Switch to fixed-dose ainuovirine, lamivudine, and tenofovir DF versus elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide in virologically suppressed people living with HIV-1: the 48-week results of the SPRINT trial, a multi-centre, randomi
We compared the efficacy and safety profiles of ainuovirine (ANV), a new-generation non-nucleoside reverse transcriptase inhibitor (NNRTI), with boosted elvitegravir (EVG), both coformulated with two nucleoside reverse transcriptase inhibitors (NRTIs), in people living with HIV-1 (PLWH) who had achieved virological suppression on previous NNRTI-based antiretroviral (ARV) regimen.
This study was a multi-centre, randomised, double-blind, active-controlled, non-inferiority trial recruiting PLWH from 10 clinical centres across China. Main inclusion criteria included age of 18-65 years (inclusive), and stably staying on an ARV regimen combining an NNRTI with a two-drug NRTI backbone for at least 12 months. Eligible participants must have maintained plasma HIV-1 ribonucleic acid (RNA) titre below 50 copies per mL confirmed on two successive tests at an interval of at least one month prior to randomisation. Participants were randomly assigned to receive ANV 150 mg plus lamivudine (3TC) 300 mg, and tenofovir disoproxil fumarate (TDF) 300 mg (ANV/3TC/TDF), or cobicistat (Cobi) 150 mg boosted EVG plus emtricitabine (FTC) 200 mg, and tenofovir alafenamide (TAF) 10 mg. The primary efficacy endpoint was the proportion of participants with HIV-1 RNA titre at 50 copies per mL or above at week 48 using the US Food and Drug Administration snapshot algorithm, with a non-inferiority margin of 4 percentage points at a two-side 95% confidence level. This trial is active, but not recruiting, and is registered with Chinese Clinical Trial Registry (ChiCTR), number ChiCTR2100051605.
Between October 2021 and February 2022, 923 patients were screened for eligibility, among whom 762 participants were randomized and had received at least one dose of ANV/3TC/TDF (n = 381) or EVG/Cobi/FTC/TAF (n = 381). At week 48, 7 (1.8%) participants on ANV/3TC/TDF and 6 (1.6%) participants on EVG/Cobi/FTC/TAF had plasma HIV-1 RNA titre at 50 copies per mL or above, including missing virological data within the time window (the Cochran-Mantel-Haenszel method, estimated treatment difference [ETD], 0.3%, 95% CI -1.6 to 2.1), establishing the non-inferiority of ANV/3TC/TDF to EVG/Cobi/FTC/TAF. The proportions of participants experiencing at least one treatment-emergent adverse events (AEs) were comparable between the two arms (97.6% versus 97.6%). A small proportion of participants discontinued study drug due to AEs (0.3% versus 0.3%). Serious AEs occurred in 11 (2.9%) participants on ANV/3TC/TDF and 9 (2.4%) participants on EVG/Cobi/FTC/TAF, respectively, none of which was considered related to study drug at the jurisdiction of the investigator. At week 48, participants on ANV/3TC/TDF showed a significantly less weight gain from baseline compared to those on EVG/Cobi/FTC/TAF (least square mean, 1.16 versus 2.05 kg, ETD -0.90 kg, 95% CI, -1.43 to -0.37). The changes in serum lipids from baseline also favoured ANV/3TC/TDF over EVG/Cobi/FTC/TAF.
In virologically suppressed PLWH on previous NNRTI-based ARV regimen, switch to ANV/3TC/TDF resulted in less weight gain, and improved lipid metabolism while maintaining virological suppression non-inferior to that to EVG/Cobi/FTC/TAF.
Jiangsu Aidea Pharmaceutical & the National "Thirteenth Five-year Period" Major Innovative Drugs Research and Development Key Project of the People's Republic of China Ministry of Science and Technology.
Zhang F
，Wu H
，Cai W
，Ma P
，Zhao Q
，Wei H
，Lu H
，Wang H
，He S
，Chen Z
，Chen Y
，Wang M
，Wan W
，Fu H
，Qin H
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Comparison of the efficacy, safety and durability of a switch to co-formulated RPV/TDF-TAF/FTC or DTG/ABC/3TC in virologically-suppressed HIV-1-infected patients in a single Italian centre: a cohort data analysis.
This study evaluated the efficacy, safety and durability of a switch to co-formulated RPV/TDF-TAF/FTC (RPV-STR) or DTG/ABC/3TC (DTG-STR) in virologically-suppressed HIV-positive patients in a single Italian centre. All HIV-infected ART-experienced patients switching to RPV-STR or DTG-STR with HIV-RNA <50 copies/mL were included. Outcomes were incidence rate and rate ratios for discontinuation due to all causes (DAC), to adverse events (DAE) and to virological failure (VF) after 4 years of follow-up. We included 402 patients (244 on RPV-STR, 158 on DTG-STR). At Year 4 of follow-up, 124 patients (30.8%) discontinued for any cause (71 on RPV-STR, 53 on DTG-STR). Fifteen patients experienced VF [13 (5.3%) on RPV-STR and 2 (1.3%) on DTG-STR; log-rank, P = 0.4413]. Overall, 46 patients (11.4%) had AEs (23 on RPV-STR, 23 on DTG-STR). Nausea/diarrhoea was more frequent with DTG-STR (4.4% vs. 0%) and neurological toxicity with RPV-STR (4.5% vs. 2.5%). The rate of DAC within the first 3 months was significantly higher with DTG-STR (aRR = 5.88, 95% CI 3.20-10.81; P < 0.001); similarly, the discontinuation rate due to AEs was significantly higher with DTG-STR compared with RPV-STR (aRR = 12.89, 95% CI 5.48-30.32; P < 0.001). No difference in VF was observed between the two groups (RR = 0.47, 95% CI 0.10-2.14; P = 0.335). Patients with undetectable viral load who switched to DTG-STR or RPV-STR maintained virological suppression with a low risk of VF. A higher discontinuation rate was observed with DTG-STR compared with RPV-STR, particularly within 3 months from switch.
Lagi F
，Botta A
，Kiros ST
，Meli M
，Borchi B
，Cavallo A
，Pozzi M
，Bartoloni A
，Sterrantino G
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