Metabolic and Inflammatory Profiles in Ugandan Youth with HIV on Dolutegravir

Overview

This study compared metabolic and inflammatory markers in youth with perinatally acquired HIV (YPHIV) on dolutegravir-based ART from urban and rural Uganda. Urban YPHIV exhibited higher metabolic risk factors such as BMI, insulin resistance, and cholesterol, whereas rural YPHIV showed elevated inflammatory markers, particularly sCD14, even after adjusting for confounders.

Background

Youth with perinatally acquired HIV (YPHIV) in sub-Saharan Africa face unique challenges, with most data derived from urban populations. Chronic inflammation and metabolic complications are concerns as these youth age, but rural populations remain understudied despite comprising a majority in Uganda. Differences in socioeconomic status, diet, and healthcare access between urban and rural settings may influence metabolic and inflammatory profiles. Understanding these differences is critical for preventing comorbidities in aging YPHIV.

Data Highlights

Key Findings

• Urban YPHIV had significantly higher BMI, insulin resistance (HOMA-IR), total cholesterol, and LDL cholesterol compared to rural YPHIV (P < .001).
• Rural YPHIV exhibited elevated inflammatory markers including sCD14, sCD163, hsCRP, IL-6, TNFRI, and LBP (P ≤ .001).
• After adjusting for demographic, socioeconomic, viral load, and ART duration, only sCD14 remained significantly elevated in rural YPHIV (β: 1.1; 95% CI, 0.2–2.0).
• β D glucan, a fungal translocation marker, was elevated in urban YPHIV after adjustments (β 1.11; 95% CI, 0.3–1.89).
• Monocyte activation marker sCD14 was associated with HIV status and remained elevated in rural YPHIV despite viral suppression and ART.
• Rural participants lived in extreme poverty compared to urban participants (P < .001), which may contribute to inflammatory differences.

Clinical Implications

Clinicians should recognize that YPHIV in rural settings may have persistent immune activation despite viral suppression, potentially increasing risk for inflammatory comorbidities. Urban YPHIV may be at higher risk for metabolic complications such as insulin resistance and dyslipidemia. Tailored interventions addressing both metabolic and inflammatory risks are needed, with increased focus on rural populations to prevent long-term complications.

Conclusion

This study highlights distinct metabolic and inflammatory profiles in Ugandan youth with perinatally acquired HIV by geographic setting, underscoring the need to include rural populations in research and clinical care strategies to mitigate comorbidities as these youth age.

References

1. Joint Clinical Research Center Uganda 2021-2023 -- Comparative Analysis of Metabolic and Inflammatory Profiles in Ugandan Youth with HIV on Dolutegravir