People with lower CD4 cell counts on antiretroviral treatment have a higher risk of developing non-AIDS defining liver, kidney and cardiovascular disorders, as well as a higher risk of developing 32 non-AIDS defining cancers, Jason Baker of the University of Minnesota reported on Monday at the Fourteenth Conference on Retroviruses and Opportunistic Infections in Los Angeles. He was presenting an analysis of data from the FIRST study, a US comparison of three different approaches to antiretroviral therapy that followed patients for five years.
Although it is well established that people who have low CD4 cell counts while taking antiretroviral therapy remain at risk of AIDS-defining opportunistic infections, the risk of non-AIDS defining illnesses in such people has been unclear.
This analysis of the FIRST study, which randomised 1,397 antiretroviral-naïve patients to either a PI-based, NNRTI-based or triple-class regimen, set out to answer the question.
The researchers looked at fatal and non-fatal illnesses in four categories:
- liver diseases such as cirrhosis and grade 4 transaminitis,
- cardiovascular-related illnesses such as myocardial infarction, stroke or coronary artery disease requiring surgery;
- Renal problems such as end-stage renal disease or renal insufficiency
- non-AIDS-defining cancers; 32 malignancies including skin, anal and lung cancers, but excluding non-Hodgkin’s lymphoma and Kaposi’s sarcoma.
They calculated the risk of these events through a multivariate analysis which adjusted for the latest viral load and CD4 cell count, age, gender, prior AIDS diagnosis, hepatitis coinfection and injecting drug use.
A total of 226 AIDS-defining events occurred during the follow-up period, and 166 non-AIDS defining events.
They found that the risk of non-AIDS defining illnesses decreased by around 16% for every 100 cell increment in CD4 cell count (HR 0.84, p<0.01), while the risk of AIDS-defining events fell by 43% for every 100 cell increment in CD4 cell count (HR 0.57, p<0.01).
Although the study was inadequately powered to investigate the risk of specific non-AIDS defining events such as myocardial infarction or cirrhosis, the analysis did show that the risk of liver-related events as a whole was reduced by approximately 13% per 100 cell increment in CD4 cell count (HR 0.87, p<0.01). The risk reduction as CD4 cell count rose was not significant for other categories of non-AIDS defining events studied, although cardiovascular events did show a trend towards lower incidence as CD4 cell counts rose.
Commenting on the findings at a press conference, Jason Baker said that if starting treatment at a higher CD4 cell count translated into even a small reduction in the individual’s risk of morbidity and mortality from non- AIDS defining illnesses, this reduction could translate into a substantial reduction in risk across the whole population of people receiving treatment.
Asked whether the incidence of non-AIDS defining events was simply a consequence of people living longer as a result of antiretroviral treatment and consequently succumbing to illnesses related to ageing and lifestyle, Baker said: “The fact that it’s associated with CD4 level starts to build the case that these people aren’t just getting these illnesses because they’re living longer.”
The findings are likely to lend support to treatment strategies that focus on maximising CD4 cell counts, such as starting treatment earlier.