Cardiometabolic Disease in Aging HIV-Positive Populations in Sub-Saharan Africa: A Scoping Review of Long-Term Antiretroviral Therapy Effects

For decades, the story of HIV in sub-Saharan Africa has been one of survival. Thanks to the widespread rollout of life-saving medication, millions of people who once faced a fatal diagnosis are now living long, productive lives. The virus has been transformed from a death sentence into a manageable chronic condition, much like diabetes or high blood pressure. However, this medical triumph has brought an unexpected complication. As people with HIV age, they are increasingly developing a cluster of health problems related to the heart and metabolism. These include high blood pressure, unhealthy cholesterol levels, diabetes, and obesity. Scientists call this collection of issues "cardiometabolic disease." The central question for researchers today is no longer just how to keep the virus at bay, but how to understand why these new health threats are appearing so frequently in this population, and whether the very medicines that saved their lives might be contributing to the problem.

A new review of existing research, conducted by a team of scientists from Mozambique and Spain, sets out to map the landscape of this emerging crisis. The researchers gathered and analyzed dozens of studies from across sub-Saharan Africa, looking specifically at people who have been taking antiretroviral therapy for many years. Their goal was to understand how common these heart and metabolic problems are, what factors make them more likely, and whether specific types of medication play a role. They approached the issue through a "syndemic" lens, a way of thinking that recognizes how biological factors, personal behaviors, and social conditions like poverty or food insecurity all interact to create a heavier burden of disease than any single factor could cause alone.

The review examined 31 different records, including original studies from countries like Ethiopia, Zambia, Nigeria, and South Africa, as well as broader summaries of data from across the region. The findings reveal a significant and growing burden of disease. The prevalence of metabolic syndrome—a condition where a person has a combination of high blood pressure, high blood sugar, excess body fat around the waist, and abnormal cholesterol—varied widely across different studies, ranging from about 21 percent to nearly 39 percent. High blood pressure was the most common individual issue, with rates in some studies reaching as high as 58 percent. Unhealthy cholesterol levels were also widespread, affecting between 29 percent and nearly 70 percent of patients in various surveys. Diabetes and pre-diabetes were found in roughly 5 to 17 percent of the populations studied, while obesity rates ranged from 8 percent to over 32 percent. These numbers are not uniform because the studies used different methods to measure these conditions and looked at different groups of people, but the overall picture is clear: cardiometabolic diseases are a major reality for aging people living with HIV in this region.

One of the most critical questions the researchers addressed was whether the length of time a person has been on medication, or the specific type of medication they take, influences these risks. The evidence suggests that the longer a person lives with HIV and takes treatment, the higher their risk of developing these conditions becomes. However, the researchers were careful to note that this does not prove the medication is the sole cause. People who have been on treatment for a long time are also older, and age itself is a powerful driver of heart disease. Furthermore, the studies reviewed were mostly snapshots in time, which makes it difficult to say for certain that the drugs caused the problems rather than just being present when the problems appeared.

The review did highlight some concerning signals regarding newer medications. For many years, the standard treatment in the region included older drugs that were known to cause severe body shape changes and metabolic issues. As these were replaced by newer, safer options, a specific drug called dolutegravir became the most common first-line treatment. Recent data from two studies in Zambia suggests that people taking dolutegravir might have a higher risk of developing metabolic syndrome compared to those on other regimens. One study found that dolutegravir users were more than twice as likely to have metabolic syndrome, while a follow-up study suggested a 50 percent increase in the rate of new cases over time. Despite these signals, the authors emphasize that this link is not yet proven. It is possible that doctors were prescribing this newer drug to patients who already had higher body weights or other risk factors, a situation known as "confounding by indication." Without randomized trials that directly compare these drugs, the exact role of dolutegravir remains an open question that requires further investigation.

The review also dismantled the idea that these health issues are solely a result of the virus or the treatment. The data shows that even people who have never taken medication for HIV, or who have only recently started, already show signs of high blood pressure and unhealthy cholesterol. This indicates that the virus itself, and the chronic inflammation it causes, plays a role in damaging the body's metabolic systems. Additionally, the researchers found that traditional risk factors like being older, being female, and having a higher body mass index are powerful predictors of these diseases. In many cases, these standard risk factors were more influential than the specific HIV treatment a person was receiving. The review also pointed out that women in sub-Saharan Africa appear to be at a particularly high risk, often showing higher rates of metabolic syndrome and obesity than men, though the reasons for this are complex and involve a mix of biology, social roles, and economic factors.

Perhaps the most significant gap the review identified is the lack of deep understanding regarding how these diseases develop in African populations. Most of the detailed biological research on the link between HIV, medication, and heart disease comes from high-income countries in Europe and North America. The researchers noted that the unique genetic makeup of African populations, combined with local challenges like food insecurity, high rates of other infections, and different patterns of urbanization, means that findings from other parts of the world cannot be simply copied and pasted. For instance, while inflammation and damage to the lining of blood vessels are known mechanisms in other regions, there is very little direct evidence from Africa measuring these specific biological processes in people with HIV.

The authors conclude that the current healthcare systems in sub-Saharan Africa are not yet ready to handle this dual burden. Most HIV clinics are designed to focus on a single disease: the virus. They often lack the equipment to routinely check blood pressure or test for diabetes, and the staff may not be trained to manage heart disease. The review argues for a fundamental shift toward integrated care, where a patient's HIV treatment is managed alongside their heart health and metabolic needs in the same visit. This would involve screening for these conditions at every appointment and ensuring that essential medications for blood pressure and diabetes are available. The researchers also call for new studies that follow patients over many years to better understand the long-term effects of modern medications and to develop risk prediction tools that are specific to the African context. Without these changes, the life-saving gains made in the fight against HIV could be undermined by the very preventable heart attacks and strokes that are now becoming common among the survivors of the epidemic.