PRO 140, a monoclonal antibody targeting CCR5, as a long-acting, single-agent maintenance therapy for HIV-1 infection
| Autor: | Derry Green, Denis Burger, Hana Mekonnen, Kazem Kazempour, Nader Pourhassan, Shide Badri, Paul J Maddon, Kush Dhody |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult Male Drug-Related Side Effects and Adverse Reactions Sustained Virologic Response medicine.drug_class viruses Injections Subcutaneous 030106 microbiology Human immunodeficiency virus (HIV) HIV Infections HIV Antibodies Humanized antibody Monoclonal antibody medicine.disease_cause Antibodies Monoclonal Humanized Maintenance Chemotherapy 03 medical and health sciences Chemokine receptor Maintenance therapy HIV Fusion Inhibitors Medicine Humans Pharmacology (medical) Single agent Longitudinal Studies Aged business.industry virus diseases Middle Aged Viral Load 030104 developmental biology Infectious Diseases Long acting Treatment Outcome PRO 140 Immunology HIV-1 Female business medicine.drug |
| Zdroj: | HIV clinical trials. 19(3) |
| ISSN: | 1945-5771 |
| Popis: | 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 loads50 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. |
| Databáze: | OpenAIRE |
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