Bariatric surgery in individuals with human immunodeficiency virus and type 2 diabetes: a case series

Background The efficacy and safety of bariatric surgery have not been fully elucidated in patients affected with human immunodeficiency virus. Although adjustable gastric banding and sleeve gastrectomy are starting to be used in patients with human immunodeficiency virus, there are limited descriptions of the outcomes of type 2 diabetes mellitus in individuals who are human immunodeficiency virus positive and undergoing these procedures. Case presentation We have evaluated retrospectively three patients who underwent adjustable gastric banding or sleeve gastrectomy, the effect in weight reduction and glycemic control as well as its impact on human immunodeficiency virus management. Case 1 (adjustable gastric banding), a 58-year-old Caucasian male, achieved 19% total weight loss, Case 2, a 33-year-old Caucasian male (sleeve gastrectomy) lost 25%, and Case 3, a 48-year-old Caucasian female (sleeve gastrectomy), lost 14% postoperation. In terms of type 2 diabetes mellitus, Case 2 achieved complete remission according to American Diabetes Association criteria, while Case 1 would also have achieved remission were it not for the continuation of metformin postoperatively. Insulin requirements and pill burden were markedly reduced in Case 3 after sleeve gastrectomy, although lack of remission was predictable given the longevity of type 2 diabetes mellitus and preoperative insulin dosage. In all three cases, human immunodeficiency virus status did not appear to be affected by the bariatric surgery which was supported by the postoperative stable CD4 count and undetectable viral load. Conclusions Bariatric surgery is a safe and effective treatment modality in patients who are human immunodeficiency virus positive with obesity and type 2 diabetes mellitus.


Background
Obesity, type 2 diabetes mellitus (T2DM), and human immunodeficiency virus (HIV) are prominent global health issues. With the advent of highly active antiretroviral treatment (HAART) and improved mortality rates, people with HIV infection increasingly present with obesity and related metabolic consequences [1]. Bariatric procedures, including adjustable gastric banding (AGB), sleeve gastrectomy (SG), and Roux-en-Y gastric bypass (RYGB), are effective therapies for morbid obesity with high rates of T2DM resolution [2]. Until recently, however, bariatric surgery in the HIV-positive population remained controversial [3].
The first report of a patient with HIV infection undergoing bariatric surgery was in 2005 [4], and, subsequently, a small number of studies, including within our own unit, have reported outcomes [5]. Bariatric surgery is now considered a safe and effective treatment for people with morbid obesity who are also infected with HIV [6]. Notably, to date, there are limited descriptions of T2DM outcomes in such individuals. Given the increasing prevalence of this combination of conditions, we present a case series to advance this discussion.

Methods of case collection
We studied 120 patients with T2DM who underwent bariatric surgery between 2010 and 2017 at Chelsea and Westminster Hospital, London. The patients groups were: AGB (n = 62) and SG (n = 58). Three patients known to be HIV antibody positive form the basis of this series. Selection for bariatric surgery was consistent with National Institute for Health and Care Excellence (NICE) guidelines with procedural type co-decided by the patient and the multidisciplinary team (MDT). Procedural descriptions are provided elsewhere [7]. Utilizing hospital pathology and electronic record systems, information was collected on: demographics; anthropometrics; weight history; surgical details; perioperative diabetes status; perioperative HIV status, and major outcomes.

Case 1
Case 1 is a 58-year-old Caucasian male with a history of HIV infection (2002), T2DM (2008), and obesity. His comorbidities included hypertension, dyslipidemia, and obstructive sleep apnea. (Table 1). Preoperatively, he was prescribed metformin 500 mg twice a day and glycated hemoglobin (HbA1c) was 40 mmol/mol. His baseline body mass index (BMI) was 47 kg/m 2 , with a weight of 162.9 kg. Multiple attempts at weight loss, including commercial diets and orlistat, had been unsuccessful. HIV prescriptions included one tablet daily of Atripla (efavirenz/emtricitabine/tenofovir). His preoperative CD4 count was 800 cells/μL and viral load was undetectable. Following assessment by the bariatric MDT, he was found to meet criteria for surgery.
In 2012 he underwent laparoscopic AGB surgery and had an uncomplicated postoperative course. Preoperative and postoperative clinical parameters are presented in Tables 1, 2, and 3 and Fig. 1 with sustained weight loss reported. As per local guidelines, this patient continued to receive metformin 500 mg twice a day postoperatively to optimize insulin sensitivity. Six months postoperatively, HbA1c was 35 mmol/mol, and there was no evidence of diabetes-related complications. His HIV infection status was not affected by surgery, and he continued to receive Atripla (efavirenz/emtricitabine/tenofovir). His CD4 count was unchanged at each postoperative visit, with undetectable viral load throughout. He continues to be on antiretroviral and antidiabetic medications as well (metformin 500 mg twice a day) and reports sustained weight loss.

Case 2
Case 2 is a 33-year-old Caucasian male who was positive for HIV (2011) with a background of T2DM, obesity, depression, and fatty liver disease (  Tables 1, 2, and 3 and Fig. 1. A laparoscopic SG was performed in 2013. He reported no complications at postoperative follow-up. T2DM was diet controlled following surgery and his HbA1c remained stable (33 mmol/mol mean). Therefore, complete diabetes remission was achieved according to American Diabetes Association (ADA) criteria [8]. Postoperatively, his viral load remained undetectable with a mean CD4 count of 735 cells/μL. Following clinical trial recruitment, antiretroviral medication was adjusted in an attempt to better stabilize mood. Depressive symptoms improved and HIV status remained stable. of sodium-glucose co-transporter-2 (SGLT-2) inhibitor, high-dose insulin sensitizer, glucagon-like peptide-1 (GLP-1) agonist, and high-dose basal insulin, her HbA1c remained elevated at 128 mmol/mol. Extensive discussions were undertaken with the patient and the MDT. Despite lack of glycemic optimization, benefits were deemed to outweigh risks and so SG was scheduled.
Preoperative and postoperative clinical parameters are presented in Tables 1, 2, and 3 and Fig. 1. Her T2DM status improved following surgery: HbA1c dropped to 90 mmol/mol 2 years postoperatively (accompanying fasting glucose of 12 mmol/L). Unsurprisingly, given T2DM duration, preceding control, and preoperative insulin requirements, diabetes remission was not achieved in this case. Following surgery, however, she benefits from a reduced pill burden and markedly reduced daily insulin requirements (38 versus 140 units preoperatively). Anti-retroviral medications were switched to Truvada (emtricitabine/tenofovir) and Rezolsta (darunavir/cobicistat) and her HIV status remained stable (CD4 count 400 cells/μL, undetectable viral load). An esophageal stricture which developed 2 years postoperatively responded to a dilatation procedure. No further complications have occurred.

Discussion
Here we present three differing cases which add to the literature supporting bariatric surgery as a safe ALB albumin, ALP alkaline phosphatase, ALT alanine aminotransferase, Bili bilirubin, Cr creatinine, CRP C-reactive protein, eGFR estimated glomerular filtration rate, FBC full blood count, Hb hemoglobin, K potassium, LFTs liver function tests, Na sodium, N/A not applicable, PLT platelet, U&Es urea and electrolytes, WCC white cell count *on admission to receive bariatric surgery,^last follow-up (> 3 years postoperation for all cases) treatment modality in individuals who are HIV positive. Our cases series is novel as we have compared the effects of bariatric surgery on weight reduction and glycemic control in patients with HIV infection as well as patients without HIV infection. T2DM prevalence and complication rates in the HIV-infected population (23-40%) are noticeably higher than the general population [9]. Traditional risk factors as well as HIV-specific factors including anti-retrovirals and lipodystrophy syndrome contribute to the pathogenesis [9]. A strong body of evidence supports the use of bariatric surgery as a treatment modality for T2DM in the context of obesity [10] with sustained remission of T2DM described [7]. Also   [8]. Data in non-HIV group were described as mean ± standard deviation reported are improvements in cardiovascular risk profile, obesity-related complications, and all-cause mortality [2,7]. Despite this, bariatric surgery remains an underutilized tool and data are limited for the HIV-infected population. Although reports [11,12] have suggested that bariatric surgery is safe, there is a paucity of data describing the outcomes of T2DM in these individuals or, in fact, the uptake of surgery. Summarized clinical outcomes for our case series (n = 3) are presented alongside outcomes for patients with T2DM who were not HIV infected (n = 117) in Table 4. Case 1 (AGB) achieved weight loss, which was 53% excessive weight loss (EWL) in excess of the figure typically quoted for this procedure (40%) [13]. This is particularly impressive as a restrictive procedure. Cases 1 and 2 were also noted to achieve greater % EWL compared to the non-HIV group for their respective procedures. Case 3, however, achieved below average % EWL for SG (30% compared to 60% reported [14]), although this was not far from the average % EWL for the non-HIV group (42% ± 20%). We speculate that several patient factors, including negative eating habits, depression, and sedentary life style, may all have contributed to this outcome.
In terms of T2DM, although only Case 2 achieved remission according to ADA criteria [8], it is notable that all cases achieved an improvement in HbA1c postoperatively. Ongoing monitoring for relapse is advisable. Case 1 would also have achieved remission were it not for the continuation of metformin postoperatively. Although T2DM outcomes for Case 3 did not objectively seem as successful, it is notable that individual insulin requirements and pill burden were reduced. Lack of remission was perhaps predictable given the longevity of T2DM and preoperative insulin dosage.
In all three cases, HIV status was not affected by bariatric surgery, which is consistent with existing literature [4,6,11,12,15]. There is a theoretical concern over drug absorption following bariatric surgery. One study to date has reported that, despite a mild reduction, drug levels following SG remained within the therapeutic range [12]. In our case series, the HIV status was not adversely affected by bariatric surgery.

Conclusions
In conclusion, our case series further supports the use of bariatric surgery as a safe treatment modality in individuals who are HIV positive [11]. Importantly, we have demonstrated the positive effect of bariatric surgery on T2DM in this group of patients. Further work would be beneficial to consolidate these findings.