Durability of viral suppression with first-line antiretroviral therapy in patients with HIV in the UK: an observational cohort study
Identifieur interne : 000917 ( Main/Exploration ); précédent : 000916; suivant : 000918Durability of viral suppression with first-line antiretroviral therapy in patients with HIV in the UK: an observational cohort study
Auteurs : Jemma O'Connor [Royaume-Uni] ; Colette Smith [Royaume-Uni] ; Fiona C. Lampe [Royaume-Uni] ; Margaret A. Johnson [Royaume-Uni] ; David R. Chadwick [Royaume-Uni] ; Mark Nelson [Royaume-Uni] ; David Dunn [Royaume-Uni] ; Alan Winston [Royaume-Uni] ; Frank A. Post [Royaume-Uni] ; Caroline Sabin [Royaume-Uni] ; Andrew N. Phillips [Royaume-Uni]Source :
- The Lancet. HIV [ 2405-4704 ] ; 2017.
Abstract
The length of time that people with HIV on antiretroviral therapy (ART) with viral load suppression will be able to continue before developing viral rebound is unknown. We aimed to investigate the rate of first viral rebound in people that have achieved initial suppression with ART, to determine factors associated with viral rebound, and to use these estimates to predict long-term durability of viral suppression.
The UK Collaborative HIV Cohort (UK CHIC) Study is an ongoing multicentre cohort study that brings together in a standardised format data on people with HIV attending clinics around the UK. We included participants who started ART with three or more drugs and who had achieved viral suppression (≤50 copies per mL) by 9 months after the start of ART (baseline). Viral rebound was defined as the first single viral load of more than 200 copies per mL or treatment interruption (for ≥1 month). We investigated factors associated with viral rebound with Poisson regression. These results were used to calculate the rate of viral rebound according to several key factors, including age, calendar year at start of ART, and time since baseline.
Of the 16 101 people included, 4519 had a first viral rebound over 58 038 person-years (7·8 per 100 person-years, 95% CI 7·6–8·0). Of the 4519 viral rebounds, 3105 (69%) were defined by measurement of a single viral load of more than 200 copies per mL, and 1414 (31%) by a documented treatment interruption. The rate of first viral rebound declined substantially over time until 7 years from baseline. The other factors associated with viral rebound were current age at follow-up and calendar year at ART initiation (p<0·0001) and HIV risk group (p<0·0001); higher pre-ART CD4 count (p=0·0008) and pre-ART viral load (p=0·0003) were associated with viral rebound in the multivariate analysis only. For 1322 (29%) of the 3105 people with observed viral rebound, the next viral load value after rebound was 50 copies per mL or less with no regimen change. For HIV-positive men who have sex with men, our estimates suggest that the probability of first viral rebound reaches a plateau of 1·4% per year after 45 years of age, and 1·0% when accounting for the fact that 29% of viral rebounds are temporary elevations.
A substantial proportion of people on ART will not have viral rebound over their lifetime, which has implications for people with HIV and the planning of future drug development.
UK Medical Research Council.
Url:
DOI: 10.1016/S2352-3018(17)30053-X
PubMed: 28479492
PubMed Central: 5489695
Affiliations:
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Post</name><affiliation wicri:level="3"><nlm:aff id="aff6">Department of Sexual Health and HIV, King's College Hospital NHS Foundation Trust, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Sexual Health and HIV, King's College Hospital NHS Foundation Trust, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Sabin, Caroline" sort="Sabin, Caroline" uniqKey="Sabin C" first="Caroline" last="Sabin">Caroline Sabin</name><affiliation wicri:level="3"><nlm:aff id="aff1">Research Department of Infection and Population Health, UCL, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Research Department of Infection and Population Health, UCL, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Phillips, Andrew N" sort="Phillips, Andrew N" uniqKey="Phillips A" first="Andrew N" last="Phillips">Andrew N. 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Lampe</name><affiliation wicri:level="3"><nlm:aff id="aff1">Research Department of Infection and Population Health, UCL, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Research Department of Infection and Population Health, UCL, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Johnson, Margaret A" sort="Johnson, Margaret A" uniqKey="Johnson M" first="Margaret A" last="Johnson">Margaret A. Johnson</name><affiliation wicri:level="3"><nlm:aff id="aff2">Royal Free London NHS Foundation Trust, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Royal Free London NHS Foundation Trust, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Chadwick, David R" sort="Chadwick, David R" uniqKey="Chadwick D" first="David R" last="Chadwick">David R. Chadwick</name><affiliation wicri:level="1"><nlm:aff id="aff3">Centre for Clinical Infection, James Cook University Hospital, Middlesbrough, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Centre for Clinical Infection, James Cook University Hospital, Middlesbrough</wicri:regionArea><wicri:noRegion>Middlesbrough</wicri:noRegion></affiliation></author><author><name sortKey="Nelson, Mark" sort="Nelson, Mark" uniqKey="Nelson M" first="Mark" last="Nelson">Mark Nelson</name><affiliation wicri:level="3"><nlm:aff id="aff4">Department of Sexual Health and HIV, Chelsea and Westminster Hospital, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Sexual Health and HIV, Chelsea and Westminster Hospital, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Dunn, David" sort="Dunn, David" uniqKey="Dunn D" first="David" last="Dunn">David Dunn</name><affiliation wicri:level="3"><nlm:aff id="aff1">Research Department of Infection and Population Health, UCL, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Research Department of Infection and Population Health, UCL, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Winston, Alan" sort="Winston, Alan" uniqKey="Winston A" first="Alan" last="Winston">Alan Winston</name><affiliation wicri:level="3"><nlm:aff id="aff5">Department of Medicine, Imperial College and St Mary's Hospital, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Medicine, Imperial College and St Mary's Hospital, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Post, Frank A" sort="Post, Frank A" uniqKey="Post F" first="Frank A" last="Post">Frank A. Post</name><affiliation wicri:level="3"><nlm:aff id="aff6">Department of Sexual Health and HIV, King's College Hospital NHS Foundation Trust, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Department of Sexual Health and HIV, King's College Hospital NHS Foundation Trust, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Sabin, Caroline" sort="Sabin, Caroline" uniqKey="Sabin C" first="Caroline" last="Sabin">Caroline Sabin</name><affiliation wicri:level="3"><nlm:aff id="aff1">Research Department of Infection and Population Health, UCL, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Research Department of Infection and Population Health, UCL, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author><author><name sortKey="Phillips, Andrew N" sort="Phillips, Andrew N" uniqKey="Phillips A" first="Andrew N" last="Phillips">Andrew N. Phillips</name><affiliation wicri:level="3"><nlm:aff id="aff1">Research Department of Infection and Population Health, UCL, London, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Research Department of Infection and Population Health, UCL, London</wicri:regionArea><placeName><settlement type="city">Londres</settlement><region type="country">Angleterre</region><region type="région" nuts="1">Grand Londres</region></placeName></affiliation></author></analytic><series><title level="j">The Lancet. HIV</title><idno type="ISSN">2405-4704</idno><idno type="eISSN">2352-3018</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><sec><title>Background</title><p>The length of time that people with HIV on antiretroviral therapy (ART) with viral load suppression will be able to continue before developing viral rebound is unknown. We aimed to investigate the rate of first viral rebound in people that have achieved initial suppression with ART, to determine factors associated with viral rebound, and to use these estimates to predict long-term durability of viral suppression.</p></sec><sec><title>Methods</title><p>The UK Collaborative HIV Cohort (UK CHIC) Study is an ongoing multicentre cohort study that brings together in a standardised format data on people with HIV attending clinics around the UK. We included participants who started ART with three or more drugs and who had achieved viral suppression (≤50 copies per mL) by 9 months after the start of ART (baseline). Viral rebound was defined as the first single viral load of more than 200 copies per mL or treatment interruption (for ≥1 month). We investigated factors associated with viral rebound with Poisson regression. These results were used to calculate the rate of viral rebound according to several key factors, including age, calendar year at start of ART, and time since baseline.</p></sec><sec><title>Results</title><p>Of the 16 101 people included, 4519 had a first viral rebound over 58 038 person-years (7·8 per 100 person-years, 95% CI 7·6–8·0). Of the 4519 viral rebounds, 3105 (69%) were defined by measurement of a single viral load of more than 200 copies per mL, and 1414 (31%) by a documented treatment interruption. The rate of first viral rebound declined substantially over time until 7 years from baseline. The other factors associated with viral rebound were current age at follow-up and calendar year at ART initiation (p<0·0001) and HIV risk group (p<0·0001); higher pre-ART CD4 count (p=0·0008) and pre-ART viral load (p=0·0003) were associated with viral rebound in the multivariate analysis only. For 1322 (29%) of the 3105 people with observed viral rebound, the next viral load value after rebound was 50 copies per mL or less with no regimen change. For HIV-positive men who have sex with men, our estimates suggest that the probability of first viral rebound reaches a plateau of 1·4% per year after 45 years of age, and 1·0% when accounting for the fact that 29% of viral rebounds are temporary elevations.</p></sec><sec><title>Interpretation</title><p>A substantial proportion of people on ART will not have viral rebound over their lifetime, which has implications for people with HIV and the planning of future drug development.</p></sec><sec><title>Funding</title><p>UK Medical Research Council.</p></sec></div></front><back><div1 type="bibliography"><listBibl><biblStruct></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Staszewski, S" uniqKey="Staszewski S">S Staszewski</name></author><author><name sortKey="Miller, V" uniqKey="Miller V">V Miller</name></author><author><name sortKey="Sabin, C" uniqKey="Sabin C">C Sabin</name></author></analytic></biblStruct><biblStruct><analytic><author><name 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Jl" uniqKey="O Connor J">JL O'Connor</name></author><author><name sortKey="Gardner, Em" uniqKey="Gardner E">EM Gardner</name></author><author><name sortKey="Mannheimer, Sb" uniqKey="Mannheimer S">SB Mannheimer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Cambiano, V" uniqKey="Cambiano V">V Cambiano</name></author><author><name sortKey="Lampe, Fc" uniqKey="Lampe F">FC Lampe</name></author><author><name sortKey="Rodger, Aj" uniqKey="Rodger A">AJ Rodger</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Stohr, W" uniqKey="Stohr W">W Stöhr</name></author><author><name sortKey="Dunn, D" uniqKey="Dunn D">D Dunn</name></author><author><name sortKey="Arenas Pinto, A" uniqKey="Arenas Pinto A">A Arenas-Pinto</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Crawford, Kw" uniqKey="Crawford K">KW Crawford</name></author><author><name sortKey="Wakabi, S" uniqKey="Wakabi S">S Wakabi</name></author><author><name sortKey="Magala, F" uniqKey="Magala F">F Magala</name></author><author><name sortKey="Kibuuka, H" uniqKey="Kibuuka H">H Kibuuka</name></author><author><name sortKey="Liu, M" uniqKey="Liu M">M Liu</name></author><author><name sortKey="Hamm, Te" uniqKey="Hamm T">TE Hamm</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Abongomera, G" uniqKey="Abongomera G">G Abongomera</name></author><author><name sortKey="Kiwuwa Muyingo, S" uniqKey="Kiwuwa Muyingo S">S Kiwuwa-Muyingo</name></author><author><name sortKey="Revill, P" uniqKey="Revill P">P Revill</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Tweya, H" uniqKey="Tweya H">H Tweya</name></author><author><name sortKey="Feldacker, C" uniqKey="Feldacker C">C Feldacker</name></author><author><name sortKey="Estill, J" uniqKey="Estill J">J Estill</name></author></analytic></biblStruct><biblStruct></biblStruct><biblStruct><analytic><author><name sortKey="Grabar, S" uniqKey="Grabar S">S Grabar</name></author><author><name sortKey="Pradier, C" uniqKey="Pradier C">C Pradier</name></author><author><name sortKey="Le Corfec, E" uniqKey="Le Corfec E">E Le Corfec</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Royaume-Uni</li></country><region><li>Angleterre</li><li>Grand Londres</li></region><settlement><li>Londres</li></settlement></list><tree><country name="Royaume-Uni"><region name="Angleterre"><name sortKey="O Connor, Jemma" sort="O Connor, Jemma" uniqKey="O Connor J" first="Jemma" last="O'Connor">Jemma O'Connor</name></region><name sortKey="Chadwick, David R" sort="Chadwick, David R" uniqKey="Chadwick D" first="David R" last="Chadwick">David R. Chadwick</name><name sortKey="Dunn, David" sort="Dunn, David" uniqKey="Dunn D" first="David" last="Dunn">David Dunn</name><name sortKey="Johnson, Margaret A" sort="Johnson, Margaret A" uniqKey="Johnson M" first="Margaret A" last="Johnson">Margaret A. Johnson</name><name sortKey="Lampe, Fiona C" sort="Lampe, Fiona C" uniqKey="Lampe F" first="Fiona C" last="Lampe">Fiona C. Lampe</name><name sortKey="Nelson, Mark" sort="Nelson, Mark" uniqKey="Nelson M" first="Mark" last="Nelson">Mark Nelson</name><name sortKey="Phillips, Andrew N" sort="Phillips, Andrew N" uniqKey="Phillips A" first="Andrew N" last="Phillips">Andrew N. Phillips</name><name sortKey="Post, Frank A" sort="Post, Frank A" uniqKey="Post F" first="Frank A" last="Post">Frank A. Post</name><name sortKey="Sabin, Caroline" sort="Sabin, Caroline" uniqKey="Sabin C" first="Caroline" last="Sabin">Caroline Sabin</name><name sortKey="Smith, Colette" sort="Smith, Colette" uniqKey="Smith C" first="Colette" last="Smith">Colette Smith</name><name sortKey="Winston, Alan" sort="Winston, Alan" uniqKey="Winston A" first="Alan" last="Winston">Alan Winston</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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