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.
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