Abstract
Human immunodeficiency virus (HIV) infection remains a significant public health burden globally. The role of viral co-infection in the rate of progression of HIV infection has been suggested but not empirically tested, particularly among children. We extracted and classified 42 viral species from whole-exome sequencing (WES) data of 813 HIV-infected children in Botswana and Uganda categorised as either long-term non-progressors (LTNPs) or rapid progressors (RPs). The Ugandan participants had a higher viral community diversity index compared to Batswana (p = 4.6 × 10−13), and viral sequences were more frequently detected among LTNPs than RPs (24% vs 16%; p = 0.008; OR, 1.9; 95% CI, 1.6–2.3), with Anelloviridae showing strong association with LTNP status (p = 3 × 10−4; q = 0.004, OR, 3.99; 95% CI, 1.74–10.25). This trend was still evident when stratified by country, sex, and sequencing platform, and after a logistic regression analysis adjusting for age, sex, country, and the sequencing platform (p = 0.02; q = 0.03; OR, 7.3; 95% CI, 1.6–40.5). Torque teno virus (TTV), which made up 95% of the Anelloviridae reads, has been associated with reduced immune activation. We identify an association between viral co-infection and prolonged AIDs-free survival status that may have utility as a biomarker of LTNP and could provide mechanistic insights to HIV progression in children, demonstrating the added value of interrogating off-target WES reads in cohort studies.
Highlights
The rates of new human immunodeficiency virus (HIV) infection in Eastern and Southern Africa increased by 50% between 2015 and 2019, despite a modest overall decline in new infections globally[1,2]
Two extreme clinical phenotypes characterise HIV-1 progression in children: (1) long-term non-progressors (LTNPs), who do not progress to AIDS for more than 10 years without antiretroviral therapy (ART) and (2) rapid progressors (RPs), who typically advance to AIDS less than 3 years after initial infection[3]
Previous studies of HIV-infected individuals as they progress to mental exposure of older LTNPs allowed for a more significant burden than the younger RPs
Summary
The rates of new human immunodeficiency virus (HIV) infection in Eastern and Southern Africa increased by 50% between 2015 and 2019, despite a modest overall decline in new infections globally[1,2]. CD4+ and CD8+ T-cell activation in HIV-1 infected children correlates significantly with CD4 T-cell percentage or absolute count, rather than viral load, which correlates strongly in adults[15]. Another recent study demonstrated that paediatric non-progressors exhibited low immune activation despite high viral loads[16], in contrast to adult elite controllers in whom the converse is true[15]
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