HIVPhase 32LADYNCT00928187

Evaluation of Three Strategies of Second-line Antiretroviral Treatment in Africa (Dakar - Bobo-Dioulasso - Yaoundé)

A Phase 3 study testing emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line), abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line) and emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation) in people with HIV and HIV Infections, run by ANRS, Emerging Infectious Diseases at 3 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Since the first line antiretroviral (ARV) treatment is now largely accessible in the Sub-Saharian Africa countries, documentation of virological failure, drug resistance patterns and second line treatment evaluation are still to be consolidated in settings where viral load monitoring is not available and non-B HIV… Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: HIV, HIV Infections
What is being tested?: emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line), abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line) and emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 454 participants
Where: 3 sitesin 3 countries
Study dates: Nov 2009to Dec 2015
Phase: Phase 3
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Patient over the age of 18 years at pre-inclusion and monitored under outpatient conditions
Documented HIV-1 infection regardless of clinical stage and CD4 lymphocyte count
Patient with treatment failure after first-line antiretroviral treatment with a combination including a non-nucleoside reverse transcriptase inhibitor and two nucleoside reverse transcriptase inhibitors, failure being defined as 2 measurements (at 1 month interval) of plasma HIV RNA levels > 1000 copies/ml after at least 6 months of uninterrupted treatment
Adherence (> 80%) to first- line antiretroviral treatment (questionnaire) at pre inclusion
Patient agrees not to take any concomitant medication during the trial without informing the investigator
Informed consent signed no later than D-15
For women in childbearing age: negative pregnancy test at inclusion, with no plan of pregnancy in the coming 12 months and agreeing to use mechanical contraception (with or without hormonal contraception) during the study

Who cannot join

Infection with HIV-2 or HIV-1 groups O or N or HIV1+2
Deficiency of the patient, making it difficult, if not impossible, for him/her to take part in the trial or understand the information provided to him/her
Participation in any other clinical trial
Presence of an uncontrolled, ongoing opportunistic infection or of any severe or progressive disease
First-line treatment with a protease inhibitor, abacavir, tenofovir or ddI
Ongoing treatment with rifampicin

Show all 14Show fewer

Severe hepatic insufficiency (TP < 50%)
ALAT > 3 x ULN
Creatinine clearance calculated by Cockcroft formula < 50 ml/min
Hb ≤ 8 g/dl
Platelets < 50,000 cells/mm3
Neutrophiles < 500 cells/ mm3
Use of drugs prohibited in the context of this trial (drugs contraindicated by the SCP of the trial drugs) - in the event of tuberculosis or malaria during the trial, a list of authorized medicines and, if necessary, a dose adjustment of the antiretroviral medication will be provided
Pregnancy or lactation

Trial locations and contacts

3 sites in 3 countries.

Country

City, postcode or hospital

3 sites in 3 countries

Burkina Faso1 site

Day Hospital, CHU Sanou Souro
Bobo-Dioulasso

Other trials in Burkina Faso

Cameroon1 site

Day Hospital, Central Hospital
Yaoundé

Other trials in Cameroon

Senegal1 site

Clinical Research and Training Center, Fann Hospital
Dakar

Other trials in Senegal

About this study

Official title: Multicentric, Non-inferiority, Randomized, Non-blinded Phase 3 Trial Comparing Virological Response at 48 Weeks of 3 Antiretroviral Treatment Regimens in HIV-1-infected Patients With Treatment Failure After 1st Line Antiretroviral Therapy (Cameroon, Burkina Faso, Senegal)

This trial aims at evaluating the efficacy and tolerance of 3 different second line treatment strategies: two recommended by WHO combine two non-nucleoside reverse transcriptase inhibitor associated with a ritonavir boosted protease inhibitor (emtricitabine-tenofovir-lopinavir/ritonavir and abacavir-didanosine-lopinavir/ritonavir); the third strategy combines emtricitabine-tenofovir-darunavir/ritonavir and is not yet evaluated in Sub-Saharian Africa. Darunavir has a potentially superior antiviral efficacy, a better tolerance and its single daily administration may facilitate treatment adherence.

Conditions: HIV, HIV Infections
Being tested: emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line), abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line), emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)
Keywords: HIV, Second line treatment, WHO recommendations, Africa, Treatment strategies, treatment experienced
Medical subject headings: HIV Infections

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)Drug
Emtricitabine 200 mg/tenofovir 300 mg 1 tablet/day with food + Lopinavir 200 mg/Ritonavir 50 mg 2 tablets in the morning and 2 tablets in the evening
abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)Drug
Didanosine 1 entero-coated capsule/day in fasting conditions (dosage 250 mg if weight < 60 kg, 400 mg if weight > 60 kg) + abacavir 300 mg 1 tablet in the morning and in the evening + Lopinavir 200 mg/Ritonavir 50 mg 2 tablets morning and evening
emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)Drug
Emtricitabine 200 mg/tenofovir 300 mg 1 tablet/day with food + darunavir 400 mg 2 tablets + ritonavir 100 mg 1 capsule, in a single dose with food

Study groups in NCT00928187
Study group	Role	What they receive
Arm A	Active comparator	emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line) Receives: Drug: emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)
Arm B	Active comparator	abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line) Receives: Drug: abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)
Arm C	Active comparator	emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation) Receives: Drug: emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Patients With Plasma HIV RNA < 50 Copies/mL
Measured: 48 weeks

Secondary outcomes (12)

Number of Patients With WHO Stage 3 and 4 HIV Related Events
patients having a diagnosis of HIV related event classified as stage 3 or 4
Measured: between baseline and 48 weeks
Patients With Plasma HIV RNA < 200 Copies/ml
number of patients with plasma HIV RNA below 200 copies/ml
Measured: 48 weeks
Gain in CD4 Cells Between Baseline and W48
median gain in circulating CD4 cells between baseline and W48
Measured: between baseline and 48 weeks
Number of Patients Discontinuing Study Treatment
number of patients discounting treatment because of adverse events
Measured: between baseline and W48
Tolerance: Gastrointestinal Complains
Gastrointestinal complaints (grade 1 to 4) between baseline and W48.
Measured: between baseline and 48 weeks
Tolerance: Neuropathies (Grade 1 to 4)
any symptom of peripheral neuropathy
Measured: between baseline and W48
Tolerance: Equal or Superior to a 25% Reduction in eGFR (Glomerular Filtration Rate)
evaluation of estimated glomerular filtration rate and number of participant with a decrease equal or superior to 25% of the baseline value
Measured: between baseline and W48
Adherence
number of patients in different categories of adherence as measured by questionnaire
Measured: between baseline and W48
Number of Patients With Resistance Mutations
number of patients with resistance mutations after second line treatment failure (HIV RNA> 1000 copies/ml)
Measured: between W12 and W48
Development of Metabolic Syndrome
number of patients developing metabolic syndrome over a period of 48 weeks
Measured: from baseline to week 48
Number of Patients With HIV Plasma Viral Load < 50 Copies/ml
Snapshot of patients with HIV viral load less then 50 copies/ml at week 24
Measured: Week 24
Number of Patients With HIV Plasma Viral Load < 200 Copies/ml
number of patients having a plasma viral load below 200 copies/ml at week 24
Measured: Week 24

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

Nov 2009Dec 2015

First posted25 Jun 2009 (estimated)
Study startNov 2009
Primary completionSep 2013
Study completionDec 2015

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIVStudies of the same condition, open and under way.
More trials run by ANRS, Emerging Infectious DiseasesThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Enrolment: 454 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT00928187
Sponsor's protocol ID: ANRS12169 2LADY
Acronym: 2LADY
Status last verified: Jan 2017
First submitted: 23 Jun 2009
Last updated: 27 Feb 2017
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes

Publications

Boyer S, Nishimwe ML, Sagaon-Teyssier L, March L, Koulla-Shiro S, Bousmah MQ, Toby R, Mpoudi-Etame MP, Ngom Gueye NF, Sawadogo A, Kouanfack C, Ciaffi L, Spire B, Delaporte E; 2-Lady Group. Cost-Effectiveness of Three Alternative Boosted Protease Inhibitor-Based Second-Line Regimens in HIV-Infected Patients in West and Central Africa. Pharmacoecon Open. 2020 Mar;4(1):45-60. doi: 10.1007/s41669-019-0157-9.
PubMed 31273686

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 27 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Multicentric, Non-inferiority, Randomized, Non-blinded Phase 3 Trial Comparing Virological Response at 48 Weeks of 3 Antiretroviral Treatment Regimens in HIV-1-infected Patients With Treatment Failure After 1st Line Antiretroviral Therapy (Cameroon, Burkina Faso, Senegal)
ClinicalTrials.gov ID: NCT00928187
Acronym / sponsor ID: 2LADY / ANRS12169 2LADY
Conditions: HIV, HIV Infections
Keywords: HIV, Second line treatment, WHO recommendations, Africa, Treatment strategies, treatment experienced
Phase: Phase 3
Study type: Interventional
Recruitment status: Completed
Enrolment: 454 participants (actual)
Lead sponsor: ANRS, Emerging Infectious DiseasesOther government
Collaborators: Gilead Sciences, Janssen Pharmaceutica
Study start: Nov 2009
Primary completion: Sep 2013 (actual)
Study completion: Dec 2015 (actual)
First posted: 25 Jun 2009 (estimated)
Results: Posted 8 Nov 2016

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Parallel groups
Masking: None (open label)
Number of arms: 3

Arm	Type	Receives
Arm A	Active comparator	Drug: emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)
Arm B	Active comparator	Drug: abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)
Arm C	Active comparator	Drug: emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (7 listed)

Patient over the age of 18 years at pre-inclusion and monitored under outpatient conditions
Documented HIV-1 infection regardless of clinical stage and CD4 lymphocyte count
Patient with treatment failure after first-line antiretroviral treatment with a combination including a non-nucleoside reverse transcriptase inhibitor and two nucleoside reverse transcriptase inhibitors, failure being defined as 2 measurements (at 1 month interval) of plasma HIV RNA levels > 1000 copies/ml after at least 6 months of uninterrupted treatment
Adherence (> 80%) to first- line antiretroviral treatment (questionnaire) at pre inclusion
Patient agrees not to take any concomitant medication during the trial without informing the investigator

Key exclusion criteria (14 listed)

Infection with HIV-2 or HIV-1 groups O or N or HIV1+2
Deficiency of the patient, making it difficult, if not impossible, for him/her to take part in the trial or understand the information provided to him/her
Participation in any other clinical trial
Presence of an uncontrolled, ongoing opportunistic infection or of any severe or progressive disease
First-line treatment with a protease inhibitor, abacavir, tenofovir or ddI

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
emtricitabine/tenofovir + lopinavir/ritonavir (WHO recommended second line)Emtricitabine 200 mg/tenofovir 300 mg 1 tablet/day with food + Lopinavir 200 mg/Ritonavir 50 mg 2 tablets in the morning and 2 tablets in the evening	Drug	Arm A
abacavir + didanosine + lopinavir/ritonavir (WHO recommended second line)Didanosine 1 entero-coated capsule/day in fasting conditions (dosage 250 mg if weight < 60 kg, 400 mg if weight > 60 kg) + abacavir 300 mg 1 tablet in the morning and in the evening + Lopinavir 200 mg/Ritonavir 50 mg 2 tablets morning and evening	Drug	Arm B
emtricitabine/tenofovir + darunavir + ritonavir (Second line strategy under evaluation)Emtricitabine 200 mg/tenofovir 300 mg 1 tablet/day with food + darunavir 400 mg 2 tablets + ritonavir 100 mg 1 capsule, in a single dose with food	Drug	Arm C

Primary outcome

Number of Patients With Plasma HIV RNA < 50 Copies/mL
Time frame: 48 weeks

12 secondary outcomes

Number of Patients With WHO Stage 3 and 4 HIV Related Events
Time frame: between baseline and 48 weeks
Patients With Plasma HIV RNA < 200 Copies/ml
Time frame: 48 weeks
Gain in CD4 Cells Between Baseline and W48
Time frame: between baseline and 48 weeks
Number of Patients Discontinuing Study Treatment
Time frame: between baseline and W48
Tolerance: Gastrointestinal Complains
Time frame: between baseline and 48 weeks
Tolerance: Neuropathies (Grade 1 to 4)
Time frame: between baseline and W48
Tolerance: Equal or Superior to a 25% Reduction in eGFR (Glomerular Filtration Rate)
Time frame: between baseline and W48
Adherence
Time frame: between baseline and W48
Number of Patients With Resistance Mutations
Time frame: between W12 and W48
Development of Metabolic Syndrome
Time frame: from baseline to week 48
Number of Patients With HIV Plasma Viral Load < 50 Copies/ml
Time frame: Week 24
Number of Patients With HIV Plasma Viral Load < 200 Copies/ml
Time frame: Week 24

Results and safety

Results posted to the registry on 8 Nov 2016, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Arm A	152	150
Arm B	147	141
Arm C	155	150

Primary outcome: Number of Patients With Plasma HIV RNA < 50 Copies/mL

Time frame: 48 weeks. Number. Unit: participants

Measure	Arm A n = 152	Arm B n = 145	Arm C n = 154
Value	105	92	97

Arm A vs Arm B: differences in proportions: 5.6 (95% CI -5.1 to 16.4)
Arm A vs Arm C: difference in proportions: 6.1 (95% CI -4.5 to 16.7)

Population analysed: ITT

12 secondary outcomes are reported in the full results.

Adverse events

Time frame: 48 Weeks. Other adverse events reported at 5% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Arm A	13 of 152 (8.6%)	131 of 152 (86.2%)	Not reported
Arm B	22 of 145 (15.2%)	122 of 145 (84.1%)	Not reported
Arm C	19 of 154 (12.3%)	118 of 154 (76.6%)	Not reported

Limitations and caveats (from the sponsor): Limitations: open label design, random imbalance at baseline. Non-inferiority not shown, results influenced by the hypothesis of 80% viral success (50 copies/mL), not reached (69% in the control group). Therefore, the study power was reduced (80%).

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Feb 2017.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 31273686Boyer S, Nishimwe ML, Sagaon-Teyssier L, March L, Koulla-Shiro S, Bousmah MQ, Toby R, Mpoudi-Etame MP, Ngom Gueye NF, Sawadogo A, Kouanfack C, Ciaffi L, Spire B, Delaporte E; 2-Lady Group. Cost-Effectiveness of Three Alternative Boosted Protease Inhibitor-Based Second-Line Regimens in HIV-Infected Patients in West and Central Africa. Pharmacoecon Open. 2020 Mar;4(1):45-60. doi: 10.1007/s41669-019-0157-9.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Sinata Koulla Shiro, PhD principal investigator

Infectious diseases department, Central Hospital, Yaounde, Cameroon

Papa Salif Sow, PhD principal investigator

Infectious Diseases Department, Fann Hospital, Dakar, Senegal

Adrien Sawadogo, MD principal investigator

Day Hospital, CHU Sanou Souro, Bobo Dioulasso, Burkina Faso

3 sites in 3 countries: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 27 Feb 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in Burkina Faso, Cameroon, Senegal. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 8 Nov 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of Patients With Plasma HIV RNA < 50 Copies/mL (time frame: 48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00928187, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Feb 2017.