Final week 192 results from the ADVANCE trial: first-line TAF/FTC/DTG, TDF/FTC/DTG vs TDF/FTC/EFV

Title

Final week 192 results from the ADVANCE trial: first-line TAF/FTC/DTG, TDF/FTC/DTG vs TDF/FTC/EFV

Presenter

Andrew Hill

Authors

W.D.F. Venter (1), B. Bosch (1), S. Sokhela (1), G. Akpomiemie (1), N. Chandiwana (1), A. Tembo (1), A. Qavi (2), B. Simmons (3), K. McCann (4), A. Hill * (5)

Institutions

(1) Ezintsha, University of the Witwatersrand, Johannesburg, South Africa, (2) Imperial College London, London, United Kingdom, (3) London School of Economics and Political Science, London, United Kingdom, (4) University of Connecticut, Connecticut, United States, (5) University Of Liverpool, Liverpool, United Kingdom

BACKGROUND: Current World Health Organization guidelines recommend first-line treatment with tenofovir disoproxil fumarate (TDF)/lamivudine (or emtricitabine (FTC)) and dolutegravir /(DTG) for HIV-1 infection.Tenofovir alafenamide (TAF) is listed as an alternative to TDF for patients with osteoporosis or impaired renal function.
METHODS: 1,053 treatment-naïve participants in South Africa were randomized to either TAF/FTC+DTG, TDF/FTC+DTG, or TDF/FTC/EFV and followed up to week 192 under a trial extension. HIV-1 RNA, vital signs and renal and bone adverse events were assessed prospectively.
RESULTS: BMI was balanced between arms at baseline. At 192 weeks, HIV-1 RNA <50 copies/mL was confirmed in 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. In the on treatment analysis, HIV RNA <50 copies/mL was 218/226 (96%) for TAF/FTC+DTG, 204/209 (98%) for TDF/FTC+DTG, and 177/179 (99%) for TDF/FTC/EFV. By Week 192, body weight increased by +8.9kg for TAF/FTC+DTG, +5.8kg for TDF/FTC+DTG, and +3.3kg for TDF/FTC/EFV participants (observed data analysis). By Week 192, 29% of patients on TAF/FTC+DTG, 21% on TDF/FTC+DTG and 15% on TDF/FTC/EFV had developed clinical obesity.The risk of clinical obesity was significantly higher if taking TAF/FTC/DTG (p<0.001), female patients (p<0.001) and those with higher baseline BMI (p<0.001). Among the women enrolled, 43% on TAF/FTC+DTG developed clinical obesity by Week 192 versus 27% on TDF/FTC+DTG and 20% taking TDF/FTC/EFV (p<0.001).Bone fracture and Grade 3 or 4 renal adverse events were rare and similar across arms.
CONCLUSIONS: In the ADVANCE trial, participants taking TAF/FTC+DTG experienced greater weight gain and clinical obesity than TDF/FTC/DTG by Week 192, particularly in women, but no significant differences in HIV RNA suppression or renal or bone-related adverse events. Both TAF/FTC/DTG and TDF/FTC/DTG had significantly higher rates of HIV RNA suppression than TDF/FTC/EFV at Week 192 in the main ITT analysis.

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