Effect of Human Immunodeficiency Virus Type 1 (HIV-1) Subtype on Disease Progression in Persons from Rakai, Uganda, with Incident HIV-1 Infection

[sharon sanders]

Thank you to the The Journal of Infectious Diseases


2008;197:707?713? 2008 by the Infectious Diseases Society of America. All rights reserved.
0022-1899/2008/19705-0015$15.00
DOI: 10.1086/527416

MAJOR ARTICLE
Effect of Human Immunodeficiency Virus Type 1 (HIV-1) Subtype on Disease Progression in Persons from Rakai, Uganda, with Incident HIV-1 Infection

Noah Kiwanuka,^1,5
Oliver Laeyendecker,^6,7
Merlin Robb,⁹
Godfrey Kigozi,¹
Miguel Arroyo,¹⁰
Francine McCutchan,¹⁰
Leigh Anne Eller,⁹
Michael Eller,⁹
Fred Makumbi,²
Deborah Birx,⁹
Fred Wabwire-Mangen,²
David Serwadda,²
Nelson K. Sewankambo,^3,4
Thomas C. Quinn,^6,7
Maria Wawer,⁸ and
Ronald Gray⁸
¹Rakai Health Sciences Program, Uganda Virus Research Institute, Entebbe, and ²School of Public Health and ³Department of Medicine and ⁴Clinical Epidemiology Unit, Faculty of Medicine, Makerere University, Kampala, Uganda; ⁵Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio; and ⁶National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Schools of ⁷Medicine and ⁸Public Health, Johns Hopkins University, Baltimore, ⁹Henry M. Jackson Foundation, Rockville, and ¹⁰Walter Reed Army Institute of Research, Silver Spring, Maryland
Background. Human immunodeficiency virus type 1 (HIV-1) subtypes differ in biological characteristics that may affect pathogenicity.

Methods. We determined the HIV-1 subtype?specific rates of disease progression among 350 HIV-1 seroconverters. Subtype, viral load, and CD4⁺ cell count were determined. Cox proportional hazards regression modeling was used to estimate adjusted hazard ratios (HRs) of progression to acquired immunodeficiency syndrome (AIDS) (defined as a CD4⁺ cell count of

250 cells/mm³) and to AIDS-associated death.

Results. A total of 59.1% of study subjects had subtype D strains, 15.1% had subtype A, 21.1% had intersubtype recombinant subtypes, 4.3% had multiple subtypes, and 0.3% had subtype C. Of the 350 subjects, 129 (37%) progressed to AIDS, and 68 (19.5%) died of AIDS. The median time to AIDS onset was shorter for persons with subtype D (6.5 years), recombinant subtypes (5.6 years), or multiple subtypes (5.8 years), compared with persons with subtype A (8.0 years;

). Relative to subtype A, adjusted HRs of progression to AIDS were 2.13 [95% confidence interval {CI}, 1.10?4.11] for subtype D, 2.16 [95% CI, 1.05?4.45] for recombinant subtypes, and 4.40 [95% CI, 1.71?11.3] for multiple subtypes. The risk of progression to death was significantly higher for subtype D (adjusted HR, 5.65; 95% CI, 1.37?23.4), recombinant subtypes (adjusted HR, 6.70; 95% CI, 1.56-28.8), and multiple subtypes (adjusted HR, 7.67; 95% CI, 1.27?46.3), compared with subtype A.

Conclusions. HIV disease progression is affected by HIV-1 subtype. This finding may impact decisions on when to initiate antiretroviral therapy and may have implications for future trials of HIV-1 vaccines aimed at slowing disease progression.


Received 3 July 2007; accepted 25 September 2007; electronically published 11 February 2008.

• (See the editorial commentary by Kuritzkes on pages 638?9.)
• Potential conflicts of interest: none reported.
  The contents of this article do not necessarily reflect the position or policies of the US Government; the US Army Medical Command, Department of the Army; the Henry M. Jackson Foundation; or the Fogarty Foundation, NIH.
  Presented in part: 13th Conference on Retroviruses and Opportunistic Infections, Denver, Colorado, 5?8 February 2006 (abstract 44LB.b); and 14th Conference on Retroviruses and Opportunistic Infections, Los Angeles, California, 25?8 February 2007 (abstract 307).
  Financial support: US Army Medical Research and Material Command, Department of the Army (cooperative agreement DAMD17?98-2?8007); Henry M. Jackson Foundation (grants 5D43TW00010 and 2 D 43 TW000010?19 from the Fogarty Foundation, National Institutes of Health [NIH]); Fogarty AIDS International Training and Research Program, Case Western Reserve University; and Division of Intramural Research, National Institute of Allergy and Infectious Diseases, NIH.

Reprints or correspondence: Dr. Noah Kiwanuka, Rakai Health Sciences Program, Uganda Virus Research Institute, PO Box 49, Entebbe, Uganda (nkiwanuka@rhsp.org).

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Daniel R. Kuritzkes. (2008) HIV‐1 Subtype as a Determinant of Disease Progression. The Journal of Infectious Diseases 197:5, 638-639
Online publication date: 1-Mar-2008.
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