Susan H Eshleman1, Ethan A Wilson2, Xinyi C Zhang2, San-San Ou2, Estelle Piwowar-Manning1, Joseph J Eron3, Marybeth McCauley4, Theresa Gamble5, Joel E Gallant6, Mina C Hosseinipour7,8, Nagalingeswaran Kumarasamy9, James G Hakim10, Ben Kalonga11, Jose H Pilotto12, Beatriz Grinsztejn13, Sheela V Godbole14, Nuntisa Chotirosniramit15, Breno Riegel Santos16, Emily Shava17, Lisa A Mills18, Ravindre Panchia19, Noluthando Mwelase20, Kenneth H Mayer21, Ying Q Chen2, Myron S Cohen3, Jessica M Fogel1. 1. a Department of Pathology , Johns Hopkins University School of Medicine , Baltimore , MD , USA. 2. b Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center , Seattle , WA , USA. 3. c Department of Medicine , University of North Carolina at Chapel Hill , Chapel Hill , NC , USA. 4. d Science Facilitation Department , FHI 360 , Washington , DC , USA. 5. e Science Facilitation Department , FHI 360 , Durham , NC , USA. 6. f Southwest CARE Center , Santa Fe , NM , USA. 7. g University of North Carolina at Chapel Hill, Institute for Global Health and Infectious Diseases , Chapel Hill , NC , USA. 8. h UNC Project-Malawi, Institute for Global Health and Infectious Diseases , Lilongwe , Malawi. 9. i YRGCARE Medical Centre, VHS , Chennai , India. 10. j Department of Medicine , University of Zimbabwe , Harare , Zimbabwe. 11. k College of Medicine-Johns Hopkins Project , Blantyre , Malawi. 12. l Hospital Geral de Nova Iguacu and Laboratorio de AIDS e Imunologia Molecular-IOC/Fiocruz , Rio de Janeiro , Brazil. 13. m Instituto Nacional de Infectologia Evandro Chagas-INI-Fiocruz , Rio de Janeiro , Brazil. 14. n National AIDS Research Institute (ICMR) , Pune , India. 15. o Research Institute for Health Sciences, Chiang Mai University , Chiang Mai , Thailand. 16. p Hospital Nossa Senhora da Conceição , Porto Alegre , Brazil. 17. q Botswana Harvard AIDS Institute , Gaborone , Botswana. 18. r Centers for Disease Control and Prevention, Division of HIV/AIDS Prevention and Kenya Medical Research Institute (KEMRI)/CDC Clinical Research Site , Kisumu , Kenya. 19. s University of the Witwatersrand, Perinatal HIV Research Unit, Soweto HPTN CRS , Soweto , South Africa. 20. t Clinical HIV Research Unit, Department of Medicine , University of the Witwatersrand , Johannesburg , South Africa. 21. u The Fenway Institute, Fenway Health/Infectious Disease Division, Beth Israel Deaconess Medical Center, Department of Medicine , Harvard Medical School , Boston , MA , USA.
Abstract
INTRODUCTION: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. OBJECTIVE: To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. METHODS:1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350-550 cells/mm3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 < 250 cells/mm3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs > 1000 copies/mL > 24 weeks after ART initiation. RESULTS: Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. CONCLUSIONS: Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.
RCT Entities:
INTRODUCTION: The HIV Prevention Trials Network (HPTN) 052 trial demonstrated that early antiretroviral therapy (ART) prevented 93% of HIV transmission events in serodiscordant couples. Some linked infections were observed shortly after ART initiation or after virologic failure. OBJECTIVE: To evaluate factors associated with time to viral suppression and virologic failure in participants who initiated ART in HPTN 052. METHODS: 1566 participants who had a viral load (VL) > 400 copies/mL at enrollment were included in the analyses. This included 832 in the early ART arm (CD4 350-550 cells/mm3 at ART initiation) and 734 in the delayed ART arm (204 with a CD4 < 250 cells/mm3 at ART initiation; 530 with any CD4 at ART initiation). Viral suppression was defined as two consecutive VLs ≤ 400 copies/mL after ART initiation; virologic failure was defined as two consecutive VLs > 1000 copies/mL > 24 weeks after ART initiation. RESULTS: Overall, 93% of participants achieved viral suppression by 12 months. The annual incidence of virologic failure was 3.6%. Virologic outcomes were similar in the two study arms. Longer time to viral suppression was associated with younger age, higher VL at ART initiation, and region (Africa vs. Asia). Virologic failure was strongly associated with younger age, lower educational level, and lack of suppression by three months; lower VL and higher CD4 at ART initiation were also associated with virologic failure. CONCLUSIONS: Several clinical and demographic factors were identified that were associated with longer time to viral suppression and virologic failure. Recognition of these factors may help optimize ART for HIV treatment and prevention.
Entities:
Keywords:
Early ART; HIV; HIV prevention; HPTN 052; Viral suppression; Virologic failure; Virologic outcomes
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