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

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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.