Ongoing High Prevalence of Severe Immune Suppression Among Children in South Africa

Abstract

Background: Among children in Southern Africa severe immune suppression (SIS) has declined, but most continue to initiate antiretroviral therapy (ART) with SIS.

Setting: Using data from South Africa, we describe SIS at ART start and on ART between 2007 and 2020, among children <5 years with a CD4%/cell count at ART start and ≥1 subsequent measure.

Methods: Gap in care was defined as >9 months without a recorded visit. We defined SIS according to age and CD4%/cell count. A multistate model was used to estimate transition probabilities between 5 states: SIS on ART; Stable, not SIS; Early Gap, commencing <9 months from ART start; Late Gap, commencing ≥9 months on ART; and Death.

Results: Among 2536 children, 70% had SIS at ART start, and 36% experienced SIS on ART. An increasing proportion were age <1 year at ART initiation (2007-2009: 43% to 2013-2020: 55%). Increasingly, SIS on ART occurred after a gap, in those with SIS on ART for >1 year, and after a period of unknown immune status. Later year of ART initiation was associated with reduced transition from SIS on ART to Stable. Infants and those initiating ART with SIS were more likely to transition from Stable to SIS. Viremia strongly predicted death from both the on ART states.

Conclusions: Increasingly SIS occurred among ART-experienced children. Those starting ART with SIS and during infancy remained especially vulnerable to SIS once on treatment. Managing ART in these children may be more complex and further reducing AIDS-related mortality is likely to remain challenging.

Figure 1:

Diagram of states and transitions of the multi-state model ART: Antiretroviral therapy SIS on ART: Severe immune suppression after ART start Stable on ART: Not severely immune suppressed after ART start Gap in care: no recorded visit for ≥9 months Early Gap: gap in care commencing ≤9 months from ART start Late Gap: gap in care commencing >9 months from ART start

Figure 2:

Proportion of on-ART person-time spent in each state by A: calendar year* and B: year on ART SIS: Severe immune suppression, ART: Antiretroviral therapy, SIS on ART: SIS after ART start Stable on ART: Not SIS after ART start *Data not shown beyond 2018 since not all cohorts reported data for this period

Figure 3:

Prior state to severe immune suppression (SIS) on ART by calendar year* SIS: Severe immune suppression, ART: Antiretroviral therapy *Data not shown beyond 2018 since not all cohorts reported data for this period