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HIV DRUG RESISTANCE IN ADULTS RECEIVING EARLY VS. DELAYED ANTIRETROVIRAL THERAPY: HPTN 052
Palumbo, Philip J. et al. | Date Issued: 2017
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
Department of Pathology. Johns Hopkins University School of Medicine. Baltimore, USA.
Department of Pathology. Johns Hopkins University School of Medicine. Baltimore, USA.
Department of Pathology. Johns Hopkins University School of Medicine. Baltimore, USA.
Vaccine and Infectious Disease Division. Fred Hutchinson Cancer Research Center. Seattle, USA.
Frontier Science and Technology Research Foundation. Amherst. NY, USA.
Frontier Science and Technology Research Foundation. Amherst, NY, USA.
Department of Pathology. Johns Hopkins University School of Medicine. Baltimore, USA.
Specialty Molecular Division. Lancet Laboratories and BARC-SA. Johannesburg, South Africa.
HIV Pathogenesis Research Unit. Faculty of Health Sciences. University of the Witwatersrand. Johannesburg, South Africa.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
Y. R. Gaitonde Centre for AIDS Research and Education. Chennai, India.
National Institute for Research in Tuberculosis, Chennai. India.
Department of Medicine. University of North Carolina at Chapel Hill. Chapel Hill, USA.
Department of Specialty Services. Southwest CARE Center. Santa Fe, USA.
HPTN Leadership and Operations Center. Washington, DC, USA.
HPTN Leadership and Operations Center. Durham, USA.
Division of Infectious Diseases. University of North Carolina at Chapel Hill. Chapel Hill, USA / UNC Project-Malawi. Institute for Global Health and Infectious Diseases. Lilongwe, Malawi.
CART CRS, YRGCARE Medical Centre. VHS. Chennai, India.
Department of Medicine. University of Zimbabwe. Harare, Zimbabwe.
Hospital Geral de Nova Iguaçu. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratorio de AIDS e Imunologia Molecular. Rio de Janeiro, RJ, Brasil.
College of Medicine-Johns Hopkins Project. Blantyre, Malawi.
Kenya Medical Research Institute (KEMRI)-Centers for Disease Control (CDC). Kisumu, Kenya.
Department of Epidemiology and Biostatistics. National AIDS Research Institute (ICMR). Pune, India.
Hospital Nossa Senhora da Conceição. Departamento de Doenças Infecciosas. Porto Alegre, RS, Brasil.
Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.
Perinatal HIV Research Unit. University of the Witwatersrand. Soweto HPTN CRS. Soweto, South Africa.
Research Institute for Health Sciences. Chiang Mai University. Chiang Mai, Thailand.
Botswana-Harvard AIDS Institute Partnership. Gaborone, Botswana.
Clinical HIV Research Unit. Department of Internal Medicine. School of Clinical Medicine. Faculty of Health Sciences. University of Witwatersrand. Johannesburg, South Africa.
Vaccine and Infectious Disease Division. Fred Hutchinson Cancer Research Center. Seattle, WA.
Department of Medicine. University of North Carolina at Chapel Hill. Chapel Hill, USA.
Department of Pathology. Johns Hopkins University School of Medicine. Baltimore, 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
 
Later version
https://www.arca.fiocruz.br/handle/icict/63710
Citation
PALUMBO, Philip J. et al. HIV drug resistance in adults receiving early versus delayed antirretroviral therapy: HPTN 052. Journal of Acquired Immune Deficiency Syndromes, v. 77, n. 5, p. 1-31, 2017.
DOI
10.1097/QAI.0000000000001623
ISSN
1525-4135