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Background. High human T lymphotropic virus (HTLV)–I provirus load (VL) has been associated with an
increased risk of HTLV-associated myelopathy, but little is known about variation in HTLV-I or -II VLs by demo-
graphic characteristics and risk behaviors.
Methods. We measured HTLV-I and HTLV-II VLs in a large cohort of 127 HTLV-I–seropositive and 328
HTLV-II–seropositive former blood donors, by use of real-time polymerase chain reaction using tax primers.
Multivariable linear regression was used to control for confounding by relevant covariates.
Results. The mean VLs were 3.28 log10 copies/106 peripheral blood mononuclear cells (PBMCs) (range, 0.5–
5.3 log10 copies/106 PBMCs) for HTLV-I and 2.60 log10 copies/106 PBMCs (range, 0.05–5.95 log10 copies/106 PBMCs)
for HTLV-II (P ! .0001). HTLV-II VLs were higher in those subjects with subtype A infection (mean, 2.82 log10
copies/106 PBMCs) than in those with subtype B infection (mean, 2.29 log10 copies/106 PBMCs) (P p .005). Higher
HTLV-I VL was associated with previous receipt of a blood transfusion (P p .04 ), and lower HTLV-II VL was
associated with female sex (P p .007 ). These associations persisted in virus-specific multivariate linear regression
models controlling for potential confounding variables.
Conclusions. VL was significantly higher in HTLV-I than in HTLV-II infection and was higher in HTLV-II
subtype A than in HTLV-II subtype B infection. Chronic HTLV VLs may be related to the infectious dose acquired
at the time of infection, with higher VLs following acquisition by blood transfusion and lower VLs following
sexual acquisition.
Human T lymphotropic virus (HTLV) types I and II mology but differ in their epidemiology and disease
are human type C retroviruses derived most likely from associations. HTLV-I is prevalent in Africa, the Carib-
simian-to-human transmission thousands of years ago bean, Brazil, and southern Japan and causes adult T
[1, 2]. The 2 HTLV types share ∼60% nucleotide ho- cell leukemia (ATL) and HTLV-associated myelopathy
(HAM) [3]. HTLV-II is prevalent among Amerindians,
African pygmies, and injection drug users (IDUs) in the
Received 24 December 2003; accepted 18 February 2004; electronically published Americas and Europe and has been linked to HAM, as
6 July 2004.
Financial support: National Heart, Lung, and Blood Institute Retrovirus Epi- well as to a higher occurrence of pneumonia and bron-
demiology Donor Study (research contracts N01-HB-97077 [superseded by N01-HB- chitis [4, 5]. HTLV-II subtype A is more prevalent among
47114], N01-HB-97078, N01-HB-97079, N01-HB-97080, N01-HB-97081, N01-HB-
97082, and R01-HL-62235 [through the HTLV Outcomes Study]). North American and European IDUs and their sex part-
a
Present affiliation: C.C.N. is retired from the American Red Cross Blood Services, ners, whereas subtype B is more prevalent among Native
Chesapeake and Potomac Region.
b
HOST investigators are listed after the text.
Americans [4].
Reprints or correspondence: Dr. Edward L. Murphy, c/o Blood Centers of the Pacific, HTLV-I and -II viral RNA is low to undetectable in
UCSF, 270 Masonic Ave., San Francisco, CA 94118 (murphy@itsa.ucsf.edu).
human serum, and viral propagation is thought to oc-
The Journal of Infectious Diseases 2004; 190:504–10
2004 by the Infectious Diseases Society of America. All rights reserved.
cur via the clonal expansion of lymphocytes with in-
0022-1899/2004/19003-0012$15.00 tegrated proviral DNA [6] or the transfer of viral RNA
RESULTS
VLs and epidemiologic data were available for 127 subjects with
HTLV-I and 328 subjects with HTLV-II (∼85 % of the HTLV Figure 1. Difference in human T lymphotropic virus (HTLV) provirus load
(VL) between HTLV-I– and HTLV-II–infected subjects (P ! .0001), from the
cohort). Demographic and risk factor characteristics of the sub-
baseline visit of the HTLV Outcomes Study (HOST). VL is presented as
jects are presented in table 1. Most subjects were middle-aged median (central line), 25th and 75th percentiles (box boundaries), and 10th
and women, and there was a substantial proportion of black and 90th percentiles (error bars). PBMCs, peripheral blood mononuclear
persons in both HTLV groups and of Hispanic persons in the cells.
history of IDU, or history of sex with an IDU. In the multi- that HTLV-I VLs were significantly higher than HTLV-II VLs
variate linear regression analysis, HTLV-I VL retained its as- and that HTLV-II VLs were significantly higher in subtype A
sociation with a history of blood transfusion (b p 0.68; P p than in subtype B infections. Analyses by demographic and
.02) but had only a borderline association with white race (b behavioral characteristics revealed higher HTLV-I VLs in those
p ⫺0.51; P p .06). subjects with a history of blood transfusion and borderline
HTLV-II VLs were significantly lower among women (mean lower HTLV-I VLs in white subjects. HTLV-II VLs were sig-
[SE], 2.45 [0.10] log10 copies/106 PBMCs) than among men nificantly lower in women than in men. There was a borderline
(mean [SE], 3.02 [0.18] log10 copies/106 PBMCs; P p .007; figure association of lower VLs with increasing numbers of sex part-
2C). There was no association between HTLV-II VL and age, ners, but this did not persist after adjusting for covariates.
race, number of sex partners, history of IDU, or history of sex HTLV-I VLs have been reported in numerous studies, rang-
with an IDU. In the multivariate linear regression analysis, HTLV- ing from !1 copy/10,000 lymphocytes to 11 copy/10 lympho-
II VL remained independently and inversely associated with fe- cytes [6, 9, 10, 14]. The results of the present study are con-
male sex (b p ⫺0.68; P p .01) and positively associated with sistent with those of previous reports, with a mean HTLV-I VL
HTLV-II subtype A (b p 0.54; P p .008). In an analysis re- of ∼1000 copies/106 PBMCs and a range of 1–100,000 copies/
stricted to women only, there was an inverse association be- 106 PBMCs. By use of an end-point dilution PCR assay, a
tween HTLV-II VL and increasing number of sex partners (b previous study revealed VLs of 20–200,000 copies/106 PBMCs
p ⫺0.22; P p .03), which did not persist after adjusting for in 49 subjects with HTLV-II, with and without HIV coinfection
other covariates (b p ⫺0.18; P p .12), although the association [17]. A competitive PCR assay found 50–162,390 copies/106
with HTLV-II subtype A remained (b p 0.65; P p .004). PBMCs in Italian IDUs [16], and those with the highest VLs
were found to have clonal expansion of HTLV-II–infected lym-
DISCUSSION
phocytes [29]. These VL results are also similar to those of the
The present study of HTLV VLs at the baseline visit of a large present study.
cohort of generally asymptomatic former blood donors found In the only other comparative study of HTLV-I and HTLV-