HIV Infections
Conditions
Keywords
Mitochondrial toxicity, Lopinavir-rtv, Nevirapine, DNA mitochondrial/DNA nuclear
Brief summary
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
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.
Interventions
DRUGLopinavir-rtv (Kaletra): 3 capsules (600 mg)/12 h
Lopinavir-rtv (Kaletra): 3 capsules (600 mg)/12 h
DRUGNevirapine (Viramune): 1 comp (200mg)/12h
Nevirapine (Viramune): 1 comp (200mg)/12h
Sponsors
Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
Germans Trias i Pujol Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Age \>= 18 years. 2. HIV-1 infected patients. 3. Patients on HAART therapy with PIs or NNRTIs. 4. Patients with an undetectable viral load (\<50/80 copies/mL) over the last 6 months (at least 2 determinations separated by 2 months). 5. Hepatic tests \< 5 times the normal value. 6. Subject able to follow the treatment period. 7. 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. 8. Signature of the informed consent
Exclusion criteria
1. Presence of opportunistic infections and/or recent tumours (\< 6 months). 2. Suspicion of resistance or documented resistance to any of the investigational drugs. 3. Suspicion of possible bad adherence. 4. Pregnancy or breastfeeding; refusal to follow reliable contraception over the treatment period. 5. Known allergic hypersensitivity to any of the investigational drugs or any similar drug. 6. Patients participating in another clinical trial.
Design outcomes
Primary
| Measure | 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
| Measure | 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 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 evaluate treatment adherence and patient quality of life (evaluated by means of the MOS_HIV questionnaire). | 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. |
Countries
Spain
Outcome results
None listed