Effects of plasma HIV RNA, CD4(+) T lymphocytes, and the chemokine receptors CCR5 and CCR2b on HIV disease progression in hemophiliacs

We have investigated the effects of plasma HIV RNA, CD4(+) T lymphocytes an d chemokine receptors CCR5 and CCR2b on HIV disease progression in hemophil iacs. We prospectively observed during follow-up 207 HIV-infected hemophili acs in the Hemophilia Growth and Development Study. Plasma HIV RNA was meas ured on cryopreserved plasma from enrollment using the Chiron Corporation b DNA (version 2.0) assay. Genoytpe variants CCR2b-64I and CCR5-Delta 32 were detected using standard molecular techniques. Those with the mutant allele for CCR2b, and to a lesser extent CCR5, had lower plasma HIV RNA, and high er CD4(+) T lymphocytes than did those without these genetic variants. Afte r controlling for the effects of plasma HIV RNA and CD4(+) T lymphocytes, t hose with the CCR2b mutant allele compared with those wild-type, had a tren d toward a lower risk of progression to AIDS, adjusted relative hazard of 1 .94 (95% confidence interval [CI], 0.9-4.18; p = .092), and AIDS-related de ath, relative hazard 1.97 (95% CI, 0.98-4.00; p = .059). We conclude that p lasma HIV RNA, CD4(+) T lymphocytes, and CCR genotypes are correlated, and the protective affect of CCR2b against HIV disease progression is not compl etely explained by plasma HIV RNA or CD4(+) T-lymphocyte number.