Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052
May
Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052
Philip J. Palumbo 0 2 3
Ethan A. Wilson 0 1 3
Estelle Piwowar-Manning 0 2 3
Marybeth McCauley 0 3
Theresa Gamble 0 3
Newton Kumwenda 0 3 4
Joseph Makhema 0 3
Nagalingeswaran Kumarasamy 0 3
Suwat Chariyalertsak 0 3 5
James G. Hakim 0 3
Mina C. Hosseinipour 0 3
Marineide G. Melo 0 3
Sheela V. Godbole 0 3
Jose H. Pilotto 0 3
Beatriz Grinsztejn 0 3
Ravindre Panchia 0 3
Ying Q. Chen 0 3
Myron S. Cohen 0 3
Susan H. Eshleman 0 2 3
Jessica M. Fogel 0 2 3
0 HIV infection
1 Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle , Washington, United States of America, 3 Science Facilitation Department, FHI 360, Washington DC, United States of America, 4 Science Facilitation Department , FHI 360, Durham, North Carolina , United States of America
2 Dept. of Pathology, Johns Hopkins Univ. School of Medicine , Baltimore, Maryland , United States of America
3 Editor: Alan Landay, Rush University , UNITED STATES
4 College of Medicine-Johns Hopkins Project, Blantyre, Malawi, 6 Botswana-Harvard AIDS Institute Partnership , Gaborone, Botswana, 7 CART CRS , YRGCARE Medical Centre, VHS , Chennai , India
5 Research Institute for Health Sciences, Chiang Mai University , Chiang Mai , Thailand , 9 Dept. of Medicine, Univ. of Zimbabwe , Harare , Zimbabwe , 10 Division of Infectious Diseases, Univ. of North Carolina at Chapel Hill, Chapel Hill, North Carolina, United States of America, 11 UNC Project-Malawi, Institute for Global Health and Infectious Diseases , Lilongwe , Malawi , 12 Hospital Nossa Senhora da ConceicËão, ServicËo de Infectologia, Porto Alegre, Brazil, 13 National AIDS Research Institute (ICMR) , Pune , India , 14 Hospital Geral de Nova Iguacu and Laboratorio de AIDS e Imunologia Molecular-IOC/Fiocruz , Rio de Janeiro , Brazil , 15 Instituto Nacional de Infectologia Evandro Chagas-INI-Fiocruz , Rio de Janeiro , Brazil , 16 Univ. of the Witwatersrand, Perinatal HIV Research Unit , Soweto HPTN CRS, Soweto , South Africa , 17 Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle , Washington, United States of America, 18 Dept. of Medicine, Univ. of North Carolina at Chapel Hill , Chapel Hill, North Carolina , United States of America
Higher HIV diversity has been associated with virologic outcomes in children on antiretroviral treatment (ART). We examined the association of HIV diversity with virologic outcomes in adults from the HPTN 052 trial who initiated ART at CD4 cell counts of 350±550 cells/ mm3. A high resolution melting (HRM) assay was used to analyze baseline (pre-treatment) HIV diversity in six regions in the HIV genome (two in gag, one in pol, and three in env) from 95 participants who failed ART. We analyzed the association of HIV diversity in each genomic region with baseline (pre-treatment) factors and three clinical outcomes: time to virologic suppression after ART initiation, time to ART failure, and emergence of HIV drug resistance at ART failure. After correcting for multiple comparisons, we did not find any association of baseline HIV diversity with demographic, laboratory, or clinical characteristics. For the 18 analyses performed for clinical outcomes evaluated, there was only one significant association: higher baseline HIV diversity in one of the three HIV env regions was associated with longer time to ART failure (p = 0.008). The HRM diversity assay may be useful in future studies exploring the relationship between HIV diversity and clinical outcomes in individuals with
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Data Availability Statement: The data generated
from this study are available in the Supplemental
files.
Funding: This work was supported by the grants
from the Division of AIDS of the U.S. National
Institute of Allergy and Infectious Diseases (NIAID);
and by the Office of AIDS Research of the U.S.
National Institutes of Health (NIH) [UM1-AI068613
(Eshleman); UM1-AI068617 (Donnell); and
UM1AI068619 (Cohen/El-Sadr)]. Study drugs used in
HPTN 052 were donated by Abbott Laboratories,
Boehringer-Ingelheim Pharmaceuticals, Inc,
Bristol-Myers Squibb, Gilead Sciences, Inc.,
GlaxoSmithKline/ViiV Healthcare, and Merck & Co.,
Inc. The funders had no role in study design, data
collection and analysis, decision to publish, or
preparation of the manuscript.
Competing interests: The authors have declared
that no competing interests exist, with the
following exceptions: MCH has received honoraria
for advisory board membership from ViiV
healthcare. MSC receives honoraria for advisory
board membership from Janssen Global Services,
Roche Molecular Systems, and Merck Research.
SHE has collaborated with Abbott Diagnostics on
evaluation of HIV-related assays; Abbott
Diagnostics has provided reagents for other
research studies. This does not alter our adherence
to PLOS ONE policies on sharing data and
materials.
Introduction
HIV genetic diversity generally increases with d (...truncated)