A third of deaths in patients with HIV are attributable to other serious illness present at time of HIV diagnosis

A substantial proportion of the mortality in HIV-positive patients is caused by serious illnesses that were present before diagnosis with HIV, Danish investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

Overall, a third of all deaths were attributable to illnesses that were already present at the time of HIV diagnosis. The study also showed that mortality rates were significantly higher in patients with HIV than in the general Danish population.

The introduction of effective antiretroviral therapy in the late 1990s transformed the prognosis of many HIV-positive patients. Non-AIDS-related diseases are an increasingly important cause of illness and death in patients with HIV, and the burden of such diseases is expected to increase as the HIV-positive population ages.

However, the impact of illnesses acquired by patients before their diagnosis with HIV on prognosis is poorly understood.

Therefore Danish investigators undertook a population-based study involving adult patients who were diagnosed with HIV in the country between 1997 and 2005. These individuals had at least two years of follow-up and each was paired with up to 99 age and sex-matched HIV-negative controls.

Details of co-morbidities were obtained from national registries. The investigators then calculated a Charlson Co-morbidity Index score for each patient and their matched controls. The Charlson C-morbidity Index includes serious illnesses which are scored from 1 to 3 according to their potential impact on mortality.

Mortality rates were calculated for individuals according to their Charlson Co-morbidity Index score (0, 1, 2, 3 and above).

A total of 1638 patients were diagnosed with HIV during the period of the study, and 195 of these individuals during 9350 person years of follow-up. This provided a mortality rate of 2.09% compared to a rate of just 0.39% in the general Danish population.

Another serious illness was present in 22% of patients at the time of their HIV diagnosis. This included 13% of patients who were co-infected with hepatitis C.

Pre-existing co-morbid conditions significantly increased the risk of death for patients. HIV-positive individuals who had one or more Charlson Co-morbidity Index points had significantly higher mortality rates than HIV-infected patients with no points on the index (mortality rate = 1.84; 95% CI, 1.32-2.57).

The investigators then compared mortality rates between HIV-positive patients and HIV-negative controls according to their Charlson Co-morbidity Index score. In each strata, HIV-positive individuals had a significantly higher mortality rate.

• Score 0: HIV =  1.70 vs. 0.27 per 100 person years.

• Score 1: HIV = 4.37 vs. 1.36 per 100 person years.

• Score 2: HIV = 8.06 vs. 2.44 per 100 person years.

• Score 3 and above: HIV = 10.15 vs. 5.84 per 100 person years.

This excess mortality in patients with HIV was explained by an interaction between HIV and the co-morbid conditions. Compared to patients with no Charlson Co-morbidity Index points, 59% of excess deaths for patients with one point could be attributed to this interaction, 66% of increased mortality for patients with two points, and 34% of excess deaths for patients with three or more points.

Overall, the investigators calculated that 32% of deaths in patients with HIV were due to serious illnesses that were present before HIV was diagnosed. Moreover, 45% of total mortality in patients with HIV was due to non-HIV-related causes.

“We found that morbidity acquired before HIV diagnosis was an independent risk factor for death,” comment the investigators.

“Almost half the mortality in persons diagnosed with HIV in a health care setting with free access to HAART [highly active antiretroviral therapy] stemmed from factors unrelated to the HIV disease or associated factors such as toxicity of antiretroviral drugs. Moreover, comorbidity acquired before HIV diagnosis acted synergistically with HIV as a risk factor for death.”

They add, “the considerable burden conferred by diseases acquired prior to HIV diagnosis, found in more than one in five patients in this study, calls for a comprehensive approach to treatment and care. Involvement of a team of medical specialists is clearly needed.”

The investigators suggest that lifestyle and self-care issues could contribute to the high prevalence of pre-existing serious illnesses present in patients at the time of their HIV diagnosis. “Further studies aiming to identify biological as well as sociocultural risk factors for comorbidity are required to increase our understanding of the complex interaction between HIV and diseases acquired before HIV.”