Abstract

MOPE022 - Poster Exhibition

Injection drug use is associated with significant levels of immune activation in the mucosal tissues and blood

S. Mehandru^1,2, D. Garmon², A. Walker³, V. Sahi², K. Rodriguez², S.-Y. Kang³, H. Mohri², S. Deren³, M. Markowitz<sup>2

1</sup>Mt Sinai School of Medicine, Medicine, New York, United States, ²Aaron Diamond AIDS Research Center, New York, United States, ³New York University College of Nursing, New York, United States

Background: Immune activation plays a pivotal role in the pathogenesis of HIV infection. It is an independent predictor of disease progression in HIV-1 infected individuals and distinguishes pathogenic SIV infection in rhesus macaques from non-pathogenic SIV infection in sooty mangabeys and African green monkeys despite comparable levels of viremia. Injection drug use (IDU) is associated with a heightened risk of HIV infection as well as accelerated progression of HIV disease. We hypothesized that IDU is associated with elevated levels of immune activation in both the systemic and mucosal compartments, providing a physiological basis for HIV disease acquisition and pathogenesis in this population.
Methods: We conducted a proof of concept, pilot study, recruiting HIV uninfected non IDUs (n=13, group 1), HIV-uninfected IDUs (n=19, group 2), viremic, HIV-1 infected non-IDUs (n=8, group 3) and viremic HIV-1 infected IDUs (n=10, group 4) to assess immune activation in blood and gastrointestinal tissue. We analyzed soluble (sCD14) and cellular markers of immune activation (CD38) and proliferation (Ki67) in the peripheral blood (PBMC) and mucosal mononuclear cells (MMC).
Results: Significantly higher levels of immune activation, proliferation and sCD14 were noted in the HIV uninfected IDUs compared to HIV uninfected non-IDUs. Among the HIV-1 infected, significantly higher levels of immune activation were noted on CD4+ PBMC and CD8+ PBMC and MMC. Differences between the expression of Ki67 and sCD14 did not reach statistical significance between groups 3 and 4 (Table)

	%CD4+CD38+		%CD8+CD38+		%CD4+Ki67+		%CD8+Ki67+		sCD14 (ng/ml)
	PBMC	MMC	PBMC	MMC	PBMC	MMC	PBMC	MMC
Grp1	4.5±2.1	1.9±1.5	1.9±1.2	2.4±1.8	0.3±0.2	2.7±1.4	0.2±0.2	3.0±1.9	1416±204
Grp2	12.2±8.8	5.3±3.4	6.9±5.7	9.0±6.9	1.3±0.7	6.5±4.3	1.0±0.7	7.1±3.8	1876±427
p	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05	<0.05
Grp3	10.5±5.4	9.0±6.6	6.2±4.9	6.9±5.7	2.2±2.5	5.0±2.0	0.8±0.5	3.4±1.9	1806±256
Grp4	21.5±10.1	14.6±9.0	24.7±7.6	21.2±14.9	2.3±1.7	7.8±4.5	0.8±0.7	4.5±1.7	2029±593
p	<0.05	0.13	<0.05	<0.05	0.8	0.08	0.9	0.2	0.3

[Table]


Conclusions: This study showed a significant increase in cellular and soluble markers of immune activation among IDUs compared to normal volunteers. Remarkably, this was noted within the mucosal compartment in addition to the peripheral blood providing a possible mechanism behind increased susceptibility of IDUs to HIV acquisition. These findings pave the way for more detailed study of the mechanisms and pathways involved.