THLBB05 - Oral Abstract Session
Effect of early versus delayed initiation of antiretroviral therapy (ART) on clinical outcomes in the HPTN 052 randomized clinical trial
Presented by Beatriz Grinsztejn (Brazil).
B. Grinsztejn1, M. Hosseinipour2, S. Swindells3, H. Ribaudo4, J. Eron5, Y.Q. Chen6, L. Wang6, S.-S. Ou6, M. Anderson6, M. McCauley7, T. Gamble8, N. Kumarasamy9, J. Hakim10, J. Kumwenda11, J. Pilotto12, S. Godbole13, S. Chariyalertsak14, B. Santos15, K. Mayer16, S. Eshleman17, E. Piwowar-Manning18, L. Cottle6, J. Makhema19, L. Mills20, R. Panchia21, I. Sanne22, V. Elharrar23, D. Havlir24, M.S. Cohen5, for the HPTN 052/ACTG Study Team
1Instituto de Pesquisa Clinica Evandro Chagas, Fiocruz, Rio de Janeiro, Brazil, 2UNC Project Malawi and University of North Carolina at Chapel Hill, Lilongwe, Malawi, 3University of Nebraska Medical Center, Omaha, United States, 4Center for Biostatistics in AIDS Research, Harvard School of Public Health, Boston, United States, 5University of North Carolina School of Medicine, Chapel Hill, United States, 6Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, United States, 7FHI 360, Washington, DC, United States, 8FHI 360, Durham, United States, 9YRG CARE Medical Centre, Chennai, India, 10University of Zimbabwe, Department of Medicine, Harare, Zimbabwe, 11College of Medicine Johns Hopkins Project, Blantyre, Malawi, 12Hospital Geral de Nova Iguaçu and Laboratorio de AIDS e Imunologia Molecular-IOC, Rio de Janeiro, Brazil, 13National AIDS Research Institute (ICMR), Pune, India, 14Research Institute for Health Sciences, Chiang Mai University, Chiang Mai, Thailand, 15Hospital Nossa Senhora da Conceição, Porto Alegre, Brazil, 16Fenway Health/Harvard Medical School, Boston, United States, 17Johns Hopkins School of Medicine, Department of Pathology, Baltimore, United States, 18Johns Hopkins University School of Medicine, Department of Pathology, Baltimore, United States, 19Botswana Harvard AIDS Institute, Gaborone, Botswana, 20KEMRI-CDC Research and Public Health Collaboration, CDC Division of HIV/AIDS Prevention, Kisumu, Kenya, 21Perinatal HIV Research Unit (PHRU), University of the Witwatersrand, Johannesburg, South Africa, 22University of Witswatersrand, Department of Medicine, Johannesburg, South Africa, 23National Institute of Allergy and Infectious Diseases, National Insti
Background: To inform optimal timing of ART initiation, we analyzed clinical outcomes during follow-up of HPTN 052 incorporating both AIDS and non-AIDS events related to HIV and ART.
Methods: HIV+ adults (CD4+350‐550/µL) from Africa, Asia, and South America were randomized to ART immediately or after CD4+ < 250/µL or AIDS (delayed). Primary clinical events were: death, WHO Stage 4, tuberculosis, severe bacterial infection, serious cardiovascular/vascular disease, serious liver disease, end stage renal disease, non‐AIDS malignancy, and diabetes mellitus. Secondary events were: WHO Stage 2/3, malaria, renal insufficiency, hepatic transaminitis, lipodystrophy, dyslipidemia, hypertension, peripheral neuropathy, lactic acidosis, and thrombocytopenia. Distributions of time to first clinical event were estimated using Kaplan-Meier method; treatment comparisons used log-rank tests. Incidence rates were estimated by arm (with 95% confidence intervals); robust standard errors accommodated repeated events.
Results: 1761 participants accrued 4038 person years follow-up (FU); median FU of 2.1 years; median CD4 at ART initiation was 230/µL and 442/µL in the delayed and immediate arms. 134 individuals experienced at least one primary clinical event, including 26 deaths and 21 non-AIDS events. Compared to immediate ART, delayed ART was associated with shorter time to first primary clinical event (P=0.07), AIDS-defining disease (P=0.03), and tuberculosis (P=0.02); also higher incidence of tuberculosis (1.8, 95% CI=[1.3, 2.6]/100 PY versus 0.8, [0.5, 1.3]/100 PY, P=0.009) and all targeted clinical events (29.0, [26.3, 31.9]/100PY versus 24.7, [22.3, 27.3]/100PY; P=0.02) (Figure). Sensitivity analysis excluding pre-specified secondary events (recurrent upper respiratory tract infections, unexplained weight loss [moderate and severe], unexplained chronic diarrhea, unexplained persistent fever, unexplained anemia, lipodystrophy and hypertension) showed a consistent result (19.9, [17.8, 22.2] /100PY versus 14.4, 12.6, 16.4]/100PY; P=0.0003 in the delayed versus immediate arms).
Conclusions: In HIV+ adults with CD4+ 350-550/µL, immediate versus delayed ART significantly reduced the incidence of clinical events, notably tuberculosis, AIDS-defining events, and WHO Stage 2/3 clinical events.
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