Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of antiretroviral-naive individuals.
OBJECTIVE
We wished to characterize the epidemiological and clinical correlates of CXCR4-using human immunodeficiency virus type 1 (HIV-1) ("X4 variants") in a cross-sectional analysis of a large population of antiretroviral-naive individuals.


METHODS
HIV-1 coreceptor use was determined in the last pretherapy plasma sample for 1191 individuals initiating triple-combination therapy in British Columbia, Canada. Baseline variables investigated included sociodemographic characteristics, plasma viral load (pVL), CD4 cell count, AIDS diagnosis, HIV-1 V3 loop sequence, and human CCR5 Delta 32 genotype.


RESULTS
Individuals harboring X4 variants (n = 178 of 979 phenotyped samples; 18.2%) displayed a poorer baseline clinical profile than individuals harboring exclusively CCR5-using HIV-1 ("R5 variants") (median pVL, 175,000 vs. 120,000 copies of HIV-1 RNA/mL [P = .0006]; median CD4 cell count, 110 vs. 290 cells/mm(3) [P < .0001]). Individuals heterozygous for the CCR5 Delta 32 deletion (n = 128 of 967; 13.2%) were at 2.5 times higher risk of harboring X4 variants, compared with those without the deletion (multivariate P = .0005). The presence of basic amino acids at codon 11 and/or codon 25 of HIV-1 V3 (n = 109 of 955; 11.4%) was associated with a 9.1 times higher risk of harboring X4 variants (multivariate P < .0001), regardless of CCR5 Delta 32 genotype. In multivariate analyses adjusting for baseline parameters, HIV-1 coreceptor use was not found to be a significant predictor of survival or treatment response.


CONCLUSIONS
Baseline CD4 cell count, pVL, HIV-1 V3 sequence, and CCR5 Delta 32 genotype were the strongest determinants of CXCR4-using HIV-1 in this population. After adjustment for baseline parameters, the presence of X4 variants before initiation of highly active antiretroviral therapy was not independently associated with a poorer outcome of therapy.
Brumme
Zabrina L
ZL
BC Centre for Excellence in HIV/AIDS, St. Paul's Hospital, and Faculty of Medicine, University of British Columbia, Canada.
Goodrich
James
J
Mayer
Howard B
HB
Brumme
Chanson J
CJ
Henrick
Bethany M
BM
Wynhoven
Brian
B
Asselin
Jerome J
JJ
Cheung
Peter K
PK
Hogg
Robert S
RS
Montaner
Julio S G
JS
Harrigan
P Richard
PR
D000328:Adult; D000704:Analysis of Variance; D019380:Anti-HIV Agents / Q000627:therapeutic use; D001955:British Columbia; D018791:CD4 Lymphocyte Count; D005260:Female; D014644:Genetic Variation; D005838:Genotype; D015658:HIV Infections / Q000188:drug therapy / Q000276:immunology / Q000517:prevention & control; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D017720:Molecular Epidemiology / Q000379:methods*; D015999:Multivariate Analysis; D010641:Phenotype; D019718:Receptors, CXCR4 / Q000235:genetics*; D016896:Treatment Outcome
D019380:Anti-HIV Agents; D019718:Receptors, CXCR4