Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052

PLOS ONE, Dec 2019

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 HIV infection.

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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 - 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)


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Philip J. Palumbo, Ethan A. Wilson, Estelle Piwowar-Manning, Marybeth McCauley, Theresa Gamble, Newton Kumwenda, Joseph Makhema, Nagalingeswaran Kumarasamy, Suwat Chariyalertsak, James G. Hakim, Mina C. Hosseinipour, Marineide G. Melo, Sheela V. Godbole, Jose H. Pilotto, Beatriz Grinsztejn, Ravindre Panchia, Ying Q. Chen, Myron S. Cohen, Susan H. Eshleman, Jessica M. Fogel. Association of HIV diversity and virologic outcomes in early antiretroviral treatment: HPTN 052, PLOS ONE, 2017, Volume 12, Issue 5, DOI: 10.1371/journal.pone.0177281