Resistance

As with all other anti-HIV drugs, strains of HIV that are resistant to Kaletra may emerge after a period of treatment. The emergence of drug-resistant strains coincides with a fall in the effectiveness of the drug .

There has been a large number of publications describing patients with prior protease inhibitors experience who have failed lopinavir treatment. However, Kaletra has a high genetic barrier to lopinavir resistance and is very effective in protease inhibitor-experienced patients, making it difficult to ascertain the combination of mutations necessary for Kaletra therapy to fail.

To date, reduced sensitivity to Kaletra has been mainly associated with mutations 46I, 54V, 71V, 82A and 84V.1 2 3 Other mutations which have been associated with resistance to Kaletra include L10F/I/R/V and L90M, as well as mutations at codons 20, 24, 32, 33, 46, 47, 50, 53, 63 and 90.1 4 5 6 One study reported that having five or more mutations at these positions or positions 33, 36, or 48 is associated with complete resistance to Kaletra, while having three or four of these mutations is linked to mild resistance.7 V47A also causes resistance to Kaletra in patients infected with HIV-2.8

All of the protease inhibitors are, to some extent, cross-resistant. This means that resistance mutations that emerge in the presence of one protease inhibitor reduce the effectiveness of other protease inhibitors. There is evidence that HIV with reduced susceptibility to Kaletra shows high-level resistance to indinavir (Crixivan) and ritonavir, intermediate resistance to amprenavir (Agenerase) and susceptibility to saquinavir (Invirase).9

References

  1. Mo H et al. Selection of resistance in protease inhibitor-experienced, human immunodeficiency virus type 1-infected subjects failing lopinavir- and ritonavir-based therapy: mutation patterns and baseline correlates. J Virol 79: 3329-3338, 2005
  2. Monno L et al. HIV-1 Phenotypic susceptibility to lopinavir (LPV) and genotypic analysis in LPV / r-naive subjects with prior protease inhibitor experience. J Acquir Immune Defic Syndr 33: 439-447, 2003
  3. Luis Jimenez J et al. Mutations at codons 54 and 82 of HIV protease predict virological response of HIV-infected children on salvage lopinavir / ritonavir therapy. J Antimicrob Chemother 56: 1081-1086, 2005
  4. Kempf DJ et al. Identification of genotypic changes in human immunodeficiency virus protease that correlate with reduced susceptibility to the protease inhibitor lopinavir among viral isolates from protease inhibitor-experienced patients. J Virol 75: 7462-7469, 2001
  5. Masquelier B et al. Human immunodeficiency virus type 1 genotypic and pharmacokinetic determinants of the virological response to lopinavir-ritonavir-containing therapy in protease inhibitor-experienced patients. Antimicrob Agents Chemother 46: 2926-2932, 2002
  6. de Mendoza C et al. Prevalence of the HIV-1 protease mutation I47A in clinical practice and association with lopinavir resistance. AIDS 20: 1071-1073, 2006
  7. de Luca A et al. Improved prediction of virological response to lopinavir / ritonavir in salvage therapy using new interpretation rules of baseline genotypic resistance. Second International AIDS Society Conference on HIV Pathogenesis and Treatment, Paris, abstract 793, 2003
  8. Rodes B et al. High rate of proV47A selection in HIV-2 patients failing lopinavir-based HAART. AIDS 20: 127-129, 2006
  9. Parkin NT et al. Isolated lopinavir resistance after virological rebound of a lopinavir / ritonavir-based regimen. 13th International HIV Drug Resistance Workshop, Costa Adeje, abstract 70, 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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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.