Impact of Heroin and HIV on Gut Integrity and Immune Activation

Abstract

Background: Altered gut integrity is central to HIV-related immune activation. Opioids may promote similar changes in gut permeability and/or increase systemic inflammation, potentially augmenting processes already occurring in people with HIV (PWH). Setting: Urban hospital systems in Cleveland, Ohio, and surrounding communities. Methods: This is a prospectively enrolled, cross-sectional study including people with and without HIV using heroin and people with and without HIV who have never used heroin, matched by age, sex, and CD4 + T-cell count (PWH only) to compare markers of gut integrity, microbial translocation, systemic inflammation, and immune activation. Results: A total of 100 participants were enrolled. Active heroin use was associated with higher concentrations of lipopolysaccharide-binding protein (LBP), beta-D-glucan (BDG), high-sensitivity C-reactive protein (hsCRP), soluble tumor necrosis factor-α-receptors I and II, soluble CD163, inflammatory monocytes, and activated CD4 + lymphocytes in adjusted models. HIV status tended to modify the effect between heroin use and LBP, BDG, hsCRP, patrolling monocytes, and activated CD4 + lymphocytes ( P < 0.15 for interactions); however, it was not as expected. The effect of heroin on these markers (except patrolling monocytes) was greatest among those without HIV rather than among those with HIV. Conclusions: Heroin use is associated with heightened microbial translocation, systemic inflammation, and immune activation. Concurrent HIV infection in virologically suppressed individuals does not seem to substantially worsen the effects heroin has on these markers.

Opioids exacerbate inflammation in people with well-controlled HIV

“…Our results aligned with previous reports examining the state of inflammation in virally suppressed PWH with IDU and OUD (9,28,32,33), showing increased expression of IL-6 (opioid use) (32), IL-8, sTNFR-II (methadone use) (28), and LBP, hsCRP, sTNFR-I, sTNFR-II, sCD14, sCD163 (heroin use) (28,32,33). In our study, plasma biomarkers were selected based on their reported association with inflammation (sTNFR-II, sTNFR-I, sCD25, TNFa, IL-6, IL-8, IL-1a, IL-1b, IL17A (Th17), IL-22 (Th17)) (34), cardiovascular disease (ICAM-I, VCAM-I, hsCRP), co-morbidities (IL-6, VCAM-I, ICAM-I, sTNFR-II, and sTNFR-I), monocyte activation and microbial translocation (sCD14, sCD163, iFABP, D-dimer, LBP) (32), HIV disease progression (MCP1/CCL2, sCD14) and mortality (sCD14) in the context of HIV.…”

Methadone use is associated with increased levels of sCD14, immune activation, and inflammation during suppressed HIV infection

“…Elevation of sCD14, as observed in opioid users 19 an in our MET group, has been associated with microbial translocation. Levels of LBP, another translocation indicator which binds LPS, were significantly correlated to sCD14 levels (p = 0.0267), but was not detected as significantly different across our groups.…”

“…14 In vivo, the effect of opioids is thought to be mostly due to increased bacterial and/or fungal translocation resulting from a disruption of the intestinal homeostasis, via an altered mucosal barrier, 15 mucus secretion, 16 and/or bile acid metabolism. 17,18 Recent work 19 indicated that opioid use is associated with elevation of biomarkers of chronic inflammation, as well as markers of microbial translocation such as soluble (s) CD14, LPS-binding protein (LBP) and beta-D-glucan, independent of HIV infection. This is associated with the expression of activation markers CD38 and HLA-DR on T cells in both tissue and blood, T cell proliferation, and myeloid activation.…”

Gut permeability is associated with lower insulin sensitivity in youth with perinatally acquired HIV

“…We observed zonulin levels in our study to be significantly higher compared to Ugandan and South African YPHIV [20,31,32]. Zonulin concentration was also higher when comparing to measurements performed in our laboratory in adults living with HIV [15,33], but similar to small cross-sectional studies in overweight and obese youth without HIV in the US and Europe [34–36]. Despite different methodologies used across studies, zonulin concentration being similar to overweight youth without HIV highlights that zonulin may play a role in the pathogenesis of metabolic disturbances in YPHIV in the Global North.…”