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 1 hour; 72h fecal fat collection on a 100g fat diet (n=20, normal >20mg/dl); 5-hr urine D-xylose collection following 5g oral D-xylose (n=15, normal >1.4g/5hrs); 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/m², 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) and lower urine D-xylose (SI, 1.45 ±0.32g/5hrs vs. 2.03 ±0.26, p=0.19) and more fat malabsorption (fecal fat ≥ 8g/24hrs in 3/8 (38%) SI vs. 1/12 (8%) p=0.26). Overall, SI subjects had greater severity of malabsorption with ≥ 1 abnormalities of GI function (SI, 7/8 (88%) vs. 5/12 (42%), p=0.07) and many had > 1 abnormalities (SI, 4/8 (50%) vs. 1/12 (8%), p=0.11). The serum cytokine profile did not differ between groups. 10/17 (59%) subjects had ≥ 1 elevated duodenal fluid pro-inflammatory cytokine. No differences were noted in pro-inflammatory cytokines by presence of SI or malabsorption.

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.

Keywords: Syncytium-inducing virus; Malabsorption; HIV-enteropathy