CD4/CD8 ratio can predict the risk of septicemia in HIV infection

Objectives There are few reports about the effect of CD4/CD8 ratio on the infection of HIV with sepsis. Here we analyze the correlation between the baseline CD4 / CD8 ratio and the pathogenic spectrum of AIDS patients with sepsis and the effect on the prognosis. Methods A retrospective analysis study(May 2010 to June 2017) was carried out using routinely colleted data from HIV with spesis at Chengdu Public Health Clinical Center. The values of clinical data, CD4/CD8 ratio and pathogenic spectrum were evaluated in the study. Results Among 322 positive blood culture HIV patients with septicemia, 208 (64.60%) were fungal infection, 64 (19.90%) were gram-negative bacterial infection, 47 (14.60%) were Gram-positive bacterial infection, and 3 (0.90%) were fungal and bacterial infection. Among the fungal infections, Cryptococcus was found in 152 cases (73.08%), followed by cyanobacteria marneffei in 53 cases (25.48%) and Candida in 3 cases (1.44%); Salmonella in 38 cases (59.38%) and Escherichia coli in 17 cases (26.56%); Staphylococcus in 28 cases (59.58%) were positive. When the CD4 / CD8 ratio ≤ 0.3, the risk of sepsis infection was signicantly higher than that of CD4 / CD8 > 0.3. The lower the ratio of CD4 / CD8 (< 0.1), the higher the risk (χ 2 =188.968,P = 0.00).When the ratio of CD4 / CD8 was less than or equal to 0.3, the incidence of fungal infection was signicantly increased (67.14%), and the incidence of gram-negative bacterial infection (18.02%) was signicantly higher than that of Gram-positive bacterial infection (13.78%), (χ 2 = 283.277, P = 0.00); when the ratio of CD4 / CD8 was greater than or equal to 0.3, the incidence of septicemia was signicantly reduced, and there was no signicant difference between the original spectrum of infection (χ 2 = 1.750, P=0.42) (cid:0) 286 patients (88.82%) were discharged after treatment, 36 patients (11.18%) died after treatment. Conclusions In Chengdu of China, the main pathogens of septicemia in AIDS patients are fungi, including Cryptococcus and cyanobacteria marneffei, next are bacteria containing Salmonella and Staphylococcus. The lower the ratio of CD4 / CD8, the higher the risk of infection with sepsis, the higher the risk of multiple infection, and the higher the mortality. Therefore, we think that CD4 / CD8 ratio is an important risk factor for HIV infection with septicemia. We should pay more attention to role of the CD4 / CD8 ratio in clinical work, and it may be help us predicting progress of HIV disease.


Introduction
AIDS is an infectious disease caused by HIV infection, and it also be called acquired immune de ciency syndrome. HIV virus in the body infects immune cells, especially CD4 + T lymphocytes, which can activate and induce cell death, leading to progressive decrease of CD4 + T lymphocytes. CD4 cell count which is used a measure of human immune function decreased, leading to HIV patients with lower immune function, thus prone to opportunistic infection and tumor. However, HIV infection does not destroy all T cell subsets, and CD8 + T cells (cytotoxic T cells) may have obvious activation and expansion. Therefore, more and more scholars begin to pay attention to cd8 T cell count and CD4 / CD8 ratio in HIV patients.
The purpose of this study is to analyze the correlation between CD4 / CD8 ratio and the distribution of pathogenic spectrum of AIDS patients with sepsis and its in uence on the prognosis of patients, to provide further reference for the diagnosis and treatment of such diseases. Materials And Methods 322 HIV/AIDS subjects were included in a retrospective case-control study. Data was obtained from histories of HIV/AIDS patients who were hospitalized at the Chengdu public health clinical center in the period from May 2010-June 2017. Bood culture test were carried out according to aseptic operation principle before antibiotic treatment in all patients after admission.The Peripheral blood samples were collected to used to obtain the CD4 cell absolute count and CD8 cell absolute count by FACS 2 Calibur ow cytometry (BD, Co.Ltd ,USA). SPSS 26.0 was used for statistical analysis and Nonparametric Test was used, P < 0.05 was considered statistically signi cant.
Prognosis analysis Among 322 AIDS patients with septicemia, 286 (88.82%) were discharged from the hospital after anti-viral, anti-infective and symptomatic treatment, 36 (11.18%) died after active treatment.In the dead patients, the CD4 / CD8 ratio was absent in 2 cases. It was found that 97.06% (33 / 34) of the dead patients with CD4 / CD8 ratio ≤ 0.3 and 61.76% (21 / 34) of the dead patients with CD4 / CD8 ratio ≤ 0.1(see table2). Therefore, we consider that when the CD4 / CD8 ratio≤ 0.3, the mortality of AIDS patients with sepsis increased signi cantly. The lower the ratio of CD4 / CD8, the higher the mortality.

Discussion
Our study revealed a correlation between baseline CD4 / CD8 ratio and HIV associated sepsis. We observed that the lower the CD4 / CD8 ratio, the higher the risk of septicemia for AIDS patients. After HIV enters the body, cd8 T cells will be more reactive before the cd4-T cells are reduced, resulting in a lower CD4 / CD8 ratio [1]. The replication of HIV virus in vivo leads to the decrease of CD4T cells and the decrease of CD4/CD8 ratio. As for the study of CD4/CD8 ratio, the prevailing view is that the inversion of CD4/CD8 ratio is an indicator of immunosenescence and is associated with increased morbidity and mortality, also it could affect the immune reaction to pathogens during their primary infection [2][3][4].In HIV negative patients, the lower the CD4 / CD8 ratio, the higher the incidence of chronic diseases (such as diabetes) and malignant tumors [5];and it can also predict the morbidity and mortality in older people [6][7] .For HIV positive patients, starting early combination antiretroviral therapy(cART) is recommended to reduce the duration of high viremia exposure and prevent HIV-related diseases and mortality. Also it can increase CD4 T cell counts [8], promote immune reconstitution and restore CD4 / CD8 ratio (≥ 1) [9]. The later the cATR is started, the less likely it is to normalize the CD4 / CD8 ratio [10].However, Mutoh, Y et al. found that even after longterm successful cART treatment, the CD4 cell count, CD4 percentage and CD4 / CD8 ratio of HIV patients with long-term viral load inhibition were di cult to recover to the level of healthy people [11].Therefore, it is con rm that the CD4 / CD8 ratio is an indicator of immune system attenuation, but it has not been reported in HIV patients with sepsis.
In our study, we found that there was a signi cant positive correlation between HIV infection with sepsis and the CD4 / CD8 ratio.When the ratio of CD4 / CD8 ≤ 0.3, the risk of sepsis infection was signi cantly higher than that of CD4 / CD8 > 0.3.The lower the CD4 / CD8 ratio (< 0.1), the higher the risk of infection.After the occurrence of septicemia, the prognosis of most patients was improved signi cantly after timely and effective treatment.When the ratio of CD4 / CD8 ≤ 0.3, the mortality of AIDS patients with sepsis increased signi cantly. And the lower the ratio of CD4 / CD8, the higher the mortality.In addition, it has been reported that the risk of non-AIDS is higher when the ratio of CD4 / CD8 is less than 0.45 [12]. Therefore, our study showed that when the ratio of CD4 / CD8 ≤ 0.3, the risk of sepsis infection and death in HIV patients will increase. The ratio of CD4 / CD8 can be used as a biomarker to predict the risk and prognosis of sepsis infection in HIV patients.
At the same time, we also found that in HIV patients with septicemia, when the ratio of CD4 / CD8 ≤ 0.3, the patients were mainly infected by fungi, followed by gram-negative bacteria and Gram-positive bacteria.When the ratio of CD4/CD8 was more than 0.3, the infection of septicemia was signi cantly reduced, and there was no signi cant difference between the original spectrum of infection.Cryptococcus neoformans and cyanobacteria marneffei were the main fungal infections;and the infection of Gramnegative bacteria was mainly Salmonella and Escherichia coli;Staphylococcus was the main Grampositive bacteria.Remarkably,when the CD4/CD8 ratio ≤ 0.1, the probability of multiple infection increased signi cantly.This is consistent with some studies which showed that HIV-infected patients with preoperative CD4 count ≤ 200 cells/µL or CD4/CD8 ratio ≤ 0.15 had overall higher postoperative sepsis morbidity [13].These ndings will help us to strengthen the awareness and vigilance of such diseases and accelerate the diagnosis and treatment of patients when we nd patients with similar clinical characteristics in clinical work.
In conclusion, our study is the rst to reveal the clinical signi cance of CD4 / CD8 ratio in HIV patients with sepsis. The lower the CD4 / CD8 ratio, the higher the risk of sepsis. When the CD4 / CD8 ratio ≤ 0.1, the risk of multiple infections and the mortality increased.Therefore, our data shows that the CD4 / CD8 ratio is an important risk factor for HIV infection with sepsis, which suggests that we should pay attention to the effect of CD4 / CD8 ratio on sepsis infection.These ndings may have a positive effect on the clinical diagnosis and treatment of HIV with sepsis.

Declarations Ethics And Consent Statements
The study was approved by the Ethics Committee of Public Health Clinical Center of Chengdu.