Analysis of the early responses to HIV-1 in matched treatment naive individuals reveals early soluble proteins that are associated with in vivo virus control

• Published in: Journal of the International AIDS Society 2021-01, Vol.24 (S1), p.35
• Main Authors: Makinde, J, Nduati, E.W, Sterrantino, A. Freni, Streatfield, C, Kibirige, C, Dalel, J, Black, S.L, Hayes, P, Macharia, G, Hare, J, King, D, Joseph, S, Mcgowan, E, Abel, B, Hunter, E
• Format: Article
• Language: English
• Subjects: AIDS (Disease); AIDS research; Care and treatment; Cellular proteins; Development and progression; Genetic aspects; Health aspects; HIV infection; Immune response
• ISSN: 1758-2652; 1758-2652
• DOI: 10.1002/jia2.25659

Background: In attempting to define the correlates associated with natural protection against HIV, extreme heterogeneity in the datasets generated from systems methodologies can be further complicated by the inherent variability encountered at the population, individual, cellular and molecular levels. Furthermore, such studies have been limited by the paucity of well-characterised samples and linked epidemiological data, including the duration of infection and clinical outcomes. Methods: We identified newly HIV-infected individuals from a multi-site HIV incidence cohort drawn from nine clinical research centres in five African countries. Selected volunteers were further characterized with regards to early and persistent in vivo control of HIV-1 replication, in the absence of antiretroviral treatment. We utilised a propensity score matching approach to control for the influence of five factors (age, risk group, virus subtype, gender, and country) known to influence disease progression on causal observations. The concentrations of fifty-two soluble plasma proteins were assessed. This approach is unique because it focuses on the specific period of dynamic immunological control of viral replication for all volunteers in the absence of treatment. Results: Among 603 volunteers, we identified three distinct groups of individuals (Low, Intermediate and High viral load volunteers) matched on all five factors and for whom samples were available at two time-points within the dynamic phase of immunological control of in vivo replication following peak viraemia (i.e., within 0 to 365 days postinfection). We were able to confirm some of the factors related to, or already known to influence disease progression such as the possession of B*57 HLA Class I allele, and the infecting virus subtype. Our results also indicate possible roles for IL-17C and MIP-1a in the early and sustained control of infection. Conclusions: Our results highlight the need to consider factors that could potentially introduce heterogeneity in datasets and mask valid differences when designing studies to define immune correlates.