HIV type 2 in New York City, 2000-2008.

BACKGROUND: Antibody cross-reactivity complicates differential diagnosis of human immunodeficiency virus (HIV) type 2 (HIV-2) using standard serologic screening and confirmatory tests for HIV. HIV type 1 (HIV-1) viral load testing does not detect HIV-2. Although HIV-2 is, in general, less pathogenic than HIV-1, it can lead to immunosuppression and clinical AIDS, and there are important differences in the selection of antiretroviral therapy for HIV-2-related immunosuppression that make it imperative to differentiate between the 2 viruses. The New York City Department of Health (New York, NY) seeks to facilitate accurate diagnosis and surveillance of HIV-2 infection in the city. METHODS: We used routine HIV-1-2+O screening and a comprehensive algorithm to differentiate between HIV-1 and HIV-2 infection, universal HIV-related laboratory test reporting, population-based surveillance of HIV infection, and active communication with clinicians. RESULTS: Between 1 June 2000 and 31 December 2008, 62 persons received a diagnosis of confirmed or probable HIV-2 infection. The majority (60 [96.8%] of 62 individuals) were foreign-born (96.7% were born in Africa) and of black race/ethnicity (93.5%). At the time of initial diagnosis, 17.7% of patients with HIV-2 infection had AIDS. Forty (64.5%) of the patients received an initial diagnosis of HIV-1 infection. Among these patients, the median lag between initial diagnosis of HIV-1 infection and identification of HIV-2 as the infecting organism was 487.5 days. CONCLUSION: HIV-2 should be ruled out in persons presenting for HIV testing who originate in or travel to West Africa and other areas in which HIV-2 is endemic, particularly those who have negative or indeterminate results on HIV-1 Western blot testing or have atypical banding patterns and/or present with clinical signs of HIV infection or unexplained immunosuppression.

Interaction of Muc2 and Apc on Wnt signaling and in intestinal tumorigenesis: potential role of chronic inflammation.

Somatic mutations of the adenomatous polyposis coli (APC) gene are initiating events in the majority of sporadic colon cancers. A common characteristic of such tumors is reduction in the number of goblet cells that produce the mucin MUC2, the principal component of intestinal mucus. Consistent with these observations, we showed that Muc2 deficiency results in the spontaneous development of tumors along the entire gastrointestinal tract, independently of deregulated Wnt signaling. To dissect the complex interaction between Muc2 and Apc in intestinal tumorigenesis and to elucidate the mechanisms of tumor formation in Muc2(-/-) mice, we crossed the Muc2(-/-) mouse with two mouse models, Apc(1638N/+) and Apc(Min/+), each of which carries an inactivated Apc allele. The introduction of mutant Muc2 into Apc(1638N/+) and Apc(Min/+) mice greatly increased transformation induced by the Apc mutation and significantly shifted tumor development toward the colon as a function of Muc2 gene dosage. Furthermore, we showed that in compound double mutant mice, deregulation of Wnt signaling was the dominant mechanism of tumor formation. The increased tumor burden in the distal colon of Muc2/Apc double mutant mice was similar to the phenotype observed in Apc(Min/+) mice that are challenged to mount an inflammatory response, and consistent with this, gene expression profiles of epithelial cells from flat mucosa of Muc2-deficient mice suggested that Muc2 deficiency was associated with low levels of subclinical chronic inflammation. We hypothesize that Muc2(-/-) tumors develop through an inflammation-related pathway that is distinct from and can complement mechanisms of tumorigenesis in Apc(+/-) mice.