Examining a Newer Therapy for Heavily Treated HIV Patients

People with multi-drug resistant (MDR) HIV have limited antiretroviral therapy (ART) options, which can leave their disease management very challenging.

“The patients who meet this definition tend to be very well known to us,” Onyema Ogbuagu, MBBCh, FACP, FIDSA, director of HIV Clinical Trials program at Yale School of Medicine, said. “I provide HIV care, and we all know many of these patients tend to be people who have long [been] in HIV care—it is typically not the newly infected.”

He says that these patients may have been diagnosed with HIV as children and now are adults or maybe they are older adults who had HIV for decades, and their ART regimens are less effective in keeping their HIV viral loads suppressed.

“Someone gave a talk today at CROI, [and the person] said that people don't fail drugs, but drugs fail people,” Ogbuagu said.

It is within this context, that treatment for these patients with multidrug resistance need an additional therapy to keep their viral loads down and prevent them from becoming vulnerable to other opportunistic infections.

There is a newer therapy, lenacapavir (Sunlenca), which has shown some promising data in addressing MDR HIV and as a potential complement to existing ART regimen in these aforementioned patients. Lenacapavir is a first-in-class, investigational long-acting HIV capsid that was FDA approved in late 2022 and is indicated for adult patients living with HIV, whose infections cannot be successfully treated with other available treatments due to resistance, intolerance, or safety consideration.

Lenacapavir is manufactured by Gilead, and at this week’s Conference on Retroviruses and Opportunistic Infections (CROI) in Denver, CO, new data was presented that demonstrated treatment benefits over a 2-year periodfrom the phase 2/3 CAPELLA trial evaluating the lenacapavir. Ogbuagu was at CROI, and is a principal investigator on the trial.

CAPELLA is a double-blinded, placebo-controlled global multicenter study designed to evaluate the antiviral activity of lenacapavir when administered every 6 months as a subcutaneous injection in heavily treatment-experienced (HTE) people with MDR HIV infection. The eligible participants had resistance to ≥2 ARVs in ≥3 of the 4 main ARV classes (NRTI, NNRTI, PI, INSTI).

The optimized background regimen (OBR) participants were selected by individual clinicians, and other investigational drugs were permitted for the study.

The investigators wrote that the OBR overall susceptibility score was the sum of susceptibility scores for each OBR ARV; 0 (no susceptibility), 0.5 (partial susceptibility) and 1 (full susceptibility) and efficacy was assessed at Weeks 26, 52, and 104. Lenacapavir and OBR ARV resistance analyses were done at virologic failure (virologic rebound ≥50 copies/mL or <1 log10 decline vs baseline).

There were 72 patients enrolled, and of them, 12 (17%) had no fully active antiretrovirals in their OBR; 6 of 12 and 1 of 12 had 1 or 2 partially active (score 0.5 each) ARVs, respectively. The investigators report the median (range) number of OBR ARVs was 4 (2–6). Overall, OBR comprised NRTI (9 participants), INSTI (8), PI (7) or NNRTI (6); 5, 2, and 2 participants were on a CD4 post-attachment inhibitor (ibalizumab), CCR5 inhibitor (maraviroc), or attachment inhibitor (fostemsavir), respectively.

The trial was conducted over a 2-year period, and Ogbuagu says this was about looking at the modality of subcutaneous injections as it related to safety, but also the long-term efficacy of the therapy.

“We found even as far out as two years or the so called 104 [week] data, that about 82% of individuals—when we excluded those who are missing— were virologically suppressed…that's unheard of numbers for this kind of patient population,” Ogbuagu said. “We have other studies with other agents that have shown lower rates of treatment success with these kinds of patients.”

Contagion spoke to Ogbuagu during CROI about lenacapavir's mechanism of action, more insights around the CAPELLA study, and the value he sees in the addition of this HIV therapy.

Reference

Ogbuagu O, Ratanasuwan W, Avihingsanon A, et al. Lenacapavir Efficacy IN CAPELLA Patients With No Fully Active Agents In Optimized Background Regimen. Poster #630 presented at CROI 2024. March 3-6, 2023. Denver, CO.