A preponderance of CCR5(+) CXCR4(+) mononuclear cells enhances gastrointestinal mucosal susceptibility to human immunodeficiency virus type 1 infection.

The gastrointestinal mucosa harbors the majority of the body's CD4(+) cells and appears to be uniquely susceptible to human immunodeficiency virus type 1 (HIV-1) infection. We undertook this study to examine the role of differences in chemokine receptor expression on infection of mucosal mononuclear cells (MMCs) and peripheral blood mononuclear cells (PBMCs) by R5- and X4-tropic HIV-1. We performed in vitro infections of MMCs and PBMCs with R5- and X4-tropic HIV-1, engineered to express murine CD24 on the infected cell's surface, allowing for quantification of HIV-infected cells and their phenotypic characterization. A greater percentage of MMCs than PBMCs are infected by both R5- and X4-tropic HIV-1. Significant differences exist in terms of chemokine receptor expression in the blood and gastrointestinal mucosa; mucosal cells are predominantly CCR5(+) CXCR4(+), while these cells make up less than 20% of the peripheral blood cells. It is this cell population that is most susceptible to infection with both R5- and X4-tropic HIV-1 in both compartments. Regardless of whether viral isolates were derived from the blood or mucosa of HIV-1-infected patients, HIV-1 p24 production was greater in MMCs than in PBMCs. Further, the chemokine receptor tropism of these patient-derived viral isolates did not differ between compartments. We conclude that, based on these findings, the gastrointestinal mucosa represents a favored target for HIV-1, in part due to its large population of CXCR4(+) CCR5(+) target cells and not to differences in the virus that it contains.

HIV-related diarrhea is multifactorial and fat malabsorption is commonly present, independent of HAART.

OBJECTIVE: Highly active antiretroviral therapy (HAART) has significantly decreased the incidence of infectious diarrhea affecting HIV-infected patients. Still, diarrhea remains a common symptom in HIV. We sought to determine the incidence of fat malabsorption as a cause of diarrhea in HIV patients receiving non-HAART (nucleoside analog only) and HAART (protease inhibitor-containing) antiretroviral regimens. METHODS: From June, 1995, to April, 1999, 88 HlV-infected patients underwent evaluation for diarrhea, which included endoscopy. We examined the incidence of fat malabsorption with a 24-h stool collection for fecal fat in a cohort of these patients (N = 33). Patients were divided into two groups, those receiving protease inhibitor-containing HAART and those receiving less intensive, nucleoside analog-only, non-HAART regimens. RESULTS: Thirty of 33 patients (90.9%) had fat malabsorption. Twenty of 21 patients not receiving HAART (95.2%) had fat malabsorption with a mean of 34 +/- 38 g of stool fat and a mean stool weight of 797 +/- 454 g. Ten of 12 patients receiving HAART (83.3%) had fat malabsorption with a mean of 46 +/- 86 g of stool fat and a mean stool weight of 800 +/- 647 g. Stool weight correlated with the degree of fat malabsorption (R = 0.77). CONCLUSION: Fat malabsorption represents a commonly undiagnosed entity in HIV-infected patients with diarrhea, whether or not they are receiving HAART therapy. Fecal fat determination should be considered a routine part of the diagnostic workup of HIV-infected patients experiencing diarrhea.

Direct determination of free triiodothyronine (T3) in undiluted serum by equilibrium dialysis/radioimmunoassay (RIA).

UNLABELLED: We have devised a practical, sensitive, and reliable assay for measurement of free T3 concentration in serum. The assay employs a convenient and disposable plastic equilibrium dialysis cell and a buffer that resembles the in vivo biochemical environment (Nelson JC, Tomei RT 1988 Clin Chem 34:1737). A 200-microliters aliquot of serum was dialyzed against 2.4 mL buffer at 37 degrees C for 18 +/- 2 h and T3 was quantified by RIA of about 1.0-mL aliquot of the dialysate buffer. The detection threshold of the RIA approximated 2 pg/ml permitting accurate measurement of > 200 pg/dL of free T3 directly. Serum specimens that contained less free T3 were spiked with 200 ng/dL of non-radioactive T3 prior to dialysis. Free T3 in the dialysate of these samples was divided by total T3 in serum (after spiking) to determine percent free T3. Free T3 was calculated by multiplying percent free T3 and serum total T3 (before spiking). Free T3 concentration (pg/dL) did not differ appreciably in a serum pool when tested both with and without spiking with exogenous T3. The between assay coefficient of variation of three specimens tested over an 8-month period averaged 20%. Serum free T3 concentration (pg/dL) was [mean +/- SD (n), range, p] [293 +/- 12 (39), 154-440] in normal subjects. It was significantly increased [742 +/- 87 (13), 525-1700, p < 0.001] in hyperthyroidism and significantly decreased in nonthyroidal illness [NTI, 138 +/- 26 (9), 53-320, p < 0.001], cord blood serum [124 +/- 7.5 (11), 93-353, p < 0.001], and third trimester of pregnancy [214 +/- 26 (8), 93-253, p < 0.02]. Serum free T3 concentration varied widely in hypothyroidism 274 +/- 92 (10), 10-923, NS]. CONCLUSIONS: We have described a practical method and initial results of direct measurements of free T3 concentration in health and disease.