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Journal of Virology, May 1999, p. 4393-4403, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
Subtypes of Human Immunodeficiency Virus Type 1 and
Disease Stage among Women in Nairobi, Kenya
Joel R.
Neilson,1
Grace C.
John,2
Jean K.
Carr,3
Paul
Lewis,1
Joan K.
Kreiss,2,4
Stephanie
Jackson,1
Ruth W.
Nduati,5
Dorothy
Mbori-Ngacha,5
Dana D.
Panteleeff,1
Sharon
Bodrug,6
Christina
Giachetti,6
Martha A.
Bott,6
Barbra A.
Richardson,7
Job
Bwayo,8
Jeckoniah
Ndinya-Achola,8 and
Julie
Overbaugh1,*
Departments of
Microbiology,1
Medicine,2
Epidemiology,4 and
Biostatistics,7 University of
Washington, Seattle, Washington; Henry M. Jackson
Foundation Research Laboratory, Rockville,
Maryland3; Gen-Probe, Incorporated,
San Diego, California6; and Departments
of Pediatrics5 and Medical
Microbiology,8 University of Nairobi, Nairobi,
Kenya
Received 20 October 1998/Accepted 4 February 1999
In sub-Saharan Africa, where the effects of human immunodeficiency
virus type 1 (HIV-1) have been most devastating, there are multiple
subtypes of this virus. The distribution of different subtypes within
African populations is generally not linked to particular risk
behaviors. Thus, Africa is an ideal setting in which to examine the
diversity and mixing of viruses from different subtypes on a population
basis. In this setting, it is also possible to address whether
infection with a particular subtype is associated with differences in
disease stage. To address these questions, we analyzed the HIV-1
subtype, plasma viral loads, and CD4 lymphocyte levels in 320 women
from Nairobi, Kenya. Subtype was determined by a combination of
heteroduplex mobility assays and sequence analyses of envelope genes,
using geographically diverse subtype reference sequences as well as
envelope sequences of known subtype from Kenya. The distribution of
subtypes in this population was as follows: subtype A, 225 (70.3%);
subtype D, 65 (20.5%); subtype C, 22 (6.9%); and subtype G, 1 (0.3%). Intersubtype recombinant envelope genes were detected
in 2.2% of the sequences analyzed. Given that the sequences analyzed
represented only a small fraction of the proviral genome, this suggests
that intersubtype recombinant viral genomes may be very common in Kenya
and in other parts of Africa where there are multiple subtypes. The
plasma viral RNA levels were highest in women infected with subtype C
virus, and women infected with subtype C virus had significantly lower
CD4 lymphocyte levels than women infected with the other subtypes. Together, these data suggest that women in Kenya who are infected with
subtype C viruses are at more advanced stages of immunosuppression than women infected with subtype A or D. There are at least two models
to explain the data from this cross-sectional study; one is that
infection with subtype C is associated with a more rapid disease
progression, and the second is that subtype C represents an older
epidemic in Kenya. Discriminating between these possibilities in a
longitudinal study will be important for increasing our understanding of the role of specific subtypes in the transmission and pathogenesis of HIV-1.
*
Corresponding author. Present address: Program in
Molecular Medicine, Fred Hutchinson Cancer Research Center, 1100 Fairview Ave. N., Seattle, WA 98195. Phone: (206) 667-4418. Fax: (206) 667-6524. E-mail: joverbau{at}fhcrc.org.
Journal of Virology, May 1999, p. 4393-4403, Vol. 73, No. 5
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.
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