A single CD4 test with 250 cells/mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria

BACKGROUND: In low-income countries, viral load (VL) monitoring of antiretroviral therapy (ART) is rarely available in the public sector for HIV-infected adults or children. Using clinical failure alone to identify first-line ART failure and trigger regimen switch may result in unnecessary use of co...

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主要な著者: Gilks, C, Walker, A, Munderi, P, Kityo, C, Reid, A, Katabira, E, Goodall, R, Grosskurth, H, Mugyenyi, P, Hakim, J, Gibb, D
フォーマット: Journal article
言語:English
出版事項: Public Library of Science 2013
_version_ 1826295676984623104
author Gilks, C
Walker, A
Munderi, P
Kityo, C
Reid, A
Katabira, E
Goodall, R
Grosskurth, H
Mugyenyi, P
Hakim, J
Gibb, D
author_facet Gilks, C
Walker, A
Munderi, P
Kityo, C
Reid, A
Katabira, E
Goodall, R
Grosskurth, H
Mugyenyi, P
Hakim, J
Gibb, D
author_sort Gilks, C
collection OXFORD
description BACKGROUND: In low-income countries, viral load (VL) monitoring of antiretroviral therapy (ART) is rarely available in the public sector for HIV-infected adults or children. Using clinical failure alone to identify first-line ART failure and trigger regimen switch may result in unnecessary use of costly second-line therapy. Our objective was to identify CD4 threshold values to confirm clinically-determined ART failure when VL is unavailable. METHODS: 3316 HIV-infected Ugandan/Zimbabwean adults were randomised to first-line ART with Clinically-Driven (CDM, CD4s measured but blinded) or routine Laboratory and Clinical Monitoring (LCM, 12-weekly CD4s) in the DART trial. CD4 at switch and ART failure criteria (new/recurrent WHO 4, single/multiple WHO 3 event; LCM: CD4<100 cells/mm(3)) were reviewed in 361 LCM, 314 CDM participants who switched over median 5 years follow-up. Retrospective VLs were available in 368 (55%) participants. RESULTS: Overall, 265/361 (73%) LCM participants failed with CD4<100 cells/mm(3); only 7 (2%) switched with CD4≥250 cells/mm(3), four switches triggered by WHO events. Without CD4 monitoring, 207/314 (66%) CDM participants failed with WHO 4 events, and 77(25%)/30(10%) with single/multiple WHO 3 events. Failure/switching with single WHO 3 events was more likely with CD4≥250 cells/mm(3) (28/77; 36%) (p = 0.0002). CD4 monitoring reduced switching with viral suppression: 23/187 (12%) LCM versus 49/181 (27%) CDM had VL<400 copies/ml at failure/switch (p<0.0001). Amongst CDM participants with CD4<250 cells/mm(3) only 11/133 (8%) had VL<400 copies/ml, compared with 38/48 (79%) with CD4≥250 cells/mm(3) (p<0.0001). CONCLUSION: Multiple, but not single, WHO 3 events predicted first-line ART failure. A CD4 threshold 'tiebreaker' of ≥250 cells/mm(3) for clinically-monitored patients failing first-line could identify ∼80% with VL<400 copies/ml, who are unlikely to benefit from second-line. Targeting CD4s to single WHO stage 3 'clinical failures' would particularly avoid premature, costly switch to second-line ART.
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spelling oxford-uuid:c5c20b7c-e5da-4b0b-8c4b-9307df0824132022-03-27T06:33:17ZA single CD4 test with 250 cells/mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteriaJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c5c20b7c-e5da-4b0b-8c4b-9307df082413EnglishSymplectic Elements at OxfordPublic Library of Science2013Gilks, CWalker, AMunderi, PKityo, CReid, AKatabira, EGoodall, RGrosskurth, HMugyenyi, PHakim, JGibb, DBACKGROUND: In low-income countries, viral load (VL) monitoring of antiretroviral therapy (ART) is rarely available in the public sector for HIV-infected adults or children. Using clinical failure alone to identify first-line ART failure and trigger regimen switch may result in unnecessary use of costly second-line therapy. Our objective was to identify CD4 threshold values to confirm clinically-determined ART failure when VL is unavailable. METHODS: 3316 HIV-infected Ugandan/Zimbabwean adults were randomised to first-line ART with Clinically-Driven (CDM, CD4s measured but blinded) or routine Laboratory and Clinical Monitoring (LCM, 12-weekly CD4s) in the DART trial. CD4 at switch and ART failure criteria (new/recurrent WHO 4, single/multiple WHO 3 event; LCM: CD4<100 cells/mm(3)) were reviewed in 361 LCM, 314 CDM participants who switched over median 5 years follow-up. Retrospective VLs were available in 368 (55%) participants. RESULTS: Overall, 265/361 (73%) LCM participants failed with CD4<100 cells/mm(3); only 7 (2%) switched with CD4≥250 cells/mm(3), four switches triggered by WHO events. Without CD4 monitoring, 207/314 (66%) CDM participants failed with WHO 4 events, and 77(25%)/30(10%) with single/multiple WHO 3 events. Failure/switching with single WHO 3 events was more likely with CD4≥250 cells/mm(3) (28/77; 36%) (p = 0.0002). CD4 monitoring reduced switching with viral suppression: 23/187 (12%) LCM versus 49/181 (27%) CDM had VL<400 copies/ml at failure/switch (p<0.0001). Amongst CDM participants with CD4<250 cells/mm(3) only 11/133 (8%) had VL<400 copies/ml, compared with 38/48 (79%) with CD4≥250 cells/mm(3) (p<0.0001). CONCLUSION: Multiple, but not single, WHO 3 events predicted first-line ART failure. A CD4 threshold 'tiebreaker' of ≥250 cells/mm(3) for clinically-monitored patients failing first-line could identify ∼80% with VL<400 copies/ml, who are unlikely to benefit from second-line. Targeting CD4s to single WHO stage 3 'clinical failures' would particularly avoid premature, costly switch to second-line ART.
spellingShingle Gilks, C
Walker, A
Munderi, P
Kityo, C
Reid, A
Katabira, E
Goodall, R
Grosskurth, H
Mugyenyi, P
Hakim, J
Gibb, D
A single CD4 test with 250 cells/mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria
title A single CD4 test with 250 cells/mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria
title_full A single CD4 test with 250 cells/mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria
title_fullStr A single CD4 test with 250 cells/mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria
title_full_unstemmed A single CD4 test with 250 cells/mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria
title_short A single CD4 test with 250 cells/mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria
title_sort single cd4 test with 250 cells mm3 threshold predicts viral suppression in hiv infected adults failing first line therapy by clinical criteria
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