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

Gilks, CF; Walker, AS; Munderi, P; Kityo, C; Reid, A; Katabira, E; Goodall, RL; Grosskurth, H; Mugyenyi, P; Hakim, J; Gibb, DM; (2013) A single CD4 test with 250 cells/mm3 threshold predicts viral suppression in HIV-infected adults failing first-line therapy by clinical criteria. PLoS One, 8 (2). e57580. ISSN 1932-6203 DOI: https://doi.org/10.1371/journal.pone.0057580

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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 approximately 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.

Item Type: Article
Keywords: Adult, Anti-HIV Agents/pharmacology/ therapeutic use, Antiretroviral Therapy, Highly Active/economics/ utilization, Biological Markers/analysis, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes/ immunology/virology, Female, HIV/ drug effects/immunology, HIV Infections/ drug therapy/immunology/virology, Humans, Male, Treatment Failure, Uganda, Viral Load/drug effects, Zimbabwe, Adult, Anti-HIV Agents, pharmacology, therapeutic use, Antiretroviral Therapy, Highly Active, economics, utilization, Biological Markers, analysis, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, immunology, virology, Female, HIV, drug effects, immunology, HIV Infections, drug therapy, immunology, virology, Humans, Male, Treatment Failure, Uganda, Viral Load, drug effects, Zimbabwe
Faculty and Department: Faculty of Epidemiology and Population Health > Dept of Infectious Disease Epidemiology
Research Centre: Centre for Global Non-Communicable Diseases (NCDs)
Tropical Epidemiology Group
PubMed ID: 23437399
Web of Science ID: 315186000112
URI: http://researchonline.lshtm.ac.uk/id/eprint/1236313


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