Metabolic Warning Signs Emerge in Zimbabweans on Widely Used HIV Drug Regimen

A cross-sectional study conducted at Parirenyatwa Group of Hospitals in Harare has revealed a striking burden of metabolic abnormalities among Zimbabwean adults living with HIV who are taking dolutegravir-based antiretroviral therapy, the regimen that has become the global standard of care. The research, published in PLOS One by a team led by Ratidzo Chirimo and Danai Tavonga Zhou, found that nearly three-quarters of the 171 participants studied had dyslipidaemia, an unhealthy profile of blood fats, while 13.4 percent showed hyperglycaemia, elevated blood sugar. Perhaps most concerning was the finding that insulin resistance, an early warning sign on the pathway to type 2 diabetes, was present in more than half of the participants at 56.1 percent. The results arrive at a critical moment, as Zimbabwe, with an estimated adult HIV prevalence of 12.9 percent, has rapidly scaled up dolutegravir-based treatment across its health system, meaning that hundreds of thousands of patients may face similar metabolic risks over the coming decades of therapy.

Dolutegravir was embraced worldwide for good reasons. The drug belongs to the integrase strand transfer inhibitor class, blocking the HIV enzyme that inserts viral DNA into the host genome. It offers a high genetic barrier to resistance, meaning the virus struggles to evolve escape mutations, and it is generally well tolerated, potent at low doses, and affordable in generic form. These properties made it the cornerstone of first-line therapy recommended by international guidelines and adopted enthusiastically across sub-Saharan Africa, where the majority of the world’s HIV infections are concentrated. However, as experience with the drug has accumulated, clinicians and researchers have reported a cluster of metabolic side effects, including abdominal obesity, hypertension, impaired glucose regulation, and abnormal lipid levels. These conditions do not occur in isolation; they tend to cluster together in the same patients, multiplying the long-term risk of cardiovascular disease and type 2 diabetes, the two conditions most likely to erode the survival gains that antiretroviral therapy has delivered.

The Zimbabwean study was designed as an exploratory, hypothesis-generating investigation to quantify this burden in a setting where such data had been scarce. Between 20 January and 13 February 2025, the researchers recruited 171 adults receiving first-line dolutegravir-based treatment at Parirenyatwa Group of Hospitals, one of Zimbabwe’s largest referral centres. Each participant completed a structured questionnaire covering demographics, lifestyle habits, and clinical history, and underwent anthropometric assessment including body mass index calculation. Blood pressure was measured with the participant at rest, and blood samples were drawn for laboratory analysis of glycated haemoglobin, fasting glucose, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. This combination of self-reported, physical, and biochemical measures allowed the team to build a reasonably complete metabolic picture of each patient in a single visit, a pragmatic approach suited to resource-constrained clinical settings.

The demographic profile of the cohort reflects the face of the HIV epidemic in Zimbabwe. Two-thirds of the participants, 67.8 percent, were female, and the median age was 42.1 years, with an interquartile range spanning 32.4 to 50.2 years. Most participants had at least a secondary education. Lifestyle risk factors were unevenly distributed: only nine participants were smokers, 23 percent reported alcohol use, and a substantial 62.2 percent reported engaging in no regular exercise. The physical measurements were already telling before any blood was analysed. More than half of the cohort, 57.9 percent, was overweight or obese, and 39.8 percent had elevated blood pressure meeting the threshold for hypertension. These figures suggest that the metabolic consequences of long-term HIV treatment in this population are not confined to laboratory values but are visible in body composition and vascular health.

The lipid results were the most dramatic finding. Dyslipidaemia, defined as one or more abnormal lipid values, affected 74.3 percent of participants. Breaking the pattern down, non-ideal high-density lipoprotein cholesterol, the so-called good cholesterol that protects arteries, was the most common abnormality at 50.5 percent, followed by raised low-density lipoprotein cholesterol at 33.3 percent, raised triglycerides at 16 percent, and hypercholesterolaemia, or elevated total cholesterol, at 10.3 percent. Low HDL cholesterol is a particularly insidious abnormality because it often produces no symptoms, yet it is strongly linked to atherosclerotic cardiovascular disease. The predominance of low HDL alongside elevated LDL mirrors the classic atherogenic lipid profile seen in metabolic syndrome and suggests that many patients on dolutegravir-based therapy are accumulating cardiovascular risk silently, years before any clinical event such as a heart attack or stroke might occur.

Glucose metabolism told a parallel story. While overt hyperglycaemia affected 13.4 percent of participants, insulin resistance was far more widespread at 56.1 percent. This gap matters clinically. Insulin resistance represents a state in which the body’s tissues respond poorly to insulin, forcing the pancreas to compensate by producing more of the hormone. This compensation can maintain normal blood sugar for years, but it is metabolically costly and often precedes frank diabetes by a decade or more. A screening strategy that measures only glucose would miss the majority of patients already on the diabetic pathway. The authors’ finding that more than half of a relatively young cohort showed insulin resistance raises the prospect of a future wave of type 2 diabetes among people living with HIV in Zimbabwe unless preventive interventions are introduced early.

To identify which factors independently predicted these metabolic abnormalities, the researchers performed multivariate analysis, a statistical technique that adjusts for the influence of multiple variables simultaneously. Two correlates emerged with statistical significance. Increasing age was independently associated with hyperglycaemia, with an adjusted odds ratio of 1.08 per year of age, a 95 percent confidence interval of 1.03 to 1.13, and a p-value of 0.002. This means that each additional year of life raised the odds of elevated blood sugar by roughly 8 percent after accounting for other factors. Meanwhile, elevated blood pressure was independently associated with dyslipidaemia, with an adjusted odds ratio of 2.64, a 95 percent confidence interval of 1.03 to 6.78, and a p-value of 0.043. Patients with high blood pressure were more than two and a half times as likely to have abnormal blood fats as those with normal readings. The co-occurrence of hypertension and dyslipidaemia is a hallmark of cardiometabolic syndrome and compounds vascular risk multiplicatively rather than additively.

The study’s cross-sectional design imposes important limits on interpretation. Because all measurements were taken at a single point in time, the analysis cannot establish whether dolutegravir itself caused the metabolic abnormalities, whether they predated treatment, or whether they stem from other contributors such as diet, physical inactivity, prior exposure to older antiretroviral drugs known to disrupt lipid metabolism, or background genetic and environmental factors in the Zimbabwean population. The authors explicitly frame the work as exploratory and hypothesis-generating rather than definitive. The modest sample size of 171, recruited from a single hospital, also means the confidence intervals around some estimates are wide, as seen with the blood pressure and dyslipidaemia association. Nevertheless, the consistency of the findings with reports from other countries where dolutegravir has been rolled out strengthens the case that metabolic monitoring deserves a central place in HIV care programmes throughout the region.

The clinical implications are nonetheless clear and actionable. As people living with HIV age on long-term dolutegravir-based therapy, the population is transitioning from a disease dominated by immune suppression to one where chronic, non-communicable conditions threaten the longevity that treatment has made possible. The authors conclude that routine, integrated screening of body mass index, blood pressure, glucose, and lipid profiles is essential to mitigate cardiometabolic risk and sustain the success of dolutegravir-based ART in Zimbabwe. Such screening is technically simple and inexpensive compared with the cost of treating advanced diabetes or cardiovascular disease, but it requires deliberate integration into HIV clinics, which have historically focused almost exclusively on viral suppression and CD4 counts. The Zimbabwean findings add to a growing body of evidence that the next frontier of HIV medicine lies not in controlling the virus, which modern therapy does remarkably well, but in managing the metabolic and cardiovascular consequences of decades of life with treated infection.

For the global HIV response, the study is a timely reminder that the success of a drug regimen must be measured not only in viral load suppression but in the long-term health of the people taking it. Dolutegravir has transformed treatment outcomes across Africa, and nothing in these findings argues for abandoning it. Instead, they argue for a broader model of care in which the HIV clinic doubles as a gateway for detecting and managing hypertension, diabetes risk, and dyslipidaemia. With 12.9 percent of Zimbabwean adults living with HIV and the vast majority now on dolutegravir-based regimens, the country has both an urgent need and a real opportunity to pioneer integrated cardiometabolic care within its antiretroviral programme. The alternative, allowing a silent epidemic of insulin resistance and abnormal blood fats to progress unchecked among a young and increasingly healthy HIV population, would squander much of the progress that antiretroviral therapy has achieved over the past two decades.

Subject of Research: Metabolic complications of dolutegravir-based antiretroviral therapy in Zimbabwean adults living with HIV

Article Title: Burden and determinants of hyperglycaemia and dyslipidaemia in Zimbabwean adults living with HIV on dolutegravir-based first-line antiretroviral therapy: A cross-sectional study

Article References: Chirimo, R., Zhou, D. T., Mudzviti, T., Ruredzo, I. M., Manasa, J., Maponga, C. C., Reginald Gomo, Z. A., Gomo, E., & Morse, G. D. (2026). Burden and determinants of hyperglycaemia and dyslipidaemia in Zimbabwean adults living with HIV on dolutegravir-based first-line antiretroviral therapy: A cross-sectional study. PLOS One, 21(10), e0359196. https://doi.org/10.1371/journal.pone.0359196

Image Credits: AI Generated

DOI: 10.1371/journal.pone.0359196

Keywords: HIV, dolutegravir, dyslipidaemia, hyperglycaemia, insulin resistance, Zimbabwe, antiretroviral therapy, cardiovascular risk, hypertension, PLOS One, metabolic syndrome, cross-sectional study