Resistance

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

Two primary mutations in the protease gene, L90M and G48V, reduce susceptibility to saquinavir.1 2 3 4 The effect of these mutations can be enhanced by the secondary mutations L10I/V, K20R, M36I/L, A71T, V82X or I84V. However, virological failure of ritonavir (Norvir)-boosted saquinavir-based regimens occurs very rarely, at least in first-line therapy. In the Staccato study, ten of 258 patients had experienced virological failure after 30 weeks of treatment, but none of these had any major protease mutations.5

Virus that is resistant to other protease inhibitors, particularly indinavir (Crixivan) and ritonavir, may show some degree of cross-resistance to saquinavir.6 7 8 Saquinavir may not therefore be a useful option after failure of an indinavir-based combination.

Conversely, HIV with certain mutations that can cause resistance to atazanavir (Reyataz), amprenavir (Agenerase) or nelfinavir (Viracept) has been shown to be hypersusceptible to saquinavir. Using saquinavir after failure of these drugs may be beneficial, although this has not been established in clinical studies.

References

  1. Katlama C et al. MIKADO: a multicentre, open-label pilot study to evaluate the antiretroviral activity and safety of saquinavir with stavudine and zalcitabine. HIV Med 2: 20-26, 2001
  2. Lawrence J et al. Clinical resistance patterns and responses to two sequential protease inhibitor regimens in saquinavir and reverse transcriptase inhibitor-experienced persons. J Infect Dis 179: 1356-1364, 1999
  3. Craig C et al. HIV protease genotype and viral sensitivity to HIV protease inhibitors following saquinavir therapy. AIDS 12: 1611-1618, 1998
  4. Pym AS et al. Presence of mutation at codon 90 may predict response to ritonavir / saquinavir combination in HIV seropositive patients pretreated with saquinavir monotherapy. First International Workshop on Drug Resistance, Treatment Strategies and Eradication, St Petersburg, abstract 84, 1997
  5. Ananworanich J et al. Absence of resistance mutations in ART-naïve patients treated with ritonavir-boosted saquinavir. Third International AIDS Society Conference on HIV Pathogenesis and Treatment, Rio de Janeiro, abstract WePe4.4C12, 2005
  6. Mayer DL et al. Prior saquinavir therapy leads to a modest decrease in subsequent responses to drug regimens containing indinavir or ritonavir. Fifth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 400, 1998
  7. Bodsworth NJ et al. Ritonavir (RTV) and indinavir (IDV) therapy at 28 weeks after 32 weeks' saquinavir (SQV) therapy: influence of HIV-1 protease mutations. Fifth Conference on Retroviruses and Opportunistic Infections, Chicago, abstract 396, 1998
  8. Deeks S et al. Activity of a ritonavir plus saquinavir-containing regimen in patients with virologic evidence of indinavir or ritonavir failure. AIDS 12: F97-F102, 1998
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
close

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.