Immunological and Virological Response to Initial Antiretroviral Therapy Among Older People Living With HIV in the Canadian Observational Cohort (CANOC)

A Zhabokritsky; L Szadkowski; AN Burchell; C Cooper; RS Hogg; M Hull; DV Kelly; M Klein; M Loutfy; A McClean; J Montaner; SL Walmsley


HIV Medicine. 2021;22(8):759-769. 

In This Article

Abstract and Introduction


Objectives: The aim of this study was to assess the adequacy of immunological recovery and virological suppression in response to antiretroviral therapy (ART) in the growing population of older people living with HIV (PLWH), as treatment regimens become more effective and tolerable.

Methods: An interprovincial Canadian cohort of treatment-naïve PLWH who initiated ART after 1 January 2000 was used and age assessed in decades. Longitudinal absolute CD4 count response to treatment was modelled using generalized estimating equations. Cumulative incidence functions and proportional hazards models with a competing risk of death were used to estimate time to: (1) CD4 ≥ 200 cells/μL, (2) CD4 ≥ 500 cells/μL, (3) virological suppression (≤ 50 copies/mL), and (4) virological failure (> 200 copies/mL).

Results: In all, 12 489 individuals starting ART between 2000 and 2016 with one or more post-treatment CD4 count or viral load were included in the analysis. Age > 60 years was associated with lower absolute CD4 recovery (adjusted β = −31 cells/μL) compared with age ≤ 30 years when pre-treatment CD4 count and other covariates were accounted for. Older age groups were less likely to achieve a CD4 ≥ 500 cells/μL, with the greatest effect in the > 60 group [adjusted hazard ratio (aHR) = 0.69, 95% confidence interval (CI): 0.57–0.84 vs. age ≤ 30). Older age groups were more likely to achieve viral suppression (age > 60, aHR = 1.20, 95% CI: 1.05–1.37) and less likely to have virological failure (age > 60, aHR = 0.46, 95% CI: 0.3–0.71) compared with those aged ≤ 30 years.

Conclusions: Older adults have robust virological responses to ART; however, individuals over the age 60 are more likely to experience blunted CD4 recovery.


Over the past two decades, the number of older adults living with HIV has steadily increased, both in high- and low- to middle-income countries.[1] This has been accompanied by a rise in the proportion of older adults living with HIV relative to other age groups,[1] with an estimated 50% now over the age of 50 in the United States and Canada.[2,3] Although life expectancy is approaching that of the general population, people living with HIV (PLWH) continue to experience fewer comorbidity free years.[4] Potentially, this is a consequence of the interplay between HIV infection, antiretroviral therapy (ART), immune activation and the ageing process, as ongoing inflammation has been linked to increased morbidity and mortality.[5] Controversies exist around the adequacy and speed of immune recovery among older adults following initiation of ART.[6–10]

With ageing, there are immune profile changes characterized by an overall increase in the number of senescent cells that have reduced proliferative capacity and decreased production of naïve T-cells accompanied by activation of proinflammatory pathways.[5,11] Similar changes have been observed with HIV infection. The combined effect of ageing and HIV infection has been linked to accelerated decline in immune function and competence, resulting in higher rates of multimorbidity, including cardiovascular disease, renal disease, neurodegeneration and malignancy.[12–14]

One of the major goals of ART is to reduce viral replication, thereby facilitating immune reconstitution, which may be particularly challenging in the ageing population. In a number of earlier studies, older age was associated with slower and overall poorer CD4 recovery with initiation of ART.[6,8,9] It has been postulated that slower CD4 recovery in older PLWH may be associated with impaired thymic function and accelerated age-related immune senescence.[15] Most of these studies were completed prior to the adoption of early ART initiation (in contrast to delaying ART until a certain CD4 threshold is reached) and before introduction of more effective and tolerable therapies, including the integrase strand transfer inhibitors (INSTIs), which are now the preferred agents for initial HIV therapy.[16] At present, it is not known how immunological and virological responses compare between individuals initiating therapy at older compared with younger ages with these advances in practice.

In the present study, we analysed the immunological and virological responses to initiation of ART in a large Canadian cohort of PLWH. We compared CD4 recovery across age groups, hypothesizing that even in the current treatment era, older adults experience worse immune reconstitution relative to their younger counterparts.