Randomised, Prospective Multicentre Clinical Study on the Effect of the Combination of Lopinavir/Rtv + Nevirapine as Maintenance Bitherapy (Without Nucleoside Analogues) in Comparison With a Triple Therapy Including Lopinavir/Rtv + Nucleoside Analogues in HIV-Infected Patients
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 67
- 试验地点
- 48
- 主要终点
- The primary outcome measures are changes in the mDNA/nDNA ratio at each visit with regard to the baseline visit.
研究概览
简要总结
The study aims to evaluate the changes in mitochondrial DNA (mDNA) by means of the mDNA/nuclearDNA (nDNA) ratio as a marker of mitochondrial toxicity following the interruption of nucleoside analogues.
详细描述
At the moment it is known that mitochondrial toxicity is the main pathogenic mechanism of toxicity associated with nucleoside analogues, including lipoatrophy, which at facial level is a stigmatising factor for patients with HIV infection.
The primary outcome measure of the design of an "NTRI-sparing" bitherapy is to retard the onset of mitochondrial toxicity or reverse it, mainly with regard to the loss of subcutaneous fat or lipoatrophy.
Lopinavir/ritonavir and nevirapine are two antiretrovirals with different mutation patterns and with high antiviral potency. Their combination therefore guarantees antiviral success. The NEKA study endorses efficacy immunologically and virologically (Negredo E. et al, NRTI-sparing regimen. XIV International AIDS Conference. Barcelona 2002. LB PeB9021).
Similarly, the protective effect of nevirapine on lipid metabolism would counteract the negative impact attributed to lopinavir/ritonavir, reducing cardiovascular risk in these patients.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age >= 18 years.
- •HIV-1 infected patients.
- •Patients on HAART therapy with PIs or NNRTIs.
- •Patients with an undetectable viral load (<50/80 copies/mL) over the last 6 months (at least 2 determinations separated by 2 months).
- •Hepatic tests < 5 times the normal value.
- •Subject able to follow the treatment period.
- •Women may not be of fertile age (defined as at least one year from menopause or undergoing any surgical sterilisation technique), or must undertake to use a barrier contraceptive method during the study.
- •Signature of the informed consent
排除标准
- •Presence of opportunistic infections and/or recent tumours (< 6 months).
- •Suspicion of resistance or documented resistance to any of the investigational drugs.
- •Suspicion of possible bad adherence.
- •Pregnancy or breastfeeding; refusal to follow reliable contraception over the treatment period.
- •Known allergic hypersensitivity to any of the investigational drugs or any similar drug.
- •Patients participating in another clinical trial.
结局指标
主要结局
The primary outcome measures are changes in the mDNA/nDNA ratio at each visit with regard to the baseline visit.
时间窗: At 24 and 48 weeks with regard to the baseline visit
次要结局
- Study of the efficacy of the therapy with Lopinavir/rtv (3 tablets every 12 h) + Nevirapine (1 tablet every 12 h) in the maintenance of viral suppression and immune recovery in patients on HAART therapy for more than 9 months(At 12, 24, 36 and 48 weeks.)
- To evaluate the tolerance and safety of the combination of Lopinavir-rtv+Nevirapine .(over 48 weeks of treatment)
- To check whether the simplified combination with the standard dose of Lopinavir/rtv with NVP is sufficient to maintain suppression of viral replication. Pharmacokinetic studies (PK) would be performed to estimate this point(At 12, 24, 36 and 48 weeks)
- To determine whether the combination with Lopinavir/rtv +Nevirapine is efficacious in avoiding progression to lipoatrophy/lipodystrophy or else the reversal thereof(At 24 and 48 weeks)
- and CV<50 copies/mL over at last 6 months(At 12, 24, 36 and 48 weeks)
- To study whether the combination with Lopinavir/rtv +Nevirapine makes it possible to control dyslipidemia associated with the use of Lopinavir/rtv on proving the "lipid-lowering" action of NVP(At 12, 24, 36 and 48 weeks.)
- To evaluate treatment adherence and patient quality of life (evaluated by means of the MOS_HIV questionnaire).(At 12, 24, 36 and 48 weeks)