Evolution of L74V or K65R Mutations in VIremic Subjects on TDF or ABC (EVITA)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 11
研究概览
简要总结
This is a multicenter, open-label, non-randomized, dual-arm pilot study to investigate the prevalence of the reverse transcriptase (RT) resistance mutations, K65R/x or L74V/x, in HIV-1 plasma from subjects experiencing confirmed first-time incomplete virologic suppression during treatment with an initial antiretroviral (ARV) regimen consisting of at least 12 weeks of TDF or ABC + emtricitabine (FTC) or lamivudine (3TC) + non-nucleoside reverse transcriptase inhibitor (NNRTI) or protease inhibitor (PI). Subjects will be followed until a substantial loss of virologic or immunologic control requires a treatment switch. Confirmed first-time incomplete virologic suppression is defined as an initial plasma HIV-1 RNA response < 400 copies/mL, and subsequent virologic rebound > 400 copies/mL measured at two consecutive times.
Subjects will have a screening genotype to establish adherence to their non-suppressive TDF- or ABC-containing regimen by the presence of M184V (or other treatment-related primary) mutation and to demonstrate that the evolution of treatment-emergent RT mutations can be characterized.
Twenty subjects (a maximum of 10 per arm) will be enrolled at 10-20 United States (U.S.) sites. If fewer than 20 subjects can be enrolled, the study may be discontinued early by the sponsor. Equal numbers of subjects on Arm A versus Arm B will be a goal.
详细描述
This is a multicenter, open-label, non-randomized, dual-arm pilot study to investigate the prevalence of the RT resistance mutations, K65R/x or L74V/x, in HIV-1 plasma from subjects experiencing confirmed first-time incomplete virologic suppression during treatment with an initial ARV regimen consisting of at least 12 weeks of TDF or ABC + FTC or 3TC + NNRTI or PI. Subjects will be followed until substantial loss of virologic or immunologic control requires a treatment switch. Confirmed first-time incomplete virologic suppression is defined as an initial plasma HIV-1 RNA response < 400 copies/mL, and subsequent virologic rebound > 400 copies/mL measured at two consecutive times.
Subjects will have screening genotype to establish adherence to their non-suppressive TDF- or ABC-containing regimen by the presence of M184V (or other treatment-related primary) mutation and to demonstrate that the evolution of treatment-emergent RT mutations can be characterized.
Twenty subjects (maximum 10 per arm) will be enrolled at 10-20 U.S. sites. If fewer than 20 subjects can be enrolled, the study may be discontinued early by the sponsor. Equal numbers of subjects on Arm A vs. Arm B will be a goal.
Inclusion Criteria
- Confirmed first-time incomplete virologic suppression during treatment with at least 12 weeks of an ARV regimen consisting of TDF or ABC + FTC or 3TC + NNRTI or PI (TDF as Truvada or individually with FTC, and ABC as Epzicom or individually with 3TC). Confirmed first-time incomplete virologic suppression is defined as an initial plasma HIV-1 RNA response < 400 copies/mL, and subsequent virologic rebound > 400 copies/mL measured at two consecutive times.
- Screening HIV-1 RNA < 20,000 copies/mL obtained within 30 days prior to study entry.
- Screening CD4 cell count ≥ 200 cells/mL.
- Screening HIV-1 genotype with M184V or at least one treatment-related primary mutation.
- Routine labs as demonstrated by last available lab panel to be:
研究设计
- 研究类型
- Observational
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Confirmed first-time incomplete virologic suppression during treatment with at least 12 weeks of an ARV regimen consisting of TDF or ABC + FTC or 3TC + NNRTI or PI (TDF as Truvada or individually with FTC, and ABC as Epzicom or individually with 3TC). Confirmed first-time incomplete virologic suppression is defined as an initial plasma HIV-1 RNA response < 400 copies/mL, and subsequent virologic rebound > 400 copies/mL measured at two consecutive times.
- •Screening HIV-1 RNA < 20,000 copies/mL obtained within 30 days prior to study entry.
- •Screening CD4 cell count ≥ 200 cells/mL.
- •Screening HIV-1 genotype with M184V or at least one treatment-related primary mutation.
- •Routine labs as demonstrated by last available lab panel to be:
- •Hemoglobin > 8.0 g/dL;
- •Platelet count > 50,000/mm3;
- •AST (SGOT) < 210 U/L;
- •ALT (SGPT) < 240 U/L;
- •Alkaline phosphatase < 625 U/L;
- •Total bilirubin < 3.25 mg/dL; and
- •Calculated creatinine clearance ≥ 50 as estimated by the Cockcroft-Gault equation.
- •If participating in sexual activity that could lead to pregnancy, female study subjects must use two forms of contraception, one of which must be a barrier method.
- •Men and women aged ≥ 18 years.
- •Ability and willingness of subjects to give written informed consent.
排除标准
- •Subjects with screening HIV-1 genotype that is wild-type or contains the resistance mutations K65R/x or L74V/x.
- •Prior or current treatment with ARV regimen consisting of only NRTIs, ZDV or d4T, more than 2 NRTIs, ritonavir-boosted or dual PI regimen.
- •Use of immunomodulators (e.g., interleukins, interferons, cyclosporine), HIV vaccine, systemic cytotoxic chemotherapy, or investigational therapy within 30 days prior to study entry. Chronic treatment with prednisone at a daily dose of 10 mg or less is permitted. For non-serious illnesses, treatment of less than 21 days with larger doses of corticosteroids is permitted.
- •Active drug or alcohol use or dependence that, in the opinion of the site investigator, would interfere with adherence to study requirements.
- •Serious illness requiring systemic treatment and/or hospitalization until subject either completes therapy or is clinically stable on therapy, in the opinion of the site investigator, for at least 7 days prior to study entry. NOTE: Oral candidiasis, vaginal candidiasis, mucocutaneous herpes simplex, and other minor illnesses (as judged by the site investigator) have no restrictions.
- •Unable to discontinue contraindicated current medications.