Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression : a randomized 48-week study
BACKGROUND: Residual viraemia is a major obstacle to HIV-1 eradication in subjects receiving HAART. The intensification with raltegravir could impact latent reservoirs and might lead to a reduction of plasma HIV-1 viraemia (viral load [VL]), complementary DNA intermediates and immune activation.
METHODS: This was a prospective, open-label, randomized study comprising 69 individuals on suppressive HAART randomly assigned 2:1 to add raltegravir during 48 weeks.
RESULTS: Total and integrated HIV-1 DNA, and ultrasensitive VL remained stable despite intensification. There was a significant increase in episomal HIV DNA at weeks 2-4 in the raltegravir group returning to baseline levels at week 48. Median CD4(+) T-cell counts increased 124 and 80 cells/µl in the intensified and control groups after 48 weeks (P=0.005 and P=0.027, respectively), without significant differences between groups. No major changes were observed in activation of CD4(+) T-cells. Conversely, raltegravir intensification significantly reduced activation of CD8(+) T-cells at week 48 (HLA-DR(+)CD38(+), P=0.005), especially in the memory compartment (CD38(+) of CD8(+)CD45RO(+), P<0.0001). Linear mix models also depicted a larger decrease in CD8(+) T-cell activation in the intensification group (P=0.036 and P=0.010, respectively). Raltegravir intensification was not associated to any particular adverse event.
CONCLUSIONS: Intensification of HAART with raltegravir during 48 weeks was safe and associated with a significant decrease in CD8(+) T-cell activation, and a transient increase of episomal HIV-1 DNA. However, raltegravir did not significantly contribute to changes in CD4(+) T-cell counts, ultrasensitive VL, and total and integrated HIV-1 DNA. These findings suggest that raltegravir impacts residual HIV-1 replication and support new strategies to impair HIV-1 persistence. ClinicalTrials.gov identifier: NCT00554398.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2012 |
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| Erschienen: |
2012 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:17 |
|---|---|
| Enthalten in: |
Antiviral therapy - 17(2012), 2 vom: 31., Seite 355-64 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Llibre, Josep M [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 23.07.2012 Date Revised 21.03.2022 published: Print-Electronic ClinicalTrials.gov: NCT00554398 Citation Status MEDLINE |
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| doi: |
10.3851/IMP1917 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM214989275 |
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| 100 | 1 | |a Llibre, Josep M |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Treatment intensification with raltegravir in subjects with sustained HIV-1 viraemia suppression |b a randomized 48-week study |
| 264 | 1 | |c 2012 | |
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| 500 | |a Date Completed 23.07.2012 | ||
| 500 | |a Date Revised 21.03.2022 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a ClinicalTrials.gov: NCT00554398 | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a BACKGROUND: Residual viraemia is a major obstacle to HIV-1 eradication in subjects receiving HAART. The intensification with raltegravir could impact latent reservoirs and might lead to a reduction of plasma HIV-1 viraemia (viral load [VL]), complementary DNA intermediates and immune activation | ||
| 520 | |a METHODS: This was a prospective, open-label, randomized study comprising 69 individuals on suppressive HAART randomly assigned 2:1 to add raltegravir during 48 weeks | ||
| 520 | |a RESULTS: Total and integrated HIV-1 DNA, and ultrasensitive VL remained stable despite intensification. There was a significant increase in episomal HIV DNA at weeks 2-4 in the raltegravir group returning to baseline levels at week 48. Median CD4(+) T-cell counts increased 124 and 80 cells/µl in the intensified and control groups after 48 weeks (P=0.005 and P=0.027, respectively), without significant differences between groups. No major changes were observed in activation of CD4(+) T-cells. Conversely, raltegravir intensification significantly reduced activation of CD8(+) T-cells at week 48 (HLA-DR(+)CD38(+), P=0.005), especially in the memory compartment (CD38(+) of CD8(+)CD45RO(+), P<0.0001). Linear mix models also depicted a larger decrease in CD8(+) T-cell activation in the intensification group (P=0.036 and P=0.010, respectively). Raltegravir intensification was not associated to any particular adverse event | ||
| 520 | |a CONCLUSIONS: Intensification of HAART with raltegravir during 48 weeks was safe and associated with a significant decrease in CD8(+) T-cell activation, and a transient increase of episomal HIV-1 DNA. However, raltegravir did not significantly contribute to changes in CD4(+) T-cell counts, ultrasensitive VL, and total and integrated HIV-1 DNA. These findings suggest that raltegravir impacts residual HIV-1 replication and support new strategies to impair HIV-1 persistence. ClinicalTrials.gov identifier: NCT00554398 | ||
| 650 | 4 | |a Clinical Trial, Phase III | |
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Randomized Controlled Trial | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 7 | |a Anti-HIV Agents |2 NLM | |
| 650 | 7 | |a DNA, Viral |2 NLM | |
| 650 | 7 | |a Pyrrolidinones |2 NLM | |
| 650 | 7 | |a RNA, Viral |2 NLM | |
| 650 | 7 | |a Raltegravir Potassium |2 NLM | |
| 650 | 7 | |a 43Y000U234 |2 NLM | |
| 700 | 1 | |a Buzón, Maria J |e verfasserin |4 aut | |
| 700 | 1 | |a Massanella, Marta |e verfasserin |4 aut | |
| 700 | 1 | |a Esteve, Anna |e verfasserin |4 aut | |
| 700 | 1 | |a Dahl, Viktor |e verfasserin |4 aut | |
| 700 | 1 | |a Puertas, Maria C |e verfasserin |4 aut | |
| 700 | 1 | |a Domingo, Pere |e verfasserin |4 aut | |
| 700 | 1 | |a Gatell, Josep M |e verfasserin |4 aut | |
| 700 | 1 | |a Larrouse, Maria |e verfasserin |4 aut | |
| 700 | 1 | |a Gutierrez, Mar |e verfasserin |4 aut | |
| 700 | 1 | |a Palmer, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Stevenson, Mario |e verfasserin |4 aut | |
| 700 | 1 | |a Blanco, Julià |e verfasserin |4 aut | |
| 700 | 1 | |a Martinez-Picado, Javier |e verfasserin |4 aut | |
| 700 | 1 | |a Clotet, Bonaventura |e verfasserin |4 aut | |
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