Related Experiment Video
Updated: Jan 1, 2026
Isolation, Transfection, and Culture of Primary Human Monocytes
Published on: December 16, 2019
Monocyte Based Correlates of Immune Activation and Viremia in HIV-Infected Long-Term Non-Progressors
Varsha M Prabhu1, Amit Kumar Singh1, Varsha Padwal1
1Department of Biochemistry and Virology, National Institute for Research in Reproductive Health, Indian Council of Medical Research, Mumbai, India.
Insights
Monitoring HIV progression requires more than CD4 counts due to immune activation causing non-AIDS events. This study reveals monocyte dysregulation, even in long-term non-progressors, highlighting CD206 as a key indicator of viral load.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- CD4 counts alone are insufficient for monitoring HIV disease progression due to ongoing immune activation and Serious non-AIDS events (SNAEs).
- SNAEs are linked to chronic inflammation driven by monocyte activation, persisting even during highly active antiretroviral therapy (HAART).
- Understanding functional monocyte signatures is crucial for a comprehensive view of HIV disease progression.
Purpose of the Study:
- To delineate functional monocyte-based signatures across different stages of HIV disease progression.
- To investigate monocyte subset distribution and activation markers in HIV-infected individuals and controls.
- To associate monocyte parameters with conventional markers of HIV disease progression and viral load.
Main Methods:
- Recruitment of four cohorts: pre-ART (PA), long-term non-progressors (LTNP), individuals on therapy (ART), and seronegative controls (SN).
- Immunophenotyping of monocyte subsets (classical, intermediate, non-classical).
- Evaluation of HIV receptors (CD4, CCR5), immune activation marker (HLA-DR), and M2 phenotype marker (CD206) on monocytes; association with CD4 count, CD4/CD8 ratio, viral load, and T cell activation.
Main Results:
- Expansion of intermediate monocytes (CD14++CD16+) and decline in classical monocytes (CD14++CD16-) in all HIV-infected groups compared to controls.
- Expansion of non-classical monocytes (CD14+CD16++) observed in LTNP.
- Elevated HLA-DR expression on monocytes in LTNP, indicating persistent immune activation despite preserved CD4 counts; CD206 expression is highest on intermediate monocytes and correlates positively with viral load in LTNP.
Conclusions:
- Monocyte dysregulation and increased activation are present in LTNP, suggesting susceptibility to systemic inflammation despite adequate CD4 counts.
- CD206 emerges as a significant non-T cell correlate of viremia, particularly in viremic non-progressors.
- Functional monocyte profiling provides critical insights into HIV pathogenesis beyond traditional markers like CD4 counts.
Abstract:
Background: Disease progression monitoring through CD4 counts alone can be inadequate in HIV infection as ongoing immune activation may result in Serious non-AIDS events (SNAEs). SNAEs involve monocyte activation driven chronic inflammation with significant sequelae observed even during HAART. Here, we attempted to delineate functional monocyte based signatures across stages of HIV disease progression. Methods: Participants spanning four cohorts were recruited-pre-ART (PA; <7 years of infection; n = 20), long-term non-progressors (LTNP; >7 years of infection, CD4 > 350 cells/μL, n = 20), individuals on therapy (ART; n = 18) and seronegative controls (SN; n = 15). Immunophenotyping of monocyte subsets and evaluation of expression of HIV-binding receptors-CD4 and CCR5, marker of immune activation- HLA-DR and M2 phenotype-mannose receptor (CD206) was followed by association of monocyte-specific parameters with conventional markers of disease progression such as absolute CD4 count, CD4/CD8 ratio, viral load, and T cell activation. Results: A significant expansion of intermediate monocytes (CD14++CD16+) with a concomitant decline in classical subset (CD14++CD16-) was observed in all infected cohorts compared to seronegative controls. In addition, an expansion of the non-classical subset (CD14+CD16++) was observed in long-term non-progressors. Dysregulation in monocyte subsets associated with CD4 count and CD4/CD8 ratio in PAs but not in LTNPs. We report for the first time that expression of CD206 is most prominent on intermediate monocytes which also have the highest expression of CD4, CCR5, and HLA-DR. Despite preserved CD4 counts, LTNPs had similar immune activation profiles to PAs, as evidenced by elevated HLA-DR expression across monocyte subsets. HLA-DR expression, similar to that in SNs, observed in the ART group indicated partial immune restoration within the monocyte compartment. Increased CD206 expression on monocytes together with frequency of activated CD4+ T lymphocytes (HLA-DR+CD38+) showed significant and positive association with viral load in LTNPs, but not PAs. Conclusion: Our results describe for the first time the presence of monocyte dysregulation involving increased activation in LTNPs, who, in spite of preserved CD4 counts, may remain susceptible to prolonged effects of systemic inflammation and highlight CD206, as a unique non-T correlate of viremia, in viremic non-progression.
