AIDS 2024: Dolutegravir with Recycled Nucleoside Reverse Transcriptase Inhibitors Maintains Better Viral Suppression than Protease Inhibitor Based Antiretroviral Therapy Over 144 Weeks VISEND Trial
Speaker: Suilanji Sivile
Dolutegravir (DTG) is recommended by the World Health Organization (WHO) as both a first-line and second-line antiretroviral therapy (ART). For second-line treatment, optimizing the Nucleoside Reverse Transcriptase Inhibitor (NRTI) backbone is advised by replacing Tenofovir disoproxil fumarate (TDF) with a thymidine analog. Usually, Zidovudine (AZT) is used as the thymidine analogue. Human Immunodeficiency Virus Drug Resistance (HIVDR) testing is often unavailable, and its use is not recommended. Emerging evidence suggests that recycling the NRTI backbone may be effective, but long-term data on the practice are limited. The report presents the 144-week findings from the Viral Suppression and Individualized Treatment in the HIV (VISEND) trial.
The VISEND trial was conducted in Lusaka, Zambia. It was an open-label, randomized controlled trial involving adults over 18 on Tenofovir, Emtricitabine (FTC), Efavirenz, or Nevirapine (NVP) who had been on ART for over six months. Participants were categorized into two groups: Arm A included individuals who were virally suppressed and transitioned to Tenofovir-lamivudine-dolutegravir (TLD) and tenofovir alafenamide (TAF), FTC, DTG (TAFED). Arm B comprised individuals failing ART and was further divided into two subgroups: B1, which received TLD and TAFED, and B2, which received standard of care, including thymidine analog-based and boosted Protease Inhibitor (PI)-based regimens.
The VISEND trial showed balanced demographics, but Arm B had higher baseline viral loads and lower CD4 counts due to treatment failure. NRTI resistance was 92% in those with high viral loads, with 64% showing Tenofovir resistance. Among those who switched to TDF and DTG, 56% had no predicted activity to Tenofovir, and 75% had no predicted activity to Lamivudine (3TC) and FTC. In contrast, 46% of those switched to standard care had an AZT-associated mutation. High virological suppression was achieved in all arms, with no significant difference between TAF and TDF in Arm A. In Arm B, those who switched to TAF or DTG showed significantly better viral suppression at 44 weeks than standard care, with a Probability (p)-value below 0.01. Similar results were observed at a 50 copies/mL cutoff.
These findings support the superior efficacy of TAF and DTG compared to traditional regimens. In conclusion, the VISEND trial demonstrated that adults with virological failure on NRTI-based regimens had better outcomes when switched to DTG with either TAF or TDF. It was in comparison to those who were switched to standard care regimens. DTG resistance was not observed in this study. Given the high toxicity of AZT and associated logistical challenges, recycling NRTI backbones should be considered in national and international treatment guidelines.
The 25th International AIDS conference (AIDS 2024). 22nd-26th July, Munich, Germany
