Positive influence of the Delta32CCR5 allele on response to highly active antiretroviral therapy (HAART) in HIV-1 infected patients.

Important note: Information in this article was accurate in 2000. The state of the art may have changed since the publication date.

Positive influence of the Delta32CCR5 allele on response to highly active antiretroviral therapy (HAART) in HIV-1 infected patients.

Eur J Med Res. 2000 Aug 18;5(8):323-8. Unique Identifier : AIDSLINE MED/20416402
Kasten S; Goldwich A; Schmitt M; Rascu A; Grunke M; Dechant C; Kalden JR; Harrer T; Department of Medicine III, University of Erlangen-Nuremberg,; Krankenhausstrasse 12, D-91054 Erlangen, Germany.

Abstract: The heterozygous 32 base pair deletion of the chemokine receptor 5 (Delta32CCR5) has been associated with a more benign course of HIV-1-infection. To study the influence of Delta32CCR5 on the response to antiviral therapy we analyzed the presence of Delta32CCR5 by PCR in PBMC from 107 randomly selected HIV-1-infected patients treated with HAART for at least three months. 24 of 107 patients were heterozygous for Delta32CCR5 (22.4%). Before initiation of HAART Delta32CCR5 heterozygous patients (d/w) did not differ from homozygous CCR5 wild-type patients (w/w) regarding viral load and CD4 counts. After a median treatment time on HAART of 17.5 months (d/w, range 6-31 months, p = n.s.) or 19 months (w/w, range 3-33 months) all 24 patients (100%) with the Delta32CCR5 mutation, but only 58/83 patients (69.9%) with wild-type CCR5 showed a suppression of HIV-1-viremia below 500 copies/ml (p = 0.0020). Furthermore, 20/24 (83.3%) of the Delta32CCR5 heterozygous patients achieved CD4 counts above 200/microliter, but only 57/83 (68.7%) of the patients homozygous for CCR5 wild-type (p = 0.011). Our data indicate that the presence of heterozygous Delta32CCR5 is associated with a better response to HAART suggesting that therapeutic strategies targeting CCR5 could be of value for a sustained suppression of HIV-1 by HAART.

Keywords: CLINICAL TRIAL JOURNAL ARTICLE RANDOMIZED CONTROLLED TRIAL Acquired Immunodeficiency Syndrome/*DRUG THERAPY/*GENETICS Alleles Anti-HIV Agents/*THERAPEUTIC USE Cohort Studies Dideoxynucleosides/*THERAPEUTIC USE Drug Resistance, Microbial/GENETICS Female Human *HIV-1 Lamivudine/THERAPEUTIC USE Male Receptors, CCR5/*GENETICS Support, Non-U.S. Gov't Zidovudine/THERAPEUTIC USE

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