article · HIV Clinical Trials
Clinical evaluation examined PRO 140, a humanised monoclonal antibody targeting the CCR5 receptor, as a weekly single-agent maintenance therapy for individuals with CCR5-tropic HIV-1 infection. In phase 2b trials, 41 adult participants who were virally suppressed on standard daily oral combination antiretroviral therapy transitioned to weekly subcutaneous injections of PRO 140. Virologic suppression was maintained in 23 out of 41 participants over an initial 12-week period. Ten participants continued long-term treatment, with nine completing over two years of monotherapy. The therapy was well tolerated, with no anti-PRO 140 antibodies detected, and no major drug-related adverse events or treatment discontinuations recorded. Participants who experienced viral rebound successfully regained viral suppression after restarting oral antiretroviral regimens. Overall, the findings indicate that PRO 140 can sustain viral suppression in selected patients and could serve as an effective element within long-acting multi-drug combinations.
Daily oral medication regimens for HIV-1 can present adherence challenges and long-term burdens for patients. Demonstrating that a weekly subcutaneous antibody injection can safely maintain viral control for over two years in responsive individuals introduces a viable long-acting alternative. This approach could reduce daily dosing frequency and support the design of future multi-agent, long-acting therapeutic combinations.
This research demonstrates an applied, clinically tested therapy at the phase 2b trial stage. PRO 140 could provide pharmaceutical developers and healthcare providers with a long-acting maintenance option for patients with CCR5-tropic HIV-1. Commercial application focuses on self-administered weekly subcutaneous maintenance, either as single-agent therapy for selected patient profiles or as a component in emerging long-acting combination treatment regimens.
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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.
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DOI: 10.1080/15284336.2018.1452842
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