'HIV disease is characterised by a mixture of immune suppression and immune activation. So far we have focused only on fixing the suppressive side of the disease.'
For many years the focus of HIV management has rightly moved from opportunistic infection treatment and prevention to control of viraemia, as advances in new drug development and clinical trials have brought a number of new drugs, and new drug classes, to the clinic. While our patients are predominantly controlling HIV replication and have heartening recoveries in CD4 cell counts, we might think that the battle is over. However, we have succeeded in only one part of a dual-faceted disease.
Our immune response to pathogens represents a two-edged sword in many respects; able to generate vigorous responses to protect us from infections, but in doing so, can also damage our body. With regard to HIV infection, the immune response has always been considered suboptimal as the majority of people are unable to clear the virus and suffer from progressive declines in CD4 cell numbers. It was recognised from the earliest reports of AIDS that the CD4 cell depletion was also accompanied by a CD8 cell increase (with a resulting inversion of the normal CD4/CD8 ratio). We have tended to ignore this CD8 evaluation, as the immune suppression is the key process that affects patient mortality. Once viral load testing became routine, the efforts of most clinicians have focused on using combination antiretroviral therapy (ART) to control replication. This we can now do effectively; with 94% of ART-treated patients at our clinic having a viral load below 50 copies/ml.
With cessation of HIV-induced immune deficiency, more attention can now be focused on the long-term effects of chronic immune stimulation. The articles in this issue focus on some of these aspects.
CARDIOVASCULAR DISEASE RISK WITH CHRONIC INFLAMMATION
Perhaps the most immediate concern with chronic inflammation is its effect on accelerating cardiovascular disease (CVD). As mortality associated with opportunistic infections has virtually disappeared, we are now facing patients whose HIV is suppressed, whose CD4 cell counts are normal or near normal; but yet who are ageing and accumulating cardiovascular risk factors. The majority of the patients seen at this clinic are males over 45, 44% of whom are smokers, with antiretroviral therapy-related increases in cholesterol, declining renal function and increasing blood pressure. In addition...