The research, led by Allan Wandera of the Department of Biochemistry at Lira University and colleagues from institutions including Soroti University, was published in BMC Endocrine Disorders. It enrolled 54 HIV-positive adults with type 2 diabetes, all of whom had been receiving both antiretroviral therapy and glucose-lowering medication for at least six months at the hospital’s Chronic Care Clinic. The study was funded by the Lira University Research and Innovations Fund, financed by the Government of Uganda for the 2023/2024 cycle, and approved by the Lira University Research Ethics Committee under approval number LUREC-2025-400, with administrative clearance from the hospital itself. Every participant provided written informed consent, and the work was conducted in line with the Declaration of Helsinki.

The clinical backdrop is important for understanding why the study exists. Dolutegravir-based regimens are now recommended widely because they are potent, durable, and have a high genetic barrier to resistance. Yet at Lira Regional Referral Hospital, diabetic patients are frequently switched away from dolutegravir onto alternative combinations, most commonly tenofovir disoproxil fumarate, lamivudine, and efavirenz, known as TDF/3TC/EFV, or onto protease inhibitor-based or abacavir-based therapies. The metabolic consequences of these non-dolutegravir regimens in patients who also have diabetes had not been systematically documented, leaving clinicians without evidence to guide treatment choices for a growing and vulnerable subgroup.

To fill that gap, the researchers combined a review of medical records with fresh laboratory investigations. Blood samples were drawn to measure glycated hemoglobin, or HbA1c, the standard long-term marker of blood glucose control, along with liver function tests, kidney function tests, lipid profiles, and CD4 cell counts. Viral load data were retrieved from patient records. Participants were then sorted into six groups according to the specific combination of antiretroviral therapy and diabetes medication they were receiving, and the investigators applied descriptive statistics and one-way analysis of variance to compare outcomes across the groups.

The virological picture was reassuring. Every participant had a documented suppressed viral load, and CD4 counts were above 350 cells per cubic millimeter in all cases, with a mean of 518.5 plus or minus 56.8 cells per cubic millimeter. In other words, whatever regimen the patients were taking, their HIV infection was well controlled. The cohort itself skewed female and middle-aged to older: 70.4 percent of participants were women, and the average age was 54.8 plus or minus 9.5 years. These demographics reflect the broader epidemiological shift in sub-Saharan Africa, where an aging population of people living with HIV is increasingly confronting non-communicable diseases.

Glycemic control, however, told a more complicated story. HbA1c values varied significantly across the six treatment groups, and the statistical analysis confirmed that this variation was unlikely to be due to chance, with an F statistic of 3.794 and a p value of 0.006. The lowest average HbA1c, 7.81 percent, was recorded in the largest group, 23 patients taking TDF/3TC/EFV combined with metformin alone. The next lowest was a small group of four patients on abacavir, lamivudine, and efavirenz without insulin or protease inhibitors, at 8.50 percent, followed by five patients on protease inhibitor-based therapy without insulin at 8.94 percent. Patients on TDF/3TC/EFV with both metformin and glibenclamide averaged 9.43 percent, those on TDF/3TC/EFV with insulin averaged 9.47 percent, and the highest figure, 11.08 percent, appeared in a group of four patients on other highly active antiretroviral combinations with insulin. Post-hoc testing pinpointed one statistically significant pairwise difference: the metformin-only group had an HbA1c 3.27 percentage points lower than the other-HAART-plus-insulin group, with a p value of 0.014.

The authors are careful about how these numbers should be interpreted. They note that the findings align with clinical practice, in which more severe diabetes cases are typically escalated to insulin or to additional oral agents. A patient whose diabetes is aggressive enough to require insulin is, almost by definition, harder to control than one who can be managed with metformin alone, so the observed differences in HbA1c likely reflect underlying disease severity as much as any direct pharmacological effect of the antiretroviral regimens themselves. This is a crucial caveat for a cross-sectional design, which captures a single moment in time and cannot establish whether a particular drug combination caused better or worse glucose control. The researchers explicitly describe their results as baseline descriptive data and call for prospective studies to examine the practice of switching diabetic patients away from dolutegravir.

Beyond glucose, the study examined a panel of metabolic and organ-function markers that are often overlooked in resource-limited settings. Alkaline phosphatase was elevated above 120 units per liter across all six groups, with the highest levels seen in the groups whose treatment included insulin. Gamma-glutamyl transferase elevations in the 40 to 60 units per liter range were observed in the metformin-only group and in the TDF/3TC/EFV-plus-insulin group. Importantly, the transaminases alanine aminotransferase and aspartate aminotransferase, the classic markers of hepatocellular injury, remained within normal ranges across all groups, with mean values of 21.7 plus or minus 12.5 and 20.5 plus or minus 5.8 units per liter respectively. Elevated total cholesterol and triglycerides appeared only in the group taking TDF/3TC/EFV with insulin, a pattern that echoes the known lipid effects of both insulin therapy and some antiretroviral agents.

Kidney function, a persistent concern for patients on tenofovir disoproxil fumarate, appeared well preserved. The estimated glomerular filtration rate, calculated using the contemporary CKD-EPI 2021 formula, averaged 97.5 plus or minus 14.8 milliliters per minute per 1.73 square meters of body surface area, a value consistent with normal renal clearance. That finding is clinically meaningful because TDF has long been associated with proximal tubular injury in some patients, and the combination of HIV, diabetes, and tenofovir could theoretically compound renal risk. In this cohort, at least over the observation window, the kidneys held their ground.

What emerges from Lira is less a verdict on any single drug than a portrait of a treatment landscape in transition. As dolutegravir becomes the default first-line option across the region, clinicians are increasingly making individualized decisions to move patients with diabetes onto older regimens, often without robust evidence about the metabolic trade-offs involved. This study provides the first quantitative baseline for such decisions in a Ugandan regional hospital, showing that HIV control remains excellent across all non-dolutegravir regimens, that glycemic outcomes differ substantially by treatment combination in ways that likely track disease severity, and that liver and kidney function are broadly preserved even as alkaline phosphatase elevations raise questions worth pursuing. The researchers, who declare no competing interests, argue that the next step must be longitudinal work that follows patients before and after a switch away from dolutegravir, so that cause and effect can finally be separated from correlation. For the growing number of people navigating both HIV and diabetes in northern Uganda and beyond, that evidence cannot come soon enough.

Subject of Research: Glycemic control and metabolic parameters in HIV-positive patients with type 2 diabetes on non-dolutegravir antiretroviral regimens in Uganda

Article Title: Glycemic control and metabolic parameters among HIV-positive diabetic patients on non-dolutegravir-based antiretroviral regimens at lira regional referral hospital, uganda: a cross-sectional study

Article References: Wandera, A., Nakaziba, R., Okello, N., Wandera, S. K., Otim, T. C., & Olwa, F. (2026). Glycemic control and metabolic parameters among HIV-positive diabetic patients on non-dolutegravir-based antiretroviral regimens at lira regional referral hospital, uganda: a cross-sectional study. BMC Endocrine Disorders. https://doi.org/10.1186/s12902-026-02597-0

Image Credits: AI Generated

DOI: 10.1186/s12902-026-02597-0

Keywords: HIV, type 2 diabetes, antiretroviral therapy, dolutegravir, glycemic control, HbA1c, metformin, efavirenz, Uganda, metabolic parameters, liver function, renal function

Esophageal squamous cell carcinoma is one of the most common and lethal malignancies worldwide, and it is particularly prevalent in parts of East Asia. Treatment decisions increasingly hinge on PD-L1, a protein that tumor cells use to dampen the immune system’s attack. When PD-L1 is abundant on the tumor surface, immune checkpoint inhibitors, drugs that block the PD-1/PD-L1 interaction, tend to work well. The standard way to measure PD-L1 is immunohistochemistry, a laboratory technique in which a biopsy sample is stained with antibodies and scored using a combined positive score, or CPS, that reflects how many tumor and immune cells display the protein. Patients whose tumors score at or above a defined threshold are typically considered candidates for immunotherapy.

The problem is that this assessment requires tissue, and obtaining it is not always straightforward. Esophageal tumors sit deep in the chest, biopsies sample only a fragment of a heterogeneous tumor, and PD-L1 expression can vary across space and change over time. A noninvasive surrogate that could be read off a scan performed before treatment would be enormously valuable, allowing clinicians to stratify patients earlier and perhaps to repeat the assessment as the disease evolves. That is the premise behind the new study, led by Jiazhong Ren and Zheng Fu of the Department of Medical Imaging and Yongbin Cui and Yong Yin of the Department of Radiation Oncology Physics and Technology at Shandong Cancer Hospital and Institute, affiliated with Shandong First Medical University and the Shandong Academy of Medical Sciences.

The physics behind the approach is elegant. 18F-FDG is a radioactive analog of glucose that is taken up by metabolically active cells, and tumors, with their voracious appetite for energy, typically accumulate far more of the tracer than surrounding healthy tissue. The PET scanner converts this accumulation into standardized uptake values, or SUVs, which quantify how much tracer concentrates in a given region. The researchers measured a family of these parameters: the maximum standardized uptake value (SUVmax), which captures the single hottest pixel in the tumor; the mean (SUVmean) and peak (SUVpeak) values, which describe average and locally averaged intensity; the standard deviation (SUVsd), which reflects how heterogeneous the uptake is; and two volumetric measures, the metabolic tumor volume (MTV), the physical volume of metabolically active tumor, and total lesion glycolysis (TLG), which combines volume with intensity.

The team enrolled 89 patients with esophageal squamous cell carcinoma in this retrospective study. All patients underwent 18F-FDG PET/CT and had PD-L1 expression evaluated by immunohistochemistry on primary tumor tissue before receiving any anti-tumor treatment. The investigators also recorded a comprehensive set of clinicopathological characteristics, including age, gender, smoking status, drinking status, tumor location, vertical tumor length, TNM stage, and pathological grade. For the analysis, patients were divided into two groups: those with PD-L1-negative tumors, defined as a combined positive score below 10, and those with PD-L1-positive tumors, defined as a CPS of 10 or higher, a cutoff commonly used in clinical decision-making.

The results showed a clear statistical pattern. Four of the six metabolic parameters, SUVmax, SUVmean, SUVpeak, and SUVsd, were significantly higher in patients whose tumors expressed PD-L1 than in those whose tumors did not, with all comparisons reaching statistical significance at P values below 0.05. In other words, tumors that glowed more brightly and more unevenly on the PET scan were more likely to be PD-L1 positive. The volumetric measures, MTV and TLG, did not show the same association, suggesting that it is the intensity and heterogeneity of glucose metabolism, rather than the sheer bulk of metabolically active tissue, that tracks with this immune marker.

To quantify how well these imaging features could actually predict PD-L1 status, the researchers turned to receiver operating characteristic curve analysis, a standard statistical technique that plots true positive rates against false positive rates across all possible cutoff values. The area under the curve, or AUC, summarizes discriminative ability on a scale from 0.5, equivalent to a coin flip, to 1.0, perfect prediction. SUVmax achieved an AUC of 0.636 with a P value of 0.029, and SUVmean achieved an AUC of 0.628 with a P value of 0.044, both statistically significant but modest in magnitude. The optimal cutoff values were 19.74 for SUVmax and 10.01 for SUVmean, thresholds that could be applied to future patients, though with considerable uncertainty.

The team then used univariate logistic regression to examine each parameter’s independent association with PD-L1 positivity. SUVmax was the strongest predictor with a P value of 0.006, followed by SUVmean at 0.011, SUVpeak at 0.022, and SUVsd at 0.024. However, a technical complication emerged: these four SUV-derived parameters are all computed from the same underlying uptake distribution and are therefore severely multicollinear, meaning they carry heavily overlapping information and cannot be meaningfully combined in a single statistical model. Because of this severe multicollinearity, the researchers selected only SUVmax, the strongest individual predictor, for the final single-predictor logistic model, which retained its significance at P = 0.006.

The authors are explicit about what these numbers do and do not mean. An AUC of 0.636 represents discriminative performance that is only modestly better than chance, far below what would be needed for a reliable diagnostic test. Consequently, the study concludes that SUVmax should serve only as an auxiliary imaging reference rather than a dependable noninvasive substitute for pathological PD-L1 detection in patients with esophageal squamous cell carcinoma. This honest framing matters, because the temptation to overread an imaging-biomarker association is real, and premature clinical adoption of an imprecise surrogate could misdirect treatment decisions with serious consequences.

Nevertheless, the research adds to a growing body of work exploring how imaging phenotypes reflect molecular tumor characteristics, a field sometimes described as radiomics or imaging genomics. The biological plausibility is compelling: PD-L1 expression is often driven by inflammatory and oncogenic signaling pathways that also reprogram tumor metabolism, so a link between glucose avidity and immune checkpoint ligand expression is not surprising. The study was supported by the National Natural Science Foundation of China under grants 12275162 and 12575365, was approved by the Ethics Committee of the Cancer Hospital Affiliated to Shandong First Medical University in accordance with the Declaration of Helsinki, and was published open access on 29 September 2026. Future studies with larger cohorts, prospective designs, and possibly machine learning approaches that combine multiple imaging features may refine the predictive power enough to bring scan-based biomarker assessment closer to the clinic.

Subject of Research: The association between 18F-FDG PET/CT metabolic imaging parameters and PD-L1 expression in esophageal squamous cell carcinoma

Article Title: The predictive value of 18F-FDG PET/CT metabolic parameters for PD-L1 expression in esophageal squamous cell carcinoma

Article References: Ren, J., Cui, Y., Fu, Z., & Yin, Y. (2026). The predictive value of 18F-FDG PET/CT metabolic parameters for PD-L1 expression in esophageal squamous cell carcinoma. BMC Cancer. https://doi.org/10.1186/s12885-026-17026-7

Image Credits: AI Generated

DOI: 10.1186/s12885-026-17026-7

Keywords: 18F-FDG PET/CT, PD-L1, esophageal squamous cell carcinoma, SUVmax, metabolic parameters, immunotherapy biomarker, immunohistochemistry, combined positive score, cancer imaging, radiomics, tumor metabolism, BMC Cancer