Background:  Gut-associated lymphoid tissue (GALT) harbors the majority of CD4⁺ T cells and is rapidly depleted in early HIV infection. Previous studies suggest that reconstitution of CD4⁺ T cells in HAART-treated individuals is less complete in GALT than in peripheral blood. Most studies have evaluated GALT by flow cytometry, which provides relative estimates of CD4⁺ T cells. We hypothesized that reconstitution of CD4⁺ T cells in GALT may have been underestimated by this method and that absolute numbers of CD4⁺ T cells reconstituted in GALT exceed those in peripheral blood.

Methods:  We enrolled 8 untreated AIDS patients in a clinical trial who underwent colonic biopsies and provided peripheral blood samples at baseline, 24 and 48 weeks after starting nevirapine (NVP)/trizivir (TZV); 4-μm sections of GALT biopsies were stained with CD3 and CD4 antibodies, and analyzed by immunofluorescent microscopy. Numbers of lamina propria CD4⁺ T cells/mm³ were calculated and tissue histology observed. A mixed model was used to account for within subject correlations.

Results:  All but 1 subject achieved a viral load <400 copies/mL by week 48. Mean peripheral blood CD4⁺ T cells/mm³ increased from 65 at baseline to 192 at week 24 (p <0.15) and 216 at week 48 (p = 0.08 vs baseline). Mean GALT CD4⁺ T cells/mm³ were 279 at baseline, which was higher than that in peripheral blood (p = 0.08). Mean GALT CD4⁺ T cells increased through week 24 to 890 cells/mm³ (p <0.0001), a larger increase than was observed in peripheral blood (p = 0.0006). Mean GALT CD4⁺ T cells decreased to 759 cells/mm³ at week 48, but remained significantly different than baseline (p <0.0001) and still reflected a larger increase than in peripheral blood (p = 0.0096). Peripheral blood and GALT reconstitution were calculated as a percentage of normal values assuming a norm of 1000 cells/mm³ in peripheral blood and using values for GALT CD4⁺ T cells obtained in 2 control colonic biopsies. At baseline, mean CD4⁺ T cells were 7% in peripheral blood and 16% in GALT of normal values (p = 0.21). At week 24, peripheral blood and GALT values were 19% and 52% (p = 0.011 GALT vs peripheral blood increase), and at week 48, 22% and 44% (p = 0.12 GALT vs peripheral blood increase over baseline) of normal values. Lymphoid aggregates were observed in colonic tissue of 1 subject at baseline, 6 subjects at week 24 (p = 0.04), and 5 subjects at week 48 (p = 0.12 vs baseline).

Conclusions:  NVP/TZV in advanced HIV-1 infection results in substantial recovery of CD4⁺ T cells and reconstitution of tissue architecture in GALT. Increases in CD4⁺ T cells are significantly larger in GALT than peripheral blood, particularly during the first 24 weeks of therapy.