Associations of CCR5, CCR2, and Stromal Cell–Derived Factor 1 Genotypes with Human Immunodeficiency Virus Disease Progression in Patients Receiving Nucleoside Therapy

Lathey, Janet L.; Tierney, Camlin; Chang, Sheng-Yung; D’Aquila, Richard T.; Bettendorf, Daniel; Alexander, Heather C.; Santini, Christopher D.; Hughes, Angela M.; Barroga, Charlene F.; Spector, Stephen A.; Landes, Jeff E.; Katzenstein, David

doi:10.1086/324427

Cited by 24 publications

(27 citation statements)

References 21 publications

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“…Our results agree with the findings of Lathey et al [20] in that SDF1-3 ′ A genotype has no effect on HIV-1 load or CD4+ cell counts of patients under antiretroviral therapy.…”

Section: Sdf1-3 ′ a And Hiv-1 In Mexicanssupporting

confidence: 93%

“…The existence of HIV-1-infected patients homozygous for the Delta-32 allele [32,33] means that there are other coreceptors contributing to virus entry, like CXCR4, CCR1, CCR8, CCR2, and CCR3B [19,34,35] , despite the lack of CCR5. For this reason, at least in part, several studies have failed to correlate the SDF1-3 ′ A genotype to coreceptor usage [14,20,36] .…”

Section: Sdf1-3 ′ a And Hiv-1 In Mexicansmentioning

confidence: 99%

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Stromal Cell-Derived Factor-1-3′A Polymorphism Favors HIV-1 Infection in Mexican Women

et al. 2015

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Objective: To evaluate the association of the stromal cell-derived factor-1 (SDF1)-3′A polymorphism to HIV-1 infection, CD4+ T-lymphocyte counts, and viral load levels in a northwestern Mexican population. Methods: We investigated allele and genotype frequencies of the SDF1-3′A polymorphism in 634 mestizo individuals from Northwest Mexico (204 HIV-1 infected persons, 256 uninfected blood donors, and 174 uninfected female sex workers) by the PCR- RFLP method and compared them using a χ2 test. We also searched for correlations between the polymorphism and CD4+ T lymphocyte and viral load counts. Results: No differences were observed in the frequencies of alleles and genotypes between patients and controls. However, in female patients we found a significantly increased prevalence of both the A allele and GA heterozygous genotype compared to male patients, female blood donors, and female sex workers. Conclusion: Here we describe the association of the SDF1-3′A polymorphism with HIV-1 infection only in women, but not to CD4+ T-lymphocyte categories, viral load levels in patients with HIV-1/AIDS, or to exposure levels in female sex workers.

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“…Our results agree with the findings of Lathey et al [20] in that SDF1-3 ′ A genotype has no effect on HIV-1 load or CD4+ cell counts of patients under antiretroviral therapy.…”

Section: Sdf1-3 ′ a And Hiv-1 In Mexicanssupporting

confidence: 93%

Section: Sdf1-3 ′ a And Hiv-1 In Mexicansmentioning

confidence: 99%

Stromal Cell-Derived Factor-1-3′A Polymorphism Favors HIV-1 Infection in Mexican Women

et al. 2015

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“…Although these results appear inconsistent, it may be that the genetic polymorphisms studied have more affect on the individual's ability to maintain suppression or virologic profile rather than on the initial suppression after HAART. For example, in a recent paper by Lathey et al [27], there was no difference in HIV-RNA suppression by genotype, but there was a difference in the distribution of syncitium-inducing virus by CCR5 ∆32 genotype among patients receiving nucleosides. There may be further genetic characteristics of the host that need to be taken into account when examining determinants of maintaining suppressed virus.…”

Section: Methodologic Challengesmentioning

confidence: 96%

Virologic and immunologic response to highly active antiretroviral therapy

2004

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Highly active antiretroviral therapy (HAART) delays clinical progression by suppressing viral replication, measured by a substantial reduction in HIV RNA, allowing the immune system to reconstitute, measured in most studies by an increase in CD4 cells. These virologic and immunologic consequences do not occur uniformly among HAART users. Markers of HIV disease stage at the time of HAART initiation are critical determinants of the progression while receiving HAART. In this report, we review studies describing the heterogeneous virologic and immunologic progression after the initiation of HAART, discuss methodologic concerns in the study of the response of biomarkers, and update findings obtained in the Multicenter AIDS Cohort Study, which show that CD4 cell count, history of antiretroviral therapy, and age at the time of initiation are independent determinants of response.

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“…A large metaanalysis [31], however, showed that the CD4 count at HAART initiation is a major prognostic factor for clinical response to HAART, in terms of AIDS and death; viral load at commencement was prognostic of subsequent clinical progression only if ! 100 000 copies/mL.In our cohort, the cell phenotypes in terms of expression of CCR5 and the viral genotypes of the circulating strains of the patients in terms of R5 or X4 were not available [32,33]. The pathophysiological mechanism underlying the better virological response in D32 heterozygotes remains unclear.…”

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confidence: 90%

Improved virological response to highly active antiretroviral therapy in HIV‐1‐infected patients carrying the CCR5 Δ32 deletion

et al. 2007

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BackgroundPatients heterozygous for the C-C chemokine receptor 5 (CCR5) D32 deletion spontaneously progress less rapidly to AIDS and death than do wild-type patients. We investigated whether the CCR5 D32 deletion has an impact on immunological, virological and clinical responses to highly active antiretroviral therapy (HAART) in HIV-1-infected patients. Patients and methodsWe included in the study 565 HIV-1-infected patients from the French HIV-1 infected cohort with documented date of serconversion (SEROCO)/haemophiliacs HIV-1 infected (HEMOCO) cohorts, who started HAART after 1996. We investigated virological responses to HAART at 6 months (defined as a plasma HIV-1 RNA measurement below the threshold of detection or a 2 log HIV-1 RNA decrease) and at 12 months (defined as a plasma HIV-1 RNA measurement below the threshold of detection) and clinical response to HAART by Kaplan-Meier survival curves, with AIDS and death as outcomes. ResultsThe D32 heterozygous patients (n 5 83; 15%) had a better virological response to HAART than wild-type patients (73 vs 53% at 6 months, P 5 0.01; and 60 vs 44% at 12 months, P 5 0.01). This better virological response was still observed after adjustment for antiretroviral status (whether or not patients were naïve to antiretroviral therapy), year of HAART initiation, number of new antiretroviral drugs and baseline viral load. There was no statistical difference between heterozygous patients and wild-type patients in terms of survival and AIDS-free survival. ConclusionsCCR5 D32 heterozygous patients were more likely to have a virological response to HAART than wild-type patients at 6 and 12 months. However, this virological response did not produce better immunological and clinical responses. The long-term impact of the D32 deletion on survival in HIV-1-infected treated patients should be investigated in a meta-analysis. Introduction C-C chemokine receptor 5 (CCR5), a receptor for the bchemokine RANTES, macrophage inflammatory protein (MIP)-1a and MIP-1b, is the most important chemokine receptor used by R5 HIV-1 strains for entry into CD4 cells.A 32-bp deletion (CCR5 D32) in the gene encoding the CCR5 coreceptor has been described [1][2][3]. Homozygous CCR5 D32/CCR5 D32 subjects are highly resistant to HIV-1 infection, although a few cases of infection have been reported [4][5][6]. Heterozygotes (CCR5 wt/CCR5 D32) are susceptible to HIV-1 infection, but progress more slowly to AIDS and death than wild-type patients (CCR5 wt/CCR5 wt) [7][8][9][10] 213 expression at the cell surface is diminished in D32 heterozygous patients and early plasma HIV-RNA viral load is lower in these patients than in wild-type patients [11]; this may explain why spontaneous HIV disease progression is slower in heterozygotes [9,10]. Since 1996, the use of highly active antiretroviral therapy (HAART) has provided substantial immunological (in terms of CD4 increase), virological (in terms of decrease in viral load) and clinical benefits to HIV-1-infected patients [12][13][14][15][16][17][18][19][20][21][...

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Associations of CCR5, CCR2, and Stromal Cell–Derived Factor 1 Genotypes with Human Immunodeficiency Virus Disease Progression in Patients Receiving Nucleoside Therapy

Cited by 24 publications

References 21 publications

Stromal Cell-Derived Factor-1-3′A Polymorphism Favors HIV-1 Infection in Mexican Women

Stromal Cell-Derived Factor-1-3′A Polymorphism Favors HIV-1 Infection in Mexican Women

Virologic and immunologic response to highly active antiretroviral therapy

Improved virological response to highly active antiretroviral therapy in HIV‐1‐infected patients carrying the CCR5 Δ32 deletion

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