When should antiretroviral therapy for HIV be started?

Publisher Website
Google Scholar
Abstract
Why have we delayed treatment? Antiretroviral therapy clearly reduces the risk of AIDS related diseases, even in those with a relatively high CD4 count. A large joint cohort analysis shows a decreased rate of AIDS after starting antiretroviral therapy, even in those with CD4 counts above 350×106/l (figure⇓).8 So what have been the reasons for delaying? View larger version: In this window In a new window Risk of AIDS over time according to CD4 count at start of antiretroviral therapy. Adapted from Egger et al8 Firstly, many antiretroviral drugs are inconvenient to take and are associated with unpleasant effects including nausea, diarrhoea, headache, and central nervous system toxicity. They may also cause occasional life threatening adverse effects such as hypersensitivity reactions, acute hepatitis, lactic acidosis, and pancreatitis.9 Furthermore, long term use of antiretroviral therapy has been linked with increased risk of myocardial infarction.10 If therapy can safely be delayed most patients would prefer to wait. Secondly, the absolute risk of AIDS related diseases has been felt to be sufficiently low at CD4 counts above 250×106/l that delay can be considered, given the disadvantages of treatment. Tables that provide the six month risk of AIDS for a person with a given CD4 count, viral load, and age6 11 indicate that a 35 year old with CD4 count 350×106/l and viral load 30 000 copies/ml has an estimated 1.6% risk of an AIDS disease, for example.11 While this risk would be reduced by antiretroviral therapy, many clinicians and patients have not considered it sufficiently high to warrant initiation of therapy. Thirdly, treatment of HIV has developed rapidly over the past 15-20 years. Patients' responses to antiretroviral therapy have improved,12 13 14 partly because of better adherence as a result of reduced toxicity, more convenient regimens, and adherence support. Furthermore, drugs with longer half lives that are more forgiving of poor adherence have become available. Understanding of resistance has also improved, as has the availability of drugs to use when extensive resistance is present. Given this ongoing improvement it has made sense to delay antiretroviral therapy. For example, a patient starting therapy in 1996 might have been put on a regimen containing either full dose ritonavir (associated with severe gastrointestinal adverse effects) or hard gel saquinavir (associated with a high rate of resistance). If he or she had been able to wait until 1999 then a regimen of combivir and efavirenz could have been started, which has proved durable success and is still widely used. In addition, it was feared that starting antiretroviral therapy too early could lead to premature exhaustion of all available treatment options because of resistance.