Third International Workshop on Salvage Therapy for HIV Infection, April 12-14, 2000, Chicago, USA
- Indinavir plus ritonavir: might exposure to higher levels of indinavir overcome protease resistant HIV and prove useful to ‘rescue’ previously failed protease inhibitor based combinations?
The Workshop on Salvage Therapy for HIV Infection has established itself as an annual meeting focused on the needs of those patients who have continued viraemia and deteriorating clinical status despite receiving antiretroviral therapy. These so-called ‘experienced’ patients have a long history of treatment with a variety of agents often dating back to zidovudine monotherapy.
Increasingly, however, their ranks are now being swelled by those who were therapy na•ve when starting triple combination therapy, but whose combination failed to make the grade either through inadequate potency, poor tolerability or difficult adherence.
The term ‘salvage’ is a much debated one, and being poorly defined, sits awkwardly in this meetings title – watch out for a possible name change for next years outing. Historically it has been noticed that virological response to any second-line regimen is always inferior to responses achieved in an antiretroviral na•ve study population. This occurs despite exposure to new agents. Indeed, even second-line combinations which contain entirely new classes of agent and consist of components to which the patient is completely naive still exhibit this blunted response.
Consequently, each serial attempt at virological control becomes that much harder to achieve. This leaves many patients and their physicians having to settle for less stringent goals where partial virological control and clinical stability is the most that can be achieved.
The causes of treatment failure for both initial and subsequent combinations are both multifactorial and complex. The following factors are currently being explored.
- Resistance – genotypic and/or phenotypic testing of viral isolates
- Pharmacokinetics – therapeutic drug monitoring
- Adherence / tolerability – talk to the patient!
- Toxicity – investigate drug levels, careful monitoring of liver function, triglycerides etc.
Inadequate knowledge and imperfect diagnostic tests make the determination of the role of each of these factors both difficult and imprecise.
The success of subsequent regimens, however, is strongly dependent on identifying (and eliminating) the contributing factors to failure of the previous regimen. Patients struggling with difficult regimens of inadequate potency deserve access to state-of-the-art diagnostics, even those yet to be perfected.