The prevalence of darunavir-associated mutations in HIV-1-infected children in the UK.
BACKGROUND: We examined the prevalence of ritonavir-boosted darunavir (DRV) resistance-associated mutations (RAMs) in HIV-infected children in the UK to determine the drug's potential clinical utility as a first-line or second-line protease inhibitor (PI). METHODS: The prevalence of DRV RAMs, i...
| Main Authors: | , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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2012
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| _version_ | 1797098389822767104 |
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| author | Donegan, K Walker, A Dunn, D Judd, A Pillay, D Menson, E Lyall, H Tudor-Williams, G Gibb, D |
| author_facet | Donegan, K Walker, A Dunn, D Judd, A Pillay, D Menson, E Lyall, H Tudor-Williams, G Gibb, D |
| author_sort | Donegan, K |
| collection | OXFORD |
| description | BACKGROUND: We examined the prevalence of ritonavir-boosted darunavir (DRV) resistance-associated mutations (RAMs) in HIV-infected children in the UK to determine the drug's potential clinical utility as a first-line or second-line protease inhibitor (PI). METHODS: The prevalence of DRV RAMs, identified from IAS 2010 and Stanford, and the Stanford susceptibility score, were estimated in PI-naive and PI-experienced children in the Collaborative HIV Paediatric Study and the UK HIV Drug Resistance Database 1998-2008. Associations between type/duration of PI exposure and area under the viraemia curve on PI with the number of RAMs were investigated using multivariate Poisson regression. RESULTS: A total of 17/417 (4%) children with a resistance test when PI-naive had one IAS DRV RAM, and 1 had a Stanford mutation; none had multiple DRV RAMs. A total of 177 PI-experienced children had a test after a median 2.7 years (IQR 1.1-5.2) on PIs; 19 (11%) had one IAS DRV RAM, 7 (4%) had two RAMs, 1 (0.6%) had three RAMs and 1 (0.6%) had four RAMs. DRV RAMs were independently associated with increased years on a PI, a larger area under the viraemia curve since starting PIs, and any exposure to PIs other than lopinavir (all P≤0.05). Only 6 (3%) PI-experienced children had intermediate-level DRV/ritonavir resistance; none had high-level resistance. CONCLUSIONS: DRV resistance was negligible in PI-naive children and those with lopinavir PI exposure alone. However resistance increased with increasing time, and with higher levels of viraemia, on PIs. Once-daily DRV/ritonavir would be valuable as a second PI or an alternative first PI, particularly if coformulated with a booster in an appropriate formulation for children. |
| first_indexed | 2024-03-07T05:08:51Z |
| format | Journal article |
| id | oxford-uuid:dadd60e9-9fce-4aec-bdb8-ecd7bffb344c |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T05:08:51Z |
| publishDate | 2012 |
| record_format | dspace |
| spelling | oxford-uuid:dadd60e9-9fce-4aec-bdb8-ecd7bffb344c2022-03-27T09:06:15ZThe prevalence of darunavir-associated mutations in HIV-1-infected children in the UK.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:dadd60e9-9fce-4aec-bdb8-ecd7bffb344cEnglishSymplectic Elements at Oxford2012Donegan, KWalker, ADunn, DJudd, APillay, DMenson, ELyall, HTudor-Williams, GGibb, DBACKGROUND: We examined the prevalence of ritonavir-boosted darunavir (DRV) resistance-associated mutations (RAMs) in HIV-infected children in the UK to determine the drug's potential clinical utility as a first-line or second-line protease inhibitor (PI). METHODS: The prevalence of DRV RAMs, identified from IAS 2010 and Stanford, and the Stanford susceptibility score, were estimated in PI-naive and PI-experienced children in the Collaborative HIV Paediatric Study and the UK HIV Drug Resistance Database 1998-2008. Associations between type/duration of PI exposure and area under the viraemia curve on PI with the number of RAMs were investigated using multivariate Poisson regression. RESULTS: A total of 17/417 (4%) children with a resistance test when PI-naive had one IAS DRV RAM, and 1 had a Stanford mutation; none had multiple DRV RAMs. A total of 177 PI-experienced children had a test after a median 2.7 years (IQR 1.1-5.2) on PIs; 19 (11%) had one IAS DRV RAM, 7 (4%) had two RAMs, 1 (0.6%) had three RAMs and 1 (0.6%) had four RAMs. DRV RAMs were independently associated with increased years on a PI, a larger area under the viraemia curve since starting PIs, and any exposure to PIs other than lopinavir (all P≤0.05). Only 6 (3%) PI-experienced children had intermediate-level DRV/ritonavir resistance; none had high-level resistance. CONCLUSIONS: DRV resistance was negligible in PI-naive children and those with lopinavir PI exposure alone. However resistance increased with increasing time, and with higher levels of viraemia, on PIs. Once-daily DRV/ritonavir would be valuable as a second PI or an alternative first PI, particularly if coformulated with a booster in an appropriate formulation for children. |
| spellingShingle | Donegan, K Walker, A Dunn, D Judd, A Pillay, D Menson, E Lyall, H Tudor-Williams, G Gibb, D The prevalence of darunavir-associated mutations in HIV-1-infected children in the UK. |
| title | The prevalence of darunavir-associated mutations in HIV-1-infected children in the UK. |
| title_full | The prevalence of darunavir-associated mutations in HIV-1-infected children in the UK. |
| title_fullStr | The prevalence of darunavir-associated mutations in HIV-1-infected children in the UK. |
| title_full_unstemmed | The prevalence of darunavir-associated mutations in HIV-1-infected children in the UK. |
| title_short | The prevalence of darunavir-associated mutations in HIV-1-infected children in the UK. |
| title_sort | prevalence of darunavir associated mutations in hiv 1 infected children in the uk |
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