Impact of HIV-1 Viral Subtype on Disease Progression and Response to Antiretroviral Therapy

Overview

Journal J Int AIDS Soc

Specialty Infectious Diseases

Date 2010 Mar 9

PMID 20205896

Citations 67

Authors

Philippa J Easterbrook

Mel Smith

Jane Mullen

Siobhan OShea

Ian Chrystie

Annemiek de Ruiter

Iain D Tatt

Anna Maria Geretti

Mark Zuckerman

Affiliations

Soon will be listed here.

Abstract

Background: Our intention was to compare the rate of immunological progression prior to antiretroviral therapy (ART) and the virological response to ART in patients infected with subtype B and four non-B HIV-1 subtypes (A, C, D and the circulating recombinant form, CRF02-AG) in an ethnically diverse population of HIV-1-infected patients in south London.

Methods: A random sample of 861 HIV-1-infected patients attending HIV clinics at King's and St Thomas' hospitals' were subtyped using an in-house enzyme-linked immunoassay and env sequencing. Subtypes were compared on the rate of CD4 cell decline using a multi-level random effects model. Virological response to ART was compared using the time to virological suppression (< 400 copies/ml) and rate of virological rebound (> 400 copies/ml) following initial suppression.

Results: Complete subtype and epidemiological data were available for 679 patients, of whom 357 (52.6%) were white and 230 (33.9%) were black African. Subtype B (n = 394) accounted for the majority of infections, followed by subtypes C (n = 125), A (n = 84), D (n = 51) and CRF02-AG (n = 25). There were no significant differences in rate of CD4 cell decline, initial response to highly active antiretroviral therapy and subsequent rate of virological rebound for subtypes B, A, C and CRF02-AG. However, a statistically significant four-fold faster rate of CD4 decline (after adjustment for gender, ethnicity and baseline CD4 count) was observed for subtype D. In addition, subtype D infections showed a higher rate of virological rebound at six months (70%) compared with subtypes B (45%, p = 0.02), A (35%, p = 0.004) and C (34%, p = 0.01)

Conclusions: This is the first study from an industrialized country to show a faster CD4 cell decline and higher rate of subsequent virological failure with subtype D infection. Further studies are needed to identify the molecular mechanisms responsible for the greater virulence of subtype D.

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References

Kantor R . Impact of HIV-1 pol diversity on drug resistance and its clinical implications. Curr Opin Infect Dis. 2006; 19(6):594-606. DOI: 10.1097/QCO.0b013e3280109122. View

Tscherning C, Alaeus A, Fredriksson R, Bjorndal A, Deng H, Littman D . Differences in chemokine coreceptor usage between genetic subtypes of HIV-1. Virology. 1998; 241(2):181-8. DOI: 10.1006/viro.1997.8980. View

Spira S, Wainberg M, Loemba H, Turner D, Brenner B . Impact of clade diversity on HIV-1 virulence, antiretroviral drug sensitivity and drug resistance. J Antimicrob Chemother. 2003; 51(2):229-40. DOI: 10.1093/jac/dkg079. View

Aggarwal I, Smith M, Tatt I, Murad S, Osner N, Geretti A . Evidence for onward transmission of HIV-1 non-B subtype strains in the United Kingdom. J Acquir Immune Defic Syndr. 2006; 41(2):201-9. DOI: 10.1097/01.qai.0000179430.34660.11. View

Monno L, Brindicci G, Caputo S, Punzi G, Scarabaggio T, Riva C . HIV-1 subtypes and circulating recombinant forms (CRFs) from HIV-infected patients residing in two regions of central and southern Italy. J Med Virol. 2005; 75(4):483-90. DOI: 10.1002/jmv.20300. View

Balotta C, Facchi G, Violin M, van Dooren S, Cozzi-Lepri A, Forbici F . Increasing prevalence of non-clade B HIV-1 strains in heterosexual men and women, as monitored by analysis of reverse transcriptase and protease sequences. J Acquir Immune Defic Syndr. 2001; 27(5):499-505. DOI: 10.1097/00126334-200108150-00012. View

Pillay D, Walker A, Gibb D, de Rossi A, Kaye S, Ait-Khaled M . Impact of human immunodeficiency virus type 1 subtypes on virologic response and emergence of drug resistance among children in the Paediatric European Network for Treatment of AIDS (PENTA) 5 trial. J Infect Dis. 2002; 186(5):617-25. DOI: 10.1086/342680. View

Fleury H, Recordon-Pinson P, Caumont A, Faure M, Roques P, Plantier J . HIV type 1 diversity in France, 1999-2001: molecular characterization of non-B HIV type 1 subtypes and potential impact on susceptibility to antiretroviral drugs. AIDS Res Hum Retroviruses. 2003; 19(1):41-7. DOI: 10.1089/08892220360473952. View

Casper C, Naver L, Clevestig P, Belfrage E, Leitner T, Albert J . Coreceptor change appears after immune deficiency is established in children infected with different HIV-1 subtypes. AIDS Res Hum Retroviruses. 2002; 18(5):343-52. DOI: 10.1089/088922202753519124. View

10.

Kiwanuka N, Laeyendecker O, Robb M, Kigozi G, Arroyo M, McCutchan F . Effect of human immunodeficiency virus Type 1 (HIV-1) subtype on disease progression in persons from Rakai, Uganda, with incident HIV-1 infection. J Infect Dis. 2008; 197(5):707-13. DOI: 10.1086/527416. View

11.

Vasan A, Renjifo B, Hertzmark E, Chaplin B, Msamanga G, Essex M . Different rates of disease progression of HIV type 1 infection in Tanzania based on infecting subtype. Clin Infect Dis. 2006; 42(6):843-52. DOI: 10.1086/499952. View

12.

Parkin N, Schapiro J . Antiretroviral drug resistance in non-subtype B HIV-1, HIV-2 and SIV. Antivir Ther. 2004; 9(1):3-12. View

13.

Gao Y, Paxinos E, Galovich J, Troyer R, Baird H, Abreha M . Characterization of a subtype D human immunodeficiency virus type 1 isolate that was obtained from an untreated individual and that is highly resistant to nonnucleoside reverse transcriptase inhibitors. J Virol. 2004; 78(10):5390-401. PMC: 400369. DOI: 10.1128/jvi.78.10.5390-5401.2004. View

14.

Thomson M, Perez-Alvarez L, Najera R . Molecular epidemiology of HIV-1 genetic forms and its significance for vaccine development and therapy. Lancet Infect Dis. 2002; 2(8):461-71. DOI: 10.1016/s1473-3099(02)00343-2. View

15.

Ping L, Nelson J, Hoffman I, Schock J, Lamers S, Goodman M . Characterization of V3 sequence heterogeneity in subtype C human immunodeficiency virus type 1 isolates from Malawi: underrepresentation of X4 variants. J Virol. 1999; 73(8):6271-81. PMC: 112705. DOI: 10.1128/JVI.73.8.6271-6281.1999. View

16.

Thomson M, Najera R . Travel and the introduction of human immunodeficiency virus type 1 non-B subtype genetic forms into Western countries. Clin Infect Dis. 2001; 32(12):1732-7. DOI: 10.1086/320764. View

17.

Laurent C, Bourgeois A, Faye M, Mougnutou R, Seydi M, Gueye M . No difference in clinical progression between patients infected with the predominant human immunodeficiency virus type 1 circulating recombinant form (CRF) 02_AG strain and patients not infected with CRF02_AG, in Western and West-Central Africa: a.... J Infect Dis. 2002; 186(4):486-92. DOI: 10.1086/341833. View

18.

Boyd A, Murad S, OShea S, de Ruiter A, Watson C, Easterbrook P . Ethnic differences in stage of presentation of adults newly diagnosed with HIV-1 infection in south London. HIV Med. 2005; 6(2):59-65. DOI: 10.1111/j.1468-1293.2005.00267.x. View

19.

Kaleebu P, French N, Mahe C, Yirrell D, Watera C, Lyagoba F . 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; 185(9):1244-50. DOI: 10.1086/340130. View

20.

Kaleebu P, Nankya I, Yirrell D, Shafer L, Kyosiimire-Lugemwa J, Lule D . Relation between chemokine receptor use, disease stage, and HIV-1 subtypes A and D: results from a rural Ugandan cohort. J Acquir Immune Defic Syndr. 2007; 45(1):28-33. DOI: 10.1097/QAI.0b013e3180385aa0. View