Is Microbial Translocation a Cause or Consequence of HIV Disease Progression?

Abstract

To the Editor—Two recent articles in the Journal of Infectious Diseases described associations between increased levels of microbial translocation as measured by plasma levels of lipopolysaccharide (LPS) and late-stage human immunodeficiency virus (HIV) disease in South Africa [1] and Guinea-Bissau [2]. These cross-sectional studies are seemingly in disagreement with a longitudinal analysis using data from Rakai, Uganda, which found no association between microbial translocation and subsequent HIV-1 disease progression [3, 4]. This apparent discrepancy in the role of microbial translocation in HIV disease has also been observed in other cross-sectional [5–8] and longitudinal human studies [9, 10]. Even in animal models, it was recently shown that LPS levels are not predictive of simian immunodeficiency virus (SIV) disease progression in rhesus macaques [11], although elevated LPS levels prior to SIV infection appear to contribute to the faster disease progression in pigtailed macaques [12]. These discrepancies are primarily due to the fact that, as the 2 groups state, one cannot infer causality from cross-sectional studies; therefore, it is impossible to determine whether the elevation of LPS levels in AIDS is a cause or a consequence of disease progression.