404b
HIV Subtype D Is Associated with a Higher Risk for Dementia than Subtype A in Sub-Saharan Africa
Ned Sacktor*1, N Nakasujja2, M Rezapour1, R Skolasky1, S Musisi2, E Katabira2, K Robertson3, D Clifford4, O Laeyendecker1, and T Quinn1
1Johns Hopkins Univ, Baltimore, MD, US; 2Makerere Univ, Kampala, Uganda; 3Univ of North Carolina at Chapel Hill, US; and 4Washington Univ, St Louis, MO, US
Background: I n East Africa, HIV clades A, C, and D
are the predominant subtypes, unlike the US where it is clade B. Subtype D
infection has been associated with a more rapid fall of CD4 cell count and
progression to death compared to subtype A. Differences in co-receptor usage
may explain the differences in progression rates, as the probability of having
an X4 virus is higher in subtype D infections than in subtype A infections. The
effect of HIV subtype on the risk of HIV dementia has not been examined.
Methods: Plasma samples of 60 unselected ART-naive
HIV+ individuals from Kampala, Uganda with a CD4 count £200 cells/µL had subtype assignments
generated by sequence analysis based on a portion of gag (HXB2 nt 1240 to 1907)
and gp41 (HXB2 nt 7867 to 8283) regions. All individuals underwent a
comprehensive clinical evaluation included a medical history, neurological
examination, neuropsychological test battery (8 tests) and functional
assessments. Exclusion criteria included age <18 years, fever >37.5oC,
a history of a central nervous system opportunistic infection, and chronic
neurologic or severe psychiatric or medical illness.
Results: A total of 33 individuals were infected
with subtype A, 2 with subtype C, 9 with subtype D, and 16 with A/D
recombinants as defined by having a discordant subtype assignment in the gag
and gp41 fragments for a given individual. There were no differences in mean
age (A: D; 33.9, 35.9 years), education (A:D; 9.0, 9.6 years), (gender, % male
A:D; 27, 44%) CD4 count (A:D; 107, 93 cells/µL) or log plasma HIV RNA level
(A:D; 5.1, 4.9 copies/mL) between the subtype A- and subtype D-infected
individuals. Of 9 subjects, 8 (89%) with subtype D had dementia compared to 7
of 33 (24%) with subtype A (p = 0.004).
Conclusions: These findings suggest that in
untreated HIV patients at a similar stage of disease, HIV dementia may be more
common among those patients with subtype D than those with subtype A. These
results provide the first evidence to demonstrate that HIV subtypes in
well-characterized patients may have different biological properties with
respect to their capacity to cause HIV-associated cognitive impairment. Further
studies are needed to confirm this observation, to define the precise mechanism
by which subtype D may lead to an increased risk of neuropathogenesis and to
determine the rate of progression of HIV-associated neurological complications
in patients with specific HIV subtypes.
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