Early Antiretroviral Treatment and/or Early Isoniazid Prophylaxis Against Tuberculosis in HIV-infected Adults (ANRS 12136 TEMPRANO)

NCT00495651 | Completed Phase 3 DMC

• 1 other identifier: ANRS 12136 TEMPRANO
• Study Type: interventional
• Target: 2,073
• Locations: 1 country
• Sites: 9

Brief Summary

The Temprano trial is based on the following assumptions:

• ART initiation at CD4 counts \<800/mm3 could significantly reduce the probability of severe HIV-related morbidity or death in the medium term.
• Tuberculosis and tuberculosis-related deaths are likely to represent a considerable proportion of morbidity and mortality among HIV-infected patients with high CD4 counts in sub-Saharan Africa. Therefore, 6-month Isoniazide Prophylaxis for Tuberculosis (IPT) and early ART could enhance each others efficacy.

Conditions

HIV Infections; Tuberculosis

Keywords

HIV; HAART; Early Intervention; Naive patients

Outcome Measures

Primary Outcomes (2)

• Death (all-cause), or severe HIV-related disease (AIDS-defining diseases, non-AIDS-defining malignancies, and non-AIDS-defining invasive bacterial diseases)

  * Severe HIV-related disease are defined as AIDS-defining diseases, non-AIDS- defining malignancies, and non-AIDS-defining invasive bacterial diseases * Invasive bacterial diseases are defined as: bacteremia, or bacterial infection of any solid organ or aseptic cavity (eg: pneumonia, pleurisy, meningitis,pyomyositis, pyelonephritis, prostatitis, orchitis, epididymitis, salpingitis, endometritis, endocarditis, cholecystitis, visceral abscesses).

  30 months

• prevalence of HIV resistance (ANRS12253 associated study)

  30 month after ARV initiation

Secondary Outcomes (10)

• Grade 3 or 4 clinical events (including cardiovascular, renal and bone disease) and laboratory test results, as defined by the ANRS classification system of drug-related adverse events

  30 months

• Tuberculosis disease or tuberculosis-related death

  30 months

• Changes in CD4 counts

  30 months

• Resistance to antiretroviral medications

  30 months

• Adherence to treatment

  30 months

Study Arms (4)

I

ACTIVE COMPARATOR

Standard of care

Drug: Antiretroviral medications

II

EXPERIMENTAL

Standard of care+Isoniazid Prophylaxis:

Drug: Antiretroviral medications+Isoniazid prophylaxis

III

EXPERIMENTAL

Early Antiretroviral therapy

Drug: Antiretroviral medications

IV

EXPERIMENTAL

Early Antiretroviral therapy + Isoniazid prophylaxis

Drug: Antiretroviral medications+Isoniazid prophylaxis

Interventions

Antiretroviral medications DRUG

Antiretroviral medications initiation at any time during the trial if at least one WHO-recommended criterion for starting ART is observed.

I

Antiretroviral medications+Isoniazid prophylaxis DRUG

* Antiretroviral initiation at any time during the trial if at least one 2009 WHO-recommended criterion for starting ART is observed. * Isoniazid prophylaxis:300 mg of INH once a day before breakfast for six months, starting one month after study inclusion

II

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• HIV-1 or HIV-1 + HIV-2 infection
• Age \>18 years
• No ongoing active tuberculosis
• Home address in any district of the greater Abidjan area
• Written informed consent before any clinic visit or laboratory test
• Clinical and immunologic status:CD4 counts \<800/mm3 and no criteria for starting ART according to the most recent WHO guidelines

You may not qualify if:

• Pregnant or breastfeeding women
• HIV-2 infection alone
• Clinical signs suggesting a severe disease (including tuberculosis) that has not yet been diagnosed, such as fever, wasting, diarrhea or unexplained cough (partial list)
• Previous ART initiation
• Known severe renal, cardiac or hepatic disease

Sponsors & Collaborators

• French National Agency for Research on AIDS and Viral Hepatitis: lead
• Gilead Sciences: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (9)

Centre de prise en charge de personnes vivant avec le VIH la pierre angulaire

Abidjan, Côte d’Ivoire

Location

Centre de Prise en Charge et de Formation ACONDA

Abidjan, Côte d’Ivoire

Location

Centre de Suivi des donneurs de sang, Centre National de Transfusion Sanguine

Abidjan, Côte d’Ivoire

Location

Centre Intégré de Recherches Biocliniques d'Abidjan

Abidjan, Côte d’Ivoire

Location

Centre médico-social El Rapha

Abidjan, Côte d’Ivoire

Location

Formation Sanitaire Urbaine Anonkoua Kouté

Abidjan, Côte d’Ivoire

Location

Hopital Général Felix Houphouet Boigny

Abidjan, Côte d’Ivoire

Location

Service des Maladies Infectieuses et Tropicales, CHU de Treichville

Abidjan, Côte d’Ivoire

Location

Unité de Soins Ambulatoires et de Conseil, CHU de Treichville

Abidjan, Côte d’Ivoire

Location

Related Publications (7)

• Moh DR, Ntakpe JB, Gabillard D, Yayo-Emieme AA, Badje A, Kouame GM, d'Aquin TT, Danel C, Anglaret X, Eholie SP. Association of cellular HIV-1 DNA and virological success of antiretroviral treatment in HIV-infected sub-Saharan African adults. BMC Infect Dis. 2022 Jan 29;22(1):100. doi: 10.1186/s12879-022-07082-2.

  PMID: 35093007 DERIVED

• Moh R, Badje A, N'takpe JB, Kouame GM, Gabillard D, Ouassa T, Ouattara E, Le Carrou J, Bohoussou F, Messou E, Eholie S, Anglaret X, Danel C. Screening for active tuberculosis before isoniazid preventive therapy among HIV-infected West African adults. Int J Tuberc Lung Dis. 2017 Dec 1;21(12):1237-1244. doi: 10.5588/ijtld.17.0016.

  PMID: 29297443 DERIVED

• Kouame GM, Boyd A, Moh R, Badje A, Gabillard D, Ouattara E, Ntakpe JB, Emieme A, Maylin S, Chekaraou MA, Eholie SP, Zoulim F, Lacombe K, Anglaret X, Danel C; French National Agency for Research on AIDS and Viral Hepatitis (ANRS) 12136 Temprano and ANRS 12240 VarBVA Study Groups. Higher Mortality Despite Early Antiretroviral Therapy in Human Immunodeficiency Virus and Hepatitis B Virus (HBV)-Coinfected Patients With High HBV Replication. Clin Infect Dis. 2018 Jan 6;66(1):112-120. doi: 10.1093/cid/cix747.

  PMID: 29020361 DERIVED

• TEMPRANO ANRS 12136 Study Group; Danel C, Moh R, Gabillard D, Badje A, Le Carrou J, Ouassa T, Ouattara E, Anzian A, Ntakpe JB, Minga A, Kouame GM, Bouhoussou F, Emieme A, Kouame A, Inwoley A, Toni TD, Ahiboh H, Kabran M, Rabe C, Sidibe B, Nzunetu G, Konan R, Gnokoro J, Gouesse P, Messou E, Dohoun L, Kamagate S, Yao A, Amon S, Kouame AB, Koua A, Kouame E, Ndri Y, Ba-Gomis O, Daligou M, Ackoundze S, Hawerlander D, Ani A, Dembele F, Kone F, Guehi C, Kanga C, Koule S, Seri J, Oyebi M, Mbakop N, Makaila O, Babatunde C, Babatounde N, Bleoue G, Tchoutedjem M, Kouadio AC, Sena G, Yededji SY, Assi R, Bakayoko A, Mahassadi A, Attia A, Oussou A, Mobio M, Bamba D, Koman M, Horo A, Deschamps N, Chenal H, Sassan-Morokro M, Konate S, Aka K, Aoussi E, Journot V, Nchot C, Karcher S, Chaix ML, Rouzioux C, Sow PS, Perronne C, Girard PM, Menan H, Bissagnene E, Kadio A, Ettiegne-Traore V, Moh-Semde C, Kouame A, Massumbuko JM, Chene G, Dosso M, Domoua SK, N'Dri-Yoman T, Salamon R, Eholie SP, Anglaret X. A Trial of Early Antiretrovirals and Isoniazid Preventive Therapy in Africa. N Engl J Med. 2015 Aug 27;373(9):808-22. doi: 10.1056/NEJMoa1507198. Epub 2015 Jul 20.

  PMID: 26193126 DERIVED

• Danel C, Kabran M, Inwoley A, Badje A, Herrmann JL, Moh R, Lecarrou J, Gabillard D, Ntakpe JB, Deschamps N, Ouattara E, Perronne C, Eholie S, Anglaret X. Quantiferon-TB Gold: performance for ruling out active tuberculosis in HIV-infected adults with high CD4 count in Cote d'Ivoire, West Africa. PLoS One. 2014 Oct 16;9(10):e107245. doi: 10.1371/journal.pone.0107245. eCollection 2014.

  PMID: 25330161 DERIVED

• Jean K, Gabillard D, Moh R, Danel C, Desgrees-du-Lou A, N'takpe JB, Le Carrou J, Badje A, Eholie S, Lert F, Anglaret X, Dray-Spira R. Decrease in sexual risk behaviours after early initiation of antiretroviral therapy: a 24-month prospective study in Cote d'Ivoire. J Int AIDS Soc. 2014 Jun 30;17(1):18977. doi: 10.7448/IAS.17.1.18977. eCollection 2014.

  PMID: 24985779 DERIVED

• Ouattara E, Danel C, Moh R, Gabillard D, Peytavin G, Konan R, Carrou JL, Bohoussou F, Eholie SP, Anglaret X. Early upper digestive tract side effects of zidovudine with tenofovir plus emtricitabine in West African adults with high CD4 counts. J Int AIDS Soc. 2013 Apr 30;16(1):18059. doi: 10.7448/IAS.16.1.18059.

  PMID: 23639243 DERIVED

Related Links

• Related Info
• ANRS 12136 Temprano trial website

MeSH Terms

Conditions

HIV Infections; Tuberculosis

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Mycobacterium Infections; Actinomycetales Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Study Officials

• Xavier Anglaret, MD, PhD

  Université Bordeaux 2

  PRINCIPAL INVESTIGATOR

• Serge Eholié, MD, MSc, Pr

  CHU de Treichville, Abidjan

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: FACTORIAL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2007
• First Posted: July 3, 2007
• Study Start: March 1, 2008
• Primary Completion: January 1, 2015
• Study Completion: January 1, 2015
• Last Updated: June 3, 2015

Record last verified: 2015-06

Locations

CÔ (9)