Evaluation of 4 New Simplified Antiretroviral Treatments in Naive HIV-1 Infected Patients in Africa (ANRS 12115 DAYANA)

This study has been completed.
Sponsor:
Collaborators:
Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
Gilead Sciences
Merck Sharp & Dohme Corp.
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis )
ClinicalTrials.gov Identifier:
NCT00573001
First received: December 12, 2007
Last updated: May 14, 2012
Last verified: May 2012
  Purpose

The goal of this trial is to demonstrate that new treatments are as effective as a reference triple-agent regimen in driving plasma viral load below the detection limit early during treatment (16 weeks). These simplified treatments involve fewer tablets and intakes, fixed-dose combinations, and also radically new strategies such as boosted protease inhibitor and tenofovir.


Condition Intervention Phase
HIV Infections
Drug: Tenofovir/Emtricitabine (Truvada) and Nevirapine
Drug: Tenofovir/Emtricitabine/Efavirenz (Atripla)
Drug: Tenofovir (Viread) and Lopinavir/Ritonavir (Aluvia)
Drug: Tenofovir/Emtricitabine (Truvada) and Zidovudine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase 3 Randomized Trial Evaluating the Virological Efficacy and the Tolerance of 4 New Simplified Antiretroviral Treatments in Naive HIV-1 Infected Patients in Dakar and Yaounde

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • Percentage of patients with viral load below 50 copies/mL [ Time Frame: week 16 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Percentage of patients with viral Load under 50 copies/ml and under 400 copies/ml [ Time Frame: W4, W12, W24, W36, W72, and W96 ] [ Designated as safety issue: No ]
  • Severe adverse event onset, metabolic alterations, lipodystrophia [ Time Frame: J0, W16, W24, W48, W72, W96 ] [ Designated as safety issue: Yes ]
  • Residual ARV plasmatic concentration [ Time Frame: W4, W48 ] [ Designated as safety issue: No ]
  • CD4 count evolution [ Time Frame: J0, W4, W16, W24, W36, W48, W72, W96 ] [ Designated as safety issue: No ]
  • quality of life parameters, observance [ Time Frame: J0, W4, W8, W12, W16, W24, W36, W48, W72, W96 ] [ Designated as safety issue: No ]

Enrollment: 120
Study Start Date: July 2008
Study Completion Date: December 2011
Primary Completion Date: July 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1 Drug: Tenofovir/Emtricitabine (Truvada) and Nevirapine
Tenofovir/Emtricitabine(Truvada) 245/200mg 1cp/day ; Nevirapine 200mg 2cp/day after first 14 days
Other Name: Truvada
Experimental: 2 Drug: Tenofovir (Viread) and Lopinavir/Ritonavir (Aluvia)
Tenofovir (Viread) 300mg 1cp/day ; Lopinavir/Ritonavir (Aluvia) 400/100mg 4cp/day
Other Names:
  • Viread
  • Aluvia
Experimental: 3 Drug: Tenofovir/Emtricitabine (Truvada) and Zidovudine
Tenofovir/Emtricitabine (Truvada) 245/200mg 1cp/day ; Zidovudine 300mg 2cp/day
Other Name: Truvada
Active Comparator: 4 Drug: Tenofovir/Emtricitabine/Efavirenz (Atripla)
Tenofovir/Emtricitabine/Efavirenz (Atripla) 300/200/600mg 1cp/day
Other Name: Atripla

Detailed Description:

The efficacy of antiretroviral treatments in sub-Saharan Africa has been demonstrated in cohort studies and pilot trials. The treatment regimens tested in these studies were derived from those used in pre-marketing trials conducted in industrialized countries.

However, the choice of antiretrovirals for national programs in poor countries is largely based on drug availability through the Access program, together with cost and supply considerations, rather than on field evaluations of recommended strategies.

Concomitantly with the development of antiretroviral access programs in the southern hemisphere, first-line treatments in industrialized countries have tended to become simpler, thereby improving their convenience and reducing the incidence and severity of their adverse effects. These simplified treatments involve fewer tablets and intakes, fixed-dose combinations, and also radically new strategies such as boosted protease inhibitor and tenofovir. These simplified strategies are being extensively evaluated in industrialized countries.

Long-term economic benefits will be a determining factor in the adoption of these strategies by poor countries.

Methods:

We will conduct a phase-III unblinded randomised trial focusing on the early virologic efficacy, tolerability and immuno-virologic efficacy of four simplified antiretroviral regimens given for 96 weeks to previously untreated HIV-1-infected patients in Senegal and Cameroon. The following four simplified treatments will be tested: TDF/FTC/NVP, LPV/TDF, TDF/FTC/AZT and TDF/FTC/EFV. The required number of patients (n=120) is compatible with the short-term recruitment capacity of two clinical investigation centers in Senegal and Cameroon.

Objective:

The goal of this trial is to demonstrate that these new treatments are as effective as a reference triple-agent regimen (TDF/FTC/EFV) in driving plasma viral load below the detection limit early during treatment. The principal objective is to identify simplified treatments capable of driving viral load below 50 copies/mL at week 16 in at least 50% of patients. If successful, the initial treatments will be continued and re-assessed at 96 weeks.

Study design:

120 patients previously unexposed to antiretroviral drugs will be recruited over a one-year period in two treatment centers in Dakar (Infectious Diseases department of Fann University Hospital) and Cameroon (Yaounde Military Hospital and Principal Hospital)

Expected results:

This study is fully in keeping with WHO/UNAIDS recommendations on antiretroviral treatment simplification in poor countries. These new treatments must be evaluated in the countries concerned, given the often very advanced stage of HIV disease at diagnosis, intercurrent health disorders, and local socioeconomic conditions.

This trial is not designed to compare these new treatments with one another, but rather to select the most promising treatments for future use. These preliminary results will help with the choice of treatment strategies for cohort studies and large-scale randomized trials.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • age over 18 years for Senegal and over 21 years for Cameroon
  • HIV-1 infected patient
  • patient naive from any antiretroviral treatment
  • CD4 cell count over 50 cells per mm3
  • contraceptive method use
  • informed consent signed

Exclusion Criteria:

  • opportunistic infection ongoing or any other serious pathology
  • ongoing treatment with rifampicine
  • severe renal or hepatic impairment
  • HbSAg positive
  • Hemoglobine under 8g/L
  • Neutrophils under 500 cells per mm3
  • ongoing pregnancy or breastfeeding
  • treatment by contra-indicated drugs (as described in study drugs notices)
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00573001

Locations
Cameroon
Hopital Central
Yaounde, Cameroon
Senegal
Hopital de Fann
Dakar, Senegal
Sponsors and Collaborators
French National Agency for Research on AIDS and Viral Hepatitis
Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
Gilead Sciences
Merck Sharp & Dohme Corp.
Investigators
Principal Investigator: Landman Roland, MD Institut de Médecine et d'Epidémiologie Appliquée - Fondation Internationale Léon M'Ba
Principal Investigator: Sow Papa Salif, MD Hopital de Fann, Dakar
Principal Investigator: Koulla Shiro Sinata, MD Hopital Central Yaoundé
  More Information

Additional Information:
No publications provided

Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis )
ClinicalTrials.gov Identifier: NCT00573001     History of Changes
Other Study ID Numbers: ANRS12115 DAYANA, IMEA 032
Study First Received: December 12, 2007
Last Updated: May 14, 2012
Health Authority: Cameroon: Ministry of Public Health
Senegal: Ministere de la sante

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
naive
HIV-1
simplified treatment
Treatment Experienced

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Zidovudine
Nevirapine
Tenofovir
Tenofovir disoproxil
Efavirenz
Efavirenz, emtricitabine, tenofovir disoproxil fumarate drug combination
Ritonavir
Lopinavir
Emtricitabine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on April 23, 2014