9th Conference on Retroviruses and Opportunistic Infections Seattle, Washington - February 24 -February 28, 2002

Conf Retroviruses Opportunistic Infect 2002 Feb 24-28;9:abstract no. 27
Brodie S, Tabet S, Krieger J, Haggitt R, Nickle D, Johnson A, Coombs RW, Mullins J, Corey L, Celum C; Univ. of Washington, Seattle

BACKGROUND: The gastrointestinal tract is both an early site of HIV infection and immune dysregulation, where mucosal leukocytes are the initial targets of virus replication.

METHODS: We measured cell-associated HIV proviral DNA and replicative HIV RNA in rectal mucosal lymphocytes, macrophages (Mj), and dendritic cells (DC) from men who shed HIV into the rectal canal (n=24).

RESULTS: All men had measurable levels of HIV DNA in rectal tissues and correspondingly high numbers of HIV DNA-positive mucosal leukocytes, irrespective of their clinical stage of infection and their antiretroviral treatment regime. Most HIV RNA-positive lymphocytes and Mj expressed the HIV coreceptor CCR5(+), however, these cells represented only a fraction of all HIV DNA-positive cells. Although mucosal lymphocytes continued to be the most prevalent HIV RNA-positive cell during both early and late stages of infection, as disease progressed Mj contained >10-fold more HIV RNA than lymphocytes. HIV tat fusion RNA, a post-transcriptional mRNA found within productively infected cells, was detected in even fewer cells, but at proportionally higher levels in Mj than lymphocytes. 92% of HIV DNA-positive Mj contained HIV tat RNA (112.3 ± 21.8 grains/Mj) compared to <50% of lymphocytes (6.7 ± 2.1 grains/lymphocytes). Men with ≥10⁴ tat mRNA copies/mg of rectal tissue shed HIV RNA from the rectal mucosa and all such men had a preponderance of tat RNA-positive Mj within the underlying mucosa. Shedders also tended to have well-developed rectal lymphoid tissues containing DC-SIGN-positive DC and DC-associated virion RNA. Inflammation and concomitant viral STDs did not appear to alter patterns of HIV co-receptor expression or levels of HIV replication, nor did specific anti-retroviral treatment regimes appear to effectively suppress rectal HIV replication and shedding (r = 0.4; p < 0.05).

CONCLUSIONS: This study demonstrates that rectal mucosa is a persistent site of HIV replication and shedding and underscores the importance of the rectum as a potential route of HIV transmission in men that have sex with men. Only men that shed HIV RNA from the rectal mucosa showed correspondingly high-levels of HIV replication in the underlying tissue and mostly within Mj. Although the rectum did not appear to be a distinct virologic compartment when compared to viruses in peripheral blood, potent antiretroviral drug combinations when administered systemically may not effectively target infected cells within the intestinal mucosa.

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Copyright © 2002 - Foundation for Retrovirology and Human Health. Reproduction of this abstract (other than one copy for personal reference) must be cleared through the Foundation for Retrovirology and Human Health. Licensed (AIDSLINE) from National Library of Medicine.