Effectiveness

Indinavir (Crixivan) is able to reduce HIV viral load below the limit of detection and increase CD4 cell counts in the majority of people who take it in combination with at least two other antiretroviral drugs.

Indinavir was approved on the basis of two studies. ACTG 320 demonstrated that patients taking the combination of indinavir, AZT (zidovudine, Retrovir) and 3TC (lamivudine, Epivir) were less likely to progress to AIDS or death than those taking AZT and 3TC alone. This was paralleled by a higher proportion of these patients having undetectable viral loads and increased CD4 cell counts.1 Similarly, study 035 demonstrated that indinavir plus AZT and 3TC had a more favourable outcome than either indinavir alone or AZT and 3TC.2

More recent studies have demonstrated that combinations including indinavir and two nucleoside reverse transcriptase inhibitors (NRTIs) are at least as effective as combinations based on the protease inhibitor saquinavir (Invirase) or the non-nucleoside reverse transcriptase inhibitor (NNRTI) nevirapine (Viramune), and triple NRTI combinations.3 4 5 However, one study found that the NNRTI efavirenz (Sustiva) was more effective than indinavir, when combined with AZT and 3TC over 72 weeks, in patients who had mostly taken no antiretroviral drugs before.6

Indinavir can also be boosted with low-dose ritonavir (Norvir), which increases indinavir levels and allows the drug to be taken less often. A range of doses of indinavir and ritonavir have been tested in trials.7 8 9 10 11 12 13 14 It is not yet clear which dose is the best option, although 400mg indinavir and 100mg ritonavir twice a day, or possibly 600 and 200mg, seems to produce adequate levels of indinavir with a low incidence of side-effects in most patients, particularly if therapeutic drug monitoring is available to ensure adequate drug exposure. Although higher doses of indinavir or ritonavir can improve exposure to indinavir, the increased rate of side-effects limits their usefulness, especially when other ritonavir-boosted protease inhibitors have similar anti-HIV efficacy to indinavir, but with fewer side-effects.15 16 17

Highly treatment-experienced individuals can often benefit from salvage combinations containing indinavir, with or without ritonavir boosting.18 19 Patients with hepatitis B or C can take 200 or 400mg indinavir boosted with 100mg ritonavir twice a day.20 21

There is some evidence that indinavir can penetrate the blood-brain barrier and reach sufficient concentrations in the cerebrospinal fluid to be active against HIV in the central nervous system.22 23 24 It can also reach anti-HIV levels in the semen.25

References

  1. AVANTI Study Group. AVANTI 2. Randomized, double-blind trial to evaluate the efficacy and safety of zidovudine plus lamivudine versus zidovudine plus lamivudine plus indinavir in HIV-infected antiretroviral-naive patients. AIDS 14: 367-374, 2000
  2. Gulick R et al. 3-year suppression of HIV viremia with indinavir, zidovudine, and lamivudine. Ann Intern Med 133: 35-39, 2000
  3. Staszewski S et al. Abacavir-lamivudine-zidovudine vs indinavir-lamivudine-zidovudine in antiretroviral naive HIV-infected adults: a randomized equivalence trial. JAMA 285: 1155-1163, 2001
  4. Cohen Stuart JWT et al. Randomized trial comparing saquinavir soft gelatin capsules versus indinavir as part of triple therapy (CHEESE study). AIDS 13: F53-F58, 1999
  5. Kirk O et al. Combination therapy containing ritonavir plus saquinavir has superior short-term antiretroviral efficacy: a randomised trial. AIDS 13: F9-F16, 1999
  6. Staszewski S et al. Efavirenz plus zidovudine and lamivudine, efavirenz plus indinavir, and indinavir plus zidovudine and lamivudine in the treatment of HIV-1 infection in adults. N Engl J Med 341: 1865-1873, 1999
  7. Ghosn J et al. Efficacy of a twice-daily antiretroviral regimen containing 100 mg ritonavir / 400 mg indinavir in HIV-infected patients. AIDS 17: 209-214, 2001
  8. Rhame FS et al. Pharmacokinetics of indinavir and ritonavir administered at 667 and 100 milligrams, respectively, every 12 hours compared with indinavir administered at 800 milligrams every 8 hours in human immunodeficiency virus-infected patients. Antimicrob Agents Chemother 48: 4200-4208, 2004
  9. Hugen PWH et al. Dose finding study of a once daily indinavir / ritonavir regimen. J Acquir Immune Defic Syndr 25: 236-245, 2000
  10. Lichterfeld M et al. Long-term efficacy and safety of ritonavir / indinavir at 400 / 400 mg twice a day in combination with two nucleoside reverse transcriptase inhibitors as first line antiretroviral therapy. HIV Med 3: 37-43, 2002
  11. Mallolas J et al. Dose-finding study of once-daily indinavir / ritonavir plus zidovudine and lamivudine in HIV-infected patients. J Acquir Immune Defic Syndr 25: 229-235, 2000
  12. Boyd MA et al. Boosted versus unboosted indinavir with zidovudine and lamivudine in nulceoside pre-treated patients: a randomized, open-label trial with 112 weeks of follow-uo (HIV-NAT 005). Antivir Ther 11: 223-232, 2006
  13. Cressey TR et al. Low-doses of indinavir boosted with ritonavir in HIV-infected Thai patients: pharmacokinetics, efficacy and tolerability. J Antimicrob Chemother 55: 1041-1044, 2005
  14. Acosta EP et al. Comparison of two indinavir / ritonavir regimens in the treatment of HIV-infected individuals. J Acquir Immune Defic Syndr 37: 1358-1366, 2004
  15. van Heeswijk RPG et al. The steady-state plasma pharmacokinetics of indinavir alone or in combination with a low dose of ritonavir in twice daily dosing regimens in HIV-1-infected individuals. AIDS 13: 95-99, 1999
  16. Burger DM et al. A retrospective, cohort-based survey of patients using twice-daily indinavir + ritonavir combinations: pharmacokinetics, safety, and efficacy. J Acquir Immune Defic Syndr 26: 218-224, 2001
  17. Konopnicki D et al. Indinavir / ritonavir-based therapy in HIV-1-infected antiretroviral therapy-naive patients: comparison of 800 / 100 mg and 400 / 100 mg twice daily. HIV Med 6: 1-6, 2005
  18. Dronda F et al. Patients failing saquinavir therapy require an early change to indinavir before HIV-1 viral load reaches high levels. Antivir Ther 4: 117-121, 1999
  19. Voigt E et al. First-line ritonavir / indinavir 100 / 800 mg twice daily plus nucleoside reverse transcriptase inhibitors in a German multicentre study: 48-week results. HIV Med 3: 277-282, 2002
  20. Bossi P et al. High indinavir plasma concentrations in HIV-1 patients co-infected with hepatitis B or C virus receiving indinavir and ritonavir low dosages: a GENOPHAR substudy. Tenth Conference on Retroviruses and Opportunistic Infections, Boston, abstract P546, 2003
  21. Dominguez S et al. Indinavir-ritonavir regimen (400mg / 100mg) in HIV / HCV co-infected patients in the Hepadose Study: the relationship between protease inhibitors plasma concentrations and liver lesions. Antiviral Therapy 8: S465, 2003
  22. Martin C et al. Indinavir-based treatment of HIV-1 infected patients: efficacy in the central nervous system. AIDS 13: 1227-1232, 1999
  23. Letendre SL et al. Indinavir population pharmacokinetics in plasma and cerebrospinal fluid. The HIV Neurobehavioral Research Center Group. Antimicrob Agents Chemother 44: 2173-2175, 2000
  24. Zhou XJ et al. Plasma population pharmacokinetics and penetration into cerebrospinal fluid of indinavir in combination with zidovudine and lamivudine in HIV-1-infected patients. AIDS 14: 2869-2876, 2000
  25. Taylor S et al. Antiretroviral drug concentrations in semen of HIV-infected men: differential penetration of indinavir, ritonavir and saquinavir. J Antimicrob Chemother 48: 351-354, 2001
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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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.