Relationship Between HIV Coreceptor Tropism and Disease Progression in Persons with Untreated Chronic HIV Infection

Overview

Journal J Acquir Immune Defic Syndr

Specialty Infectious Diseases

Date 2009 Feb 6

PMID 19194318

Citations 26

Authors

Matthew Bidwell Goetz

Robert Leduc

Jay R Kostman

Ann M Labriola

Yolanda Lie

Jodi Weidler

Eoin Coakley

Michael Bates

Roberta Luskin-Hawk

Affiliations

Soon will be listed here.

Abstract

Objective: To assess the effect of HIV coreceptor tropism (CRT) on the relative risk of progression to a composite outcome of CD4 count < or =350 cells per microliter, treatment initiation, or death.

Methods: CRT assays were performed after study closure in baseline samples obtained from enrollees in a prospectively monitored cohort of treatment-naive adults with > or =450 CD4 cells per microliter and > or =1000 HIV-1 RNA copies per milliliter.

Results: Dual/mixed (D/M) and R5 CRT were detected in 32 and 282 patients, respectively. The baseline CD4 count (617 versus 694 cells/microL; P = 0.05) differed in patients with D/M versus R5 CRT. Otherwise, baseline laboratory characteristics were similar.The relative risk of progression to the composite end point was 2.15 (P = 0.002) for D/M versus R5 CRT, 2.07 per 1.0 log10 higher viral load (P < 0.001) and 0.87 per 50 cells per microliter higher CD4 cell count (P < 0.001). The effect of D/M CRT was also significant in separate analyses of time to initiation of antiretroviral therapy or CD4 cell count < or =350 cells per microliter.

Conclusions: Untreated patients with D/M rather than R5 CRT had a faster rate of disease progression, whether assessed by a composite outcome of time to CD4 count < or =350 cells per microliter, treatment initiation, or death or by separate analyses of time to CD4 count < or =350 cells per microliter or treatment initiation.

Citing Articles

Unraveling clinical outcomes of long-term cART treatment in HIV-1 patients with or without the Brazilian GWGR motif in the V3 loop.

Folgosi V, Komninakis S, Lopes L, Monteiro M, Assone T, Fonseca L Rev Inst Med Trop Sao Paulo. 2024; 66:e38.

PMID: 39052025 PMC: 11251515. DOI: 10.1590/S1678-9946202466038.

Quasispecies Nature of RNA Viruses: Lessons from the Past.

Singh K, Mehta D, Dumka S, Chauhan A, Kumar S Vaccines (Basel). 2023; 11(2).

PMID: 36851186 PMC: 9963406. DOI: 10.3390/vaccines11020308.

Targeting CCR5 as a Component of an HIV-1 Therapeutic Strategy.

Mohamed H, Gurrola T, Berman R, Collins M, Sariyer I, Nonnemacher M Front Immunol. 2022; 12():816515.

PMID: 35126374 PMC: 8811197. DOI: 10.3389/fimmu.2021.816515.

Role of pretreatment variables on plasma HIV RNA value at the sixth month of antiretroviral therapy including all first line drugs in HIV naïve patients: A path analysis approach.

Mengoli C, Basso M, Andreis S, Scaggiante R, Cruciani M, Ferretto R PLoS One. 2019; 14(3):e0213160.

PMID: 30856186 PMC: 6411145. DOI: 10.1371/journal.pone.0213160.

HIV-1 coreceptor tropism: A syllogistic connection with The Veterans Aging Cohort Study Index and the CD4/CD8 ratio.

Leone A, De Gennaro N, Fabrizio C, Scudeller L, Lepore L, Lagioia A PLoS One. 2019; 14(2):e0212882.

PMID: 30818365 PMC: 6394994. DOI: 10.1371/journal.pone.0212882.

References

Hunt P, Harrigan P, Huang W, Bates M, Williamson D, McCune J . Prevalence of CXCR4 tropism among antiretroviral-treated HIV-1-infected patients with detectable viremia. J Infect Dis. 2006; 194(7):926-30. DOI: 10.1086/507312. View

Koot M, Keet I, Vos A, de Goede R, Roos M, Coutinho R . Prognostic value of HIV-1 syncytium-inducing phenotype for rate of CD4+ cell depletion and progression to AIDS. Ann Intern Med. 1993; 118(9):681-8. DOI: 10.7326/0003-4819-118-9-199305010-00004. View

Richman D, Bozzette S . The impact of the syncytium-inducing phenotype of human immunodeficiency virus on disease progression. J Infect Dis. 1994; 169(5):968-74. DOI: 10.1093/infdis/169.5.968. View

Daar E, Lynn H, Donfield S, Lail A, OBrien S, Huang W . Stromal cell-derived factor-1 genotype, coreceptor tropism, and HIV type 1 disease progression. J Infect Dis. 2005; 192(9):1597-605. DOI: 10.1086/496893. View

Blaak H, vant Wout A, Brouwer M, Hooibrink B, Hovenkamp E, Schuitemaker H . In vivo HIV-1 infection of CD45RA(+)CD4(+) T cells is established primarily by syncytium-inducing variants and correlates with the rate of CD4(+) T cell decline. Proc Natl Acad Sci U S A. 2000; 97(3):1269-74. PMC: 15592. DOI: 10.1073/pnas.97.3.1269. View

Shepherd J, Jacobson L, Qiao W, Jamieson B, Phair J, Piazza P . Emergence and persistence of CXCR4-tropic HIV-1 in a population of men from the multicenter AIDS cohort study. J Infect Dis. 2008; 198(8):1104-12. PMC: 2753263. DOI: 10.1086/591623. View

Jensen M, Li F, van t Wout A, Nickle D, Shriner D, He H . Improved coreceptor usage prediction and genotypic monitoring of R5-to-X4 transition by motif analysis of human immunodeficiency virus type 1 env V3 loop sequences. J Virol. 2003; 77(24):13376-88. PMC: 296044. DOI: 10.1128/jvi.77.24.13376-13388.2003. View

Bleul C, Wu L, Hoxie J, Springer T, Mackay C . The HIV coreceptors CXCR4 and CCR5 are differentially expressed and regulated on human T lymphocytes. Proc Natl Acad Sci U S A. 1997; 94(5):1925-30. PMC: 20019. DOI: 10.1073/pnas.94.5.1925. View

Skrabal K, Low A, Dong W, Sing T, Cheung P, Mammano F . Determining human immunodeficiency virus coreceptor use in a clinical setting: degree of correlation between two phenotypic assays and a bioinformatic model. J Clin Microbiol. 2006; 45(2):279-84. PMC: 1829003. DOI: 10.1128/JCM.01118-06. View

10.

Taylor Jr J, Kimbrell K, SCOGGINS R, Delaney M, Wu L, Camerini D . Expression and function of chemokine receptors on human thymocytes: implications for infection by human immunodeficiency virus type 1. J Virol. 2001; 75(18):8752-60. PMC: 115120. DOI: 10.1128/jvi.75.18.8752-8760.2001. View

11.

OBrien S, Nelson G . Human genes that limit AIDS. Nat Genet. 2004; 36(6):565-74. DOI: 10.1038/ng1369. View

12.

Sufka S, Ferrari G, Gryszowka V, Wrin T, Fiscus S, Tomaras G . Prolonged CD4+ cell/virus load discordance during treatment with protease inhibitor-based highly active antiretroviral therapy: immune response and viral control. J Infect Dis. 2003; 187(7):1027-37. DOI: 10.1086/368359. View

13.

. Differences in CD4 cell counts at seroconversion and decline among 5739 HIV-1-infected individuals with well-estimated dates of seroconversion. J Acquir Immune Defic Syndr. 2003; 34(1):76-83. DOI: 10.1097/00126334-200309010-00012. View

14.

Alexander L, Weiskopf E, Greenough T, Gaddis N, Auerbach M, Malim M . Unusual polymorphisms in human immunodeficiency virus type 1 associated with nonprogressive infection. J Virol. 2001; 74(9):4361-76. PMC: 111953. DOI: 10.1128/jvi.74.9.4361-4376.2000. View

15.

Hughes M, Johnson V, Hirsch M, Bremer J, Elbeik T, Erice A . Monitoring plasma HIV-1 RNA levels in addition to CD4+ lymphocyte count improves assessment of antiretroviral therapeutic response. ACTG 241 Protocol Virology Substudy Team. Ann Intern Med. 1997; 126(12):929-38. DOI: 10.7326/0003-4819-126-12-199706150-00001. View

16.

Connor R, Mohri H, Cao Y, Ho D . Increased viral burden and cytopathicity correlate temporally with CD4+ T-lymphocyte decline and clinical progression in human immunodeficiency virus type 1-infected individuals. J Virol. 1993; 67(4):1772-7. PMC: 240220. DOI: 10.1128/JVI.67.4.1772-1777.1993. View

17.

Benito J, Lopez M, Soriano V . The role of CD8+ T-cell response in HIV infection. AIDS Rev. 2004; 6(2):79-88. View

18.

Brumme Z, Goodrich J, Mayer H, Brumme C, Henrick B, Wynhoven B . Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of antiretroviral-naive individuals. J Infect Dis. 2005; 192(3):466-74. DOI: 10.1086/431519. View

19.

Correa R, Munoz-Fernandez M . Viral phenotype affects the thymic production of new T cells in HIV-1-infected children. AIDS. 2001; 15(15):1959-63. DOI: 10.1097/00002030-200110190-00007. View

20.

Ioannidis J, Rosenberg P, Goedert J, Ashton L, Benfield T, Buchbinder S . Effects of CCR5-Delta32, CCR2-64I, and SDF-1 3'A alleles on HIV-1 disease progression: An international meta-analysis of individual-patient data. Ann Intern Med. 2001; 135(9):782-95. DOI: 10.7326/0003-4819-135-9-200111060-00008. View