicate if dose reductions are necessary and safe in terms of preserving the anti-viral effect of the treatment. Studies have shown that dose reductions of up to 400mg can reduce kidney problems without increasing the chance of viral rebound.6 7

If a patient develops kidney stones while taking indinavir, it may be necessary to interrupt indinavir for one to three days, or to stop taking it altogether.

The most commonly reported side-effect from long-term use of indinavir is increased levels of bilirubin in the blood.8 Although not dangerous, this side-effect causes yellowing of the skin and the whites of the eyes, and can be stigmatising. Hyperbilirubinaemia is more common in patients with a polymorphism in the gene for the enzyme that removes bilirubin from the body.9

Indinavir may cause a worsening of pre-existing low level of platelets in the blood or it may cause anaemia. One study has found that people taking indinavir have an increased risk of blood clots, although further research into this association is needed.10

Short-term side-effects of indinavir use tend to resolve after the first few weeks of treatment. These include nausea, headache, fatigue, abdominal pain, vomiting, rash, dry skin and strange tastes in the mouth. Intestinal wind and bloating have also been reported.

Other side-effects include ingrowing toe nails and inflammation around the nail, as well as severe skin dryness and cracked lips.11 12 These occur in 1 to 4% of people taking the drug. There is some evidence that reducing the dose of indinavir may reduce the severity of these side-effects. However, this must only be attempted if it is judged to be safe in terms of controlling viral load.

As a class, protease inhibitors have been associated with a syndrome of fat and metabolic irregularities. This includes altered fat distribution, high lipid levels in the blood, insulin resistance, diabetes, increased levels of blood sugar and increased bleeding in haemophiliacs.13 For more details see Metabolic changes while on ART.

References

  1. Boubaker K et al. Changes in renal function associated with indinavir. AIDS 12: F249-F254, 1998
  2. Brodie SB et al. Variation in incidence of indinavir-associated nephrolithiasis among HIV-positive patients. AIDS 12: 2433-2437, 1998
  3. Grases F et al. Indinavir crystallization and urolithiasis. Int Urol Nephrol 31: 23-29, 1999
  4. Herman JS et al. Incidence and risk factors for the development of indinavir-associated renal complications. J Antimicrob Chemother 48: 355-360, 2001
  5. Kohan AD et al. Indinavir urolithiasis: an emerging cause of renal colic in patients with HIV. J Urol 161: 1765-1768, 1999
  6. Dieleman J et al. Urologic complaints in relation to indinavir plasma levels in HIV-1 infected patients. AIDS 13: 473-478, 1999
  7. Boyd MA et al. The use of pharmacokinetically guided indinavir dose reductions in the management of indinavir-associated renal toxicity. J Antimicrob Chemother 57: 1161-1167, 2006
  8. Stein DS et al. A 24-week open-label phase I / II evaluation of the HIV protease inhibitor MK-639 (indinavir). AIDS 10: 485-492, 1996
  9. Rotger M et al. Gilbert syndrome and the development of antiretroviral therapy-associated hyperbilirubinemia. J Infect Dis 192: 1381-1386, 2005
  10. Sullivan PS et al. Epidemiology of thrombosis in HIV-infected individuals. The Adult / Adolescent Spectrum of HIV Disease Project. AIDS 14: 321-324, 2000
  11. Bourezane Y et al. Ingrown toenail and indinavir: case-control study demonstrates strong relationship. AIDS 13: 2181-2182, 1999
  12. Bouscarat F et al. Paronychia and pyogenic granuloma of the great toes in patients treated with indinavir. N Engl J Med 338: 1776-1777, 1998
  13. Schwarz JM et al. Indinavir increases glucose production in healthy HIV-negative men. AIDS 18: 1852-1854, 2004
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

Together, we can make it happen

We can end HIV soon if people have equal access to HIV drugs as treatment and as PrEP, and have free choice over whether to take them.

Launched today, the Community Consensus Statement is a basic set of principles aimed at making sure that happens.

The Community Consensus Statement is a joint initiative of AVAC, EATG, MSMGF, GNP+, HIV i-Base, the International HIV/AIDS Alliance, ITPC and NAM/aidsmap
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This content was checked for accuracy at the time it was written. It may have been superseded by more recent developments. NAM recommends checking whether this is the most current information when making decisions that may affect your health.

NAM’s information is intended to support, rather than replace, consultation with a healthcare professional. Talk to your doctor or another member of your healthcare team for advice tailored to your situation.