HIV-positive individuals whose anti-HIV therapy succeeds in suppressing viral load to undetectable levels, but who nevertheless fail to experience an increase in their CD4 cell count above 200 cells/mm3, remain at a high risk of experiencing progression to AIDS and death in the first year of HIV treatment, according to a study presented to the Forty-Sixth Interscience Conference on Antimicrobial Agents and Chemotherapy in San Francisco last week. The investigators, from the University of British Columbia, say that this finding is “concerning”.
The objective of anti-HIV therapy is to suppress the replication of HIV in the blood to undetectable levels (below 50 copies/ml). This allows the immune system, measured by CD4 cell count, to strengthen, therefore preventing the emergence of AIDS-defining infections and tumours. A CD4 cell count above 200 cells/mm3 is considered to be the minimum level needed to protect against potentially life-threatening AIDS-defining illnesses.
However some patients who commence antiretroviral therapy experience what is called an “immunologically discordant” response to their HIV therapy. This means that although their viral load is suppressed to undetectable levels, their CD4 cell count fails to increase to above 200 cells/mm3.
Canadian investigators wished to determine if a failure to achieve a CD4 cell count above 200 cells/mm3, despite having an undetectable viral load, was associated with an increased risk of progression to AIDS and death. They therefore conducted a study involving 299 individuals who started treatment with potent anti-HIV therapy between 1996 and 2003.
To be included in the study, patients needed to have had two consecutive viral loads below 50 copies/ml. The investigators then divided patients into two groups according to their CD4 cell count response to therapy – individuals whose CD4 cell count had increased to at least the target level of 200 cells/mm3, and those whose CD4 cell count had not. Rates of progression to AIDS and death were then compared between the two groups during the first year of anti-HIV therapy.
The median age of the study population at baseline was 42 years, 86% were male, 15% were (or had been) injecting drug users, 27% had been diagnosed with AIDS, and median CD4 cell count was 80 cells/mm3.
A total of 97 patients (32%) failed to experience an increase in their CD4 cell count during the first year of antiretroviral therapy, despite having effective control of HIV. There were 21 new AIDS-defining events, and six deaths. When the investigators looked at the factors associated with an risk of HIV disease progression, they found that patients whose CD4 cell count did not increase to at least 200 cells/mm3 a year after commencing virologically effective antiretroviral therapy had a hazard ratio of progression to AIDS or death of 3.94 compared to patients whose CD4 cell count increased to above 200 cells/mm3.
“HIV-infected patients taking combination antiretroviral therapy who achieve complete viral suppression but fail to have a CD4 cell increase above the desired target of 200 cells/mm3 have an increased rate of clinical events in the first year of combination antiretroviral therapy”, conclude the investigators.
Lutfy MR et al. Increased clinical events in HIV-infected patients who achieve full virologic suppression but fail to attain a CD4 count equal or above 200 cells/mm3 after 1 year of cART. Forty-Sixth Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, abstract H-1403, 2006.