Antiretroviral Drugs: Current Therapy, Recent Developments and Future Perspectives

The treatment of human immunodeficiency virus (HIV) infection has been a great success story of our time; from the widespread panic in the early 1980’s when the virus was identified as the cause of AIDS, to the availability of a whole plethora of drugs to treat and effectively control HIV infection, developed after millions of dollars of research funding investments. However, this treatment is not entirely problem-free. From the early days of antiretroviral (ARV) monotherapy, to the mid 1990’s when triple therapy (highly active antiretroviral treatment, HAART) was discovered to be not only more effective but less toxic, there has been ongoing work to change the face of HIV treatment. This work can be broadly split into three categories, being:

1. developing drugs to target different stages of the life cycle.

2. developing novel drugs and refining the use of current drugs to reduce toxicities and side effects.

3. reducing the pill burden and the impact of daily therapy.

In part I, the life cycle of HIV and the targets of current therapy will be presented in terms of their individual actions and side effects. This section is completed by an exploration of wider issues surrounding anti-HIV therapy including distribution, cost and regular access. Part II will examine three key aspects of new drugs in development. This examination will be of new ARV agents in development, including some agents very recently licensed. The first aspect will be drugs in the pipeline which are directed against existing drug targets; potential differences between these drugs compared to current agents will be outlined. The second aspect is the most exciting, focusing on the development of novel drugs for novel targets in the HIV life cycle. The final aspect of part II will be to examine the role of these new drugs in adding to an already complex treatment arena - are these drugs for patients who have failed other therapies, or do their new actions and side effect profiles make them more useful for first line treatment? Will their expense or mode of delivery make them simply inaccessible to people living with HIV?

Part III will contain the conclusions pertaining to the preceding section, and will examine potential for the development of even newer drugs in terms of targets, efficacy, toxicities and acceptability. The two facets that will be explored are the potential for the correction of deficits in current treatment and potential new drugs.

Keywords: Adverse effects, adherence, antiretroviral drug development, HIV, HIV life cycle.