Only modest benefits from starting HIV therapy with a CD4 cell count above 500 compared to 350

Starting HIV therapy with a CD4 cell count above 500 cells/mm³ has only minimal additional benefits compared to initiating therapy with a CD4 cell count in the region of 350-500 cells/mm³, Australian investigators report in the online edition of the Journal of Acquired Immune Deficiency Syndromes.

The study was restricted to patients with started antiretroviral treatment when their CD4 cell count was above 350 cells/mm³.

Patients with CD4 cell counts between 350-500 cells/mm³ rapidly achieved increases to above 500 cells/mm³. Moreover, 72 months after the commencement of treatment, patients had broadly comparable CD4 cell counts, regardless of their immune status at baseline.

Starting treatment at higher CD4 cell counts had clinical benefits, but overall these were modest.

The study will inform the ongoing debate about the best time to start antiretroviral therapy.

Individuals who start treatment before their CD4 cell count falls below 350 cells/mm³ are known to have a lower risk of illness and death from both HIV-related and some non-HIV-related diseases. However, the benefits of therapy at higher CD4 cell counts are unclear. Some doctors believe that the threshold for initiating therapy should be 500 cells/mm³.

A large randomised clinical trial called the START study is currently examining this question, but  its results are not expected for a number of years. Therefore Australian investigators performed an observational study involving 432 individuals who started HIV therapy when their CD4 cell count was above 350 cells/mm³.

The patients were stratified into three groups on the basis of their baseline CD4 cell count (350-500; 501-650; above 650 cells/mm³), and were followed for 72 months, with investigators monitoring changes in CD4 cell counts between the three groups.

Using data obtained from other large studies, the investigators calculated the impact of baseline CD4 cell strata on the risk of progression to AIDS or death.

After twelve months of HIV therapy, mean CD4 cell counts had increased to above 500 cells/mm³ for patients in all baseline CD4 cell strata (means 596, 717, and 881 cells/mm³ respectively).

“Patients who commenced treatment with a baseline CD4 cell count 351-500 cells/mm³, typically and rapidly…achieved and maintained a CD4 cell count greater than 500 cells/mm³,” comment the investigators.

After 72 months of therapy, mean CD4 cell counts were broadly comparable regardless of baseline CD4 cell strata (689, 746 and 742 cells/mm³ respectively).

The investigators then turned their attention to the impact of baseline CD4 cell count on the risk of death or AIDS.

Using data from another study, the investigators estimated that patients who started treatment when their CD4 cell count was above 650 cells/mm³ had a projected 8% reduction in mortality over 72 months compared to individuals who initiated therapy when their CD4 cell count was in the region of 350-500 cells/mm³, an absolute risk reduction of 0.33 per 1000 patient years.

Comparison with patients in the 500-650 cells/mm³ strata showed that individuals with a CD4 cell count above 650 cells/mm³ had a 4% reduction in their risk of death over six years, an absolute reduction of 0.16 per 1000 person years.

Extrapolation of data from two other studies showed that patients who started therapy with a CD4 cell count above 650 cells/mm³ reduced their risk of progressing to AIDS or death by 14% compared to individuals who initiated therapy with a CD4 cell count between 350-500 cells/mm³.

“Our results shows that potentially, initiating cART (combination antiretroviral therapy) at CD4 cell counts >650 cells/mm³ could yield the prevention of hundreds or thousands or AIDS events or illnesses,” write the authors.

They conclude, “our analysis suggests that patients who start cART at CD4 counts >650 cells/mm³ have better preserved immune function, but only to a relatively modest degree…furthermore the extent to which this might be expected to result in better clinical outcomes we show to be uncertain.”

Wright ST et al. CD4 cell responses to combination antiretroviral therapy in patients starting therapy with high CD4 cell counts. J Acquir Immune Defic Syndr, online edition, doi: 10.1097/QAI.0b013e318225ba62 (click here for the free abstract).