Study on the Effect of Kaletra + Nevirapine as Maintenance Bitherapy Compared to a Triple Therapy Including Kaletra + Analogues in HIV Patients

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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HIV Infections

Intervention / Treatment
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* Drug: Lopinavir-rtv (Kaletra): 3 capsules (600 mg)/12 h
* Drug: Nevirapine (Viramune): 1 comp (200mg)/12h


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: 1<br>Lopinavir-rtv (Kaletra): 3 capsules (600 mg)/12 h | Drug: Lopinavir-rtv (Kaletra): 3 capsules (600 mg)/12 h<br>* Lopinavir-rtv (Kaletra): 3 capsules (600 mg)/12 h<br>|
| No Intervention: 2<br>Nevirapine (Viramune): 1 comp (200mg)/12h | Drug: Nevirapine (Viramune): 1 comp (200mg)/12h<br>* Nevirapine (Viramune): 1 comp (200mg)/12h<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary outcome measures are changes in the mDNA/nDNA ratio at each visit with regard to the baseline visit. |  | At 24 and 48 weeks with regard to the baseline visit | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | 
| and CV<50 copies/mL over at last 6 months |  | 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 | 
| 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 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 evaluate the tolerance and safety of the combination of Lopinavir-rtv+Nevirapine . |  | over 48 weeks of treatment | 
| To evaluate treatment adherence and patient quality of life (evaluated by means of the MOS_HIV questionnaire). |  | At 12, 24, 36 and 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Mitochondrial toxicity, Lopinavir-rtv, Nevirapine, DNA mitochondrial/DNA nuclear