At a regional referral hospital in northern Uganda, a quiet clinical dilemma is unfolding at the intersection of two of the world’s most consequential epidemics. People living with HIV are living longer, thanks to antiretroviral therapy, and as they age, chronic conditions such as type 2 diabetes are increasingly appearing alongside the virus. Managing both diseases at once is far from straightforward, because the drugs that suppress HIV can interact with the medications that control blood sugar, and some antiretroviral regimens appear to worsen metabolic health. A new cross-sectional study conducted at Lira Regional Referral Hospital offers one of the first detailed snapshots of how patients caught in this double diagnosis are faring when they are treated with antiretroviral regimens that exclude dolutegravir, the integrase inhibitor that has become the backbone of HIV treatment across much of Africa.
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
News Source: Ophelia Keating. (October 4, 2026). When HIV Therapy Meets Diabetes: Ugandan Study Maps Blood Sugar Control on Older Drug Regimens. Scienmag.
