Background
PRO 140 is a humanized
monoclonal antibody targeting CCR5 with potent
antiviral activity in patients with CCR5-tropic HIV-1
infection. In phase 2b studies, we evaluated the long-term efficacy, safety, and tolerability of
PRO 140 monotherapy in maintaining viral suppression for over 24 months in patients who were stable on
combination antiretroviral therapy on entry into the trials. Methods and Results Forty-one adult patients, infected exclusively with CCR5-tropic HIV-1 with viral loads <50 copies/mL, were switched from daily oral combination ART regimens to weekly
PRO 140 monotherapy for 12 weeks. Participants who completed 12 weeks of treatment without experiencing virologic rebound were allowed to self-administer
PRO 140 as a 350 mg
subcutaneous injection weekly, for up to an additional 160 weeks. Participants were monitored bi-weekly for one year, and every four weeks thereafter for virologic rebound.
PRO 140 provided virologic suppression in 23/41 (56.1%) participants for 12 weeks and was well tolerated. Ten (10) participants are currently ongoing, of which nine participants have completed more than two years of monotherapy treatment (47-129 weeks). Participants experiencing virologic rebound achieved full viral suppression upon re-initiation of oral combination ART regimen. Anti-
PRO 140 antibodies were not detected in any patient, and no
drug-related major adverse events or treatment discontinuations were reported. Conclusions
PRO 140 has a potential to address an unmet need for a long-acting, single-agent, maintenance regimen for
HIV infection in selected patients. Studies are underway to determine host and/or virologic factors that may predict treatment success on
PRO 140 monotherapy. Moreover, it has sufficient potency for a prolonged period of monotherapy that it would be an excellent component of a multi long-acting
drug combination.