Increased Microbial Translocation in ≤180 Days Old... : The Pediatric Infectious Disease Journal (original) (raw)

Original Studies

Increased Microbial Translocation in ≤180 Days Old Perinatally Human Immunodeficiency Virus-positive Infants as Compared With Human Immunodeficiency Virus-exposed Uninfected Infants of Similar Age

Papasavvas, Emmanouil PhD*; Azzoni, Livio MD, PhD*; Foulkes, Andrea ScD†; Violari, Avy FCPaed‡; Cotton, Mark F. MMed, PhD§; Pistilli, Maxwell MS*; Reynolds, Griffin BS*; Yin, Xiangfan MS*; Glencross, Deborah K. MD, MMed¶; Stevens, Wendy S. FCPath¶; McIntyre, James A. FRCOG‡∥; Montaner, Luis J. DVM, MSc, PhD*

From the *The Wistar Institute, Philadelphia, PA; †University of Massachusetts, Amherst, MA; ‡Perinatal HIV Research Unit, University of the Witwatersrand, Soweto, Johannesburg, South Africa; §KID-CRU–Tygerberg Children's Hospital, Stellenbosch University, Cape Town, South Africa; ¶University of the Witwatersrand and National Health Laboratory Service, Johannesburg, South Africa; and ∥Anova Health Institute, Johannesburg, South Africa.

Accepted for publication March 29, 2011.

E.P. and L.A. contributed equally in this work.

Supported by the National Institute of Allergy and Infectious Disease NIH AI062512 (to L.J.M.). Additional support was provided by The Philadelphia Foundation (Robert I. Jacobs Fund), The Stengel-Miller family, AIDS funds from the Commonwealth of Pennsylvania and from the Commonwealth Universal Research Enhancement Program, Pennsylvania Department of Health, as well as by the Cancer Center Grant (P30 CA10815). Support for the CIPRA-SA CHER study was provided by the National Institute of Allergy and Infectious Diseases (NIAID) of the US National Institutes for Health (NIH), through the Comprehensive International Program of Research on AIDS (CIPRA) network, grant number U19 AI53217. The Departments of Health of the Western Cape and Gauteng, South Africa and GlaxoSmithKline plc provided additional support.

The CIPRA-SA CHER study was also conducted as an Investigational New Drug (IND) Number: IND 71,494 under the supervision of the Food and Drug Administration.

The authors have no other funding or conflicts of interest to disclose.

The content of this publication does not necessarily reflect the views or policies of NIAID, nor does mention of trade names, commercial projects, or organizations imply endorsement by the US Government.

Address for correspondence: Luis J. Montaner, DVM, MSc, PhD, The Wistar Institute, 3601 Spruce St, Philadelphia, PA 19104. E-mail: [email protected].

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (www.pidj.com).

Abstract

Background:

The effect of early versus deferred antiretroviral treatment (ART) on plasma concentration of lipopolysaccharide (LPS) and host LPS-binding molecules in human immunodeficiency virus (HIV)-infected infants up to 1 year of age was investigated.

Methods:

We evaluated 54 perinatally HIV-infected and 22 HIV-exposed uninfected infants (controls) at the first and second semester of life. All HIV-infected infants had a baseline CD4 of ≥25%, participated in the Comprehensive International Program of Research on AIDS Children with HIV Early Antiretroviral Therapy trial in South Africa, and were randomized in the following groups: group 1 (n = 20), ART deferred until CD4 <25% or severe HIV disease; and group 2 (n = 34), ART initiation within 6 to 12 weeks of age. LPS, endotoxin-core antibodies, soluble CD14 (sCD14), and LPS-binding protein (LBP) were measured in cryopreserved plasma. T-cell activation was measured in fresh whole blood.

Results:

At the first semester, LPS concentration was higher in HIV-infected infants than in controls; sCD14, LBP, and T-cell activation were higher in group 1 than in group 2 and controls. Although LPS was not correlated with study variables, viral load was positively associated with sCD14, LBP, or endotoxin-core antibodies. At the second semester, LPS was not detectable and elevated host LPS-control molecules values were sustained in all groups and in conjunction with ART in all HIV-infected infants.

Conclusions:

Although plasma concentration of LPS was higher in perinatally HIV-infected infants 0 to 6 months of age than in controls independent of ART initiation strategy, concentration of LPS-control molecules was higher in infants with deferred ART, suggesting the presence of increased microbial translocation in HIV-infected infants with sustained early viral replication.