HIV-positive people with multi-class drug experience should be treated with the aim of suppressing viral load below detectable levels, the revised US treatment guidelines published last week emphasise. To do this, patients should seriously consider using a boosted protease inhibitor such as tipranavir/ritonavir in combination with enfuvirtide (T-20, Fuzeon) in order to maximise the chances of virologic suppression.
The guidelines state: “The goal of treatment for patients with prior drug exposure and drug resistance is to re-establish maximal virologic suppression. Adding a drug with activity against drug-resistant virus (e.g. a potent ritonavir-boosted PI) and a drug with a new mechanism of action (e.g. HIV entry inhibitor) to an optimized background antiretroviral regimen can provide significant antiretroviral activity”.
“These guidelines clearly set more ambitious goals for the management of treatment-experienced patients now that we have potent therapies such as the combination of tipranavir and enfuvirtide,” commented Dr Anton Pozniak, Chelsea and Westminster Hospital, London.
At a symposium on Current Controversies in HIV Management hosted by NAM in June 2005, Dr Cal Cohen said: “The paucity of new drugs over the next few years needs to be appreciated by our field and the use of a new class is critical to your chances of suppression, so until integrase and maturation inhibitors come along, it’s got to be a discussion about making the best use of what’s available.”
Highlighting the impact of using enfuvirtide with a boosted protease inhibitor, Professor Richard Haubrich of the University of California, San Diego, presented an analysis of three data sets at the IDSA meeting in San Francisco earlier this month showing that the addition of enfuvirtide to a new boosted protease inhibitor increased the chances of a virologic response three-fold.
In the case of lopinavir/ritonavir and TMC-114, the addition of enfuvirtide increased the chances of achieving a viral load below 50 copies more than three-fold, whilst the addition of enfuvirtide to tipranavir/ritonavir increased the chance of viral suppression below 400 copies by 2.7-fold. The overall odds of a viral load below the limits of quantification when adding enfuvirtide to a new boosted protease inhibitor were 3.2 (95% confidence interval 2.4 – 4.2).
However the authors caution that the differences in odds ratios between boosted protease inhibitors shouldn’t be used for the purposes of comparison, since each study had slightly different entry criteria.
“These results suggest that optimal antiviral responses are achieved when a boosted protease inhibitor and enfuvirtide are initiated simultaneously.”
Haubrich R et al. Improved virologic response in three-class experienced patients when an active boosted protease inhibitor is combined with enfuvirtide (ENF). 43rd Annual Meeting of the Infectious Diseases Society of America, San Francisco, abstract 785, 2005.