TY - JOUR
T1 - Differences in HIV-1 pol sequences from female genital tract and blood during antiretroviral therapy
AU - De Pasquale, Maria Pia
AU - Brown, Andrew J Leigh
AU - Cu Uvin, Susan
AU - Allega-Ingersoll, Jessica
AU - Caliendo, Angela M.
AU - Sutton, Lorraine
AU - Donahue, Shannon
AU - D'Aquila, Richard T.
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2003/9/1
Y1 - 2003/9/1
N2 - Objective: To determine whether HIV-1 replicates locally in the female genital tract during therapy, and to study whether endocervix is the dominant source of virus in cervicovaginal lavage fluid. Design: Sequence analyses of HIV-1 pol were performed from cervicovaginal secretions and blood plasma of HIV-infected women failing antiretroviral therapy with detectable viral load in both compartments, as well as from drug-naive subjects. Methods: Viral RNA was extracted from cervicovaginal lavage fluid, endocervical secretions collected by Sno-strips, and blood plasma. Population sequencing of HIV-1 pol was performed using cycle sequencing. Drug resistance mutations were analyzed. Phylogenies were constructed based on synonymous positions in the sequences. Results: Resistant virus was detected concordantly in blood and genital tract specimens, consistent with drug selection pressure in both compartments. However, drug-selected mutations often differed in each compartment, and phylogenetic analysis showed differences in virus lineage in these compartments, consistent with local replication in female genital tract. Viruses in cervicovaginal lavage and endocervical secretions were genetically distinguishable, suggesting that endocervix is not the only source of virus found in cervicovaginal lavage. Conclusion: These data support the hypothesis that HIV replication is compartmentalized within the female genital tract during antiretroviral therapy, which has implications for pathogenesis and for epidemiologic surveillance of drug-resistant virus.
AB - Objective: To determine whether HIV-1 replicates locally in the female genital tract during therapy, and to study whether endocervix is the dominant source of virus in cervicovaginal lavage fluid. Design: Sequence analyses of HIV-1 pol were performed from cervicovaginal secretions and blood plasma of HIV-infected women failing antiretroviral therapy with detectable viral load in both compartments, as well as from drug-naive subjects. Methods: Viral RNA was extracted from cervicovaginal lavage fluid, endocervical secretions collected by Sno-strips, and blood plasma. Population sequencing of HIV-1 pol was performed using cycle sequencing. Drug resistance mutations were analyzed. Phylogenies were constructed based on synonymous positions in the sequences. Results: Resistant virus was detected concordantly in blood and genital tract specimens, consistent with drug selection pressure in both compartments. However, drug-selected mutations often differed in each compartment, and phylogenetic analysis showed differences in virus lineage in these compartments, consistent with local replication in female genital tract. Viruses in cervicovaginal lavage and endocervical secretions were genetically distinguishable, suggesting that endocervix is not the only source of virus found in cervicovaginal lavage. Conclusion: These data support the hypothesis that HIV replication is compartmentalized within the female genital tract during antiretroviral therapy, which has implications for pathogenesis and for epidemiologic surveillance of drug-resistant virus.
KW - Anatomic compartmentalization
KW - Drug resistance
KW - Female genital tract
KW - HIV
KW - Pol
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U2 - 10.1097/00126334-200309010-00005
DO - 10.1097/00126334-200309010-00005
M3 - Article
C2 - 14501791
AN - SCOPUS:0041412835
SN - 1525-4135
VL - 34
SP - 37
EP - 44
JO - Journal of Acquired Immune Deficiency Syndromes
JF - Journal of Acquired Immune Deficiency Syndromes
IS - 1
ER -