HIV-1 Infection
Conditions
Keywords
First-line therapy, Protease inhibitor, Non-Nucleoside Reverse transcriptase Inhibitor, Resource-limited setting
Brief summary
In resource-limited setting, concerns remain regarding the emergence of virologic failure and high-level drug resistance mutations (DRM) during WHO recommended first-line antiretroviral therapy (ART) with non-nucleoside reverse transcriptase inhibitors (NNRTI) based regimens for Human immunodeficiency virus 1 (HIV1) infected patients. The study hypothesis is that a boosted-protease inhibitor regimen has a better outcome than a NNRTI-based regimen with a low genetic barrier to resistance. The study is a randomized, multicenter, factorial trial (conducted in Congo), in treatment- naïve adults receiving for 96 weeks ritonavir- boosted lopinavir(LPV/r) or nevirapine (NVP) each in combination with tenofovir (TDF) /emtricitabine (FTC) or zidovudine (ZDV)/lamivudine (3TC). The primary end point is the incidence of therapeutic (clinical and/or virologic)failure by study week 24.
Interventions
DRUGnevirapine
Nevirapine 200 mg twice daily or 400 mg once daily per os during 96 weeks
ritonavir-boosted lopinavir 800/200 mg once daily or 400/100 mg twice daily per os during 96 weeks
tenofovir 300 mg/emtricitabine 200 mg fixed-dose combination once daily, per os for 96 weeks
zidovudine 300 mg/lamivudine 150 mg twice daily fixed-dose generic combination, per os for 96 weeks
Sponsors
University of Liege
Ministry of Public Health, Democratic Republic of the Congo
Pierre and Marie Curie University
University Paris 7 - Denis Diderot
Gilead Sciences
Abbott
Centre Hospitalier Universitaire Saint Pierre
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Antiretroviral-therapy naïve HIV-1 infected Adults * WHO clinical stage 3 and CD4 \<350/mm3 or * WHO clinical stage 4 or * CD4 cell count \< 200/mm3 * Negative pregnancy test
Exclusion criteria
* Hemoglobin \< 8.5 g/dL (female) or 9.0 g/dL (male) * Estimated Glomerular Filtration Rate \< 50 ml/ minute (Cockcroft-Gault equation) * Hepatic transaminases (AST and ALT)\> 3 x upper limit of normal * Active tuberculosis * Pregnancy * Females who are breastfeeding
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Incidence of therapeutic failure | At week 48 with follow-up until week 96 | The primary end point is the proportion of patients with therapeutic failure defined as: * the occurence or relapse by week 24 of a World Health Organization (WHO) stage 4 or 3 event, or * death by week 24, or * discontinuation of study drugs due to toxicity at any time, or * virological failure defined as HIV-1 RNA \> 1000 copies/ml by week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| HIV-1 resistance mutations | At baseline and at the time of virologic failure | — |
| HIV-1 RNA viral load less than 50 copies/ml | Through week 96 | The percentage of patients with HIV-1 RNA \< 50 copies/ml |
| Immunologic response | Through week 96 | Cluster of differentiation 4 (CD4) cell count change from baseline |
| Safety and tolerability | Through week 96 | Incidence of adverse events and laboratory abnormalities |
| Changes in laboratory parameters | Through week 96 | — |
Countries
Republic of the Congo
Outcome results
None listed