Immunologic Non-Response Despite Viral Suppression

For HIV-positive individuals who begin antiretroviral therapy (ART) at CD4 counts below 500 cells/mm³, immunologic non-response has been shown in prior research to be associated with increased risk for AIDS, serious non-AIDS diseases, and death. Although risk factors for non-response are well understood for these patients, data are lacking on such risk factors among those beginning ART at CD4 counts above 500 cells/mm³.

Among participants randomized to immediate ART in the Strategic Timing of AntiRetroviral Therapy (START) trial—initiated to study immediate versus delayed ART in HIV-positive adults—Jeffrey A. Boatman, PhD, and colleagues investigated immunologic non-response in participants beginning antiretroviral therapy with CD4 counts over 500 cells/mm³. For the study, published in JAIDS, low CD4 recovery (immunologic non-response) was defined as a CD4 increase of less than 50 cells/mm³ from baseline after 8 months despite viral load of 200 copies/mL or lower. Risk factors for low recovery were investigated with logistic regression.

“Immunologic non-response was observed in 39.7% of participants in the immediate treatment group,” explains Dr. Boatman. “Risk factors were similar to those previously reported for HIV-positive participants beginning treatment at lower CD4 counts, including male gender (odds ratio [OR], 1.53), lower pre-treatment CD4 cell count (OR, 1.09 per 100 fewer cells/mm³), higher pre-treatment CD8 cell count (OR, 1.05 per 100 more cells/mm³, and lower HIV RNA levels (OR, 1.93 per log₁₀ decrease).”

Dr. Boatman notes that although the study team may be able to address long-term implications of poor recovery with ongoing follow-up with START participants, the current study lacked the power to determine whether poor CD4 recovery among HIV-positive individuals starting ART at high CD4 cell counts is associated with an increased risk of clinical outcomes, such as AIDS and non-AIDS conditions. “Studies examining the genetic risk factors for low CD4 recovery, and additional follow-up data from START, may provide insight,” he adds.