CROI 2017 Abstract e-Book

Abstract eBook

Poster and Themed Discussion Abstracts

Results: The median age was 28, 35, and 33 years for AHI, CHI, and CO, respectively. 71% of HIV+ and 50% of HIV- were male. Plasma sCD163 (p-sCD163) levels pre-ART in FI/ II (98.4ng/ml) were lower compared to FIII (150.0ng/ml, p=0.002) or CHI (565.6ng/ml, p<0.0001), but were similar to CO (101.9ng/ml). At 48 weeks (wks) post-cART, p-sCD163 decreased in FIII (93.1ng/ml; p<0.0001) to levels that did not differ from CO. However, although CHI p-sCD163, levels decreased (301.6ng/ml; p<0.0001) after cART, these levels remained elevated compared to CO (p<0.0001). CSF sCD163 (c-sCD163) pre-ART was elevated in both FIII (12.2ng/ml) and CHI (11.6ng/ml) compared to FI/II (7.6ng/ml; p=0.008 and p=0.017, respectively) or CO (7.7ng/ml; p=0.008 and p=0.014, respectively). Post-cART, c-sCD163 in FIII (24 wks; 6.4ng/ml) and CHI (48 wks; 8.5 ng/ml) decreased compared to pre-cART (p<0.001 and p=0.003, respectively) to CO levels. In FI/II pre-cART, higher p-sCD163 correlated with higher GP scores (r=0.627; p=0.044) but higher c-sCD163 post cART in FIII correlated with lower NPZ-4 (r=-0.522; p=0.020) and with lower N-acetylaspartate in basal ganglia (r=-0.500; p=0.031). In AHI, p-sCD163 associated negatively with CT 1 (p<0.0001) and positively with GP (p=0.0043). c-sCD163 associated negatively with TM-A (p<0.0001) and GP (p=0.0052). Conclusion: Initiation of cART early in AHI (FI/II) may decrease inflammation, preventing shedding of CD163, lowering the risk of brain injury.

Poster and Themed Discussion Abstracts

206 CMV REPLICATION DURING PRIMARY HIV INFECTION IS ASSOCIATED WITH T-CELL DYSFUNCTION Jennifer M. Dan 1 , Antoine Chaillon 2 , Masato Nakazawa 1 , Davey M. Smith 1 , Milenka Vargas 2 , Rachel Schrier 2 , Susan J. Little 2 , Sara Gianella 1 1 Univ of California San Diego, La Jolla, CA, USA, 2 Univ of California San Diego, San Diego, CA, USA

Background: More than half of HIV-infected men shed cytomegalovirus (CMV) DNA in their semen during primary HIV infection and subclinical CMV replication has been associated with increased T cell dysfunction and higher levels of HIV RNA transcription. The effect of persistent CMV exposure during primary HIV infection on viral specific immune responses and immune exhaustion has not been evaluated. Methods: Paired seminal and blood samples from 53 ART-naïve early HIV-infected men from the San Diego Primary Infection Cohort (< 6 months from estimated date of infection) and 23 at-risk HIV-uninfected CMV-seropositive controls were evaluated. Levels of seminal CMV DNA and HIV RNA were measured by RT-PCR, and expression of intracellular interferon (IFN)-γ and Granzyme B production were measured by flow cytometry from peripheral blood mononuclear cells (PBMC) following overnight stimulation with whole CMV and HIV lysate. Levels of programmed death receptor-1 (PD-1) were measured on unstimulated PBMCs. Immunological and virologic markers were compared between groups (i.e. HIV-negatives, HIV-positives, CMV shedders and non shedders) using Mann-Whitney U tests. Results: CMV DNA was detected in semen of 31 HIV-positive (58%) and 3 HIV-negative (13%) individuals (P<0.001). Overall, early HIV-infected participants presented significantly increased PD-1 expression on CD8+ (P<0.01), greater Granzyme B production by CD8+ after ex vivo stimulation with CMV (P=0.07), increased HIV-specific CD8+ immune response (IFN-γ expression) compared to HIV-uninfected, but no differences in CMV-specific immune response. Among HIV-positives, shedding of CMV DNA was associated with higher levels of seminal HIV RNA (P<0.01), increased PD-1 expression on CD4+ (p=0.03) and CD8+ T cells (p=0.08), reduced HIV-specific CD8+ immune response (P=0.02) but no differences in CMV-specific immune response. Interestingly, HIV-infected participants with no evidence of CMV shedding had similar levels of PD-1 expression on CD4+ and CD8+ compared to HIV-uninfected controls. Conclusion: Subclinical CMV replication during early HIV-infection (but not HIV infection alone) is associated with T cell exhaustion and with impaired HIV-specific CD8+ T cell response. These findings could explain the connections between subclinical CMV replication and higher levels of seminal HIV shedding, as well as increased HIV DNA levels in blood and worse HIV disease progression. CMV might be the “smoking gun” of immune dysfunction among co-infected individuals. 207 IMPACT OF MSM-ASSOCIATED MICROBIOTA ON IMMUNE ACTIVATION AND IN VITRO HIV INFECTION Sam Li , Abigail Armstrong, Charles P. Neff, Catherine Lozupone, Brent E. Palmer Univ of Colorado, Aurora, CO, USA Background: Several studies have shown that HIV infection is associated with alterations in gut microbiota composition. Recent findings from a European cohort suggest that the main alterations are associated with sexual behavior of men who have sex with men (MSM) rather than with infection itself. Given that MSM are at higher risk of becoming infected with HIV, it is of importance to understand the impact of MSM-associated microbiota on immune cells in the gut as it relates to disease and HIV transmission. Methods: The fecal microbiota of a US cohort (n=210), including HIV-negative high-risk MSM (n=42) and low-risk heterosexual men (n=22), were analyzed using 16S rRNA gene sequencing. Feces from three representative MSM and three representative heterosexual men were used to gavage gnotobiotic mice (n≥4 mice per fecal sample), and mice were analyzed for immune activation following colonization. Bacterial cells were isolated from original fecal samples (n=8 MSM, 8 heterosexual men) using density centrifugation, and used to stimulate human peripheral blood mononuclear cells (PBMCs) and gut lamina propria cells (LPMCs). After stimulation, PBMC were analyzed for activation, and LPMCs were infected with HIV bal and stained for p24 expression at 5 days post infection. Results: Within our cohort of HIV-negative MSM in the US, the majority of subjects harbor a Prevotella-rich/Bacteroides-poor microbiome, similar to that of HIV-infected subjects and compositionally distinct from low risk HIV-negative subjects which harbor a Prevotella-poor/Bacteroides-rich microbiome. Following fecal microbial transplantation to gnotobiotic mice, T cells in the lamina propria exhibited higher CD69 expression (p=0.017), and macrophages in the mesenteric lymph node showed higher CD86 expression (p=0.006), when mice were colonized with feces fromMSM. Stimulation of human PBMCs with bacteria isolated fromMSM feces resulted in higher levels of HLA-DR+ CD38+

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CROI 2017