HIV-1 coreceptor use in triple-class treatment-experienced patients: baseline prevalence, correlates, and relationship to enfuvirtide response.
OBJECTIVE
We wished to assess, in heavily treatment-experienced patients, the prevalence of and baseline characteristics associated with HIV-1 coreceptor use and their relationship to responses to enfuvirtide treatment.


METHODS
Samples were obtained from participants in phase 3 studies of enfuvirtide. Multiple logistic regression and analysis of covariance were performed on data for baseline coreceptor use, virological and immunological response, and changes in coreceptor use during treatment.


RESULTS
Baseline envelopes were phenotyped for 724 patients; 50% harbored R5 strains, 48% harbored dual/mixed (D/M) strains, and 2% harbored X4 strains. D/M strains were associated with significantly lower CD4(+) cell counts but comparable viral loads, compared with R5 strains (P=.0005). Virological and immunological responses to enfuvirtide-based treatment showed no correlation with baseline coreceptor use. Changes in virus tropism from D/M to R5 strains during treatment were common, particularly in patients who received enfuvirtide (27%, vs. 14% who received no enfuvirtide; P<.05).


CONCLUSIONS
At baseline, D/M strains were associated with lower CD4(+) cell counts but similar viral loads, compared with R5 strains, and were common across CD4(+) cell count strata. The comparable virological and immunological responses and bias toward shifts from D/M to R5 strains in patients who received enfuvirtide support its use in triple-class treatment-experienced patients and its study as a therapeutic partner for coreceptor-binding inhibitors.
Melby
Tom
T
Trimeris, Morrisville, NC 27560, USA. tmelby@trimeris.com
Despirito
Michael
M
Demasi
Ralph
R
Heilek-Snyder
Gabrielle
G
Greenberg
Michael L
ML
Graham
Neil
N
D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D000077560:Enfuvirtide; D005260:Female; D015700:HIV Envelope Protein gp41 / Q000627:therapeutic use*; D015658:HIV Infections / Q000188:drug therapy* / Q000378:metabolism* / Q000821:virology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000627:therapeutic use*; D015995:Prevalence; D012367:RNA, Viral; D015728:Receptors, HIV / Q000378:metabolism*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
D019380:Anti-HIV Agents; D015700:HIV Envelope Protein gp41; D010446:Peptide Fragments; D012367:RNA, Viral; D015728:Receptors, HIV; D000077560:Enfuvirtide