The Pharmaceutical Journal
Vol 277 No 7413 p182
12 August 2006

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Systematic strategy outlined for heavily treated HIV-infected patients

A strategy for dealing with heavily treated HIV-infected patients who are experiencing treatment failure with multiple classes of antiretrovirals is proposed in the latest issue of Lancet Infectious Diseases (2006;6:496).

Infectious disease specialists from the US and Italy suggest that resistance testing should be used to determine the optimum salvage regimen, and that it should be conducted while the patient is on therapy or within four weeks of drug discontinuation.

They explain that phenotypic resistance testing provides a quantitative measure of the likely activity of each drug and identifies hypersusceptibility to a particular agent more reliably than genotypic testing.

As part of their strategy they recommend inclusion of at least two drugs with activity against resistant virus. They also warn that delaying a switch from a failing regimen could result in accumulation of additional resistant mutations, diminishing future treatment options. However, for patients with no active antiretroviral treatment options available to them, the specialists say that continuation of the failing regimen should be considered.

Another option is double-boosted protease inhibitors. However, the specialists point out that a lack of evidence for increased efficacy and the emergence of new protease inhibitors and other classes of antiretrovirals make this a less attractive alternative.

Structured treatment interruption, a strategy designed to reverse resistant mutations and increase the likelihood of durable virological suppression when therapy is reintroduced, is not favoured by the specialists.

Finally, they propose that therapeutic drug monitoring, integrated with resistance test results, should be incorporated into the treatment strategy to predict virological response.

They conclude: “Although the best overall strategy might be to take the necessary steps to avoid development of resistance earlier in the course of treatment, a systematic approach like the one we have outlined could lead to a successful outcome even in [heavily treated patients].”