One in five on dolutegravir HIV therapy in East Africa shows hyperglycemia

Dolutegravir has transformed HIV care across the world. The integrase strand transfer inhibitor is potent, has a high genetic barrier to resistance, and is now the backbone of first-line antiretroviral therapy in most countries, including much of East Africa where millions of people living with HIV have transitioned onto dolutegravir-based regimens. Yet as the drug has scaled up, clinicians have reported a growing list of metabolic concerns, including weight gain, dyslipidemia, and elevated blood glucose. A new systematic review and meta-analysis published in BMC Infectious Diseases by researchers at Wolaita Sodo University and Haramaya University in Ethiopia now provides the most comprehensive regional estimate to date of one of those concerns: hyperglycemia among adults on dolutegravir-based therapy in East Africa.

The team, led by corresponding author Amanuel Arota Minota, followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses, the standard framework for conducting and reporting evidence syntheses. They searched PubMed, Google Scholar, Science Direct, AJOL, and the Cochrane Library for observational studies published through February 2026. After screening, twelve studies covering a combined 3,552 participants made it into the final analysis. The pooled prevalence of hyperglycemia among patients receiving dolutegravir-based antiretroviral therapy was 21.54 percent, with a 95 percent confidence interval of 15.16 to 28.74. In practical terms, roughly one in five adults on this regimen in East Africa shows elevated blood glucose.

That headline number, however, comes with an important statistical caveat. The studies displayed substantial heterogeneity, with an I-squared statistic of 96.1 percent and a p value below 0.0001, meaning the variation between individual studies far exceeds what chance alone would explain. Differences in how hyperglycemia was defined, in the populations sampled, in the duration of dolutegravir exposure, and in local healthcare contexts likely all contribute. The researchers used a random-effects model precisely because it accounts for this kind of between-study variability, and they performed sensitivity analyses to confirm that the pooled estimate was robust rather than driven by any single outlier study.

Country-level subgroup analysis sharpened the regional picture. Ethiopia showed the highest pooled prevalence at 20.41 percent (95 percent CI: 13.16 to 27.66), while Uganda recorded the lowest at 15.05 percent (95 percent CI: 11.69 to 18.41). The spread between countries, while narrower than the overall confidence interval might suggest, still points to real differences in study design, patient demographics, and possibly in how extensively blood glucose testing is performed in routine HIV care. Egger’s test found no evidence of publication bias, which means smaller studies with dramatic results were not disproportionately shaping the pooled estimate, a common worry in meta-analyses of observational data.

Beyond prevalence, the analysis identified which factors were significantly associated with hyperglycemia in this population. Overweight carried the largest effect size, with an odds ratio of 7.30 (95 percent CI: 1.02 to 52.33), though the extremely wide confidence interval signals considerable uncertainty around that point estimate. A family history of diabetes more than doubled the risk in a modest but statistically reliable way, with an odds ratio of 1.59 (95 percent CI: 1.13 to 2.25). Elevated total cholesterol, defined as 200 milligrams per deciliter or higher, was associated with an odds ratio of 2.12 (95 percent CI: 1.32 to 3.39). Physical inactivity raised the odds by 1.67 (95 percent CI: 1.15 to 2.44).

These associations fit a coherent biological narrative. Dolutegravir has been linked in other research to weight gain and metabolic changes, possibly through effects on adipose tissue, insulin signaling, or appetite regulation, though the exact mechanisms remain under investigation. Overweight status and physical inactivity are classic drivers of insulin resistance, the physiological state in which cells respond less effectively to insulin and blood glucose rises. Elevated cholesterol often travels alongside insulin resistance as part of the metabolic syndrome cluster. A family history of diabetes points to inherited susceptibility that antiretroviral drugs may unmask or accelerate. In other words, the factors flagged in this meta-analysis are not random; they map onto the same metabolic pathways that clinicians worry about when dolutegravir and glucose dysregulation are discussed together.

The findings arrive at a moment when East African health systems are still absorbing the massive transition from older regimens, such as efavirenz-based therapy, onto dolutegravir. That transition was justified by dolutegravir’s superior viral suppression, once-daily dosing, and resistance profile, and those advantages remain real. But the metabolic side effects that have emerged in pharmacovigilance signals and cohort studies worldwide now have a regional evidence base to contend with. The authors of the new analysis emphasize that routine monitoring of blood glucose and metabolic factors may facilitate early identification of hyperglycemia, particularly in settings with limited pharmacovigilance capacity, where adverse drug reactions may otherwise go undetected until they cause serious harm.

There are limits to what a meta-analysis of observational studies can establish. Observational designs cannot prove that dolutegravir causes hyperglycemia; they can only document that the two co-occur at a certain frequency and identify factors that travel with it. Confounding by diet, socioeconomic status, prior antiretroviral exposure, and baseline metabolic health is difficult to fully adjust for across heterogeneous studies. The wide confidence interval around the overweight association in particular suggests the underlying data are sparse or variable for that factor. Still, the consistency of the overall signal, the absence of publication bias, and the robustness checks all strengthen the case that hyperglycemia is a genuine and substantial clinical issue in this population rather than a statistical artifact.

For clinicians and program managers in East Africa, the practical implications are concrete. Blood glucose testing should be integrated into routine HIV care visits for patients on dolutegravir-based therapy, not reserved for symptomatic patients. Weight, lipid profiles, and physical activity levels deserve attention as modifiable risk factors that can be addressed through counseling, dietary support, and exercise programs. Patients with a family history of diabetes may warrant closer surveillance. As dolutegravir-based regimens continue to expand globally, the East African data add to a growing body of evidence that the drug’s metabolic footprint must be monitored as carefully as its virologic benefits are celebrated.

The full analysis, including the study-by-study breakdown, subgroup estimates, and sensitivity analyses, is available open access in BMC Infectious Diseases under DOI 10.1186/s12879-026-14641-4, allowing clinicians, researchers, and policymakers across the region and beyond to examine the underlying data directly.

Subject of Research: Hyperglycemia and its associated factors among adults living with HIV on dolutegravir-based antiretroviral therapy in East Africa: a systematic review and meta-analysis

Article Title: Hyperglycemia and its associated factors among adults living with HIV on dolutegravir-based antiretroviral therapy in East Africa: a systematic review and meta-analysis

Article References: Minota, A. A., Adagn, T. A., Bayisa, F. S., & Wakeyo, M. U. (2026). Hyperglycemia and its associated factors among adults living with HIV on dolutegravir-based antiretroviral therapy in East Africa: a systematic review and meta-analysis. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14641-4

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14641-4

Keywords: Hyperglycemia, associated, factors, adults, living, dolutegravir-based, antiretroviral, therapy, East, Africa, systematic, review