Inflammatory pathways amongst people living with HIV in Malawi differ according to socioeconomic status
Authors: Kelly Christine , Tinago Willard , Alber Dagmar , Hunter Patricia , Luckhurst Natasha , Connolly Jake , Arrigoni Francesca , Abner Alejandro Garcia , Kamngona Ralph , Sheha Irene , Chammudzi Mishek , Jambo Kondwani , Mallewa Jane , Rapala Alicja , Mallon Patrick WG , Mwandumba Henry , Klein Nigel , Khoo Saye 
Published: June 2020

Background

Non-communicable diseases (NCDs) are increased amongst people living with HIV (PLWH) and are driven by persistent immune activation. The role of socioeconomic status (SES) in immune activation amongst PLWH is unknown, especially in low income sub Saharan Africa (SSA), where such impacts may be particularly severe.

Methods

We recruited Malawian adults with CD4<100 cells/ul two weeks after starting ART in the REALITY trial (NCT01825031), as well as volunteers without HIV infection. Clinical assessment, socioeconomic evaluation, blood draw for immune activation markers and carotid femoral pulse wave velocity (cfPWV) were carried out at 2 and 42 weeks post-ART initiation. Socioeconomic risk factors for immune activation and arterial stiffness were assessed using linear regression models.

Results

Of 279 PLWH, the median (IQR) age was 36 (31-43) years and 122 (44%) female. Activated CD8 T-cells increased from 70% amongst those with no education to 88% amongst those with a tertiary education (p=0.002); and from 71% amongst those earning less than 10 USD/month to 87% amongst those earning between 100-150 USD/month (p=0.0001). Arterial stiffness was also associated with higher SES (car ownership p=0.003, television ownership p=0.012 and electricity access p=0.029). Conversely, intermediate monocytes were higher amongst those with no education compared to a tertiary education (12.6% versus 7.3%; p=0.01) and amongst those earning less than 10 USD/month compared to 100-150 USD/month (10.5% versus 8.0%; p=0.08). Water kiosk use was protective against T cell activation (p=0.007), as well as endothelial damage (MIP1β, sICAM1 and sVCAM1 p=0.047, 0.026 and 0.031 respectively).

Conclusions

Socioeconomic risk factors for persistent inflammation amongst PLWH in SSA differ depending on the type of inflammatory pathway. Understanding these pathways and their socioeconomic drivers will help identify those at risk and target interventions for NCDs. Future studies assessing drivers of inflammation amongst PLWH should include an SES assessment.

Key points

What is already known?

Persistent immune activation drives an increased risk of non-communicable diseases amongst people living with HIV. The aetiology of persistent immune activation amongst PLWH is complex and includes microbial translocation, subclinical co-infection and continued low level HIV viral replication. However, the contribution of socioeconomic factors has not previously been investigated, and may be especially relevant amongst those living in low income settings.

What are the new findings?

The contribution of socioeconomic factors to persistent inflammation differs according to the type of inflammatory pathway. PLWH with higher socioeconomic status are at increased risk of T cell activation and arterial stiffness, perhaps as a result of more sedentary lifestyles. Conversely, evidence of innate immune activation is seen amongst those with lower socioeconomic status. Water kiosk use is associated with a favourable inflammatory profile.

What do the findings imply?

The phenotype of chronic immune activation amongst PLWH in a low-income sub-Saharan Africa setting differs according to socioeconomic status. We recommend incorporation of socioeconomic factors into future studies assessing the relationship between chronic inflammation and non-communicable diseases amongst HIV populations.