In study CD01 participants who achieved viral suppression with daily oral antiretroviral therapy switched to PRO 140 monotherapy, injected weekly at a subcutaneous dose of 350 mg. Participants received PRO 140 monotherapy for up to 12 weeks, overlapping one week with oral therapy. In an open-label, single-arm, phase 2b extension of CD01, participants who maintained viral suppression in CD01 through 12 weeks of PRO 140 monotherapy became eligible to continue weekly self-administered monotherapy.
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Participants in the extension study needed CCR5-using virus, a viral load below 50 copies/mL for the past 12 months on a stable antiretroviral regimen and nadir and current CD4 counts above 200 and 350 cells/mm3. Enrollees could not have hepatitis B infection, a history of an AIDS-defining illness, grade 4 lab abnormalities, substance abuse or dependence or a history of a medical or psychologic condition that might interfere with study requirements.
The 16 participants had a median age of 54.9 years (range 26 to 68), two were women, three non-Caucasian and four Hispanic. Median time since HIV diagnosis was 12.5 years (range two to 37) and median baseline CD4 count 593 cells/mm3 (range 365 to 1059). Of the 16 participants who entered the extension, one withdrew consent because of relocation and five had virologic failure (consecutive viral loads above 400 copies/mL) in an average 329 days (range 106 to 691). The researchers did not report whether poor adherence explained any of these failures.
Among the 10 participants who maintained viral suppression, seven had HIV RNA undetectable by a single-copy assay and six had a target-not-detectable reading on a standard HIV RNA assay. The three detectable viral loads were 4, 10 and 19 copies/mL on the single-copy assay. Weeks taking suppressive PRO 140 monotherapy ranged from 41 to 123, with all but one participant beyond two years. CD4 counts remained stable throughout follow-up.
One serious adverse event developed, a bile duct stone. No serious adverse events were judged related to PRO 140, no one stopped the monoclonal antibody because of adverse events, no severe adverse events developed and no toxicity pattern emerged. The researchers judged two adverse events definitely related to PRO 140, two probably related and eight possibly related. Transient and self-resolving injection-site reactions affected fewer than 10% of participants. No anti-PRO 140 antibodies or coreceptor switches could be detected in any study participant.
The investigators are working to identify predictors of PRO 140 treatment success. Currently recruiting phase 2b/3 trials are testing PRO 140 as maintenance monotherapy in 300 virologically suppressed people and PRO 140 (versus placebo) combined with other antiretrovirals in 30 treatment-experienced people with ongoing replication and HIV-1 resistant to several antiretroviral classes.
Mark Mascolini writes about HIV infection.