Genotype vs treatment history

The French VIRADAPT study assessed 108 patients who were on failing treatment and were allocated a new combination based on either their doctor's assessment plus clinical guidelines, or the results of genotypic resistance testing. Six months after switching treatment, the group who switched on the basis of genotypic testing had significantly lower viral loads. 1 Experts have questioned whether the superiority of the genotypic arm could be entirely attributed to genotypic testing, since more aggressive management of people in the genotypic arm of VIRADAPT could simply be appropriate to this group.

Further analysis showed that people whose treatment was adjusted according to the results of genotypic testing did better if they also maintained optimum concentrations of their prescribed protease inhibitor during the first six months of the study. 2 These data indicate that both genotypic resistance testing and drug concentrations predict response to treatment.

CPCRA 046, also known as the GART study, recruited 153 patients who had evidence of viral load rebound after more than 16 weeks on a triple combination regimen. Patients were randomised either to receive a genotypic antiretroviral resistance testing (GART) and expert advice to guide selection of their new combination, or to switch to a new regimen selected purely according to treatment history. After twelve weeks the GART group had a 0.44 log10 greater viral load reduction. 3

The study also showed that the number of new and active drugs was a significant predictor of response, regardless of whether genotypic testing was carried out. 4 This finding has led some experts to suggest that genotypic testing may not be necessary after the failure of first-line therapy. Instead, they argue, all the drugs should be changed and blood should be stored for genotypic testing if the second-line therapy fails. Others argue that a completely new regimen does not rule out the risk of cross-resistance.

The GART study also demonstrated the importance of expert interpretation of genotypic results: after twelve weeks, viral loads were nearly 0.5 log lower in patients whose doctors followed expert advice more often.

The ARGENTA study randomised 174 patients with detectable viral load despite antiretroviral therapy to switch therapy on the basis of genotyping or to receive the standard of care. Treatment experience varied, with a quarter having more than three failed antiretroviral drug regimens. Responses at twelve weeks showed a benefit in the group that was tested by genotype, but this was lost by 24 weeks. 5

References

  1. Clevenburgh P et al. Persisting long-term benefit of genotype-guided treatment for HIV-infected patients failing HAART. The Viradapt Study: week 48 follow-up. Antiviral Therapy 5(1):65-70, 2000
  2. Durant J et al. Importance of protease inhibitor plasma levels in HIV-infected patients treated with genotypic-guided therapy: pharmacological data from the Viradapt Study. AIDS 14: 1333-1339, 2000
  3. Baxter JD et al. A randomized study of antiretroviral management based on plasma genotypic antiretroviral resistance testing in patients failing therapy. CPCRA 046 Study Team for the Terry Beirn Community Programs for Clinical Research on AIDS. AIDS 14: F83-F93, 2000
  4. Baxter JD et al. Both baseline HIV-1 drug resistance and antiretroviral drug levels are associated with short-term virologic responses to salvage therapy. AIDS 16: 1131-1138, 2002
  5. Cingolani A et al. Usefulness of monitoring HIV drug resistance and adherence in individuals failing highly active antiretroviral therapy: a randomised study (ARGENTA). AIDS 16: 369-379, 2002
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.