CompletedNCT00495651TEMPRANOUpdated Jun 3, 2015

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

A Phase 3 interventional study of Antiretroviral medications and Antiretroviral medications+Isoniazid prophylaxis in HIV Infections and Tuberculosis, sponsored by French National Agency for Research on AIDS and Viral Hepatitis. Completed at 9 sites in Côte d’Ivoire. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2015-06-03.

Sponsored by French National Agency for Research on AIDS and Viral Hepatitis · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 2,073
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study 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.

Read the detailed description

The main individual benefit of very early ART initiation is likely a reduction in early severe AIDS-defining and non-AIDS-defining morbidity. While the diseases that might justify earlier initiation in high-income countries are generally non-infectious (non-AIDS-defining malignancies, renal diseases and cardiovascular diseases), the leading cause of early severe AIDS-defining morbidity in sub-Saharan Africa is tuberculosis and the main causes of severe non-AIDS-defining morbidity are non-invasive bacterial diseases. As a result of poor access to diagnosis and care, some HIV-infected people die from early infectious diseases before reaching current WHO criteria for starting ART.
Although the Côte d'Ivoire National Tuberculosis Program (PNLT) does not authorize the use of prophylaxis against tuberculosis, it has allowed the Temprano trial to provide a six-month course of isoniazid (INH) prophylaxis to half of the study subjects. This will allow us to (i) put early ART in perspective with a early 6-month INH prophylaxis use, in a setting where tuberculosis is the first cause of severe HIV-associated morbidity; and (ii) to describe and assess the feasibility of a six-month course of INH prophylaxis among patients with high CD4 counts.
Some drug toxicities are immediate but reversible. If early ART is compared to no ART in the short term, these toxicities may demonstrate erroneously that early ART is unfavorable. The risks and benefits of early ART initiation should therefore be evaluated over the long term. In the Temprano trial, we will: (i) follow patients for at least 30 months and analyze the primary outcome at 30 months; (ii) follow some study subjects for 80 months and evaluate the evolution of the ART efficacy / toxicity ratio from month 30 to month 80 as a secondary endpoint, to inform future policies if early ART is found to be beneficial at 30 months.

Main objective: To assess the benefits and risks of starting ART immediately and/or to receive a 6-month IPT among HIV-infected adults with CD4 counts \<800mm3 and no criteria for starting ART immediately according to the most recent WHO guidelines.

Location: Abidjan, Côte d'Ivoire.

Methods: randomized 2x2 factorial superiority trial

Main inclusion criteria: (i) HIV-1 or HIV-1+2 infection; (ii) age >18 years; (iii) nadir CD4 count \<800/mm3 and no criteria for starting ART immediately according to the most recent WHO guidelines; and (iv) no active tuberculosis.

Trial arms: Arm I: ART initiation according to WHO criteria, at any time during follow-up; Arm II: INH prophylaxis (300 mg/day) for six months and ART initiation according to WHO criteria, at any time during follow-up; Arm III: immediate ART initiation, before reaching the WHO criteria; Arm IV: INH prophylaxis (300 mg/day) for six months and immediate ART initiation, before reaching the WHO criteria.

First-line ART regimens

Tenofovir / emtricitabine + efavirenz for all HIV-1-infected men and all HIV-1-infected women who meet the following requirements: on effective contraception and no history of nevirapine use for the prevention of mother-to-child transmission of HIV (PMTCT).
Tenofovir / emtricitabine + lopinavir / ritonavir for all HIV-1+2-infected patients and all women who do not use effective contraception or who have a history of nevirapine use for PMTCT.

Primary endpoint: Death (all-cause), AIDS-defining disease, non-AIDS-defining malignancy, or non-AIDS-defining invasive bacterial disease.

Main secondary endpoint: Grade 3 or 4 clinical event (including renal and cardiovascular events) or laboratory test result, as defined by the ANRS classification system of drug-related adverse events.

Final primary analysis: It will be performed once the last patient has reached 30 months of follow-up. Time-dependent analyses will compare the primary outcome : (i) among patients initiating ART immediately (arms III and IV) versus patients initiating ART according to the WHO criteria (arms I and II); (ii) among patients who were prescribed a 6-months (arms II and IV) IPT versus those who were not (arms I and III).

Intermediate analysis on safety criteria:

Toxicity: all-cause mortality. We have not planned to perform any intermediate analyses for this criterion. If the number of observed deaths is higher than anticipated, however, the DSMB may decide to carry one out. In this case, we will adjust the alpha coefficient using the method suggested by Pocock to account for the large variety of available tests.
Efficacy: incidence of severe morbidity. Intermediate analysis: We have not planned any intermediate analyses for this criterion. If the number of severe morbidity evens is higher than anticipated once all patients have reached 12 months of follow-up, the DSMB may decide to carry one out. In this case, we will adjust the alpha coefficient using the method suggested by Haybittle-Peto, to account for the large variety of available tests.

Conditions studied

HIV Infections
Tuberculosis

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Keywords

HIV
HAART
Early Intervention
Naive patients

In context

HIV Infections

4,340 studies on the registry are indexed under HIV Infections; 240 are open to participants now.

This study's enrollment of 2,073 is above the median of 83 across 3,312 interventional studies indexed under HIV Infections.

Browse HIV Infections studies →

Lead sponsor

French National Agency for Research on AIDS and Viral Hepatitis is the lead sponsor of 86 studies on the registry; none are open to participants now.

Counted across the registry records on this site, refreshed daily.

Who can participate

Ages eligible: 18 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

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

Exclusion criteria

Exclusion Criteria:

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

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Factorial assignment
Masking: None (open label)
Enrollment: 2,073 participants (actual)

Study arms

Active comparator
I
Standard of care
Drug: Antiretroviral medications
Experimental
II
Standard of care+Isoniazid Prophylaxis:
Drug: Antiretroviral medications+Isoniazid prophylaxis
Experimental
III
Early Antiretroviral therapy
Drug: Antiretroviral medications
Experimental
IV
Early Antiretroviral therapy + Isoniazid prophylaxis
Drug: Antiretroviral medications+Isoniazid prophylaxis

Interventions

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

What researchers measure

Primary outcomes

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).
Time frame: 30 months
prevalence of HIV resistance (ANRS12253 associated study)
Time frame: 30 month after ARV initiation

Secondary outcomes

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
Time frame: 30 months
Tuberculosis disease or tuberculosis-related death
Time frame: 30 months
Changes in CD4 counts
Time frame: 30 months
Resistance to antiretroviral medications
Time frame: 30 months
Adherence to treatment
Time frame: 30 months
Individual socio-economic factors
Time frame: 30 months
Quality of life
Time frame: 30 months
Conversions and reversions of repeated QuantiFERON® TB Gold tests between inclusion and month 12 (M12)(ANRS12224 associated study)
Time frame: 12 months
Cost-effectiveness of each trial arm in the short- and long-term
Time frame: 30 months
Death
Time frame: 60 months

Study locations

9 sites

Centre de prise en charge de personnes vivant avec le VIH la pierre angulaire
Abidjan, Côte d’Ivoire
Centre de Prise en Charge et de Formation ACONDA
Abidjan, Côte d’Ivoire
Centre de Suivi des donneurs de sang, Centre National de Transfusion Sanguine
Abidjan, Côte d’Ivoire
Centre Intégré de Recherches Biocliniques d'Abidjan
Abidjan, Côte d’Ivoire
Centre médico-social El Rapha
Abidjan, Côte d’Ivoire
Formation Sanitaire Urbaine Anonkoua Kouté
Abidjan, Côte d’Ivoire
Hopital Général Felix Houphouet Boigny
Abidjan, Côte d’Ivoire
Service des Maladies Infectieuses et Tropicales, CHU de Treichville
Abidjan, Côte d’Ivoire
Unité de Soins Ambulatoires et de Conseil, CHU de Treichville
Abidjan, Côte d’Ivoire

References and documents

Publications

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. PubMed 35093007 ↗
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. PubMed 29297443 ↗
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. PubMed 29020361 ↗
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. PubMed 26193126 ↗
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. PubMed 25330161 ↗
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. PubMed 24985779 ↗
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. PubMed 23639243 ↗

Timeline

Tracking since Sep 25, 2026

Not marked actual or estimatedDates not marked actual or estimated

The record gives a start of Mar 2008, a primary completion of Jan 2015 and a completion of Jan 2015. It does not say whether these dates are actual or estimated.

How these figures are worked out, and which studies are left out of them.

Registered: Jul 2, 2007
First posted: Jul 3, 2007
Start: Mar 2008
Primary completionActual: Jan 2015
CompletionActual: Jan 2015
Last update: Jun 3, 2015

What these dates mean

Start.: When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.: When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.: When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.: Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.

No changes since tracking began. The registry record was last updated on Jun 3, 2015, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗

Registry details

Key details

Study ID: NCT00495651
Lead sponsor: French National Agency for Research on AIDS and Viral Hepatitis
Collaborators: Gilead Sciences, Merck Sharp & Dohme LLC
Responsible party: Sponsor
First posted: Jul 3, 2007
Start date: Mar 2008
Primary completion: Jan 2015
Completion: Jan 2015
Last update: Jun 3, 2015

Study contacts

Xavier Anglaret, MD, PhD

principal investigator · Université Bordeaux 2

Serge Eholié, MD, MSc, Pr

principal investigator · CHU de Treichville, Abidjan

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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This study is completed, as verified in Jun 2015. You cannot join it, but the record below documents what was studied.

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