Immune reconstitution in HIV infection

The weight of the published evidence suggest that there is clinically significant immune recovery in a sizable fraction of HIV-infected patients who achieve suppression of viral replication. At the same time, it is clear that very few patients regain normal (i.e. equivalent to pre-infection) immune function, at least after the follow-up periods available so far. The experience from bone-marrow transplantation or intensive chemotherapy in adults suggests that such kind of immune reconstitution is unlikely (at least with treatments limited to stopping virus replication) once the immune system has been sufficiently damaged. It is also clear that effective immunity to HIV is not achieved in a significant proportion of patients. These findings have implications for both basic research and clinical practice. From the laboratory perspective, besides the urgent need to characterize the protective immunity to HIV (if it exists), it would be desirable to find some simple measure of the immune function of patients who receive therapy. The combination of markers of immune activation together with CD4 cell count and viral load should be further evaluated in this context. Regarding clinical practice, it is likely that prophylaxes for opportunistic infections can be discontinued uneventfully in the majority of patients responding to HAART. Although the evidence is not yet conclusive, all available data suggest this will be the case. Given that there is significant immune reconstitution even in advanced disease, it is tempting to consider if this fact can be used to support antiviral therapy recommendations that are less aggressive than the current ones. HIV eradication by pharmacologic means alone does not seem possible yet, and no effective immune response to HIV seems to be generated by starting therapy in the asymptomatic (as opposed to acute infection) stage of the disease. At the same time, the follow-up studies on prolonged antiretroviral therapy suggest that virologic failure will take place despite many months of seemingly adequate suppression. This fact, taken together with the side effects and inconvience of current antiretroviral regimens, can be used to support an argument in favor of evaluating strategies to treat later rather than earlier.