BackgroundPeople living with HIV (PLHIV) who have low CD4 counts require advanced clinical care (ACC) to minimise morbidity and mortality risk. These patients include immunological non-responders (INRs) with low CD4 counts despite a suppressed viral load.ObjectivesTo determine the proportion of patients with low CD4 counts after antiretroviral therapy (ART) initiation and to describe INRs within that group.MethodsRoutine Three Interlinked Electronic Registers.Net (TIER.Net) data from four South African districts were analysed for adult PLHIV on ART > 12 months. Immunological non-responders were defined as patients on ART > 4 years who were virally suppressed (viral load < 1000 copies/mL) with a CD4 count ≤ 350 cell/mm3.ResultsBaseline CD4 was recorded for 80.9% of the 869 571 patients newly initiating ART, with 37.2% of those starting ART since 2017 having baseline counts ≤ 200 cells/mm3. Amongst all 1 178 190 patients on ART, only 46.5% had a CD4 test after ART initiation and of these, 14.3% had CD4 ≤ 200 cells/mm3. This proportion was highest amongst patients on ART ≤ 2 years (19.7%) (p < 0.001). Amongst virally suppressed patients, 20.0% were INRs. Immunological non-response was significantly more likely amongst patients on second-line ART (adjusted odds ratio [aOR] 1.79), those aged 35-45 and ≥ 45 years (aOR 1.15 and 1.50, respectively), males (aOR 2.28) and patients with confirmed TB (aOR 2.49), and was significantly less likely in cases with higher baseline CD4 count (aOR 0.35).ConclusionCD4 testing subsequent to ART initiation is poorly implemented and there is a notable proportion of patients with low CD4 counts. Guidelines regarding CD4 testing and ACC need to be more widely implemented to identify patients with low CD4 counts and improve their outcomes.