The immune synapses reveal aberrant functions of CD8 T cells during chronic HIV infection

It is well-established that chronic HIV infection causes persistent low-grade inflammation that induces premature aging of the immune system in HIV patient including senescence of memory and effector CD8 T cells. To uncover the reasons of gradually diminished potency of CD8 T cells from chronically HIV infected people, we have analyzed cellular morphology and dynamics of the synaptic interface followed exposure of peripheral polyclonal CD8 T cells at various differentiation stages to planar lipid bilayers. The above parameters were linked to pattern of degranulation that determines efficiency of CD8 T cells cytolytic response. We found a large fraction of naive T cells from HIV infected people developing mature synapses and demonstrating focused degranulation, a signature of a differentiated T cells. Further differentiation of aberrant naive T cells leads to development of anomalous effector T cells undermining their capacity to control HIV and other viruses that could be contained otherwise.

897. Trends and Correlation of HIV-1 Reservoir in Acute HIV Infection and Chronic HIV Infection in China

Background Among acute HIV infection （AHI）and chronic HIV infection（CHI）,the association of HIV-1 DNA and HIV-1 RNA is currently a hot spot of concern. We studied HIV-1 DNA levels in patients with AHI and CHI before initiation of ART to explore the growth characteristics of the HIV reservoir. Methods From 2016/10/31 to 2020/11/23, 97 patients were enrolled in the first hospital of Changsha in China. According to the patient’s epidemiological history, HIV-1 antibody conversion time, presence of opportunistic infection（OI）, to determine whether the patients were in the acute or chronic infection period, and divided into two arms: AHI and CHI. Lleukomonocyte, HIV-1 RNA, and CD4/8 of all patients were collected. The HIV-1 DNA in peripheral blood mononuclear (PBMC) was detected by PCR-Fluorescence Probing. The results were analyzed by SPSS 22.0 and GraphPad Prism 8.0. P-value < 0.05 were statistically significant. Results 93 of 97 were male and 85 of 97 with sexual transmission. In AHI arm, the mean of HIV-1 RNA was 5.15 log10 copies/ml, and the mean of HIV-1 DNA was 2.83 log10 copies/106 PBMCs. In CHI Arm, the mean value of HIV-1 RNA was 4.90 log10 copies/ml, and the mean value of HIV-1 DNA was 3.19 log copies/106 PBMCs. The HIV-1 DNA of CHI group was higher than that of AHI group (p = 0.002) , but the HIV-1 RNA of CHI group was lower than that of AHI Group (p = 0.183) . There were no significant differences between AHI and CHI in age, sex, body weight, route of infection, ART, other viral infection, leukomonocyte, CD4+ T cell count, CD4+ T cell percentage, CD8+ T cell count, CD8+ T cell percentage and CD4/CD8 ratio (P > 0.05).In Group AHI, HIV-1 DNA was positively correlated with HIV-1 RNA (r = 0.548, p < 0.001), but not in Group CHI (r = 0.14, p = 0.347). Conclusion Patients with AHI have lower HIV-1 DNA levels and smaller viral reservoir than those with CHI. These data have illustrates the benefits of rapid treatment. The correlation between HIV-1 DNA and HIV-1 RNA in patients with acute infection is strong,the level of HIV-1 DNA increased with the increase of HIV-1 RNA level, but was not related to CD4 + T cells, CD8 + T cells and CD4/CD8 ratio. Disclosures All Authors: No reported disclosures

Alteration in Oral Microbiome Among Men Who Have Sex With Men With Acute and Chronic HIV Infection on Antiretroviral Therapy

Despite the antiretroviral therapy (ART), human immunodeficiency virus (HIV)-related oral disease remains a common problem for people living with HIV (PLWH). Evidence suggests that impairment of immune function in HIV infection might lead to the conversion of commensal bacteria to microorganisms with increased pathogenicity. However, limited information is available about alteration in oral microbiome in PLWH on ART. We performed a longitudinal comparative study on men who have sex with men (MSM) with acute HIV infection (n=15), MSM with chronic HIV infection (n=15), and HIV-uninfected MSM controls (n=15). Throat swabs were collected when these subjects were recruited (W0) and 12 weeks after ART treatment (W12) from the patients. Genomic DNAs were extracted and 16S rRNA gene sequencing was performed. Microbiome diversity was significantly decreased in patients with acute and chronic HIV infections compared with those in controls at the sampling time of W0 and the significant difference remained at W12. An increased abundance of unidentified Prevotellaceae was found in patients with acute and chronic HIV infections. Moreover, increased abundances of Prevotella in subjects with acute HIV infection and Streptococcus in subjects with chronic HIV infection were observed. In contrast, greater abundance in Lactobacillus, Rothia, Lautropia, and Bacteroides was found in controls. After effective ART, Bradyrhizobium was enriched in both acute and chronic HIV infections, whereas in controls, Lactobacillus, Rothia, Clostridia, Actinobacteria, and Ruminococcaceae were enriched. In addition, we found that lower CD4+ T-cell counts (<200 cells/mm3) were associated with lower relative abundances of Haemophilus, Actinomyces, unidentified Ruminococcaceae, and Rothia. This study has shown alteration in oral microbiome resulting from HIV infection and ART. The results obtained warrant further studies in a large number of subjects with different ethnics. It might contribute to improved oral health in HIV-infected individuals.

General Practitioners as partners for a shared management of chronic HIV infection: An insight into the perspectives of Italian People Living with HIV

Is it possible to achieve a collaboration between Infectious Diseases (ID) Specialists and General Practitioners (GPs) in the management of chronic HIV infection? A cross sectional survey was conducted among People Living with HIV (PLWHIV) attending the outpatient services of four Italian Infectious Diseases Centers to understand to which extent patients trust their GPs and involve them in the management of their chronic condition. Information about level of communication with GPs, subjective perception of the disease, and presence of co-medications were collected and matched with socio-demographic data using χ2statistics. A p<0.05 was considered statistically significant. From December 2019 to February 2020, 672 patients completed the survey, 59% males and 56% >50 years. Overall, 508 patients (76%) had informed GPs about HIV-positivity. Communication of diagnosis was significantly associated with age >50years, lower education level, history of disease >10 years and residency in Northern Italy. The “Undetectable = Untrasmittable” (U = U) concept was investigated as an indirect measure of perceived stigma. 23% of subjects was unaware of its meaning. Despite undetectable status, 50% of PLWHIV found difficult to communicate their condition to GPs, especially married (52% vs 48% of unmarried, p = 0.003), well-educated patients (51% vs 48, p = 0.007), living in Southern vs Northern Italy (52% vs 46%, p< 0.001). More than 75% of the participants consulted the ID specialist for co-medications and DDIs management, often complaining a lack of communication of the former with GPs. Overall, a good level of communication between PLWHIV and GPs was outlined, even if a wider involvement of the latter in HIV care is desirable.

Impact of Delaying Antiretroviral Treatment during Primary HIV Infection on Telomere Length

Background Telomere length (TL) shortens during aging, HIV-seroconversion and untreated chronic HIV infection. It is unknown whether early antiretroviral therapy (ART) start is associated with less TL shortening during primary HIV infection (PHI). Methods We measured TL in peripheral blood mononuclear cells by quantitative PCR in participants of the Zurich PHI Study with samples available for &gt;6 years. We obtained uni-/multivariable estimates from mixed-effects models and evaluated the association of delaying ART start or interrupting ART with baseline and longitudinal TL. Results In 105 participants with PHI (median age 36 years, 9% women), median ART delay was 25, 42, and 60 days, respectively, in the 1 st (shortest), 2 nd, and 3 rd (longest) ART delay tertile. First ART delay tertile was associated with longer baseline TL (p for trend=0.034), and longer TL over 6 years, but only with continuous ART (p&lt;0.001), not if ART was interrupted &gt;12 months (p=0.408). In multivariable analysis, participants in the 2 nd and 3 rd ART delay tertile had 17.6% (5.4-29.7%; p=0.004) and 21.5% (9.4-33.5%; p&lt;0.001) shorter TL, after adjustment for age, with limited effect modification by clinical variables. Discussion In PHI, delaying ART start for even a matter of weeks was associated with significant and sustained TL shortening.

Validation of a Quick Flow Cytometry-Based Assay for Acute Infection Based on CD64 and CD169 Expression. New Tools for Early Diagnosis in COVID-19 Pandemic

Objectives: Several parameters aid in deciphering between viral and bacterial infections; however, new tools should be investigated in order to reduce the time to results and proceed with an early target-therapy. Validation of a biomarker study, including CD64 and CD169 expression, was conducted.Material and Methods: Patients with active SARS-CoV-2 infection (ACov-2), bacterial infection (ABI), healthy controls, and antiretroviral-controlled chronic HIV infection were assessed. Whole blood was stained and, after lysing no-wash protocol, acquired by flow cytometry. The median fluorescence intensity (MFI) of CD64 and CD169 was measured in granulocytes, monocytes, and lymphocytes. The CD64 MFI ratio granulocytes to lymphocytes (CD64N) and CD169 MFI ratio monocytes to lymphocytes (CD169Mo) were evaluated as biomarkers of acute bacterial and viral infection, respectively.Results: A CD64N ratio higher than 3.3 identified patients with ABI with 83.3 and 85.9% sensitivity and specificity, with an area under the curve (AUC) of 83.5%. In contrast, other analytic or hematological parameters used in the clinic had lower AUC compared with the CD64N ratio. Moreover, a CD169Mo ratio higher than 3.3 was able to identify ACov-2 with 91.7 and 89.8 sensitivity and specificity, with the highest AUC (92.0%).Conclusion: This work confirms the previous data of CD64N and CD169Mo ratios in an independent cohort, including controlled chronic viral HIV infection patients as biomarkers of acute bacterial and viral infections, respectively. Such an approach would benefit from quick pathogen identification for a direct-therapy with a clear application in different Health Care Units, especially during this COVID pandemic.