AIDS: Why is a cure so difficult to find?

Used with permission The current strategy of HAART (Highly Active Anti-Retroviral Therapy) is to simultaneously administer several drugs to attack HIV at different stages of its life cycle. The most common drug regimes administer reverse transcriptase inhibitors to try to avoid the initial infection of cells (by preventing the all important step in HIV infection of viral RNA making viral DNA) in combination with drugs such as protease inhibitors which inhibit the production of new viruses in already infected cells. Some more recently developed drugs try to prevent infection by blocking the initial stage of fusion of HIV’s envelope with the membrane of the target cell. However, in many instances HIV becomes resistant to drugs (especially if the patient does not adhere strictly to the drug regime) and individuals living with HIV have to regularly modify the particular combination of drugs they take. Why is HIV so persistent?

The key lies in HIV’s reverse transcriptase, an enzyme that is highly prone to errors. As a result of mistakes in the reverse transcribed viral DNA, many different types (known as viral strains) of HIV are continuously being generated within the same infected individual. Eventually, a strain of HIV that is resistant to a particular drug(s) is produced and replicates uncontrollably. Unless other drugs to which this new viral strain is sensitive are administered, the high levels of this new strain of HIV in blood results in the gradual loss of CD4+ T helper cells and progression to disease follows.

As you can imagine, differences between strains of HIV from different infected individuals are even greater than those within a single individual. The following fact may help you place the high genetic variation of HIV in perspective: a chimpanzee and a human are genetically more similar to each other than two HIV strains isolated from different individuals. This high genetic variability is also responsible for the difficulty in creating vaccines against HIV. In fact, HIV cannot be considered as a single enemy but as a multitude, as it rapidly mutates to overcome every single defence provided by our own immune system and by administered drugs.