The seemingly large number of possible antiretroviral drug combinations is only apparent. Therapeutic options are actually limited by cross reactivity within the currently available classes of antiretroviral drugs. New drugs with increased potency that are safer, easier to take, with more favourable pharmacologic properties and with activity against drug-resistant viruses, are needed. Validation of drug resistance testing for use in clinical practice will provide clinicians with a helpful patient management tool and the choice of therapy will hopefully be guided by individual resistance profiles, allowing for more effective treatment.

It is becoming increasingly evident that the course and the outcome of HIV infection are mostly determined by events that take place during primary infection. Future treatment strategies, through controlled studies, will focus on the early recognition and treatment of primary HIV infection.

There is evidence that a specific and effective cellular immune response to HIV occurs in infected subjects. This has led to the exploration of alternative approaches to therapy that would aim at enhancing this host immune response such as therapy with drugs like Interleukin 2 and with certain HIV-derived immunogens. Studies are ongoing to design further strategies of treatment based on immunologic intervention.

The example of the “long term non-progressor” (individuals whose HIV infection is effectively controlled by their own specific CD4+ T cell response) suggests that enhancing the immune response may lead to a stable equilibrium between virus and host. A similar response is observed in other persistent viral infections such as those caused by herpesviruses, where the host’s immune system is able to keep a virus silent. One approach to ART that is under investigation is antiretroviral therapy with structured treatment interruptions. The hope is that intermittent interruptions in ART, by allowing host immunity to be exposed to HIV, may act to augment the duration and the strength of host immune responses to HIV and therefore increase immunologic control of the infection. Additional potential advantages of structured interruptions of ART are: reduced toxicity improved tolerance, greater adherence to treatment and reduced overall cost. Results from a few uncontrolled studies are available which indicate that the majority of patients seem to experience a rapid rebound in plasma HIV-RNA during treatment interruptions as well as a rapid decline in CD4+ cell counts. The implications of these results and the possibility of boosting HIV-specific immune responses through this approach still remain controversial and need to be further clarified by controlled studies.

A variety of other approaches to stimulating the immune system are under investigation. While research into eradication of HIV also continues, a combination of potent ART with immune-based therapies may be the most durable approach to achieving long term containment of HIV replication.