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

TitleVirological failure and development of new resistance mutations according to CD4 count at combination antiretroviral therapy initiation.
Publication TypeJournal Article
Year of Publication2016
AuthorsJose S, Quinn K, Dunn D, Cox A, Sabin C and Fidler S
Corporate AuthorsUK CHIC and UK HDRD Steering Committees
JournalHIV Med
Volume17
Issue5
Pagination368-72
Date Published2016 May
ISSN1468-1293
KeywordsAnti-HIV Agents, Antiretroviral Therapy, Highly Active, CD4 Lymphocyte Count, Drug Resistance, Viral, Female, HIV Infections, Humans, Male, Mutation, Treatment Failure
Abstract

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.

DOI10.1111/hiv.12302
Alternate JournalHIV Med.
PubMed ID26306942
PubMed Central IDPMC4949527
Grant List097410 / / Wellcome Trust / United Kingdom
MR/M004236/1 / / Medical Research Council / United Kingdom
G0600337 / / Medical Research Council / United Kingdom
G0000199 / / Medical Research Council / United Kingdom
G0900274 / / Medical Research Council / United Kingdom
MC_UU_12023/15 / / Medical Research Council / United Kingdom
M004236 / / Medical Research Council / United Kingdom