Clinical reactivations of herpes simplex virus type 2 infection and human immunodeficiency virus disease progression markers.
BACKGROUND
The natural history of HSV-2 infection and role of HSV-2 reactivations in HIV disease progression are unclear.


METHODS
Clinical symptoms of active HSV-2 infection were used to classify 1,938 HIV/HSV-2 co-infected participants of the Women's Interagency HIV Study (WIHS) into groups of varying degree of HSV-2 clinical activity. Differences in plasma HIV RNA and CD4+ T cell counts between groups were explored longitudinally across three study visits and cross-sectionally at the last study visit.


RESULTS
A dose dependent association between markers of HIV disease progression and degree of HSV-2 clinical activity was observed. In multivariate analyses after adjusting for baseline CD4+ T cell levels, active HSV-2 infection with frequent symptomatic reactivations was associated with 21% to 32% increase in the probability of detectable plasma HIV RNA (trend p = 0.004), an average of 0.27 to 0.29 log10 copies/ml higher plasma HIV RNA on a continuous scale (trend p<0.001) and 51 to 101 reduced CD4+ T cells/mm(3) over time compared to asymptomatic HSV-2 infection (trend p<0.001).


CONCLUSIONS
HIV induced CD4+ T cell loss was associated with frequent symptomatic HSV-2 reactivations. However, effect of HSV-2 reactivations on HIV disease progression markers in this population was modest and appears to be dependent on the frequency and severity of reactivations. Further studies will be necessary to determine whether HSV-2 reactivations contribute to acceleration of HIV disease progression.
Aumakhan
Bulbulgul
B
Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, United States of America. baumakhan@hivresearch.org
Gaydos
Charlotte A
CA
Quinn
Thomas C
TC
Beyrer
Chris
C
Benning
Lorie
L
Minkoff
Howard
H
Merenstein
Daniel J
DJ
Cohen
Mardge
M
Greenblatt
Ruth
R
Nowicki
Marek
M
Anastos
Kathryn
K
Gange
Stephen J
SJ
D000328:Adult; D015415:Biomarkers / Q000032:analysis; D018791:CD4 Lymphocyte Count; D018450:Disease Progression; D005260:Female; D015658:HIV Infections / Q000150:complications*; D006558:Herpes Genitalis / Q000150:complications*; D018258:Herpesvirus 2, Human / Q000502:physiology*; D006801:Humans; D008137:Longitudinal Studies; D012367:RNA, Viral / Q000097:blood; D014775:Virus Activation
D015415:Biomarkers; D012367:RNA, Viral