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

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

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.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Drug: Lopinavir-rtv (Kaletra): 3 capsules (600 mg)/12 h; Drug: Nevirapine (Viramune): 1 comp (200mg)/12h

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.

• Study Type: Interventional
• Enrollment (Actual): 67
• Phase: Phase 4

Contacts and Locations

Study Locations

• Spain
  • Alicante, Spain, 03010
    • Hospital General Universitario de Alicante
  • Barcelona, Spain, 08025
    • Hospital de Sant Pau
  • Barcelona, Spain, 08304
    • Hospital de Mataró
  • Madrid, Spain, 28040
    • Hospital C. San Carlos
  • Santander, Spain, 39008
    • Hospital Marques de Valdecilla
  • Tarragona, Spain, 43007
    • Hospital Universitario Joan XXIII de Tarragona
  • Valencia, Spain, 46015
    • Hospital Arnau De Vilanova
  • Valencia, Spain, 46010
    • Hospital Clinico de Valencia
  • Vigo, Spain, 36204
    • Hospital Xeral Cies de Vigo
  • A Coruña
    • Santiago, A Coruña, Spain, 15706
      • Hospital C. Universitario de Santiago
  • Alicante
    • Elche, Alicante, Spain, 03203
      • Hospital General Universitario de Elche
  • Baleares
    • Ibiza, Baleares, Spain, 07800
      • Hospital Can Mises
  • Barcelona
    • Badalona, Barcelona, Spain, 08916
      • Hospital Universitari Germans Trias i Pujol
    • Granollers, Barcelona, Spain, 08400
      • Hospital de Granollers
    • Terrassa, Barcelona, Spain, 08221
      • Mútua de Terrassa
  • Castellón
    • Castello, Castellón, Spain, 12004
      • Hospital General de Castellón
  • Girona
    • Figueres, Girona, Spain, 17600
      • Hospital de Figueres
    • Palamós, Girona, Spain, 17230
      • Hospital de Palamós
  • Menorca
    • Mahón, Menorca, Spain, 07701
      • Hospital Virgen del Toro
  • Murcia
    • Cartagena, Murcia, Spain, 30071
      • Hospital Nuestra Señora del Rosell
  • Málaga
    • Malaga, Málaga, Spain, 29010
      • Hospital C. Universitario Virgen de la Victoria
    • Marbella, Málaga, Spain, 29600
      • Hospital Costa Del Sol
  • Oviedo
    • Asturias, Oviedo, Spain, 33006
      • Hospital Central de Asturias
  • Tarragona
    • Reus, Tarragona, Spain, 43201
      • Hospital Sant Joan de Reus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome 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 Outcome Measures

Outcome 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 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

Collaborators and Investigators

• Sponsor: Germans Trias i Pujol Hospital
• Collaborators: Fundación FLS de Lucha Contra el Sida, las Enfermedades Infecciosas y la Promoción de la Salud y la Ciencia

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start: October 1, 2003
• Primary Completion (Actual): March 1, 2006
• Study Completion (Actual): March 1, 2006

Study Registration Dates

• First Submitted: June 8, 2006
• First Submitted That Met QC Criteria: June 9, 2006
• First Posted (Estimate): June 12, 2006

Study Record Updates

• Last Update Posted (Estimate): February 29, 2008
• Last Update Submitted That Met QC Criteria: February 19, 2008
• Last Verified: June 1, 2007

More Information

Terms related to this study

• Keywords: Nevirapine; Mitochondrial toxicity; Lopinavir-rtv; DNA mitochondrial/DNA nuclear
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; HIV Infections; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Protease Inhibitors; Cytochrome P-450 CYP3A Inhibitors; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme Inducers; Cytochrome P-450 CYP3A Inducers; HIV Protease Inhibitors; Viral Protease Inhibitors; Nevirapine; Lopinavir
• Other Study ID Numbers: MULTINEKA