The effect of age on the outcomes of combination antiretrovrial treatment in resource limited settings

Abstract

Background: HIV is one of the most closely monitored epidemics in the world. Despite this, little attention has been placed on older adults living with HIV, especially in resource limited settings. Objectives: The objectives of this research were to estimate 1) the association between age at combination antiretroviral therapy (cART) initiation and mean CD4 cell count over time by strata of baseline CD4 cell count as well variability of immune reconstitution, and 2) whether older age is associated with more rapid regimen change due to cART associated toxicities and side-effects. Methods: We conducted a retrospective cohort study of adults who initiated cART between August 1, 2004 and September 1, 2012 in 157 PEPFAR funded clinics supported by AIDSRelief in four countries in sub-Saharan Africa. Results: Of the 452,819 patients enrolled, 181,354 met the study eligibility criteria. Patients age 40 and older had significantly lower mean CD4 cell counts and less variability as compared to patients aged 20 - 39 with each strata of baseline CD4 cell count up to five years after cART initiation. The differences in mean CD4 cell count were more pronounced in the higher strata of baseline CD4 cell count than in lower strata. Older patients progressed to regimen change due to toxicity or side-effect more rapidly than younger patients within regimens containing D4T and AZT. There was no difference in the hazard of regimen change within TDF containing regimens comparing older to younger patients. Conclusions: While we found statistically significant differences at most time points following the initiation of cART for all strata, it was only in the highest strata of baseline CD4 cell count (> 350 cells/mm3) that the difference between age groups was what we, a priori, defined as an important difference of 50 cells. Older groups may demonstrate less variability in CD4 cell reconstitution than younger groups. The faster progression to regimen change among older adults on D4T and AZT warrants a discussion on closer monitoring of older patients for toxicity and side-effects earlier after the initiation of cART.