Phenotype vs treatment history

Comparisons of treatment switches based on phenotypic analysis have shown mixed results beyond the very short term.

In the VIRA 3001 study, 272 participants were randomised to phenotypic resistance testing (PRT) or standard of care (SOC), having failed one protease inhibitor and multiple NRTIs. After 16 weeks, significantly more of the PRT group had viral loads below 400 copies/ml compared with the SOC group. The benefit of resistance testing was greatest in individuals who had not commenced an NNRTI. There was a high drop-out rate, which undermines the impact of these results. 1

A second prospective, randomised study of 115 heavily pre-treated individuals found a significantly greater viral load reduction and CD4 cell count increase in the group who received phenotypic testing, but these benefits were not borne out at week 16. 2

Another study CCTG 575, failed to show benefit from phenotypic testing. This randomised, prospective study compared treatment response in two groups of participants. The first group (PHENO) changed their failing HIV therapy with the results from a phenotypic resistance test performed while still on the failing regimen; the second (SOC; standard of care) changed without a test. CCTG 575 found no difference overall between those who received a phenotypic test and those who did not in their response to their new regimen at either six or twelve months. 3

However, phenotypic testing did provide a benefit (viral load below 400 copies/ml at six months) in those who began with resistance to at least three PIs.

The CCTG 575 study team has proposed a series of possible explanations for the lack of benefit associated with phenotypic testing observed in their study, given that this result does not appear to fit with that of other trials. In comparison with other studies, participants in CCTG 575 were not particularly drug experienced and many had yet to use drugs from the NNRTI class. It is suggested therefore that participants in both trial groups should have had a range of viable treatment options available to them.

A further important consideration is that phenotypic tests are currently basing predictions of drug sensitivity on break-points which have not been clinically validated. While this affects all current antiretrovirals to a greater or lesser extent, it is suggested that it may be a particular problem for ddI and d4T. In the CCTG 575 study, these drug were used more often in the PHENO arm, which could have caused that arm to under-perform if the break-points used for these drugs were inaccurate.

References

  1. Cohen C et al. A randomized trial assessing the impact of phenotypic resistance testing on antiretroviral therapy. AIDS 16: 579-588, 2002
  2. Melnick D et al. Impact of phenotypic antiretroviral drug resistance testing on the response to salvage antiretroviral therapy (ART) in heavily experienced patients. Seventh Conference on Retroviruses and Opportunistic Infections, San Francisco, abstract 786, 2000
  3. Haubrich R et al. A randomized, prospective study of phenotype susceptibility testing versus standard of care to manage antiretroviral therapy: CCTG 575. AIDS 19: 295-302, 2005
Community Consensus Statement on Access to HIV Treatment and its Use for Prevention

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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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