Virological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation

OBJECTIVES: No randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer...

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Detalles Bibliográficos
Autores principales: Jose, S, Quinn, K, Dunn, D, Cox, A, Sabin, C, Fidler, S, Ainsworth, Jonathan, Allan, Sris, Anderson, Jane, Babiker, Abdel, Chadwick, David, Delpech, Valerie, Fisher, Martin, Gazzard, Brian, Gilson, Richard, Gompels, Mark, Hay, Phillip, Hill, Teresa, Johnson, Margaret, Kegg, Stephen, Leen, Clifford, Martin, Fabiola, Nelson, Mark, Orkin, Chloe, Palfreeman, Adrian, Phillips, Andrew, Pillay, Deenan, Post, Frank, Pritchard, Jillian, Sachikonye, Memory, Schwenk, Achim, Tariq, Anjum, Walsh, John, Thornton, Alicia, Glabay, Adam, Perry, N, Tilbury, S, Youssef, E, Churchill, D, Everett, R, Asboe, D, Mandalia, S, Korat, H, Taylor, C, Gleisner, Z, Ibrahim, F, Campbell, L, Brima, N, Williams, I, Youle, M, Lampe, F, Smith, C, Tsintas, R, Chaloner, C, Hutchinson, S, Huntington, S, Mackie, N, Winston, A, Weber, J, Ramzan, F, Carder, M, Lynch, J, Hand, J, Souza, C, Munshi, S, Miller, S, Wood, C, Wilson, A, Morris, S, Allan, S, Palfreeman, A, Memon, K, ewszuk, A, Chadwick, D, Cope, E, Gibson, J, Kegg, S, Main, P, Mitchell, Dr, Hunter, Dr, Hay, P, Dhillon, M, Martin, F, Russell‐Sharpe, S, Harte, A, Clay, S, Tariq, A, Spencer, H, Jones, R, Atkinson, C, Delpech, V, Sachikonye, M, Aitken, Celia, Pozniak, Anton, Cane, Patricia, Clark, Duncan, Collins, Simon, Douthwaite, Samuel, White, Ellen, Fraser, Christophe, Geretti, Anna Maria, Hale, Antony, Hué, Stéphane, Kaye, Steve, Kellam, Paul, Lazarus, Linda, Leigh‐Brown, Andrew, Mbisa, Tamyo, Moses, Samuel, Nastouli, Eleni, Smit, Erasmus, Templeton, Kate, Tilston, Peter, Webster, Daniel, Zhang, Hongyi, Greatorex, Jane, Mullen, Jane, Tandy, Richard, Fawcett, Tracy, Hopkins, Mark, Ashton, Lynn, Booth, Claire, Garcia‐Diaz, Ana, Shepherd, Jill, Schmid, Matthias L, Payne, Brendan, Pere, Spiro, Hubb, Jonathan, Kirk, Stuart, Gunson, Rory, Bradley‐Stewart, Amanda
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2015
Materias:
Short Communication
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4949527/
https://www.ncbi.nlm.nih.gov/pubmed/26306942
http://dx.doi.org/10.1111/hiv.12302
Descripción
Sumario:OBJECTIVES: No randomized controlled trials have yet reported an individual patient benefit of initiating combination antiretroviral therapy (cART) at CD4 counts > 350 cells/μL. It is hypothesized that earlier initiation of cART in asymptomatic and otherwise healthy individuals may lead to poorer adherence and subsequently higher rates of resistance development. METHODS: In a large cohort of HIV‐positive individuals, we investigated the emergence of new resistance mutations upon virological treatment failure according to the CD4 count at the initiation of cART. RESULTS: Of 7918 included individuals, 6514 (82.3%), 996 (12.6%) and 408 (5.2%) started cART with a CD4 count ≤ 350, 351–499 and ≥ 500 cells/μL, respectively. Virological rebound occurred while on cART in 488 (7.5%), 46 (4.6%) and 30 (7.4%) with a baseline CD4 count ≤ 350, 351–499 and ≥ 500 cells/μL, respectively. Only four (13.0%) individuals with a baseline CD4 count > 350 cells/μL in receipt of a resistance test at viral load rebound were found to have developed new resistance mutations. This compared to 107 (41.2%) of those with virological failure who had initiated cART with a CD4 count < 350 cells/μL. CONCLUSIONS: We found no evidence of increased rates of resistance development when cART was initiated at CD4 counts above 350 cells/μL.

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