Clinical trial NCT00335686: Study on the Effect of Kaletra + Nevirapine as Maintenance Bitherapy Compared to a Triple Therapy Including Kaletra + Analogues in HIV Patients
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: HIV Infections
Keywords: Mitochondrial toxicity
Lopinavir-rtv
Nevirapine
DNA mitochondrial/DNA nuclear
Lead sponsor: Germans Trias i Pujol Hospital
Sponsor class: OTHER
Collaborators: name: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia
First posted: 2006-06-12
Enrollment: 67
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: The primary outcome measures are changes in the mDNA/nDNA ratio at each visit with regard to the baseline visit.
timeFrame: At 24 and 48 weeks with regard to the baseline visit
Secondary outcomes:
measure: 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
timeFrame: At 12, 24, 36 and 48 weeks.
measure: and CV<50 copies/mL over at last 6 months
timeFrame: At 12, 24, 36 and 48 weeks
measure: To determine whether the combination with Lopinavir/rtv +Nevirapine is efficacious in avoiding progression to lipoatrophy/lipodystrophy or else the reversal thereof
timeFrame: At 24 and 48 weeks
measure: 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
timeFrame: At 12, 24, 36 and 48 weeks.
measure: 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
timeFrame: At 12, 24, 36 and 48 weeks
measure: To evaluate the tolerance and safety of the combination of Lopinavir-rtv+Nevirapine .
timeFrame: over 48 weeks of treatment
measure: To evaluate treatment adherence and patient quality of life (evaluated by means of the MOS_HIV questionnaire).
timeFrame: At 12, 24, 36 and 48 weeks
Other outcomes:
Locations:
city: Santiago
country: Spain
facility: Hospital C. Universitario de Santiago
state: A Coruña
city: Elche
country: Spain
facility: Hospital General Universitario de Elche
state: Alicante
city: Ibiza
country: Spain
facility: Hospital Can Mises
state: Baleares
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Barcelona
city: Granollers
country: Spain
facility: Hospital de Granollers
state: Barcelona
city: Terrassa
country: Spain
facility: Mutua de Terrassa
state: Barcelona
city: Castello
country: Spain
facility: Hospital General de Castellón
state: Castellón
city: Figueres
country: Spain
facility: Hospital de Figueres
state: Girona
city: Palamós
country: Spain
facility: Hospital de Palamós
state: Girona
city: Mahón
country: Spain
facility: Hospital Virgen del Toro
state: Menorca
city: Cartagena
country: Spain
facility: Hospital Nuestra Señora del Rosell
state: Murcia
city: Malaga
country: Spain
facility: Hospital C. Universitario Virgen de la Victoria
state: Málaga
city: Marbella
country: Spain
facility: Hospital Costa del Sol
state: Málaga
city: Asturias
country: Spain
facility: Hospital Central de Asturias
state: Oviedo
city: Reus
country: Spain
facility: Hospital Sant Joan de Reus
state: Tarragona
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital de Sant Pau
city: Barcelona
country: Spain
facility: Hospital de Mataró
city: Madrid
country: Spain
facility: Hospital C. San Carlos
city: Santander
country: Spain
facility: Hospital Marqués de Valdecilla
city: Tarragona
country: Spain
facility: Hospital Universitario Joan XXIII de Tarragona
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Valencia
country: Spain
facility: Hospital Arnau de Vilanova
city: Vigo
country: Spain
facility: Hospital Xeral Cies de Vigo
Study officials:
affiliation: Lluita contra la Sida Foundation-HIV Unit
name: Bonaventura Clotet, MD,PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Negredo E, Miro O, Rodriguez-Santiago B, Garrabou G, Estany C, Masabeu A, Force L, Barrufet P, Cucurull J, Domingo P, Alonso-Villaverde C, Bonjoch A, Moren C, Perez-Alvarez N, Clotet B; MULTINEKA Study Group. Improvement of mitochondrial toxicity in patients receiving a nucleoside reverse-transcriptase inhibitor-sparing strategy: results from the Multicenter Study with Nevirapine and Kaletra (MULTINEKA). Clin Infect Dis. 2009 Sep 15;49(6):892-900. doi: 10.1086/605440.