HIV continues to have enormous global impact, particularly in the developing world. Around 40 million people are infected worldwide and new infections occur at a rate of 14 000 per day. Currently in Australia, approximately 22 100 people are HIV positive and to October 2002, 6184 deaths had occurred due to AIDS.3Eradication of HIV by continuous therapy is highly unlikely, due to the very long half-life and latency of some immune cells infected with HIV. No cure is in sight and a preventive vaccination will not be available in the near future.
New drugs within the existing classes of antiretrovirals and further classes of drugs (such as vaccines, fusion inhibitors and co-receptor antagonists) have been developed. These are variously available through trials and special access schemes. Modifications to existing drugs have sought to improve dosing schedules, with once-daily treatments and the combination of up to three drugs in a single tablet. Attention has been focused on the need to improve and maintain compliance to maximise the impact and duration of whatever treatment regimen is adopted. Consequently, there is a need to tailor treatment to suit each individual and the lifestyle they lead.
From the late 1990s to the present time, HIV treatments have come under increasing scrutiny. Long-term treatment with HAART is clearly not straightforward or without consequences. Developing alternative regimens for those in whom treatment has failed, simplifying regimens to improve compliance and managing the wide range of adverse effects is a challenge.
HIV treatment has become increasingly complex and clinicians must confront numerous issues and dilemmas, without a clear consensus on the best treatment strategy to adopt.
Awareness of the complications and adverse effects related to antiretroviral therapy has made many clinicians more cautious about advocating early treatment, in contrast to the 'hit hard and early' approach initially adopted with HAART. The current Australian, American and British guidelines for starting antiretroviral therapy are much more conservative than those released in 1997. Protease inhibitors are now used less frequently in early treatment regimens than they were when HAART first came into vogue and nearly every drug combination included at least one protease inhibitor.
Treatment of symptomatic HIV infection or AIDS extends life and most clinicians would offer therapy in these situations. However, in asymptomatic patients, current recommendations suggest that treatment does not start until the CD4 T cell count falls below 350/microlitre or the HIV load exceeds 50 000 copies/mL. These recommendations are based on the risk of developing AIDS within six years without treatment (Table 1).4
In just over 20 years AIDS has grown from a cluster of cases into a substantial global health problem. In the Western world, the disease has changed from being predictably fatal to a chronic manageable condition, for those in whom the drugs work well. In the world's poorest nations, however, little has changed and effective therapy is almost completely unattainable. The epidemic continues to rage out of control and the main concerns are more basic; prevention, diagnosis, access to health care and palliation.
