CD4 cell count and viral load accurately predict risk of disease progression, regardless of which antiretroviral used

CD4 cell count and viral load provide an accurate guide to the risk of progression to AIDS and death for all antiretroviral regimens, according to a study published in the February 18^th edition of AIDS.

In 1997, the way in which trials assessed the efficacy of anti-HIV drugs changed fundamentally. Instead of being required to show that a drug reduced the rate of new AIDS events and deaths, it became sufficient to demonstrate that an agent reduced HIV viral load and increased CD4 cell count. This decision was based on evidence from clinical trials looking at the use of antiretroviral drugs as mono or dual therapy showing that a fall in viral load and increase in CD4 cell count was strongly correlated with the clinical efficacy of a regimen.

Nelfinavir, abacavir, nevirapine, efavirenz and lopinavir are amongst the “newer” drugs included in the investigators' analysis which were approved on the basis of their effect on viral load and CD4 cell count alone.

Investigators from the EuroSIDA cohort study wished to evaluate if the assumption that the link between viral load, CD4 cell count and disease progression was equally accurate for all antiretroviral regimens. Accordingly, they described the risk of AIDS and death according to the latest CD4 cell count and viral load for several different antiretroviral regimens.

Data for 6,814 patients until the end of November 2003 were available for analysis. The majority of patients (78%) were male, the median date for starting HAART was March 1997, and the median age was 37 years. A total of 70% of patients had taken antiretroviral drugs as either monotherapy or dual therapy prior to starting at HAART. At the time when HAART was started, the median CD4 cell count was 184 cells/mm³ and the median viral load was 26, 000 copies/ml.

A total of 22, 766 patient years of follow-up were available for analysis. The last median CD4 cell count was 353 cells/mm³ and the last median viral load was 199 copies/ml.

During the follow-up period a total of 779 new AIDS-defining events were recorded and 125 deaths. New AIDS events and deaths for any given CD4 cell count and viral load were similar regardless of the specific drug regimen used. The investigators then repeated their analysis, restricting it to patients who had started HAART with a CD4 cell count below 200 cells/mm3. Once again, they found that new AIDS events and deaths were similar for any given CD4 cell count, regardless of the HIV agent used.

“Reassuringly, we found that rates of disease and death for…the most recent HIV- RNA/CD4 cell count do not appear to differ between drugs for which there is some direct evidence of clinical efficacy (AZT, ddI, 3TC, indinavir, ritonavir, saquinavir) and the newer drugs which are currently widely used, for which there is no such evidence”, write the investigators.

They add, “for a given CD4 cell count, HIV-RNA…the risk of AIDS or death is the same, regardless of the specific antiretroviral drug used.”

“AIDS/death rate ratios do not appear to differ significantly for various regimens for patients having the same CD4 cell count or HIV-RNA levels. This implies that markers currently used for gauging patients’ risk of clinical progression can be interpreted similarly, regardless of which regimen the patient is taking”, conclude the investigators.