Therapeutic Management and Treatment of HIV – Past, Present & Future

The natural history of HIV infection, as it plays out in most patients, is for gradual deterioration in the cell mediated immune system and a progression through minor opportunistic conditions, to major opportunistic conditions and finally death. From the recognition of AIDS cases in 1081 until the widespread introduction of effective combination therapy (HAART) in 1996, most patients suffered this poor prognosis and poor outcome. With the advent of effective combination therapy in 1996 the outcome was transformed. Those patients who had access to effective treatment and who adhered to there medication generally had a good outcome. Their HIV viral load was suppressed and their CD4 count was maintained or raised to normal levels. The optimum CD4 count for commencing HARRT was much debated in the early days. As most major opportunistic conditions occurred with a CD4 count below 200, many physicians would wait until the CD4 count fell close to that level before offering therapy. However, it became clear that those people starting at a higher CD4 count did better over the long-term and most protocols recommend starting at least with a CD4 count of 350. Further evidence suggests that the starting level may need to be higher although the jury is still out as there are conflicting results from different studies. The armamentarium has expanded rapidly since the first treatment, AZT was introduced in 1986. Now there are at least 5 different major targets for anti-HIV therapy within the HIV replicated life cycle. There are over 25 licensed agents and more being introduced into practice each year. Providing someone is diagnosed with HIV early, they adhere well to the anti-HIV therapy and do not suffer any major adverse effects; HIV itself now is unlikely to affect their prognosis or life expectancy to any major degree. From the early days it was recognized that all anti-HIV therapies have adverse side-effects. These are many and protean and range from initial hypersensitivity reactions through to chronic metabolic disturbances. Occasionally the side-effects can be severe and life threatening. Recently it has been understood that many of the manifestations of HIV are due to chronic activation of the immune system. In other words it is not a depressed immune system that is causing the problems but the reverse. It is this activation which makes HIV a pro-inflammatory condition and will exacerbate a tendency in patients to have cardiovascular and metabolic effects. Therefore the challenges for the future, in terms of therapy, are:

1. To introduce regimens that can be better tolerated and taken less frequently in order to improve adherence.
2. To have medication that does not target host enzymes and cause unwanted metabolic and other side-effects.
3. To manage the immune activation and inflammatory responses of HIV itself.

This talk will further highlight the problems of the past, the successes of the present and the challenges and hopes for future treatments of HIV.