Gut-Associated Lymphoid Tissue a Source of Persistent HIV

HIV persists in gut-associated lymphoid tissue (GALT) despite long-term treatment with antiretroviral drugs, according to a report in the March 1st issue of The Journal of Infectious Diseases.

"We need better strategies to reduce HIV burden in various tissue compartments," Dr. Tae-Wook Chun from the National Institute of Allergy and Infectious Diseases, Bethesda, Maryland told Reuters Health. "Early initiation of intensified versions of antiretroviral therapy should be explored further."

Dr. Chun and colleagues sought to determine the level of CD4+ T cell depletion and HIV persistence in GALT of 8 HIV-infected patients who had been on effective antiretroviral therapy for 5 to 10 years.

The mean percentage of CD4+ T cells in GALT of study participants was lower than that in GALT of healthy individuals, the authors report, suggesting incomplete recovery of CD4+ T cells in that compartment despite years of antiretroviral therapy.

Moreover, the report indicates, the frequency of cells carrying HIV proviral DNA was highest in the GALT compartment when compared with resting CD4+ T cells and activated CD4+ T cells in the peripheral blood mononuclear cell compartment.

This suggests "that CD4+ T cells in GALT, even when present in low numbers, may support low but readily detectable levels of HIV replication in infected individuals, despite their having received years of effective antiretroviral therapy that resulted in sustained, undetectable levels of plasma viremia," the investigators say.

Based on these findings, the authors conclude, "Intensification of existing drug regimens by the addition of new classes of antiretroviral drugs, such as HIV entry or integrase inhibitors, may be necessary to abrogate the low levels of ongoing viral replication that originate from the GALT."

This strategy is now being investigated, Dr. Chun said. "We chose to use raltegravir."

In an editorial, Dr. Steven Yukl and Dr. Joseph K. Wong from Veterans Affairs Medical Center San Francisco and the University of California San Francisco, write: "We should not treat [these findings] as an incidental observation to be filed away or simply as a cause for concern about the limitation of existing treatments, but rather as an opportunity to better understand the persistence of HIV and as a guide for improving existing HIV treatment paradigms."

J Infect Dis 2008;197:714-720,640-642.