Research from Uganda indicates that adults over 40 on dolutegravir-based antiretroviral therapy face increased risks of hyperglycaemia, prompting calls for targeted glucose monitoring amidst expanding HIV treatment in Africa.
In a retrospective cohort from Mbarara Regional Referral Hospital in southwestern Uganda, adults receiving dolutegravir-based antiretroviral therapy developed documented hyperglycaemia at a rate of 2.54 cases per 1,000 person-years, according to a peer-reviewed study published by Dove Medical Press. The analysis covered 8,856 adults with positive follow-up time and found 74 incident events over 29,157.74 person-years, with the hazard rising after treatment started, peaking at about 1.1 years and then easing. The authors said the pattern suggests the first year after dolutegravir introduction may be a particularly important period for glucose surveillance.
The study adds to a growing body of evidence that metabolic complications are increasingly relevant in long-term HIV care. As antiretroviral therapy has extended life expectancy, non-communicable diseases such as diabetes have become more prominent among people living with HIV, especially in sub-Saharan Africa. The Ugandan researchers noted that dolutegravir is now widely used because of its potency, tolerability and resistance profile, but that concerns persist about weight gain, insulin resistance, hyperglycaemia and diabetes after a switch to the drug. A narrative review published on PubMed Central also points to several possible mechanisms, including mitochondrial toxicity linked to earlier nucleoside reverse transcriptase inhibitors such as stavudine and zidovudine, chronic inflammation and impaired insulin sensitivity.
Older age emerged as the clearest predictor in the Mbarara cohort, with each 10-year increase associated with a 70% higher hazard of documented hyperglycaemia. Prior exposure to thymidine analogue nucleoside reverse transcriptase inhibitors was also linked to greater risk, as was having lived with HIV treatment for 15 years or more before starting dolutegravir. The authors argued that these findings fit with known metabolic vulnerability in ageing populations and with the lingering effects of older antiretroviral regimens, which have long been associated with lipodystrophy and insulin resistance. By contrast, sex, marital status and residence were not independently associated with the outcome.
The Ugandan findings sit alongside other African studies suggesting that hyperglycaemia is not rare among people on dolutegravir-based therapy, although the estimates vary widely depending on setting and study design. A cross-sectional study in central Uganda reported a prevalence of 20.55% among 219 people living with HIV on dolutegravir for at least a year, with overweight and abnormal waist-to-hip ratio linked to higher risk. Another Ugandan study at Kiruddu National Referral Hospital found hyperglycaemia in 12.8% of 398 participants on dolutegravir, with age over 40 and hypertension standing out as risk factors. In Niger, a multicentre cross-sectional study of 633 records reported a prevalence of 36.4% and found higher educational attainment and a history of hypertension were associated with hyperglycaemia. A separate case-control study at Mulago ISS Clinic in Kampala found prior dolutegravir exposure was associated with about sevenfold higher odds of a later hyperglycaemia diagnosis. A study from Ethiopia likewise pointed to overweight and obesity as important correlates.
The Mbarara researchers cautioned that their results should not be read as a reason to avoid dolutegravir, which remains a preferred and effective option in HIV care. Instead, they argued for risk-stratified monitoring, particularly in older patients, those with long antiretroviral histories and those exposed to older thymidine analogue drugs. They also noted important limitations: glucose testing was not protocolled, several key metabolic variables were unavailable, and the study relied on routine-care records rather than active follow-up. Even so, the work strengthens the case for closer metabolic observation as dolutegravir use expands across Africa, where the burden of HIV and diabetes increasingly overlaps.
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