The Impact of Asymptomatic Human Immunodeficiency Virus-Positive Disease Status on Inpatient Complications Following Spine Surgery: A Propensity Score-Matched Analysis

In the United States, nearly 1.2 million people > 12 years old have human immunodeficiency virus (HIV), which is associated with postoperative complications following orthopedic procedures. Little is known about how asymptomatic HIV (AHIV) patients fare postoperatively. This study compares complications after common spine surgeries between patients with and without AHIV. The Nationwide Inpatient Sample (NIS) was retrospectively reviewed from 2005–2013, identifying patients aged > 18 years who underwent 2–3-level anterior cervical discectomy and fusion (ACDF), ≥4-level thoracolumbar fusion (TLF), or 2–3-level lumbar fusion (LF). Patients with AHIV and without HIV were 1:1 propensity score-matched. Univariate analysis and multivariable binary logistic regression were performed to assess associations between HIV status and outcomes by cohort. 2–3-level ACDF (n = 594 total patients) and ≥4-level TLF (n = 86 total patients) cohorts demonstrated comparable length of stay (LOS), rates of wound-related, implant-related, medical, surgical, and overall complications between AHIV and controls. 2–3-level LF (n = 570 total patients) cohorts had comparable LOS, implant-related, medical, surgical, and overall complications. AHIV patients experienced higher postoperative respiratory complications (4.3% vs. 0.4%,). AHIV was not associated with higher risks of medical, surgical, or overall inpatient postoperative complications following most spine surgical procedures. The results suggest the postoperative course may be improved in patients with baseline control of HIV infection.


Introduction
Nearly 40 million people worldwide currently live with human immunodeficiency virus (HIV), with about 1.2 million individuals aged > 12 years living in the United States (US) [1,2]. HIV is a retrovirus that causes a decline in CD4+ T cell number and function over time [3]. While the 1980s showcased the devastating introduction of this deadly infection into the US, HIV has become a more manageable condition since the inception of antiretroviral therapy (ART) regimens [4].
These advances in HIV treatment have led to marked improvements in life expectancy in this population with an estimated global increase of 14.4 million life-years in adults from 1995 to 2009 [5,6]. Samji et al. [7] noted that an HIV-positive young adult living in the US or Canada who is treated with ART can be expected to live well into their early 70s. In an aging population, there is an increase in conditions such as osteoarthritis, adult spinal deformity, and degenerative disc disease, with operative management available as a treatment option [8][9][10].
In the absence of acute HIV-related illnesses or the progression towards acquired immunodeficiency syndrome (AIDS), patients experience asymptomatic HIV (AHIV). Patients can remain in this chronic, asymptomatic state for 10 years or longer [11]. Studies have shown that early initiation of ART during this asymptomatic phase can delay the progression from HIV to AIDS as well as prevent complications associated with HIV including death [12].
Extensive research has demonstrated an increased risk of postoperative complications among those with symptomatic HIV undergoing orthopedic procedures [13][14][15][16][17]. However, the literature investigating the AHIV population is scant. With the success of HIV treatment and its ability to increase life expectancy, the asymptomatic population of HIV patients will continually age, and a presumably higher proportion of affected patients will experience and develop degenerative musculoskeletal pathologies.
Many of these degenerative disease processes impact the spine, including cervical radiculopathy and myelopathy. In many cases, anterior cervical discectomy and fusion (ACDF) has become the standard method of treatment, with most outcomes having satisfactory results. However, hematoma and recurrent laryngeal nerve palsy are notable for being possible complications [18]. Conditions such as degenerative disc disease also prove to be very common throughout the US and can affect up to two-thirds of adults throughout their lifetime [19]. Lumbar fusion is often accepted as an effective technique in the treatment of such disease, with common complications including dural tear and nerve root injury [20]. In the case of adult spinal deformity (ASD), although surgical techniques, such as thoracolumbar fusion, have improved significantly over the past years, complications such as implant failure remain common and may be a significant source of patient morbidity [21].
Taking into consideration that symptomatic HIV patients are at increased risk of postoperative complications following orthopedic surgery [13][14][15][16][17], the goal of this study was to determine if risks of adverse postoperative outcomes do not increase in patients with AHIV. This study compared the postoperative outcomes of patients with and without AHIV who underwent spine surgery. This study investigated postoperative complications of those undergoing ACDF for cervical radiculopathy or myelopathy, thoracolumbar fusion for ASD, and lumbar fusion for degenerative disc disease.

Data Source, Patient Selection and Inclusion Criteria
The Nationwide Inpatient Sample (NIS) was retrospectively reviewed from 2005-2013. Using the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, adult patients (>18 years of age) were selected if they underwent spinal fusion for an included diagnosis. This study was deemed exempt from review by our institutional review board (Study ID: 1847009-2).
Patients were divided into three cohorts based on the spinal region fused. The first cohort consisted of patients with cervical radiculopathy (72. 10 Patients in each procedural cohort were then stratified based on the presence or absence of AHIV (ICD9 CM code V08), indicating if a patient is positive for HIV infection but no longer has detectable levels.

Exclusion Criteria
Patients with any other form of HIV, history or presence of an HIV-related illness, or AIDS were excluded. Patients were excluded if they had osteomyelitis, pathologic fractures, traumatic fractures, or any cancer.

Statistical Analysis
Within each procedural cohort, patients with and without AHIV were 1:1 propensity score-matched by age, sex, race, and insurance status. The outcome measures analyzed included length of stay (LOS), total hospital charges, medical complications, surgical complications, and mortality. The NIS tracks outcomes during the inpatient stay following the index surgery through discharge from the hospital. Univariate analysis was used to compare demographics and outcomes measures in each cohort between patients with and without AHIV. Chi-squared analysis was used to compare categorical variables and two-tailed independent t-tests were used to compare continuous variables. Multivariable logistical regression was used to identify independent predictors of adverse outcomes among each surgical cohort, with AHIV status, age, sex, and race as covariates. Statistical significance was set at p < 0.05. All analyses were completed using SPSS Statistics version 24.0 (IBM Corp., Armonk, NY, USA).

Discussion
With the advent of ART regimens and its positive effect on life expectancy, the last several decades have witnessed a rise in the number of people living with HIV [2]. Life expectancies have been projected to be as high as 78 years in Europe and North America, with ART maintaining HIV-positive patients in a chronic, asymptomatic stage [22]. However, increased life expectancy has associated age-related orthopedic conditions, such as osteoarthritis, adult spinal deformity, and degenerative disc disease, with consequent potential need for surgical management [9,10,23]. While current research shows increased complication rates in symptomatic HIV patients undergoing orthopedic procedures when compared to the general population [13][14][15][16][17], the focus of the current study was on asymptomatic HIV patients and the impact of AHIV on outcomes after ACDF, thoracolumbar fusion, and short-segment lumbar fusion.
Across all three surgical procedures, patients with and without AHIV had a similar rate of complications to patients without AHIV. These results support the preliminary findings in the study performed by Young et al. [24], which investigated elective spinal surgery in asymptomatic HIV patients. While their sample was limited to 11 patients, it included procedures such as ACDF, LF, and discectomy. Their results showed only 2 out of 11 patients incurred postoperative complications. A retrospective cohort study of the PearlDiver Patient Records Database found that AHIV patients who underwent lumbar fusion were not at greater risk of major complications except for respiratory complications within 90 days compared to non-HIV patients [25]. The authors of this study have suggested higher rates of smoking in patients with HIV as an explanation for the increased rates of respiratory complications [25]. Our results reinforce and build on these findings with a retrospective analysis of a larger cohort of AHIV patients being analyzed following three different spinal surgeries.
The results of this study also corroborate research carried out in other orthopedic disciplines. For example, Bahebeck et al. [26] found comparable infection rates between patients with AHIV and patients without HIV in a variety of orthopedic procedures in which implants were used, including intramedullary nailing, plating, pinning, or arthroplasty, if on an ART regimen and antibiotics. In addition, Hoekman et al. [27] found comparable postsurgical infection rates between AHIV patients and HIV-negative patients undergoing open reduction and internal fixation (0% and 5%, respectively), while symptomatic HIV patients had a greater infection rate of 23%. These findings can help orthopedic surgeons optimize patients preoperatively and underscore the importance of maintaining HIV-positive patients in an asymptomatic state.
On the other hand, O'Brien et al. [28] found higher postoperative infection rates in patients with AHIV patients compared to patients without HIV undergoing tibial fracture fixation. Four out of the total 15 patients had postoperative infections, with 3 out of 4 attributed to the AHIV cohort. Furthermore, Paiement et al. [29] found that trauma patients with AHIV had greater rates of postoperative infections compared with HIV-negative trauma patients (16.7% and 5.4%, respectively), especially among those with open fractures, with an even greater difference of 55.6% vs. 11.3%, respectively. However, both of these studies have a smaller sample size and were performed nearly two decades ago. Since that time, there have been substantial advancements in HIV treatment, which has the ability to impact outcomes [30]. Further research to quantify the impact of HIV treatment in orthopedic surgery is warranted [31].
This study is not without limitations. This study retrospectively reviewed the NIS database, in which only inpatient data without identifiers for longitudinal follow-up were provided. A second limitation was the ICD-9 coding used to identify complications and HIV status. The true CD4 count of patients is not known; thus, there is a strong reliance on coding to appropriately identify HIV and AHIV patients. Additionally, there was a lack of data on other risk factors for postoperative infections, such as intraoperative bleeding and duration of the surgery. As an administrative database, there is also inherent variability in the coding and inclusion of different diagnoses and procedures. Another limitation was the small patient population, which ranged from 594 in our ACDF cohort to 86 patients in our TLSF cohort. It is possible that the cohorts are potentially smaller than they may truly be, as identification of these patients required the ICD-9 code for AHIV to be included in the patient's record. Yet, though small, this study represents the most comprehensive analysis of AHIV patients and the impacts on objective medical and surgical outcomes following three common spine surgical procedures.

Conclusions
This study investigated the rate of complications among those with AHIV compared to those without HIV following ACDF, thoracolumbar fusion for ASD, and short-segment lumbar fusion for degenerative disc disease. AHIV was not associated with an increased risks of overall, medical, or surgical complications among patients undergoing these spinal procedures. Overall respiratory complications were observed to be higher among AHIV patients when compared to non-HIV (4.3% vs. 0.4%) patients following short-segment lumbar fusion, supporting previously reported findings. These results suggest that baseline asymptomatic HIV status lacks association with incidence of overall adverse postoperative complications following surgery. It is unclear whether medical optimization of HIV-positive patients is impacted by gaining or maintaining asymptomatic status. These results can help spine surgeons counsel HIV-positive patients on treatment risks and expectations as part of their preoperative discussions when considering spine surgery.

Institutional Review Board Statement:
This study was performed in line with the principles of the Declaration of Helsinki. This study was found exempt from IRB approval.