Article Text

PDF
33 HIV-1 SYNCYTIUM-INDUCING VIRUS ASSOCIATED WITH INTESTINAL MALABSORPTION
  1. K. M. Rufner1,3,
  2. L. Lai2,
  3. C. M. Thorpe1,3,
  4. C. A. Wanke1,3,
  5. T. A. Knox1,3
  1. 1Tufts University School of Medicine, Boston, MA
  2. 2Washington Hospital Center
  3. 3Louisville VAMC

Abstract

Background Malabsorption and weight loss remain highly prevalent in HIV disease resulting in negative outcomes. The aggressive syncytium-inducing (SI) subtype can infect intestinal mucosa and induce pro-inflammatory chemokines that impair absorptive function in vitro. This pilot study examines how SI and pro-inflammatory cytokines associate with clinical and laboratory measures of malabsorption.

Methods 20 men on HAART were enrolled from the Nutrition for Healthy Living cohort with an age of 45.7 ± 1.50 years (mean ± SE), CD4 count 0.261 ± 0.0589 cells/mL, and viral load 35008.8 ± 17260.6 copies/mL. Subjects were studied with: serum D-xylose at 2 hours (n = 20, normal>20 mg/dL); 72 h fecal fat collection on a 100 g fat diet (n = 20, normal ( 8 g/24 hrs); 5-hr urine D-xylose collection following 5 g oral D-xylose (n = 15, normal>1.4 g/5 hrs); upper endoscopy with collection of duodenal fluid and biopsies (n = 18). TNF-α, IFN-γ, IL-1β, IL-6, and IL-8 were quantified by the novel approach of ELISA on duodenal fluid. Quantities ≥ 10 times the lower limit of detection were considered significant. SI phenotype was predicted by bioinformatic analysis of sequenced ENV V3 domains from serum-isolated HIV.

Results 8/20 (40%) had serum SI. Serum viral loads and CD4 count did not differ among those with SI vs. non-SI or by malabsorption. Subjects with SI showed a trend towards more malabsorption: lower BMI in SI subjects (22.8 ± 1.1 kg/m≤, mean ± SE) vs. non-SI (26.1 ± 1.2, p = 0.07); more wasting in 5/8 (63%) of SI subjects vs. 5/12 (42%, p = 0.65); lower serum D-xylose (SI, 25.1 ± 4.9 mg/dL vs. 38.2 ± 5.4, p = 0.11); lower urine D-xylose (SI, 1.45 ± 0.32 g/5 hrs vs. 2.03 ± 0.26, p = 0.19) and more fat malabsorption (fecal fat ≥ 8 g/24 hrs in 3/8 (38%) SI vs. 1/12 (8%) p = 0.26). Overall, SI subjects had greater severity of malabsorption with ≥ 1 abnormality of GI function (SI, 7/8 (88%) vs. 5/12 (42%), p = 0.07) and many had>1 abnormality (SI, 4/8 (50%) vs. 1/12 (8%), p = 0.11). 10/17 (59%) subjects had ≥ 1 elevated duodenal pro-inflammatory cytokine. No differences were noted in pro-inflammatory cytokines in serum or duodenal fluid by presence of SI, malabsorption, or serum viral load.

Conclusions Subjects infected with SI display increased clinical and laboratory evidence of malabsorption. A majority of HIV-infected subjects have easily detectable pro-inflammatory cytokines in their duodenal fluid. Further studies elucidating the intestinal microenvironment in HIV-induced malabsorption are needed.

Statistics from Altmetric.com

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.