Comparing Lenacapavir and Other Treatments for Patients with Multi-Drug Resistant HIV

According to a poster featured at AMCP 2022, a percentage of people with human immunodeficiency virus (HIV) are heavily treatment-experienced (HTE) but are unable to achieve viral suppression (VS) with combination antiretroviral therapy (ART). Lead author I. Chatzidaki and collaborators noted this is often due to multi-drug resistance (MDR), intolerance, or safety concerns.

To explore treatment options for this population, they compared optimized background regimen (OBR) alone, lenacapavir with OPR, fostemsavir with OPR, and ibalizumab with OPR in the context of VS outcomes. The study’s authors concluded that lenacapavir with OBR was “favored in terms of relative efficacy at week 24 to 26, offering significantly higher odds of VS in people with HIV [PWH] with MDR versus fostemsavir with OBR, ibalizumab with OBR, and OBR alone.”

The comparative study utilized 177 records from 35 randomized controlled trials and interventional studies on HIV-1 treatments in THE PWH. VS outcomes for fostemsavir and ibalizumab were based on data from both drugs’ pivotal trials, while data for lenacapavir was collected from the CAPELLA trial. Indirect treatment comparisons were performed for VS outcomes, based on odds ratios (ORs) and adjusted for up to four baseline characteristics from: age, viral load, CD4 cell count, prior ARTs, active ARTs, overall susceptibility score, and years since HIV diagnosis.

According to the article, lenacapavir with OBR had 4.29 times higher odds of achieving successful VS in week 24 to 26 compared to fostemsavir (95% confidence interval [CI], 1.34–13.77), 8.93 times higher odds compared to ibalizumab (95% CI, 2.07–38.46), and 12.74 higher odds compared to OBR alone (95% CI, 1.70–95.37)—all of which were statistically significant. Follow-up sensitivity analysis maintained the advantages of lenacapavir over ibalizumab with OBR and OBR alone. Adjusted comparisons still favored lenacapavir and OBR, with statistically significant odds.

Based on their systematic review and indirect treatment comparisons, the study’s authors proposed that lenacapavir with OBR appears to be superior to fostemsavir with OBR and ibalizumab with OBR, with regards to achieving VS in HTE PWH with MDR.