Weight gain with dolutegravir and TAF in ADVANCE study continues out to week 192

Polly Clayden, HIV i-Base

Participants in the ADVANCE trial, taking tenofovir alafenamide, emtricitabine and dolutegravir (TAF/FTC/DTG) had greater weight gain, risk of metabolic syndrome and clinical obesity than tenofovir disoproxil fumarate (TDF)/FTC/DTG with longer term follow up. This was particularly notable in women.

These findings were presented at AIDS 2022.

There were no significant differences in viral load suppression or renal or bone-related adverse events between the two DTG-based regimens. But both TAF/FTC/DTG and TDF/FTC/DTG had significantly higher rates of viral load suppression than TDF/FTC/efavirenz (EFV) at week 192 in the main ITT analysis.

WHO guidelines recommend first-line HIV treatment with TDF/lamivudine (3TC) or FTC/DTG. TAF is recommended only as an alternative to TDF for people with osteoporosis or impaired renal function.

ADVANCE compared the two DTG regimens to EFV-based ART (previous first-line standard of care). The study showed non-inferiority at 48, 96 and 144 weeks but greater weight gain in the DTG arms, which was most pronounced among those taking TAF/FTC/DTG.

ADVANCE was extended to 192 weeks to assess the weight gain – as well as safety and efficacy – longer term. Participants were reconsented for the study extension.

A total of 1,053 treatment-naive participants in South Africa were randomised to one of the three regimens. The study assessed viral load, vital signs and renal and bone adverse events prospectively. BMI was similar in the three arms at baseline.

At 192 weeks, 218/351 (62.3%) in the TAF/FTC/DTG arm, 204/351 (58.1%) in the TDF/FTC/DTG arm, and 177/351 (50.4%) in the TDF/FTC/EFV arm had viral load <50 copies/mL. In the on treatment analysis, these respective proportions were: 218/226 (96%), 204/209 (98%) and 177/179 (99%).

Body weight increased by +8.9 kg for participants in the TAF/FTC/DTG arm, +5.8 kg for TDF/FTC/DTG, and +3.3 kg for TDF/FTC/EFV.

Twenty nine per cent of participants taking TAF/FTC/DTG, 21% TDF/FTC+DTG and 15% TDF/FTC/EFV had developed clinical obesity.

The risk of clinical obesity was significantly higher among participants taking TAF/FTC/DTG, women and those with higher baseline BMI (all p<0.001).

Among the women in the study, 43% taking TAF/FTC/DTG developed clinical obesity by week 192 compared to 27% TDF/FTC/DTG and 20% TDF/FTC/EFV (p<0.001).

The risk of metabolic syndrome, as defined by the International Diabetes Foundation, was significantly higher in the TAF/FTC/DTG arm compared with the TDF/FTC/DTG and TDF/FTC/EFV arms (p<0.001). The investigators noted that this is associated with increased risk of diabetes, stroke and heart disease.

Bone fracture and Grade 3 or 4 renal adverse events were rarely seen in ADVANCE and similar across arms.


DTG and TAF continue to be associated with weight gain in ADVANCE. Particularly among women: 43% developed clinical obesity by week 192.

At 96 weeks, 27% of women in ADVANCE had developed clinical obesity so there appears to be no sign of a plateau in weight gain. [2]

As previously noted, according to QDIABETES algorithm, if weight rises by 10 kg, the risk of diabetes rises by 3 cases per 1000 people treated. This might not sound much, but in countries like South Africa, where millions of people need ART, the absolute numbers could be very substantial and create a huge extra burden on health services.

The ADVANCE investigators are looking into potential strategies to mitigate ART-associated weight gain, including weight loss drugs and alternative newer antiretrovirals.


  1. Venter WF et al. Final week 192 results from the ADVANCE trial: first-line TAF/FTC/DTG, TDF/FTC/DTG vs TDF/FTC/EFV. AIDS 2022. Montreal, Canada. 29 July – 2 August. Poster abstract PELBB01. (abstract)–tdf-ftc-dtg-vs-tdf-f (poster)
  2. Clayden P. Weight gain and metabolic syndrome with dolutegravir and TAF: results from the ADVANCE trial. HTB. 15 November 2019.

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