Distinct Metabolic and Inflammation Signatures in Urban vs Rural Ugandan Youth With HIV on Dolutegravir

Abstract

Background: In sub-Saharan Africa, the majority of the metabolic data are from youth living in urban areas. In youth with perinatally acquired HIV (YPHIV) and seronegative (HIV-), we examined inflammatory and metabolic signatures in urban versus rural Uganda.

Methods: YPHIV (n = 100) were enrolled from urban and rural Uganda in an observational cohort study along with age- and sex- matched, population-based HIV- (n = 99) comparators. YPHIVs were on antiretroviral with HIV-1 RNA level ≤400 copies/mL. We compared variables using Wilcoxon rank-sum tests and chi-squared tests. General linear regression models were used to assess factors associated with metabolic and inflammatory biomarkers, adjusting for HIV status, socioeconomic factors, and other covariates.

Results: Median age was 16.2 years, 52% rural versus 96% urban YPHIV had HIV-RNA <50 copies/mL, 93% of YPHIV were on Tenofovir, Lamivudine, and Dolutegravir. Overall, rural participants lived in extreme poverty compared to urban participants (P < .001). Urban YPHIV were more likely to have higher body mass index, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), total cholesterol, and low-density lipoprotein than rural YPHIV (P < .001); however sCD14, sCD163, high sensitivity C-reactive protein, interleukin-6, soluble tumor necrosis factor alspha receptor I (TNFRI), and lipopolysacchiride binding protein (LBP) were higher in rural YPHIV (P ≤ .001). After adjusting for demographic, socioeconomic, viral load and antiretroviral duration, only sCD14 remained elevated in the rural YPHIV (β: 1.1; 95% confidence interval, .2-2.0), and β D glucan in urban YPHIV (β 1.11; 95% confidence interval, .3-1.89).

Conclusions: The monocyte activation marker sCD14, was associated with HIV status and remained elevated in rural YPHIV even after adjusting for differences in HIV factors. Increasing the inclusion of rural populations in sub-Saharan Africa is paramount as we focus on preventing comorbidities in aging YPHIV.

Keywords: dolutegravir; dyslipidemia; inflammation; insulin resistance; perinatally acquired HIV.

Figure 1.

Orthogonal partial least squares discriminant analysis and volcano plots for all participants by sites. A, Orthogonal partial least squares discriminant analysis (OPLS-DA) demonstrating group discrimination based on metabolic outcomes and gut inflammatory markers between urban (red or the circle to the left) and rural (blue or the circle on the right) participants. B, Volcano plot illustrating the comparison of metabolic outcomes and inflammatory markers between urban and rural participants. The y-axis displays the log10 of the false discovery rate (FDR)-adjusted P values, whereas the x-axis represents the log2-transformed fold change (FC). The horizontal reference line (------) denotes the threshold for statistical significance, with points above the line being significant and points below considered not significant. The 2 vertical reference lines correspond to FC values of 0.8 and 1.25, respectively. All markers contributing to the differentiation between sites are labeled in blue.

Figure 2.

Orthogonal partial least squares discriminant analysis and volcano plots for perinatally acquired HIV (PHIV) participants only by site. A, Orthogonal partial least squares discriminant analysis (OPLS-DA) demonstrating group discrimination based on metabolic outcomes and gut inflammatory markers between urban (red) and rural (blue) PHIV participants. B, Volcano plot illustrating the comparison of metabolic outcomes and inflammatory markers between urban and rural PHIV participants. The y-axis displays the log10 of the false discovery rate (FDR)-adjusted P values, whereas the x-axis represents the log2-transformed fold change (FC). The horizontal reference line denotes the threshold for statistical significance, with points above the line being significant and points below considered not significant. The 2 vertical reference lines correspond to FC values of 0.8 and 1.25, respectively. All markers contributing to the differentiation between sites are labeled in blue.