Background: Both the natural history of HIV infection and the response to a
ntiretroviral therapy are heterogeneous. Polymorphisms in chemokine recepto
r genes modulate the natural history of HIV-1 infection. In comparison with
subjects with other genotypes, the prognosis for HIV-1-infected CCR5-Delta
32 heterozygotes is more favorable and that for CCR5 promoter allele 59029
A homozygotes is less favorable.
Methods: HIV-1-infected adults with a CD4+ lymphocyte count greater than or
equal to 200 cells x 10(6)/l and a plasma HIV RNA level greater than or eq
ual to 1000 copies/ml were treated with indinavir, zidovudine and lamivudin
e for 6 months. HIV RNA levels were measured at 4-week intervals. Genotypin
g for chemokine receptor gene polymorphisms (CCR5-Delta 32, CCR5 59029A/G,
CCR2-64l) was performed. We examined whether the time to first HIV RNA < 20
0 copies/ml, frequency of viral suppression failure (HIV RNA greater than o
r equal to 200 copies/ mi between weeks 16 and 28 of therapy), or reduction
from the pre-treatment HIV RNA level differed by genotype.
Results: Time to first HIV RNA < 200 copies/ml was not predicted by genotyp
e. Among 272 Caucasian patients, viral suppression failure was more common
among patients with the CCR5 +/+ / CCR2+/+ \ CCR5-59029 A/A genotype (28%)
than among all other subjects combined (relative risk, 2.0; P = 0.06). Afte
r 24 weeks of therapy, genotype groups differed in the reduction of the HIV
RNA level from baseline (P = 0.02); patients with the CCR5 +/+ / CCR2+/+ \
CCR5-59029 A/A genotype had a mean reduction of 2.12 log(10) copies/ml com
pared to 2.64 log(10) copies/ml among all other groups combined.
Conclusion: Polymorphisms in chemokine receptor genes may explain some of t
he heterogeneity in sustaining viral suppression observed among patients re
ceiving potent antiretroviral therapy. (C) 2000 Lippincott Williams & Wilki
ns.