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Target trial emulation in Johannesburg shows dolutegravir associated with greater weight and blood pressure increases versus efavirenzNew HIV drug linked to higher weight and blood pressure in South Africa

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Key Takeaway
Note that dolutegravir initiation is associated with greater weight and blood pressure increases versus efavirenz in this South African cohort.

This target trial emulation evaluated treatment-naive individuals in Johannesburg, South Africa. The study compared initiation of dolutegravir with initiation of efavirenz. The population consisted of 2930 participants followed for 24.0 months. No specific safety data or discontinuation rates were reported in the input.

Regarding weight, the mean difference was 2.9 kg at 12-months and 1.9 kg at 24-months favoring dolutegravir. The 95% CI for weight at 12-months was -0.3, 5.5 and at 24-months was -1.3, 5.1. For BMI, the mean difference was 0.8 kg/m at 12-months and 0.6 kg/m at 24-months. The 95% CI for BMI at 12-months was -0.3, 1.9 and at 24-months was -0.6, 1.9.

Blood pressure changes showed a mean difference of 3.9 mmHg for systolic BP at 12-months and 1.7 mmHg at 24-months. The 95% CI for systolic BP at 12-months was 1.2, 6.6 and at 24-months was -1.8, 5.1. Diastolic BP showed a mean difference of 1.6 mmHg at 12-months and -0.4 mmHg at 24-months. The 95% CI for diastolic BP at 12-months was -0.7, 3.9 and at 24-months was -1.8, 5.1. Incident hypertension risk rose by 35% at 12-months and 22% at 24-months. The 95% CI for incident hypertension at 12-months was 0.04, 0.5 and at 24-months was -0.1, 0.4.

A key limitation is that future research is needed to determine whether this reflects a direct effect of dolutegravir or the weight-suppressing effects of efavirenz. Funding or conflicts of interest were not reported.

A new HIV treatment option is now available in South Africa, but a recent comparison raises questions about its side effects. Researchers looked at nearly 3,000 people who had never taken HIV medication before. They compared a new drug called dolutegravir with an older drug called efavirenz. The study followed these patients for two years in Johannesburg.

The results show that people on the new drug gained more weight and had higher blood pressure. At one year, the average weight gain was nearly three kilograms for the new drug group. By the two-year mark, that gain was still higher than the older drug group. Blood pressure also rose more in the new drug group at the one-year point.

The study found a 35 percent higher risk of developing high blood pressure at one year for those on the new drug. However, the confidence intervals for these findings are wide. This means the data is not perfectly clear. The researchers note that future work is needed to see if the new drug directly causes these changes or if the older drug actually helps control weight.

What this means for you:
New HIV drug linked to higher weight and blood pressure in South Africa

Study Details

Study typeRct
EvidenceLevel 2
Follow-up24.0 mo
PublishedMay 2026
View Original Abstract ↓
OBJECTIVE: Using the Target Trial Emulation Framework, we evaluated the impact of initiating dolutegravir versus efavirenz on 12- and 24-month weight, body mass index (BMI), blood pressure (BP), and incident hypertension among treatment-naïve individuals in Johannesburg, South Africa from 2019 to 2022. METHODS: We used linear models to estimate the mean difference in weight, BMI, BP and a log-binomial model to estimate the causal risk difference of incident hypertension, adjusting for patient characteristics via inverse probability weighting. RESULTS: Among 2930 people initiating treatment from 2019 to 2022, 1847 initiated dolutegravir and 1083 initiated efavirenz. At 12-months, mean difference comparing dolutegravir to efavirenz in weight was 2.9 kg (95% Confidence Interval (CI): -0.3, 5.5), BMI was 0.8 kg/m (95% CI: -0.3, 1.9), diastolic BP was 1.6 mmHg (95% CI: -0.7, 3.9) and systolic BP was 3.9 mmHg (95% CI: 1.2, 6.6). Risk of incident hypertension rose by 35% (95% CI: 0.04, 0.5). At 24-months, mean weight difference was 1.9 kg (95% CI: -1.3, 5.1), BMI was 0.6 kg/m (95% CI: -0.6, 1.9), diastolic BP was -0.4 mmHg (95% CI: -1.8, 5.1) and systolic BP was 1.7 mmHg (95% CI: -1.8, 5.1). Risk of incident hypertension rose by 22% (95% CI: -0.1, 0.4). CONCLUSIONS: Dolutegravir was associated with greater increases in weight, systolic BP, and incident hypertension over 24-months, particularly in the first 12-months. Future research is needed to determine whether this reflects a direct effect of dolutegravir or the weight-suppressing effects of efavirenz.
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