Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/63710

Type
Article
Copyright
Open access
Collections
Share

Statistics
Metadata
Show full item record

HIV DRUG RESISTANCE IN ADULTS RECEIVING EARLY VERSUS DELAYED ANTIRETROVIRAL THERAPY: HPTN 052
Palumbo, Philip J. et al. | Date Issued: 2018
Author
Palumbo, Philip J.
Fogel, Jessica M.
Hudelson, Sarah E.
Wilson, Ethan A.
Hart, Stephen
Hovind, Laura
Piwowar-Manning, Estelle
Wallis, Carole
Papathanasopoulos, Maria A.
Morgado, Mariza G.
Saravanan, Shanmugam
Tripathy, Srikanth
Eron, Joseph J.
Gallant, Joel E.
McCauley, Marybeth
Gamble, Theresa
Hosseinipour, Mina C.
Kumarasamy, Nagalingeswaran
Hakim, James G.
Pilotto, Jose H.
Kumwenda, Johnstone
Akelo, Victor
Godbole, Sheela V.
Santos, Breno R.
Grinsztejn, Beatriz
Panchia, Ravindre
Chariyalertsak, Suwat
Makhema, Joseph
Badal-Faesen, Sharlaa
Chen, Ying Q.
Cohen, Myron S.
Eshleman, Susan H.
Affilliation
Johns Hopkins University School of Medicine. Department of Pathology. Baltimore, MD, USA.
Johns Hopkins University School of Medicine. Department of Pathology. Baltimore, MD, USA.
Johns Hopkins University School of Medicine. Department of Pathology. Baltimore, MD, USA.
Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA.
Frontier Science and Technology Research Foundation. Amherst, NY, USA.
Frontier Science and Technology Research Foundation. Amherst, NY, USA.
Johns Hopkins University School of Medicine. Department of Pathology. Baltimore, MD, USA.
Lancet Laboratories and BARC-SA. Specialty Molecular Division. Johannesburg, South Africa.
University of the Witwatersrand. Faculty of Health Sciences. HIV Pathogenesis Research Unit. Johannesburg, South Africa.
Oswaldo Cruz Foundation. Oswaldo Cruz Institute. Laboratory of AIDS and Molecular Immunology. Rio de Janeiro, RJ, Brazil.
Y. R. Gaitonde Centre for AIDS Research and Education. Chennai, India.
National Institute for Research in Tuberculosis. Chennai, India.
University of North Carolina at Chapel Hill. Department of Medicine. Chapel Hill, NC, USA.
Southwest CARE Center. Department of Specialty Services. Santa Fe, NM, USA.
HPTN Leadership and Operations Center. Washington, DC, USA.
HPTN Leadership and Operations Center. Durham, NC, USA.
University of North Carolina at Chapel Hill. Division of Infectious Diseases. Chapel Hill, NC, USA / Institute for Global Health and Infectious Diseases. UNC Project-Malawi. Lilongwe, Malawi.
CART CRS. YRGCARE Medical Centre. VHS, Chennai, India.
University of Zimbabwe. Department of Medicine. Harare, Zimbabwe.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Hospital Geral de Nova Iguaçu. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
College of Medicine-Johns Hopkins Project. Blantyre, Malawi.
Kenya Medical Research Institute. Centers for Disease Control. Kisumu, Kenya.
National AIDS Research Institute. Department of Epidemiology and Biostatistics. Pune, India.
Hospital Nossa Senhora da Conceição. Departamento de Doenças Infecciosas. Porto Alegre, RS, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Rio de Janeiro, RJ, Brasil.
University of the Witwatersrand. Soweto HPTN CRS. Perinatal HIV Research Unit. Soweto, South Africa.
Chiang Mai University. Research Institute for Health Sciences. Chiang Mai, Thailand.
Botswana-Harvard AIDS Institute Partnership. Gaborone, Botswana.
University of Witwatersrand. Faculty of Health Sciences. School of Clinical Medicine. Department of Internal Medicine. Clinical HIV Research Unit. Johannesburg, South Africa.
Fred Hutchinson Cancer Research Center. Vaccine and Infectious Disease Division. Seattle, WA, USA.
University of North Carolina at Chapel Hill. Department of Medicine. Chapel Hill, NC, USA.
Johns Hopkins University School of Medicine. Department of Pathology. Baltimore, MD, USA.
Abstract
Introduction: We evaluated HIV drug resistance in adults who received early vs. delayed antiretroviral therapy (ART) in a multinational trial [HIV Prevention Trials Network (HPTN) 052, enrollment 2005-2010]. In HPTN 052, 1763 index participants were randomized to start ART at a CD4 cell count of 350-550 cells/mm (early ART arm) or <250 cells/mm (delayed ART arm). In May 2011, interim study results showed benefit of early ART, and all participants were offered ART regardless of CD4 cell count; the study ended in 2015. Methods: Virologic failure was defined as 2 consecutive viral loads >1000 copies/mL >24 weeks after ART initiation. Drug resistance testing was performed for pretreatment (baseline) and failure samples from participants with virologic failure. Results: HIV genotyping results were obtained for 211/249 participants (128 early ART arm and 83 delayed ART arm) with virologic failure. Drug resistance was detected in 4.7% of participants at baseline; 35.5% had new resistance at failure. In univariate analysis, the frequency of new resistance at failure was lower among participants in the early ART arm (compared with delayed ART arm, P = 0.06; compared with delayed ART arm with ART initiation before May 2011, P = 0.032). In multivariate analysis, higher baseline viral load (P = 0.0008) and ART regimen (efavirenz/lamivudine/zidovudine compared with other regimens, P = 0.024) were independently associated with higher risk of new resistance at failure. Conclusions: In HPTN 052, the frequency of new drug resistance at virologic failure was lower in adults with early ART initiation. The main factor associated with reduced drug resistance with early ART was lower baseline viral load.
Keywords
HIV
HPTN 052
Early ART
Virologic failure
Resistance
 
Publisher
Lippincott Williams & Wilkins
Citation
PALUMBO, Philip J. et al. HIV drug resistance in adults receiving early versus delayed antiretroviral therapy: HPTN 052. Journal of Acquired Immune Deficiency Syndromes, v. 77, n. 5, p. 1-19, Apr. 2018.
Previous version
https://www.arca.fiocruz.br/handle/icict/29102
DOI
10.1097/QAI.0000000000001623
ISSN
1525-4135
Notes
Conflicts of Interest: None of the authors has a conflict of interest, with the following exceptions: CW served as a consultant for Celera for development of software updates related to the HIV drug resistance algorithm used with the ViroSeq HIV-1 Genotyping System. JJE receives honoraria for advisory board membership from Bristol-Myers Squibb, Gilead Sciences, Janssen Therapeutics, Merck & Co., ViiV Healthcare and research support from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Therapeutics, Merck & Co., Sangamo BioSciences, ViiV Healthcare through contracts to the University of North Carolina. JEG receives honoraria for advisory board membership from Bristol-Myers Squibb, Gilead Sciences, Theratechnologies, Merck & Co., ViiV Healthcare. JEG’s organization receives research support from AbbVie, Bristol-Myers Squibb, Gilead Sciences, Janssen Therapeutics, Merck & Co., Sangamo BioSciences, ViiV Healthcare. 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 investigators from Abbott Diagnostics on research studies. For the remaining authors none were declared.