**2. Why should we look beyond the HAART?**

The major problem faced with HAART is that it only controls the infection and never eliminates it. When used continually on a lifelong basis, the HAART provides an infected individual with a significant improvement of clinical condition, enhancement of the quality of life and drastic reduction of circulating viral load. Nevertheless, treatment cessation at any point results in a rebound viremia, stripping off all the benefits that the patient had enjoyed during therapy. This could be stated as the inherent flaw in HAART, which exerts its inhibitory effect only against the actively replicating viruses in circulation and has little or no effect in destroying the quiescent viruses hidden in the latent cellular and anatomical reservoirs. Due to several reasons, this proviral reservoir gets activated at a later date proceeding to active viral replica‐ tion and viremia, which can occur unchecked upon discontinuation of HAART [1-4].

Another worrisome aspect of HIV is its ability to undergo rapid genetic evolution as a consequence of its voracious mutating capacity. For a virus with such a feature, lifelong therapy with anti-retroviral drugs can be deleterious by itself, as the constant drug pressure eventually selects the resistant mutant viral populations. Such mutant viruses, resistant to the currently used anti-retroviral drugs have already emerged and are being disseminated in various countries across the globe. There is a possibility that these strains may replace the drug susceptible ones and render the HAART inactive.

Lifelong HAART also faces the practical constraint of continuous patient adherence to the prescribed regimen and also its discontinuation due to adverse drug effects. Optimistic predictions of worldwide HIV control using HAART would be just a mirage if the impending failure of the HAART in the future is not foreseen from the present. In the light of these issues, any attempt to curtail the HIV pandemic warrants the need for novel anti-retroviral agents and/or strategies to supplement, if not to supplant the HAART [5].
