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, Oliver B. Laeyendecker, Merlin Robb, Godfrey Kigozi, Miguel Arroyo, Francine McCutchan, Leigh Anne Eller, Michael Eller, Fred Makumbi, Deborah Birx, Fred Wabwire-Mangen, David Serwadda, Nelson K. Sewankambo, Thomas C Quinn, Maria J Wawer, Ronald H Gray

Research output: Contribution to journalArticle

Abstract

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; P = .022). 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.

Original languageEnglish (US)
Pages (from-to)707-713
Number of pages7
JournalJournal of Infectious Diseases
Volume197
Issue number5
DOIs
StatePublished - Mar 1 2008

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Uganda
Virus Diseases
Disease Progression
HIV-1
Acquired Immunodeficiency Syndrome
Confidence Intervals
CD4 Lymphocyte Count
Viral Load
Virulence
Vaccines
HIV

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health
  • Immunology

Cite this

Effect of human immunodeficiency virus type 1 (HIV-1) subtype on disease progression in persons from Rakai, Uganda, with incident HIV-1 infection. / Kiwanuka, Noah; Laeyendecker, Oliver B.; Robb, Merlin; Kigozi, Godfrey; Arroyo, Miguel; McCutchan, Francine; Eller, Leigh Anne; Eller, Michael; Makumbi, Fred; Birx, Deborah; Wabwire-Mangen, Fred; Serwadda, David; Sewankambo, Nelson K.; Quinn, Thomas C; Wawer, Maria J; Gray, Ronald H.

In: Journal of Infectious Diseases, Vol. 197, No. 5, 01.03.2008, p. 707-713.

Research output: Contribution to journalArticle

Kiwanuka, N, Laeyendecker, OB, Robb, M, Kigozi, G, Arroyo, M, McCutchan, F, Eller, LA, Eller, M, Makumbi, F, Birx, D, Wabwire-Mangen, F, Serwadda, D, Sewankambo, NK, Quinn, TC, Wawer, MJ & Gray, RH 2008, 'Effect of human immunodeficiency virus type 1 (HIV-1) subtype on disease progression in persons from Rakai, Uganda, with incident HIV-1 infection', Journal of Infectious Diseases, vol. 197, no. 5, pp. 707-713. https://doi.org/10.1086/527416
Kiwanuka, Noah ; Laeyendecker, Oliver B. ; Robb, Merlin ; Kigozi, Godfrey ; Arroyo, Miguel ; McCutchan, Francine ; Eller, Leigh Anne ; Eller, Michael ; Makumbi, Fred ; Birx, Deborah ; Wabwire-Mangen, Fred ; Serwadda, David ; Sewankambo, Nelson K. ; Quinn, Thomas C ; Wawer, Maria J ; Gray, Ronald H. / Effect of human immunodeficiency virus type 1 (HIV-1) subtype on disease progression in persons from Rakai, Uganda, with incident HIV-1 infection. In: Journal of Infectious Diseases. 2008 ; Vol. 197, No. 5. pp. 707-713.
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abstract = "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; P = .022). 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.",
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T1 - Effect of human immunodeficiency virus type 1 (HIV-1) subtype on disease progression in persons from Rakai, Uganda, with incident HIV-1 infection

AU - Kiwanuka, Noah

AU - Laeyendecker, Oliver B.

AU - Robb, Merlin

AU - Kigozi, Godfrey

AU - Arroyo, Miguel

AU - McCutchan, Francine

AU - Eller, Leigh Anne

AU - Eller, Michael

AU - Makumbi, Fred

AU - Birx, Deborah

AU - Wabwire-Mangen, Fred

AU - Serwadda, David

AU - Sewankambo, Nelson K.

AU - Quinn, Thomas C

AU - Wawer, Maria J

AU - Gray, Ronald H

PY - 2008/3/1

Y1 - 2008/3/1

N2 - 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; P = .022). 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.

AB - 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; P = .022). 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.

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