500 Quantification of the HIV reservoir in the gut-associated lymphoid tissue

OBJECTIVES/GOALS: The major obstacle to an effective cure or remission for HIV infection is the integration of HIV into the genome of long-lived resting cells which constitute the so-called viral reservoir. With this study we want to elucidate the changes of the gut-associated HIV reservoir at different stages of viral suppression METHODS/STUDY POPULATION: Recent studies have shown that after long-term (>7 years) clinical suppression of peripheral HIV RNA, the circulating viral reservoir does not seem to decline further and, in fact may expand. The gastrointestinal associated lymphoid tissue (GALT) harbors by far the largest fraction of the latently infected cells, however not much is known about its changes over time.We thus quantified the HIV viral reservoir in the GALT by identifying HIV viral transcripts via 10X single-cell RNA sequencing at two GALT-sites in five PWH and compared the amount of HIV RNA found in the group of PWH with early ( 7years) peripheral virological suppression (plasma HIV RNA 7yrs, 0 (0-4) HIV transcripts were identified in the ileum and 7 (14-11) in the colon. Based on these preliminary results we plan to expand our cohort and confirm these results using Proviral DNA quantification. We anticipate that the viral decay in the GALT will follow a slower dynamic than what has been reported for the peripheral blood achieving a steady state after more than 7 years of peripheral viral suppression. DISCUSSION/SIGNIFICANCE: Despite the remarkable progress the survival and quality of life of PWH, after forty years from its first discovery, HIV infection remains uncurable. Considering its critical role, efforts are needed to better understand the dynamics of the GALT-associated HIV reservoir

Mortality of HIV-Infected Patients with or without Cancer: Comparison with the General Population in Italy

Background HAART has reduced mortality in HIV-infected patients; however, the risk of non-AIDS-related events has increased, including cancer. We compared mortality in HIV-infected patients with or without cancer with the general population in Italy. Methods Eligible patients were recorded in the San Raffaele Infectious Diseases Department database. The ratio of observed deaths to expected all-cause deaths (standardized mortality ratio [SMR]) was standardized for age and gender, and stratified by cancer occurrence or year of HIV infection (≤1998 or &gt;1998). Expected all-cause deaths were obtained from the Istituto Superiore di Sanità (Rome, Italy; 2002 data). Results Among 6,495 HIV-infected patients, contributing 75,171 person-years, the SMR was 6.0 (95% CI 5.7, 6.4); SMRs decreased as age increased. Mortality rates were significantly higher than the general population for patients with or without cancer (SMR=15.1 [95% CI 13.6, 16.7] and 4.8 [95% CI 4.5, 5.1], respectively). For patients with or without cancer, SMRs were higher in those aged &lt;45 years than older patients. SMRs for patients with cancer were almost stable in those infected with HIV ≤1998 (15.3; 95% CI 13.7, 17.0) or &gt;1998 (13.5; 95% CI 9.2, 19.1). Among patients with cancer diagnosed with HIV &gt;1998, age-adjusted SMRs ranged from 216.0 (95% CI 43.4, 631.3) to 6.8 (95% CI 4.7, 9.7) in patients &lt;30 years or ≥70 years, respectively. Conclusions Mortality in HIV-infected patients remains higher than the general population in Italy, with marked differences according to age, and cancer contributing to an increased excess of mortality. </jats:sec