Dolutegravir-Based or Low-Dose Efavirenz–Based Regimen for the Treatment of HIV-1
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| Titel: | Dolutegravir-Based or Low-Dose Efavirenz–Based Regimen for the Treatment of HIV-1 |
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| Autoren: | Kouanfack, C., Mpoudi-Etame, Mireille, Omgba Bassega, P., Eymard-Duvernay, S., Leroy, S., Boyer, S., Peeters, M., Calmy, A., Delaporte, E., Aghokeng Fobang, Avelin |
| Weitere Verfasser: | Aiello, Mélisande, Calmy, Alexandra |
| Quelle: | New England Journal of Medicine, Vol. 381, No 9 (2019) pp. 816-826 |
| Verlagsinformationen: | Massachusetts Medical Society, 2019. |
| Publikationsjahr: | 2019 |
| Schlagwörter: | Adult, Cyclopropanes, Male, INFECTIOUS_DISEASES, Pyridones, HIV Infections/drug therapy, HIV Infections, THERAPY, Piperazines, Tenofovir/administration & dosage, 03 medical and health sciences, Benzoxazines/administration & dosage/adverse effects, 0302 clinical medicine, Pregnancy, Oxazines, Humans, RNA, Viral/blood, HIV Integrase Inhibitors, Obesity, Tenofovir, ddc:616, Weight Gain/drug effects, ADULTS, Heterocyclic Compounds, 3-Ring/administration & dosage/adverse effects, 16. Peace & justice, Viral Load/drug effects, HIV-1/genetics/isolation & purification, Benzoxazines, 3. Good health, AIDS, Lamivudine/administration & dosage, Lamivudine, [SDV.SP.PHARMA] Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology, Alkynes, CAMEROON, HIV Integrase Inhibitors/adverse effects/therapeutic use, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, HIV-1, Obesity/chemically induced, RNA, Viral, Drug Therapy, Combination, Female, Heterocyclic Compounds, 3-Ring |
| Beschreibung: | An efavirenz-based regimen (with a 600-mg dose of efavirenz, known as EFV600) was the World Health Organization preferred first-line treatment for human immunodeficiency virus type 1 (HIV-1) infection until June 2018. Given concerns about side effects, dolutegravir-based and low-dose efavirenz-based combinations have been considered as first-line treatments for HIV-1 in resource-limited settings.We conducted an open-label, multicenter, randomized, phase 3 noninferiority trial in Cameroon. Adults with HIV-1 infection who had not received antiretroviral therapy and had an HIV-1 RNA level (viral load) of at least 1000 copies per milliliter were randomly assigned to receive either dolutegravir or the reference treatment of low-dose efavirenz (a 400-mg dose, known as EFV400), combined with tenofovir and lamivudine. The primary end point was the proportion of participants with a viral load of less than 50 copies per milliliter at week 48, on the basis of the Food and Drug Administration snapshot algorithm. The difference between treatment groups was calculated, and noninferiority was tested with a margin of 10 percentage points.A total of 613 participants received at least one dose of the assigned regimen. At week 48, a viral load of less than 50 copies per milliliter was observed in 231 of 310 participants (74.5%) in the dolutegravir group and in 209 of 303 participants (69.0%) in the EFV400 group, with a difference of 5.5 percentage points (95% confidence interval [CI], -1.6 to 12.7; P1000 copies per milliliter) was observed in 3 participants in the dolutegravir group (with none acquiring drug-resistance mutations) and in 16 participants in the EFV400 group. More weight gain was observed in the dolutegravir group than in the EFV400 group (median weight gain, 5.0 kg vs. 3.0 kg; incidence of obesity, 12.3% vs. 5.4%).In HIV-1-infected adults in Cameroon, a dolutegravir-based regimen was noninferior to an EFV400-based reference regimen with regard to viral suppression at week 48. Among participants who had a viral load of at least 100,000 copies per milliliter when antiretroviral therapy was initiated, fewer participants than expected had viral suppression. (Funded by Unitaid and the French National Agency for AIDS Research; NAMSAL ANRS 12313 ClinicalTrials.gov number, NCT02777229.). |
| Publikationsart: | Article |
| Dateibeschreibung: | application/pdf; pdf |
| Sprache: | English |
| ISSN: | 1533-4406 0028-4793 |
| DOI: | 10.1056/nejmoa1904340 |
| Zugangs-URL: | https://pubmed.ncbi.nlm.nih.gov/31339676 https://pubmed.ncbi.nlm.nih.gov/31339676/ https://hal.archives-ouvertes.fr/hal-02479607/document https://hal.archives-ouvertes.fr/hal-02479607 https://www.ncbi.nlm.nih.gov/pubmed/31339676 https://hal.science/hal-02479607v1 https://hal.science/hal-02479607v1/document https://doi.org/10.1056/nejmoa1904340 https://archive-ouverte.unige.ch/unige:145652 https://archive-ouverte.unige.ch/unige:145652 https://doi.org/10.1056/nejmoa1904340 http://hdl.handle.net/20.500.12204/e89TSJQBiCFEh8T3c_Om |
| Rights: | URL: http://www.nejmgroup.org/legal/terms-of-use.htm |
| Dokumentencode: | edsair.doi.dedup.....b8f97a7b4605ac78a60ffa320ad36429 |
| Datenbank: | OpenAIRE |
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Nájsť tento článok vo Web of Science | Abstract: | An efavirenz-based regimen (with a 600-mg dose of efavirenz, known as EFV600) was the World Health Organization preferred first-line treatment for human immunodeficiency virus type 1 (HIV-1) infection until June 2018. Given concerns about side effects, dolutegravir-based and low-dose efavirenz-based combinations have been considered as first-line treatments for HIV-1 in resource-limited settings.We conducted an open-label, multicenter, randomized, phase 3 noninferiority trial in Cameroon. Adults with HIV-1 infection who had not received antiretroviral therapy and had an HIV-1 RNA level (viral load) of at least 1000 copies per milliliter were randomly assigned to receive either dolutegravir or the reference treatment of low-dose efavirenz (a 400-mg dose, known as EFV400), combined with tenofovir and lamivudine. The primary end point was the proportion of participants with a viral load of less than 50 copies per milliliter at week 48, on the basis of the Food and Drug Administration snapshot algorithm. The difference between treatment groups was calculated, and noninferiority was tested with a margin of 10 percentage points.A total of 613 participants received at least one dose of the assigned regimen. At week 48, a viral load of less than 50 copies per milliliter was observed in 231 of 310 participants (74.5%) in the dolutegravir group and in 209 of 303 participants (69.0%) in the EFV400 group, with a difference of 5.5 percentage points (95% confidence interval [CI], -1.6 to 12.7; P1000 copies per milliliter) was observed in 3 participants in the dolutegravir group (with none acquiring drug-resistance mutations) and in 16 participants in the EFV400 group. More weight gain was observed in the dolutegravir group than in the EFV400 group (median weight gain, 5.0 kg vs. 3.0 kg; incidence of obesity, 12.3% vs. 5.4%).In HIV-1-infected adults in Cameroon, a dolutegravir-based regimen was noninferior to an EFV400-based reference regimen with regard to viral suppression at week 48. Among participants who had a viral load of at least 100,000 copies per milliliter when antiretroviral therapy was initiated, fewer participants than expected had viral suppression. (Funded by Unitaid and the French National Agency for AIDS Research; NAMSAL ANRS 12313 ClinicalTrials.gov number, NCT02777229.). |
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| ISSN: | 15334406 00284793 |
| DOI: | 10.1056/nejmoa1904340 |