HIV drug may be linked to increased risk of hypertension

In 2019, the World Health Organization formally recommended the drug dolutegravir (DTG) as the preferred antiretroviral therapy (ART) for people living with HIV in low and middle-income countries (LMICs), citing that it is more effective and tolerable, less costly, and less prone to developing drug resistance than the previously recommended first-line treatment efavirenz (EFV).

Since then, several clinical trials have shown that DTG is associated with substantial weight gain among people taking it, compared to people who take EFV.

Now, a new study led by a Boston University School of Public Health (BUSPH) researcher has confirmed these findings about DTG and weight gain, and it also found that people living with HIV who take DTG may also have a higher risk of developing high blood pressure.

Published in eClinicalMedicine, a journal of The Lancet Discovery Science, the study found that patients on ART gained on average 1.78 kg (3.92 pounds) in 12 months after switching from EFV to DTG, compared to patients who remained on EFV. The results also showed that patients taking DTG increased their risk of developing hypertension by 14 percentage points, compared to patients who remained on EFV.

As DTG will likely remain the drug of choice in first-line ART in LMICs, the researchers say that more studies are needed to understand whether weight gain from DTG is sustained over time, and if it is indeed linked to increased risk for hypertension and other non-communicable diseases, such as type 2 diabetes.

"The gain in weight was expected—this has been described in many other studies, and appears to be a weight-gain mitigating effect of efavirenz in a substantial number of patients, rather than dolutegravir causing weight gain," says study lead author Dr. Alana Brennan, assistant professor of global health at BUSPH. "The blood pressure rise data is less clear, and in some ways more worrying if linked to the drug, as it appears fairly quickly after exposure. This needs to be carefully confirmed, and prior randomized controlled trials and observational evidence should be scrutinized before any conclusions are made."

For the study, Dr. Brennan and colleagues from BUSPH and the University of the Witwatersrand in Johannesburg, South Africa compared absolute and percentage weight change and hypertension risk among Black patients living with HIV who were of African descent, ages 16 and older, and who began their ART regimen between January 2010 and December 2020. The team matched 794 patients who switched from DTG TO EFV, to 794 patients who remained on EFV, and examined a range of factors including sex, age, first ART regimen, number of months on ART, haemoglobin, body mass index (BMI), blood pressure, viral load, and CD4 count.

In addition to the average increase in weight among patients taking DTG, the findings showed that, regardless of whether patients switched to DTG, patients who had a lower BMI (less than 30), were younger than 50 years old, and received ART treatment for less than a year gained more weight than those who had higher BMI, were 50 or older, or whose regimen extended beyond 12 months, respectively.

The team also observed that patients with existing high blood pressure at the start of the study had an increased risk of hypertension 12 months later. Female patients also had a slightly higher risk of developing high blood pressure, compared to male patients.

The researchers say additional clinical trials will provide deeper insight into possible effects of DTG on long-term chronic illnesses among people living with HIV in LMICs. In the US, the drug bictegravir (BIC) is the preferred ART, but both BIC and DTG treatment have similar chemical compositions, side effects, and resistance, so "it will be important to scrutinize their databases in the same way," says study senior author Dr. Francois Venter, research professor in the Faculty of Health Sciences at the University of the Witwatersrand.

But the team cautions not to dismiss the effectiveness of DTG as a life-saving HIV treatment.

"It is important not to leap to conclusions—this class of drugs confer huge benefits in terms of side effects and resistance benefits," says Venter. "But we need to interrogate existing datasets quickly—blood pressure is routinely collected in pretty much everyone, so we should be able to quickly see whether this is something to worry about or not."