In a late-breaker presentation at the 2017 Conference on Retroviruses and Opportunistic Infections (CROI), a new monoclonal antibody drug called ibalizumab reduced viral loads in individuals with multi-drug resistant HIV. The results showed that adding the drug to a failing regimen may help treatment-experienced people who have few options to control their virus.
Ibalizumab is a humanized antibody that attaches to the CD4 receptor to block the HIV life cycle. It is given by IV every two weeks. In earlier study, ibalizumab was effective against a wide range of HIV strains with no evidence of cross-resistance to current HIV drugs.
To be eligible, everyone had to have had a strain of HIV that was still sensitive to at least one drug for their optimized background regimen (OBR), of which nearly half (43%) took the experimental entry inhibitor fostemsavir. Those who were excluded were people with an active AIDS illness, previous use of ibalizumab, recent use of immune system therapy such as steroids and any serious lab abnormality.
The 24-week TMB-301 study enrolled 40 people on stable treatment for at least 8 weeks but with an HIV strain that was resistant to three (53%) or four (35%) classes or all HIV meds (16%). Average time living with HIV was 21 years. Average age was 51, 85% were male and nearly half were non-white. Average CD4 count was 73, nearly half had CD4s <50 and average viral load was around 35,000 with 18% above 100,000.
At study entry, participants stayed on their current regimen. At day 7, ibalizumab IV was given. At day 14, the OBR was added and then ibalizumab IV was given again at day 21 and every other week through 24 weeks.
After the first 7 days of the first ibalizumab dose, 83% saw their viral loads reduced at least by half. By week 24, the average decrease in viral load was 55% for those with a 1 log reduction and 48% for those with a 2 log reduction. In addition, half the participants saw their viral loads drop below 200 copies while 43% dropped below 50.
Small average increases of 15 CD4 cells occurred for those who started with <50 cells. For those with higher CD4s, the average increase was 75-81 cells. There was no evidence that antibodies to ibalizumab developed in any participant, which is possible with a monoclonal antibody.
Nine stopped the study (3 unrelated deaths, 3 withdrawals and 2 lost to follow-up). Most side effects were mild to moderate, and nine patients reported serious side effects.
These are promising results given the growing number of people who face decreasing treatment options due to resistance to many classes of drugs. The expanded access TMB-311 study is now enrolling additional people. A new intra-muscular injection is also being studied.
S Lewis, et al. Long-Acting Ibalizumab in Patients with Multi-Drug resistant HIV-1: A 24-Week Study. 2017 CROI, Seattle. Abstract 449LB.