Positive data were released today by ViiV Healthcare – a global HIV company majority-owned by GlaxoSmithKline plc (GSK), in partnership with Pfizer and Shionogi – from 48 weeks of the Paso Doble study (Gesida study 11720), the largest randomized, head-to-head, Phase IV clinical trial evaluating the 2-drug regimen dolutegravir/lamivudine (DTG/3Tc) versus the 3-drug regimen bictegravir/emtricitabine/tenofovir alafenamide fumarate (BIC/FTC/TAF) for the treatment of HIV-1 in virologically suppressed people who may benefit from therapeutic optimization. The results – it is stated in a note – showed that the switch to Dtg/3Tc, in virologically suppressed adults with HIV, demonstrated non-inferior efficacy in maintaining virological suppression compared to the switch to Bic/Ftc/Taf. These data will be presented at the 25th International AIDS Conference (AIDS 2024), held in Munich, Germany (July 22-26).
“The Paso Doble results show that DTG/3Tc demonstrated non-inferior efficacy compared to BIC/FTC/TAF and that the mean weight gain for study participants taking DTG/3Tc was significantly less than those taking BIC/FTC/TAF over the course of a year,” said Harmony P. Garges, M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., and … M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D., M.D.
In the Paso Doble clinical trial, 553 virologically suppressed HIV patients switched treatment to either Dtg/3Tc (277) or Bic/Ftc/Taf (276). The study population included individuals taking therapy that could be optimized, such as multiple-tablet regimens, regimens containing pharmacokinetic enhancers, or drugs associated with cumulative toxicity, such as efavirenz or tenofovir disoproxil fumarate. The study met its primary endpoint when Dtg/3Tc demonstrated non-inferiority compared to Bic/Ftc/Taf based on the percentage of participants with viral RNA greater than or equal to 50 copies/milliliter at 48 weeks according to the FDA snapshot analysis and a non-inferiority margin of 4% in the exposed intention-to-treat population. At 48 weeks, Dtg/3Tc was non-inferior to Bic/Ftc/Taf (risk difference between Dtg/3Tc [2,2%] less Bic/Ftc/Taf [0,7%] of 1.4%, 95% CI -0.5 to 3.4). One participant in the Bic/Ftc/Taf arm and zero in the Dtg/3Tc arm had confirmed, protocol-defined virologic failure through week 48 (HIV-1 RNA ≥50 c/mL followed by a second consecutive assessment of HIV-1 RNA ≥200 c/mL).
In a key secondary endpoint, the study found that weight increased significantly more in participants who switched to Bic/Ftc/Taf (adjusted mean change 1.81 kg, 95% CI 1.28-2.34) compared with those who switched to Dtg/3Tc (adjusted mean change 0.89 kg, 95% CI 0.37-1.41). [differenza 0,92 kg, Ic 95% 0,17-1,66] up to week 48. Similarly, the percentage of participants with greater than 5% weight gain at week 48 was significantly higher, at 29.9%, for Bic/Ftc/Taf, compared with 20% for Dtg/3Tc (adjusted OR 1.81, 95% CI 1.19-2.76). Weight change with Dtg/3Tc did not differ between men and women or based on participants’ previous regimen, while the percentage of study participants who experienced greater than 5% weight gain with Bic/Ftc/Taf was approximately 45% higher than those taking Dtg/3Tc when the previous regimen contained abacavir (30.6% Bic/Ftc/Taf vs 21.1% Dtg/3Tc) and approximately 2-fold higher when the previous regimen contained Tdf (40.7% Bic/Ftc/Taf vs 19.5% Dtg/3Tc).
Safety was comparable through week 48 and consistent with known safety profiles. There were few discontinuations due to adverse events in either study arm (Dtg/3Tc=1, 0.4%; Bic/Ftc/Taf=2, 0.7%), with no differences between arms.
“The HIV treatment regimens commonly prescribed today,” noted Esteban Martínez, Chief Executive Investigator of the Paso Doble study and Senior Consultant in Infectious Diseases at Hospital Clínic de Barcelona, ”are all highly effective, which makes it essential to study the impact of these therapies beyond simple virological suppression. The Paso Doble results show that Dtg/3Tc, a 2-drug regimen, not only demonstrated the same efficacy as a 3-drug regimen, but also showed less weight gain than Bic/Ftc/Taf over 48 weeks.”
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