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Microbial Translocation and HIV Infection
Abstract & Commentary
By Dean L. Winslow, MD, FACP, FIDSA, Vice Chair, Department of Medicine, Chief, Division of AIDS Medicine, Santa Clara Valley Medical Center, Section Editor, HIV, is Associate Editor for Infectious Disease Alert.
Dr. Winslow reports no financial relationships relevant to this field of study.
Synopsis: Patients infected with both HIV-1 and HIV-2 underwent measurement of plasma lipopolysaccharide (LPS). LPS was elevated in patients with AIDS vs. earlier-stage infection. LPS levels were correlated inversely with CD4+ lymphocyte count and positively correlated with plasma HIV RNA levels in both HIV-1- and HIV-2-infected patients.
Source: Nowroozalizadeh S, et al. Microbial translocation correlates with the severity of both HIV-1 and HIV-2 infections. J Infect Dis. 2010; 201:1150-1154.
Twenty-one patients with HIV-1/AIDS, seven patients with hiv-2/aids, 43 patients with HIV-1 chronic infection, and 66 patients with HIV-2 chronic infection in Guinea-Bissau were studied along with 66 HIV-negative policemen. LPS was measured by limulus amebocyte lysate assay, and IL-12 and IFN-alpha were measured in whole blood following mitogen and toll-like receptor (TLR) stimulation. Elevated microbial translocation (as assessed by LPS levels) was correlated with the presence of AIDS, lower CD4+ lymphocyte count, and higher viral load, but was independent of type of HIV infection (HIV-1 vs. HIV-2). In addition, defective mitogen and innate immune responsiveness was correlated with LPS level.
Over the last several years, increasing recognition has been given to the role of microbial translocation in HIV pathogenesis in both adults and children.1,2 Studies in non-human primates have shown that very early in the course of experimental SIV infection, a dramatic depletion of CD4+ lymphocytes from gut-associated lymphoid tissue (GALT) occurs, and that this correlates with increased microbial translocation. Studies in HIV-1 infected humans reveal similar CD4+ depletion from GALT and increased microbial translocation as well. There is increasing evidence that much of the "pro-inflammatory" state associated with HIV infection may be related to this phenomenon and may contribute to acceleration of atherosclerosis and more rapid progression of liver disease associated with chronic hepatitis B and C virus infections. While nonspecific immune activation is commonly seen in HIV infection, hyporesponsiveness to specific pathogens is also characteristic.
This study is important since it demonstrates a significant correlation between disease stage and microbial translocation, as assessed by LPS levels. While HIV-2 infection is generally associated with slower disease progression than HIV-1 infection, this study also shows that when controlled for clinical disease state and CD4+ count that microbial translocation is similar in HIV-1- and HIV-2-infected patients. The data suggest that earlier institution of antiretroviral therapy (ARV) might be beneficial, although small studies presented to date have not conclusively demonstrated that ARVs are very effective in reversing GALT CD4+ depletion and in reducing microbial translocation. At any rate, the data presented in this study are interesting and worthy of larger follow-up studies that include correlation of LPS levels with specific HIV disease manifestations.