Earlier deaths in people with HIV due to drugs, alcohol, co-infections, poorly controlled HIV - not rapid ageing

Patients taking antiretroviral therapy have the same mortality risk as individuals in the general population, according to Danish research published in the open-access journal PLoS One. However, this was only the case when the patients responded to treatment and did not have other factors that increased the risk of serious illness and death, such as co-infections or co-morbidities, or drug and alcohol misuse.

“Mortality was associated mainly with well-known HIV and non-HIV-associated risk factors which are identifiable prior to or in the initial phase of HAART [highly active antiretroviral therapy] treatment,” comment the investigators. “Mortality in HIV-infected patients with no identifiable risk factors was almost identical to that of the general population with no risk factors.”

Effective antiretroviral therapy means that many HIV-positive patients have an excellent prognosis. Nevertheless, numerous studies have shown that the overall mortality risk of patients treated with anti-HIV drugs is still higher relative to that observed in the general population.

A number of reasons for this have been proposed including HIV-related illness, co-infections, lifestyle issues, treatment side-effects and accelerated ageing.

Danish investigators wanted to establish a better understanding of this important question.

They therefore designed a study with two aims. The first was to establish the impact on mortality of risk factors that could be identified at the time HIV treatment was started. The second was to estimate the relative risk of death for patients with and without such factors when compared to age- and sex-matched controls from the general population.

The study population comprised 2267 people aged between 25 and 65 who started HIV therapy between 1998 and 2010. The medical records of each patient were checked to see if they had risk factors that could increase the risk of death. These were divided into three broad categories:

• Inadequate control of HIV. This was defined as a detectable viral load or a CD4 cell count below 200 cells/mm³.

• Co-morbidities and co-infections.

• Drug or alcohol abuse.

Each patients was matched with four HIV-negative controls from the general population.

Patients aged between 45 and 65 who had a good response to antiretroviral treatment and who did not have any co-morbidities/co-infections or drug/alcohol problems had a mortality risk ratio (MRR) of 1.14, comparable to that observed in the control population. The risk was somewhat higher for younger patients (25 to 45) who were doing well on therapy, but who had no additional risk factors (MRR = 2.02).

However, the risk of death was increased between four-fold and 20-fold for patients with either co-morbidities/co-infections or problems with drug/alcohol use.

“Increased risk of death was observed only in patients registered with one or more risk factors in the initial phase of HAART treatment,” emphasise the authors.

Individuals in the control group had an 88% probability of surviving until they were 65. The overall chance of survival to this age for patients with HIV was much lower at only 48%.

However, the probability of survival was massively affected by the presence of identifiable risk factors.

Patients with poor response to HIV therapy had a 58% chance of surviving until 65 years of age. This fell to 30% for patients with co-morbidities or co-infections, and to just 3% in those with high levels of drug or alcohol use.

In contrast, patients with none of these risk factors had a chance of survival to age 65 that was comparable to that seen in the general population (86 vs 88%).

“As we did not observe substantially increased mortality among HIV patients without risk factors, our data does not support the theory of premature ageing,” write the authors. “Rather, the data establish that the increased risk of death in the HIV population mainly stems from classic risk factors.”

They conclude: “Future management of the HIV-infected population should focus on early diagnosis, timely and effective HAART, and treatment of co-morbidity and alcohol/drug abuse.”

The authors also believe that it is important to give patients optimistic and accurate information about their potential prognosis, commenting: “Stressing the impact of HIV on mortality after HAART initiation may severely hamper the patients’ quality of life and be at odds with present data.”

Obel N et al. Impact of non-HIV and HIV risk factors on survival in HIV-infected patients on HAART: a population-based nationwide cohort study. PLoS One 6 (7): e22698. Doi:10/1371/journal.pone.0022698, 2011 (click here for the free paper).