Reply to Redd et al

To the Editor—We appreciate that Redd et al [1] discuss elevated microbial translocation in advanced human immunodeficiency virus (HIV) disease, as has been reported by us and others [2–5]. We agree with them that longitudinal studies are important to clarify causal relationships between microbial translocation and disease progression. Thus, we wrote, “Further studies on the impact of microbial translocation during the follow-up of HIV-1 and HIV-2 infection disease courses may reveal important implications for the clinical outcome of HIV-infected individuals” [2]. Longitudinal studies comparing the disease course of HIV-1– and HIV-2–infected individuals within the same cohort or geographic area would optimally include individuals with known time for infection, because both infections display highly variable rates of disease progression. This would require access to samples stored in optimal conditions over extended periods, which is a challenging task in settings where these infections circulate. From our own report it is, however, clear that lipopolysaccharide (LPS) levels in plasma of individuals with chronic HIV-1 or HIV-2 infection without signs or symptoms of AIDS are not elevated when compared with HIV-negative individuals [2]. Thus, detectable elevation of plasma LPS levels appears to be restricted to advanced disease, suggesting that disease progression plays a role in the triggering of microbial translocation. However, it may well be that once microbial translocation arises, it contributes to acceleration of disease progression during the advanced disease phase. Intriguingly, we also found elevated plasma LPS levels in HIV-2–infected persons with severe immunodeficiency (CD4+ T cell count, <200 /μL), despite the fact that the median plasma viral load in HIV-2–infected individuals is at least 1 log lower than that in HIV-1–infected persons matched for CD4+ T cell count [2, 6, 7]. Accordingly, viremia may not be the sole determinant for induction of microbial translocation, and we look forward to further studies on this important topic.