Abstract:

The introduction of Maraviroc which is a CCR5 antagonists as an antiretroviral drug necessitates the need to study HIV tropism for other HIV 1 subtypes especially those present in other countries in South East Asia and Sub Saharan Africa which accounts for a majority of the burden of the infection. The study under review was undertaken to evaluate HIV-1 co-receptor tropism in the developing world where non-B subtypes predominate, in order to assess the therapeutic and prophylactic potential of CCR5 antagonists in these regions.

In this vain, this review aims to highlight the prevalence of R5 and X4-tropic HIV-1 among samples obtained from patients with HIV-1 subtype C infection from India and South Africa, and with subtype A/A1 and D infection from Uganda, and to explore the demographic and clinical characteristics associated with R5 infection. In addition, the review will also highlight the ability of the Trofile® assay to determine tropism of non-B subtypes of HIV-1, which previously had not been explored in a large study.

References:

1.      Brumme ZL, Goodrich J, Mayer HB, Brumme CJ, Henrick BM, Wynhoven B, Asselin JJ, Cheung PK, Hogg RS, Montaner JS, Harrigan PR. Molecular and clinical epidemiology of CXCR4-using HIV-1 in a large population of antiretroviral-naive individuals. J Infect Dis. 2005;15:466–474. doi: 10.1086/431519. [PubMed] [Cross Ref]

2.      Buonaguro L, Tornesello ML, Buonaguro FM. Human immunodeficiency virus type 1 subtype distribution in the worldwide epidemic: pathogenetic and therapeutic implications. J Virol.2007;15:10209–10219. doi: 10.1128/JVI.00872-07. [PMC free article] [PubMed] [Cross Ref]

3.      Cornelissen M, Mulder-Kampinga G, Veenstra J, Zorgdrager F, Kuiken C, Hartman S, Dekker J, van der HL, Sol C, Coutinho R. Syncytium-inducing (SI) phenotype suppression at seroconversion after intramuscular inoculation of a non-syncytium-inducing/SI phenotypically mixed human immunodeficiency virus population. J Virol. 1995;15:1810–1818. [PMC free article] [PubMed]

4.      Coakley E, Petropoulos CJ, Whitcomb JM. Assessing chemokine co-receptor usage in HIV. Curr Opin Infect Dis. 2005;15:9–15. doi: 10.1097/00001432-200502000-00003. [PubMed] [Cross Ref]

5.      de Roda Husman AM, Koot M, Cornelissen M, Keet IP, Brouwer M, Broersen SM, Bakker M, Roos MT, Prins M, de Wolf F, Miedema F, Goudsmit J, Schuitemaker H. Association between CCR5 genotype and the clinical course of HIV-1 infection. Ann Intern Med. 1997;15:882–890.[PubMed]

6.      Hu DJ, Buve A, Baggs J, van der GG, Dondero TJ. What role does HIV-1 subtype play in transmission and pathogenesis? An epidemiological perspective. AIDS. 1999;15:873–881. doi: 10.1097/00002030-199905280-00002. [PubMed] [Cross Ref]

7.      Kaleebu P, French N, Mahe C, Yirrell D, Watera C, Lyagoba F, Nakiyingi J, Rutebemberwa A, Morgan D, Weber J, Gilks C, Whitworth J. Effect of human immunodeficiency virus (HIV) type 1 envelope subtypes A and D on disease progression in a large cohort of HIV-1-positive persons in Uganda. J Infect Dis. 2002;15:1244–1250. doi: 10.1086/340130. [PubMed] [Cross Ref]

8.      Keet IP, Krijnen P, Koot M, Lange JM, Miedema F, Goudsmit J, Coutinho RA. Predictors of rapid progression to AIDS in HIV-1 seroconverters. AIDS. 1993;15:51–57. doi: 10.1097/00002030-199301000-00008. [PubMed] [Cross Ref]

9.      Kijak GH, McCutchan FE. HIV diversity, molecular epidemiology, and the role of recombination.Curr Infect Dis Rep. 2005;15:480–488. doi: 10.1007/s11908-005-0051-8. [PubMed] [Cross Ref]

10.  Nielsen C, Pedersen C, Lundgren JD, Gerstoft J. Biological properties of HIV isolates in primary HIV infection: consequences for the subsequent course of infection. AIDS. 1993;15:1035–1040. doi: 10.1097/00002030-199308000-00002. [PubMed] [Cross Ref]

11.  Moyle GJ, Wildfire A, Mandalia S, Mayer H, Goodrich J, Whitcomb J, Gazzard BG. Epidemiology and predictive factors for chemokine receptor use in HIV-1 infection. J Infect Dis. 2005;15:866–872. doi: 10.1086/428096. [PubMed] [Cross Ref]

12.  Moore JP, Kitchen SG, Pugach P, Zack JA. The CCR5 and CXCR4 coreceptors--central to understanding the transmission and pathogenesis of human immunodeficiency virus type 1 infection. AIDS Res Hum Retroviruses. 2004;15:111–126. doi: 10.1089/088922204322749567. [PubMed][Cross Ref]

13.  Ranga U. Human immunodeficiency virus-1 subtypes: could genetic diversity translate to differential pathogenesis. J Indian Inst Sci. 2002;15:73–91.

14.  Spira S, Wainberg MA, Loemba H, Turner D, Brenner BG. Impact of clade diversity on HIV-1 virulence, antiretroviral drug sensitivity and drug resistance. J Antimicrob Chemother. 2003;15:229–240. doi: 10.1093/jac/dkg079. [PubMed] [Cross Ref]

15.  Thomson MM, Perez-Alvarez L, Najera R. Molecular epidemiology of HIV-1 genetic forms and its significance for vaccine development and therapy. Lancet Infect Dis. 2002;15:461–471. doi: 10.1016/S1473-3099(02)00343-2. [PubMed] [Cross Ref]