Dissecting Drivers of Immune Activation in Chronic HIV-1 Infection

• DOI: 10.2139/ssrn.3991617
• Publication Date: 2022-01-21T03:07:25Z
• Authors: Hendrik Streeck; Alvino Maestri; Daniel Habermann; Trevor A. Crowell; Allahna Esber; Gowoon Son; Leigh Anne Eller; Michael A. Eller; Ajay Parikh; Peter A. Horn; Lucas Maganga; Yakubu Adamu; Francis Kiweewa; Jonah Maswai; John Owuoth; Merlin L. Robb; Nelson L. Michael; Christina Polyak; Daniel Hoffmann; Julie A. Ake; AFRICOS Study Group
• Keywords: Viremia

Background: Immune activation is a significant contributor to HIV pathogenesis and disease progression. In virally-suppressed individuals on ART, low-level immune has been linked several non-infectious comorbid diseases. However, studies have not systematically performed in sub-Saharan Africa thus the impact of demographics, ART regional endemic co-infections known. We therefore comprehensively evaluated large multinational African cohort markers for its distribution various settings. Methods: 2747 specimens from 2240 people living with (PLWH) 477 without observational Cohort Study (AFRICOS) were analyzed 13 parameters. Samples collected along medical history, sociodemographic comorbidity data at 12 clinics across 5 programs Uganda, Kenya, Tanzania Nigeria. Data univariate multivariate methods such as random forests principal component analysis.Findings: was markedly different between PLWH detectable viral loads, sites. Among viremic PLWH, we found that all parameters significantly correlated load except IFN-α. The overall inflammatory profile distinct men women HIV, off viremia. observed stronger differences increasing Using machine learning methods, geographic contributed unique profiles. also among age presence infectious and/or noninfectious comorbidities showed patterns, biomarkers may be used predict some comorbidities.Interpretation: Our findings show chronic HIV-1 infection influenced by load, sex, age, region use. These predictors, well associations coinfections, influence associated noncommunicable diseases.Funding Information: This work supported President’s Emergency Plan AIDS Relief via cooperative agreement Henry M. Jackson Foundation Advancement Military Medicine, Inc., U.S. Department Defense [W81XWH-11-2-0174, W81XWH-18-2-0040].Declaration Interests: There no competing interest any member author group.Ethics Approval Statement: study approved institutional review boards Walter Reed Army Institute Research, Makerere University School Public Health, Kenya Medical Research Institute, National Nigerian Ministry Defence. All participants provided written informed consent prior enrollment.