PMID- 28891813
OWN - NLM
STAT- MEDLINE
DCOM- 20171019
LR  - 20180619
IS  - 1558-8238 (Electronic)
IS  - 0021-9738 (Linking)
VI  - 127
IP  - 10
DP  - 2017 Oct 2
TI  - No evidence of HIV replication in children on antiretroviral therapy.
PG  - 3827-3834
LID - 10.1172/JCI94582 [doi]
LID - 94582 [pii]
AB  - It remains controversial whether current antiretroviral therapy (ART) fully
      suppresses the cycles of HIV replication and viral evolution in vivo. If
      replication persists in sanctuary sites such as the lymph nodes, a high priority 
      should be placed on improving ART regimes to target these sites. To investigate
      the question of ongoing viral replication on current ART regimens, we analyzed
      HIV populations in longitudinal samples from 10 HIV-1-infected children who
      initiated ART when viral diversity was low. Eight children started ART at less
      than ten months of age and showed suppression of plasma viremia for seven to nine
      years. Two children had uncontrolled viremia for fifteen and thirty months,
      respectively, before viremia suppression, and served as positive controls for HIV
      replication and evolution. These latter 2 children showed clear evidence of virus
      evolution, whereas multiple methods of analysis bore no evidence of virus
      evolution in any of the 8 children with viremia suppression on ART. Phylogenetic 
      trees simulated with the recently reported evolutionary rate of HIV-1 on ART of 6
      x 10-4 substitutions/site/month bore no resemblance to the observed data. Taken
      together, these data refute the concept that ongoing HIV replication is common
      with ART and is the major barrier to curing HIV-1 infection.
FAU - Van Zyl, Gert U
AU  - Van Zyl GU
AD  - Division of Medical Virology, Stellenbosch University and National Health
      Laboratory Service (NHLS) Tygerberg, Cape Town, South Africa.
FAU - Katusiime, Mary Grace
AU  - Katusiime MG
AD  - Division of Medical Virology, Stellenbosch University and National Health
      Laboratory Service (NHLS) Tygerberg, Cape Town, South Africa.
FAU - Wiegand, Ann
AU  - Wiegand A
AD  - HIV Dynamics and Replication Program, National Cancer Institute (NCI), Frederick,
      Maryland, USA.
FAU - McManus, William R
AU  - McManus WR
AD  - HIV Dynamics and Replication Program, National Cancer Institute (NCI), Frederick,
      Maryland, USA.
FAU - Bale, Michael J
AU  - Bale MJ
AD  - HIV Dynamics and Replication Program, National Cancer Institute (NCI), Frederick,
      Maryland, USA.
FAU - Halvas, Elias K
AU  - Halvas EK
AD  - Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
FAU - Luke, Brian
AU  - Luke B
AD  - Advanced Biomedical Computing Center, Leidos Biomedical Research Inc. and
      Frederick National Laboratories for Cancer Research, Frederick, Maryland, USA.
FAU - Boltz, Valerie F
AU  - Boltz VF
AD  - HIV Dynamics and Replication Program, National Cancer Institute (NCI), Frederick,
      Maryland, USA.
FAU - Spindler, Jonathan
AU  - Spindler J
AD  - HIV Dynamics and Replication Program, National Cancer Institute (NCI), Frederick,
      Maryland, USA.
FAU - Laughton, Barbara
AU  - Laughton B
AD  - Department Pediatrics and Child Health, Tygerberg Children's Hospital and Family 
      Clinical Research Unit, Stellenbosch University, Cape Town, South Africa.
FAU - Engelbrecht, Susan
AU  - Engelbrecht S
AD  - Division of Medical Virology, Stellenbosch University and National Health
      Laboratory Service (NHLS) Tygerberg, Cape Town, South Africa.
FAU - Coffin, John M
AU  - Coffin JM
AD  - Department of Molecular Biology and Microbiology, Tufts University, Boston,
      Massachusetts, USA.
FAU - Cotton, Mark F
AU  - Cotton MF
AD  - Department Pediatrics and Child Health, Tygerberg Children's Hospital and Family 
      Clinical Research Unit, Stellenbosch University, Cape Town, South Africa.
FAU - Shao, Wei
AU  - Shao W
AD  - Advanced Biomedical Computing Center, Leidos Biomedical Research Inc. and
      Frederick National Laboratories for Cancer Research, Frederick, Maryland, USA.
FAU - Mellors, John W
AU  - Mellors JW
AD  - Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.
FAU - Kearney, Mary F
AU  - Kearney MF
AD  - HIV Dynamics and Replication Program, National Cancer Institute (NCI), Frederick,
      Maryland, USA.
LA  - eng
GR  - U01 CA200441/CA/NCI NIH HHS/United States
GR  - R35 CA200421/CA/NCI NIH HHS/United States
GR  - HHSN261200800001C/RC/CCR NIH HHS/United States
GR  - HHSN261200800001E/CA/NCI NIH HHS/United States
GR  - R01 MH105134/MH/NIMH NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
DEP - 20170911
PL  - United States
TA  - J Clin Invest
JT  - The Journal of clinical investigation
JID - 7802877
RN  - 0 (Anti-Retroviral Agents)
SB  - AIM
SB  - IM
MH  - Anti-Retroviral Agents/*administration & dosage
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - HIV Infections/*drug therapy/genetics/metabolism
MH  - HIV-1/*physiology
MH  - Humans
MH  - Infant
MH  - Infant, Newborn
MH  - Male
MH  - *Viremia/drug therapy/genetics/metabolism
MH  - Virus Replication/*drug effects
PMC - PMC5617669
EDAT- 2017/09/12 06:00
MHDA- 2017/10/20 06:00
CRDT- 2017/09/12 06:00
PHST- 2017/04/13 00:00 [received]
PHST- 2017/07/26 00:00 [accepted]
PHST- 2017/09/12 06:00 [pubmed]
PHST- 2017/10/20 06:00 [medline]
PHST- 2017/09/12 06:00 [entrez]
AID - 94582 [pii]
AID - 10.1172/JCI94582 [doi]
PST - ppublish
SO  - J Clin Invest. 2017 Oct 2;127(10):3827-3834. doi: 10.1172/JCI94582. Epub 2017 Sep
      11.