Immunological failure despite virological suppression in HIV seropositive individuals on antiretroviral therapy

Some individuals experience a discordant response during antiretroviral therapy (ART), with a blunted CD4+ cell count response despite low HIV-1 RNA plasma levels.

CD4 counts and viral load of 251 individuals on ART referred to the center were analysed for immunological failure. The viral load tests of 28 patients revealed a discordant response, characterized by low CD4 counts despite viral suppression (<47 copies in 23, <5000 in 4 patients and <10000 in one patient). Univariate and multiple regression analysis was done to determine factors associated with immunological failure in patients with viral suppression.

Twenty-eight patients developed immunological failure over a duration of 3.7±1.14 years despite viral suppression. In univariate analysis of discordant patients, low CD4 counts(<100cells/μl) at start of ART(P=0.0261), less than 50% gain in CD4 count (P=0.048) after one year of start of ART and duration on ART for more than 3 years (P=0.0436) were associated with immunological failure. In multiple regression, duration on ART, age and nadir CD4 count (lowest ever) on treatment were predictors of immunological failure in these patients. Overall females (n=8) demonstrated much higher CD4 counts of 136±72 than males (n=20) 79±38 cells/μl at the time of diagnosis of immunological failure.

Discordance was observed in 13.59% of patients. Detection of failure to first line therapy based on immunologic criteria, without viral load testing, can result in unnecessary switches to 2(nd) line therapy.