Chemokine (C-C motif) receptor 5 -2459 genotype in patients receiving highly active antiretroviral therapy: race-specific influence on virologic success.

BACKGROUND: In patients receiving highly active antiretroviral therapy (HAART), antiretroviral drug-metabolizing enzyme and transporter gene polymorphisms, as well as chemokine receptor gene polymorphisms, may influence response to treatment. METHODS: In a North American, treated, adherent human immunodeficiency virus (HIV)-positive cohort (self-identified whites, n = 175; blacks, n = 218), we investigated whether CYP2B6 (516G>T, 983T>C), UGT2B7 (IVS1+985A>G, 802C>T), MDR1 3435C>T, chemokine (C-C motif) receptor 2 (CCR2) 190G>A, and CCR5 (-2459G>A, Δ32) polymorphisms influenced the time to achieve virologic success (TVLS). RESULTS: No difference in TVLS was observed between races. In Kaplan-Meier analyses, only 516G>T (log-rank P = .045 for comparison of GG, GT, and TT and P = .02 GG + GT vs TT) and -2459G>A (log-rank P = .04 for GG, GA, and AA and P = .02 for GG + GA vs AA) genotypes were significantly associated with TVLS in black patients but not in white patients. However, in the Cox proportional hazards model that included age, sex, baseline CD4(+) T cell count, and baseline viral load, no significant association was observed between 516G>T and TVLS, whereas the association between -2459G>A and TVLS remained significant even after including CCR2 190G>A as well as all the drug-metabolizing enzyme and transporter genotypes. CONCLUSIONS: These findings suggest that CCR5 -2459G>A genotype had a strong, race-specific influence on TVLS in this cohort. Understanding the possible mechanisms underlying this influence requires further studies.

Molecular-based assay for simultaneous detection of four Plasmodium spp. and Wuchereria bancrofti infections.

Four major malaria-causing Plasmodium spp. and lymphatic filariasis-causing Wuchereria bancrofti are co-endemic in many tropical and sub-tropical regions. Among molecular diagnostic assays, multiplex polymerase chain reaction (PCR)-based assays for the simultaneous detection of DNAs from these parasite species are currently available only for P. falciparum and W. bancrofti or P. vivax and W. bancrofti. Using a post-PCR oligonucleotide ligation detection reaction-fluorescent microsphere assay (LDR-FMA), we developed a multiplex assay that has the capability to simultaneously detect all four Plasmodium spp. and W. bancrofti infections in blood samples. Compared with microfilarial positivity in the blood, the LDR-FMA assay is highly concordant (91%), sensitive (86%), and specific (94%), and has high reproducibility for Plasmodium spp. (85-93%) and W. bancrofti (90%) diagnoses. The development of this assay for the simultaneous diagnosis of multiple parasitic infections enables efficient screening of large numbers of human blood and mosquito samples from co-endemic areas.