Single CD4 test with 250 Cells/Mm(3) threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria

Gilks, Charles F., Walker, A. Sarah, Munderi, Paula, Kityo, Cissy, Reid, Andrew, Katabira, Elly, Goodall, Ruth L., Grosskurth, Heiner, Mugyenyi, Peter, Hakim, James and Gibb, Diana M. (2013) Single CD4 test with 250 Cells/Mm(3) threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria. PloS One, 8 2: . doi:10.1371/journal.pone.0057580


Author Gilks, Charles F.
Walker, A. Sarah
Munderi, Paula
Kityo, Cissy
Reid, Andrew
Katabira, Elly
Goodall, Ruth L.
Grosskurth, Heiner
Mugyenyi, Peter
Hakim, James
Gibb, Diana M.
Title Single CD4 test with 250 Cells/Mm(3) threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria
Formatted title
Single CD4 test with 250 Cells/Mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria
Journal name PloS One   Check publisher's open access policy
ISSN 1932-6203
Publication date 2013-02-21
Year available 2013
Sub-type Article (original research)
DOI 10.1371/journal.pone.0057580
Open Access Status DOI
Volume 8
Issue 2
Total pages 9
Place of publication San Francisco, CA, United States
Publisher Public Library of Science
Collection year 2014
Language eng
Formatted abstract
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/mm3) 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/mm3; only 7 (2%) switched with CD4≥250 cells/mm3, 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/mm3 (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/mm3 only 11/133 (8%) had VL<400copies/ml, compared with 38/48 (79%) with CD4≥250 cells/mm3 (p<0.0001).

Conclusion: Multiple, but not single, WHO 3 events predicted first-line ART failure. A CD4 threshold ‘tiebreaker’ of ≥250 cells/mm3 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.
Keyword Receiving antiretroviral therapy
Resource-limited settings
Non-inferiority trial
Cell count
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ
Additional Notes Article # e57580

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Public Health Publications
 
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