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CXCR4-using HIV-1 in antiretroviral-naive patients with primary or chronic infection

Abstract number: O527

Parisi S., Boldrin C., Cruciani M., Scaggiante R., Panese S., Scotton P.G., Ferretto R., Manfrin V., Bosco O., Andreoni M., Palù G.

Objectives: To characterise correlates of CXCR4-using (X4) or CCR5-using (R5) HIV-1 strains in a cross-sectional analysis of therapy-naive patients (pts).

Methods: Plasma from 26 pts with acute-recent-infection (<1 year, AR), 22 with early-chronic- (>300 cd4/ul, ECh) and 24 with advanced-chronic-infection (<300 cd4/ul, AdvCh), all harbouring HIV-1-B-subtype, were evaluated by sequencing a 35-amino-acids region from env gene, and by interpretation with PSSM-genotype prediction. In a subset of pts, peripheral blood mononuclear cells (PBMC) and cerebrospinal fluid (CSF) were tested.

Results: The cd4 median was 606 (range 230–1143), 395 (304–1145) and 153 (2–291) cells/ul for AR, ECh- and AdvCh-infected, cd4 percentage was 25 (8–44.5), 29.5 (15–36.6), and 14 (2.4–24.2), HIV-RNA plasma viraemia was 150,600 (145–450,294), 78,566 (45–262,900) and 65,403 (2725–665,993) copies/ml, and HIV-DNA proviral loads was 864 (93–18,005), 1279 (55–6357) and 3237 (45–17,308) copies/106 PBMC, respectively. At sequence evaluation R5-strains were found in all pts, with the exception of five X4-strains among AR (19.2%) and four X4-strains in AdvCh (16.6%) (p = not significant in any possible comparison by Fisher exact test). Among AR pts, those with X4-strains had similar cd4 (578 vs 633), lower cd4 percentage (24.5 vs 28.6), similar HIV-RNA plasma levels (150,600 vs 167,616) and higher DNA-load (2441 vs 696) with respect to R5-strain-harbouring subjects.

At PBMC-strain analysis, 4 AdvCh-pts with plasma-X4-strains revealed a concordant X4-strain in 3 cases, and an R5-strain in 1. 8 AdvCh-pts with plasma-R5-strains revealed a concordant R5 strain in 7 cases, and an X4-strain in 1.

Among 5 plasma-X4 AR-pts, 1 R5-strain was found in PBMC. 7 plasma-R5 acute-pts had an R5-strain in PBMC. Among few CSF studied, an X4 was found, from a AR-pt harbouring R5-strains in plasma and PBMC.

Conclusion: The presence of X4 variants is described to be more frequent in the late stages of the disease, but frequently can be transmitted as a X4/R5 mixture and X4-strains can be demonstrated without clonal analysis in the early phase of infection. In AdvCh-pts discordant pictures in different compartments can be found. These evidences may have implications for therapy, suggesting a co-receptor-use analysis of both plasma- and PBMC-strains as soon as possible after diagnosis. Cautions have to be maintained before using CCR5-inhibitors in the very early stages of disease, monitoring for an early selection of X4 variants.

Session Details

Date: 19/04/2008
Time: 00:00-00:00
Session name: 18th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Barcelona, Spain
Presentation type:
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