The Role of HIV in Serious Diseases Other Than AIDS

Andrew N. Phillips; James Neaton; Jens D. Lundgren

Disclosures

AIDS. 2008;22(18):2409-2418. 

In This Article

Introduction

Now that we are over 10 years into the HAART era in resource-rich countries the major clinical impact of this therapy on reduced AIDS events and AIDS deaths has been well described[1] and in the past few years the focus has turned to describing and understanding what residual clinical disease remains in populations of HIV-infected individuals. As death rates may be still falling in HIV-infected patients,[2,3] at 0.5-1.0% per year, there is still a considerable excess risk compared with the general population. The breakdown of causes of death of patients has been described based on a study of deaths occurring in 2005 in France.[4] AIDS diseases were responsible for only 36% of deaths, with a further 5% due to non-AIDS infections. Other leading causes of death were non-AIDS cancers (16%), liver disease (15%), cardiovascular disease (9%), and suicide (5%). In a United States study, Lau et al.[5] found that risk of death from non-AIDS conditions was greater than that for AIDS conditions for persons with CD4 count above 200/mm3.

Now with fewer AIDS deaths we have of course observed an increase in the proportion of deaths due to non-AIDS causes, however, this does not mean to say that there has been an increase in the rate of non-AIDS - quite the reverse in fact. Unpublished data from EuroSIDA on trends over calendar time in rates of non-AIDS death (Fig. 1) indicate that the start of the HAART era was actually accompanied by a decline in the rate of death from non-AIDS causes ([6] and Personal communication), a finding that has been observed in other studies.[7] This at first somewhat puzzling observation suggests that perhaps HIV may be playing a role in other diseases well beyond the 26 diseases which characterize AIDS. As we keep people with HIV alive for longer there will be an ever-growing number of people with HIV. If HIV is influencing risk of these events, particularly if it does so in the higher CD4 count range where the majority of treated patients hopefully will be, then it is very important to be aware of this and to study it. In this article we briefly consider what rationale (i.e., potential mechanisms) there might be to hypothesize that HIV may play a role in causing diseases such as non-AIDS malignancy, liver cirrhosis, end stage renal disease and serious cardiovascular events (e.g., myocardial infarction, stroke and surgery for coronary artery disease). Collectively, we refer to these as serious non-AIDS events. We then go on to review studies, which have data on incidence of serious non-AIDS disease, death, or both, from these diseases to build up a picture of the current state of knowledge. We finish by suggesting the implications for future research and current clinical care of patients. This review is not intended to consider adverse effects due to antiretroviral drugs (ART), although it is recognized that it is not always easy to separate the effects of HIV from the effects of ART.

Figure 1.

Rate of non-AIDS death by calendar time: EuroSIDA. Adapted with permission from.[6]

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