In this issue, Hessamfar-Bonarek et al.1 studied the cause of death among HIV-infected men and women in France in 2005. The study was based on a national survey in which physicians were asked to report deaths among HIV-infected adults. Each case was documented by a standardized questionnaire. Deaths attributed to conditions included in the Centers for Disease Control and Prevention (CDC) classification of AIDS-defining conditions2 were categorized as ‘AIDS deaths’; all others were ‘non-AIDS deaths’. More women died of ‘AIDS deaths’ and differences in cause of death by gender were explained by age, substance use (drugs, tobacco and alcohol) and socio-economic precariousness. The authors conclude that socially and economically precarious individuals, particularly women, should be targeted for engagement with health care.
Although their conclusion seems reasonable, cause of death analyses are useful when addressing whether a death is or is not due to a single, unambiguously defined, precipitating event; for example, a violent vs non-violent death. The analyses become, however, increasingly less meaningful as the complexity of the disease increases. Complex chronic disease is present when multiple aetiologies (ageing, disease progression, disease interactions with comorbid conditions and with treatment toxicity) combine to cause progressive loss of physiological reserve with resulting morbidity and mortality.3 These aetiologies do not act independently, but cumulatively and, at times, synergistically.
Treated HIV infection is a complex chronic disease where multiple aetiologies of morbidity and mortality are the rule rather than the exception. Results from a randomized trial, Strategies for Management of Antiretroviral Therapy (SMART),4 suggest that many ‘non-AIDS’ conditions (renal disease, liver disease and cardiovascular disease) are caused or exacerbated by HIV disease progression. Based on observational studies, this list of ‘non-AIDS’ conditions associated with HIV disease and mortality continues to grow and includes anaemia,5 thrombosis,6 obstructive lung disease,7 intracranial haemorrhage8 and several ‘non-AIDS’ cancers.9 Progression of hepatitis B and C infection is accelerated among those with HIV infection.10 Further, the association between CDC AIDS-defining conditions and death is highly variable11 and not uniformly stronger than that for ‘non-AIDS’ conditions and death. For example, disseminated herpes simplex disease (an AIDS-defining event) has no association with death,11 whereas hepatitis C has a strong independent association with mortality and this association is stronger among those co-infected with HIV and hepatitis C.10
The SMART investigators observed more ‘non-AIDS’ than serious AIDS events and only 8% of the deaths were AIDS-defining.4 Failing to recognize ‘non-AIDS’ conditions that are caused by multiple aetiologies including HIV infection will cause us to dramatically underestimate the burden of HIV disease. Because the frequency of these ‘non-AIDS’ HIV-associated conditions varies by race/ethnicity, gender, age and health behaviours, cause of death data may lead us to underestimate the effects of HIV among those at greatest risk: the older patients, economically disadvantaged patients, and those who smoke, drink or abuse drugs.