From the very beginning of AIDS research there has been disagreement between virologists and immunologists about the relative importance of the virus and the immune system in the pathogenesis of AIDS.

From the perspective of virologists, the important factor driving the pathway is the success of the virus in replicating, which is measured as the viral load. They are interested in why different strains of HIV have different preferences for either CD4 T-cells or macrophages as host cells and for different places in the body, such as the gut or brain. These variations in function are called phenotypes and they are related to single or multiple changes in the virus's genes. There are even different phenotypes in terms of sensitivity to drugs. An important area of interest is how the virus evades the immune system or drugs by mutating and varying the structure of proteins. Virologists are interested in how the virus itself could kill CD4 T-cells directly (such as during the process when HIV buds off cells). A priority is the development of anti-HIV drugs.

Immunologists are interested in how CD4 cells could be killed by immune responses and the abnormalities which develop in the immune system during HIV infection. They are interested in why the immune system fails to control or eradicate HIV as it does with other viral infections, such as influenza or measles. For immunologists the functions of various immune cells and the effects of cytokines are important. Ultimately, they would like to find treatments that restore the immune abnormalities in HIV infection. They would also like to develop a vaccine that prevents HIV infection or induces immune responses that eliminate or control HIV in people who are already infected.

The points of view of virologists and immunologists are not necessarily in conflict as each would recognise that both the virus and the immune system are inseparable players in the process leading to AIDS. While most treatments are directed against the virus, other strategies targeting the immune system may also be beneficial, especially when combining both types of approach. Of course, a consequence of HIV research has been a huge advance in basic knowledge about viruses and the immune system which will be helpful in the fight not only against HIV, but also other diseases.