The acquired immunodeficiency syndrome (AIDS) epidemic, caused by the human immunodeficiency virus (HIV), is an ongoing global health crisis. HIV attacks and weakens the immune system, making it difficult for the body to fight infections and diseases (1, 2). According to the World Health Organization (WHO), as of 2021, there were an estimated 38 million people living with HIV worldwide, with the majority of cases occurring in sub-Saharan Africa (3). Despite significant progress in the development of effective antiretroviral therapies (ARTs) and prevention programs, HIV continues to be a major public health issue, especially in low- and middle-income countries. In 2021, the WHO estimated that there were approximately 2.3 million new HIV infections and 770,000 AIDS-related deaths worldwide. The WHO 2022–2030 global health sector strategy on HIV aims to reduce HIV infections from 1.5 million in 2020 to 335 000 by 2030, and deaths from 680 000 in 2020 to under 240 000 in 2030 (4).

HIV attacks the immune system and disrupts bone metabolism. Moreover, the side effects of oral antiviral drugs often lead to decreased bone density, and, the incidence of osteoporosis in AIDS patients is significantly increased (5). Patients with HIV often have various orthopedic diseases and require surgical treatment. However, because of the combination of immunodeficiency, malnutrition, multiple diseases (such as tuberculosis, syphilis, hepatitis C, and hepatitis B), and various opportunistic infections, many studies have shown that HIV-positive patients have a significantly higher risk of surgical site infections (SSI) than patients with normal orthopedic diseases (6–8).

The HIV/AIDS epidemic is characterized by a low prevalence rate, with an estimated 0.1% of the adult population living with HIV/AIDS; the number of infections is also increasing annually in China (9). Currently, in China the only effective treatment is antiretroviral therapy (ART), commonly known as “cocktail” therapy. This therapy also increases the number of CD4 T lymphocytes in patients with AIDS, rebuilds immune function, and reduces mortality. As part of a surgical treatment plan, patients should be fully evaluated before surgery, especially for CD4 T lymphocyte levels. Many studies have shown that CD4 T lymphocyte counts are negatively correlated with the risk of incision infection after orthopedic surgery (6, 10, 11). However, these studies had small sample sizes and many variables meaning that they were prone to large biases. In addition, data from Chinese hospitals is scarce, particularly for HIV-positive patients with fractures.

The CD4/CD8 ratio is a marker of immune dysfunction and systemic inflammation in the body and may be a good indicator of disease progression, treatment response, morbidity, and mortality (12). Further evidence suggests an overall increase in morbidity and mortality in HIV-positive individuals who fail to normalize their ratios (13, 14). Our study fills this gap by investigating the CD4/CD8 ratio as an independent predictor of surgical site infection risk among HIV-positive adults. By considering this specific immunological marker, we aim to provide novel insights into the underlying mechanisms of surgical site infections and potentially identify new avenues for intervention and prevention strategies. Furthermore, our study contributes to the existing literature by conducting the research within a Chinese hospital setting, which provides insights specific to this population. This geographical diversity adds value and expands the generalizability of the findings, as risk factors and outcomes may vary across different regions and healthcare settings.

As far as we know, little research has focused on the relationship between the CD4/CD8 ratio and the risk of SSI, and this issue has not yet been addressed. Compared with previous foreign studies, we used a larger sample size and recorded the variables for each patient in detail. Our goal was to explore the risk factors for incision site infection in orthopedic surgery by focusing on the relationship between the CD4/CD8 ratio and the risk of SSI. We hypothesized that a lower CD4/CD8 ratio in HIV-positive patients would increase the risk of SSI.

Our study found that the SSI rate in HIV-positive patients was 10.6%. However, previous studies have shown that the rate of SSI in patients with AIDS during the perioperative period can be as high as 30–75%, and the rate in HIV-negative patients is approximately 1–5% (19–21). In our study, the incidence of SSI was much lower than that reported in other domestic and foreign studies. We speculate that this may be due to our standardized preoperative preparation, including regular antiviral treatment before surgery, as well as the prophylactic use of antibiotics within 24 h before and 48 h after surgery.

Our research has shown that a decrease in CD4 T lymphocyte counts can lead to a decline in immune function, which increases the risk of SSI. Our conclusions are consistent with those of previous studies similar to our own (6, 10, 11, 20, 21). This is because CD4 T lymphocytes are a key type of cell in the immune system that help fight infections. Specifically, through antigen recognition, activation of immune responses, differentiation into specialized subsets, support of antibody production, and formation of memory cells, CD4+ T cells play a central role in orchestrating and coordinating the immune response against infections. These are some of the ways in which CD4+ T cells contribute to fighting infections. However, the CD4 T lymphocyte counts are reduced due to the viral attack, which results in a decline in immune function in HIV/AIDS patients. Therefore, a decrease in CD4 T lymphocyte count may increase the risk of SSI.

Although it is generally believed that a high CD4 count is a protective factor against SSI based on the results of previous studies, there is no consensus on the minimum CD4 count required to protect against infections. For example, Abalo et al. (6) found that CD4 counts below 500 were associated with SSI in 36 HIV-positive patients who underwent surgery for orthopedic trauma. In addition, an analysis of 64 HIV-positive patients with fractures indicated that CD4 counts below 300 were associated with postoperative infections (11). Previous Chinese studies have usually used values of 200 and 500 as cut-off points for CD4 counts. Similarly, previous studies have pointed out that the lower CD4 counts are a risk factor for SSI in patients with fractures (21–23). This conclusion was consistent with HIV-positive patients undergoing abdominal surgery (10, 24).

However, other studies have reached different conclusions, some researchers thought the CD4 count was not related to an increased risk of SSI in 77 HIV-positive women who underwent hysterectomy (25). Another study found that the relationship between HIV, CD4 count, viral load, and surgical site infection was not robust and was uncertain after sensitivity analysis in a meta-analysis of 18 cohort studies (8). Similarly, whether or not to extract teeth in HIV-positive patients was unrelated to CD4 count in 231 HIV-positive patients who underwent tooth extraction (26).

Furthermore, we explored the relationship between the CD4/CD8 ratio and the risk of SSI and found that the CD4/CD8 ratio may be a useful predictor of SSI risk. Moreover, we suggest that doctors should ensure that the CD4/CD8 ratio is at least 0.9 before the internal fixation of fractures to reduce the risk of SSI. The CD4/CD8 ratio could be a useful indicator of postoperative sepsis in HIV-infected patients undergoing abdominal surgery. A previous study found that when the CD4+ T lymphocyte count was consistently above 200 and the CD4/CD8 ratio was above 0.15, the risk of sepsis during abdominal surgery was reduced (27). Low ratios were associated with poorer survival in PLWH after analyzing 67 patients with right colon cancer (RCC) who underwent surgery (28). Moreover, this ratio not only predicts patient prognosis but can be used as a predictor of mortality in HIV-positive patients. Overall, some researchers have concluded that a lower CD4/CD8 ratio is associated with an increased risk of non-AIDS-defining events or death (29–32).

However, other researchers have different views on this matter. A previous study of 13 European and North American cohorts found little evidence that the CD4/CD8 ratio could be used to predict overall mortality after adjusting for other factors (33). In addition, AIDS-related mortality decreased as the CD4/CD8 ratio increased and the CD8 count decreased, and there was almost no evidence that the CD4/CD8 ratio or CD8 count had prognostic value for non-AIDS mortality. The Swiss Cohort Study indicated that an increase in the CD8 cell count may be a moderate risk factor for stroke, but that CD4 counts, CD8 counts, and the CD4/CD8 ratio were not associated with an increased risk of coronary artery disease (34). The CD8 count was found to be a predictor of clinical progression, but the CD4/CD8 ratio could not be used to predict an increased risk of death within seven years. Overall, many researchers do not agree on this issue (35).

We first reported that HIV-positive patients with hepatitis B or C were at higher risk of developing SSI than HIV-negative patients. This may be due to the immunocompromised state of HIV-positive individuals, which makes them more vulnerable to infections. This highlights the importance of screening for and treating hepatitis in HIV-positive patients before surgery to reduce the risk of SSI. Co-infection with the hepatitis c virus (HCV) was significantly associated with SSI in a cohort study of 305 Italian patients for the first time in 2009 (7). A comparison of four patient groups (patients with HIV, HCV, HBV, or HIV and HBV or HCV who underwent TJA) showed that the patients with HIV, HBV, or HCV had an increased risk of postoperative medical and surgical complications after TJA. However, patients with HBV or HCV infections had a higher risk of infection within 90 days than patients with HIV (36). The risk of revision was higher, but the risk of infection did not appear to increase in patients who were only infected with HIV. Up to 28% of HIV-positive patients had hepatitis C, and patients with hepatitis C had an increased risk of fracture in a retrospective study of 1981 HIV-positive patients in Massachusetts, USA (37).

This is the first and most innovative research on HIV-positive patients with fractures, and reports in this area are rare, especially in China. The Chinese scholar examined 175 clinical records and gene sequences from HCV-infected patients, including 89 (51%) HIV/HCV co-infected patients (38). They found that HCV genotypes 6a or 3a appeared most frequently in HIV/HCV co-infections and that fibrosis increased with HCV genotype 3a infections in southeast China. However, in an HIV-negative population, HIV or HCV infection was not associated with surgical site infection in a multicenter study of 1442 patients with ankle fractures (39).

The extent to which albumin is present has been shown to be a strong predictor of SSI in HIV-positive patients (23–25, 40). By providing essential nutrients, maintaining proper fluid balance, modulating inflammation, exerting antioxidant effects, and supporting immune function, albumin plays a crucial role in wound healing and immune function, and low levels of albumin can impair these processes. In addition, HIV-positive patients with low albumin levels often have other underlying conditions, such as malnutrition and inflammation, which can further increase the risk of SSI. Therefore, it is important for surgeons and healthcare providers to carefully monitor albumin levels in HIV-positive patients before and after surgery and implement interventions such as nutritional support and infection prevention measures to reduce the risk of SSI.

According to our study, HIV-positive patients with high viral loads, longer operative durations, and open fractures were more likely to develop SSI after surgery than those with low viral loads. This is consistent with the conclusions drawn from previously reported research (8, 21). These findings suggest that controlling the HIV RNA load before surgery may be an important factor in reducing the risk of SSI in HIV-positive patients. Antiretroviral therapy (ART), which is the standard treatment for HIV, can help reduce the viral load and improve immune function. Treating HIV-positive patients with open fractures requires prophylactic antibiotics and proper wound care to prevent SSI from developing in open fractures. Healthcare professionals should consider ways to optimize the efficiency of surgeries and minimize their duration, such as using minimally invasive techniques or reducing the number of surgical team members, to reduce the risk of SSI in HIV-positive patients.

There is currently no consensus among researchers on whether CD4 counts and the CD4/CD8 ratio can be used as predictors of SSI after fracture surgery in HIV-positive patients. Our study has several strengths. First, our sample size was significantly larger than those in previous studies to reduce bias and make the conclusions more reliable. Second, there are relatively few similar reports in the field of orthopedics, especially in China, and our study is the first and most innovative. Finally, we used smooth curve fitting and searched for inflection points in the study, which means that our results can provide important guidance for practical clinical work. The limitations of our study are that, compared to other large-cohort studies, the sample size was small, which may have resulted in certain errors, and the follow-up time was short. We believe that a multicenter study in China would provide the most convincing results.

Our study showed that the CD4/CD8 ratio can be used as a predictor for SSI in HIV-positive patients with fractures. The risk of SSI in HIV-positive patients increased significantly during the perioperative period when the CD4/CD8 ratio was lower than 0.913. This suggests that it is necessary for doctors to reconstruct the immune function of HIV-positive patients before surgery.

The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.

This study was approved by the Ethics Committee of the Beijing Ditan Hospital, Capital Medical University. All procedures involving human participants were performed in accordance with the institutional and/or National Research Council ethical standards and the 1964 Declaration of Helsinki and its subsequent amendments, or equivalent ethical standards.

BL performed data analysis and wrote the manuscript. KL, RZ, and SL contributed to data collection. KL, RZ and SL performed a literature search. QZ oversaw and managed the research. All authors contributed to the article and approved the submitted version.