Genetic characterization of rebounding human immunodeficiency virus type 1 in plasma during multiple interruptions of highly active antiretroviral therapy.
Various strategies of interrupting highly active antiretroviral therapy (HAART) are being investigated for the treatment of human immunodeficiency virus (HIV) infection. Interruptions of greater than 2 weeks frequently result in rebound of plasma HIV RNA. In order to discern changes in the viral population that might occur during cycles of treatment interruption, we evaluated the homology of HIV-1 envelope gene sequences over time in 12 patients who received four to seven cycles of 4 weeks off HAART followed by 8 weeks on HAART by using the heteroduplex tracking assay and novel statistical tools. HIV populations in 9 of 12 patients diverged from those found in the first cycle in at least one subsequent cycle. The substantial genetic changes noted in HIV env did not correlate with increased or decreased log changes in levels of plasma HIV RNA (P > 0.5). Thus, genetic changes in HIV env itself did not contribute in a systematic way to changes in levels of plasma viremia from cycle to cycle of treatment interruption. In addition, the data suggest that there may be multiple compartments contributing to the rebound of plasma viremia and to viral diversity from cycle to cycle of intermittent therapy.
Dybul
Mark
M
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA. mdybul@nih.gov
Daucher
Marybeth
M
Jensen
Mark A
MA
Hallahan
Claire W
CW
Chun
Tae-Wook
TW
Belson
Michael
M
Hidalgo
Bertha
B
Nickle
David C
DC
Yoder
Christian
C
Metcalf
Julia A
JA
Davey
Richard T
RT
Ehler
Linda
L
Kress-Rock
Diane
D
Nies-Kraske
Elizabeth
E
Liu
Shuying
S
Mullins
James I
JI
Fauci
Anthony S
AS
D023241:Antiretroviral Therapy, Highly Active / Q000379:methods*; D004334:Drug Administration Schedule; D015752:Genes, env / Q000235:genetics; D014644:Genetic Variation; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000187:drug effects / Q000235:genetics*; D020180:Heteroduplex Analysis; D006801:Humans; D012367:RNA, Viral / Q000097:blood; D012008:Recurrence; D017422:Sequence Analysis, DNA; D019562:Viral Load
D012367:RNA, Viral