Long-Acting HIV Therapy for Injection Drug Users

说明（由申请人提供）：抗逆转录病毒联合疗法使许多艾滋病毒感染者获得了接近正常的预期寿命，前提是他们能够获得护理，并能终生严格遵守每日或更频繁的治疗方案。抗逆转录病毒治疗方案病毒学失败的最重要因素是患者对完整和适当剂量的依从性差。感染艾滋病毒的注射吸毒者在保持最佳依从性方面面临着充分证明的挑战。因此，占美国艾滋病毒流行人数约四分之一的这一群体尚未充分受益于现有的抗逆转录病毒疗法。改善抗逆转录病毒药物依从性的各种干预措施，从咨询到直接观察治疗和其他结构性干预，只取得了有限的成功。我们提出了一种新的治疗策略，包括系统地给予长效抗逆转录病毒治疗，以确保在易于药物依从性差的hiv感染人群中有效地给药和抑制病毒。我们提出了一项随机、双盲、安慰剂对照的研究，将CCR5单克隆抗体PRO 140与标准护理口服抗逆转录病毒治疗方案联合进行每周皮下治疗。PRO 140是唯一适合这种用途的，因为它是唯一一种无需缓慢静脉输注即可证明长效病毒抑制的HIV药物。这项试点研究的成功将确定一种新的战略，以改善对受艾滋病毒感染的注射吸毒者和其他弱势群体的护理，这些人得不到当前这一代抗逆转录病毒药物的服务。积极的结果可能会促进这一领域的发展，并刺激在这一人群中开发和测试其他长效艾滋病药物。

DESCRIPTION (provided by applicant): Combination antiretroviral therapy has provided many HIV-infected individuals with a near-normal life expectancy, provided they have access to care and can maintain strict lifetime adherence to the daily or more frequent treatment regimens. The most important factor in the virologic failure of an antiretroviral regimen is poor adherence of the patient to complete and proper dosing. HIV-infected IDUs face well-documented challenges to maintaining optimal adherence. Accordingly, this group, which represents approximately one- quarter of the U.S. HIV epidemic, has yet to derive the full benefits of the available antiretroviral therapies. Various interventions to improve antiretroviral drug adherence, ranging from counseling to directly-observed therapy and other structural interventions, have had only modest success. We propose a novel treatment strategy involving systemic administration of long-acting antiretroviral therapy as a means to ensure effective drug delivery and viral suppression in HIV-infected populations prone to poor drug-adherence. We propose a randomized, double-blind, placebo-controlled study of weekly subcutaneous treatment with the CCR5 monoclonal antibody PRO 140 in combination with a standard-of-care oral antiretroviral regimen. PRO 140 is uniquely suited for this use as it is the only HIV drug to demonstrate long-acting viral suppression without the need for slow IV infusion. Success in this pilot study would identify a new strategy for improving the care of HIV-infected IDUs and other vulnerable populations that are underserved by the current generation of antiretroviral medications. Positive results could catalyze this field and spur development and testing of other long-acting HIV drugs in this population. PUBLIC HEALTH RELEVANCE: Combination antiretroviral therapy has provided many HIV-infected individuals with a near- normal life expectancy, provided they have access to care and can maintain strict lifetime adherence to the daily or more frequent treatment regimens. HIV-infected injection drug users (IDUs) face well-documented challenges to maintaining optimal adherence. Accordingly, this group, which represents approximately one-quarter of the HIV epidemic in the United States, has yet to derive the full benefits of the available antiretroviral therapies. We propose a novel treatment strategy involving systemic administration of long-acting antiretroviral therapy as a means to ensure effective drug delivery and viral suppression in HIV-infected populations prone to poor drug-adherence.