The effect of HIV treatment interruption on subsequent immunologic response

Abstract

CD4 count recovery after antiretroviral treatment (ART) initiation has been thoroughly examined in HIV infection. However, immunologic response after ART restart following care interruption is less well studied. We compare the CD4 trends before disengagement from care and after ART re-initiation. Data were obtained from the East-Africa International epidemiology Databases to Evaluate AIDS (IeDEA) Collaboration (N= 62,534). CD4 trends before disengagement, during disengagement, and after ART re-initiation were simultaneously estimated through a linear mixed model with two subject-specific knots placed at the time of disengagement and treatment re-initiation. We also estimated CD4 trends conditional on the baseline CD4 value. 10,961 patients returned to care after disengagement from care, with the median (IQR) time of gap in care being 2.7 (2.1, 5.4) months. Our model showed that CD4 increases after ART re-initiation were much slower than those before disengagement. Assuming that disengagement from care occurs 12 months after ART initiation and a three-month treatment gap, CD4 counts at 3 years since ART initiation would be lower by 36.5 cells/$\mu L$ than those obtained under no disengagement. Given that poorer CD4 restoration is associated with increased mortality/morbidity, specific interventions targeting at better retention to care are urgently required.