Geoffrey Fatti1,2, Ashraf Grimwood1, Jean B Nachega3,4,5,6, Jenna A Nelson3, Kelsea LaSorda3, Gert van Zyl7, Nelis Grobbelaar8, Helen Ayles9,10, Richard Hayes11, Nulda Beyers12, Sarah Fidler13, Peter Bock12. 1. Kheth'Impilo AIDS Free Living, Cape Town, South Africa. 2. Division of Epidemiology and Biostatistics, Department of Global Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. 3. Department of Epidemiology, University of Pittsburgh Graduate School of Public Health, Pennsylvania. 4. Department of Infectious Diseases and Microbiology, University of Pittsburgh Graduate School of Public Health, Pennsylvania. 5. Department of Epidemiology and International Health, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland. 6. Department of Medicine and Centre for Infectious Diseases, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town. 7. Division of Medical Virology, Faculty of Medicine and Health Sciences, Stellenbosch University and National Health Laboratory Service, Tygerberg, South Africa. 8. Anova Health Institute, Paarl, South Africa. 9. Department of Clinical Research, London School of Hygiene and Tropical Medicine, United Kingdom. 10. Zambart, Ridgeway Campus University of Zambia, Lusaka. 11. Department of Infectious Disease Epidemiology, London School of Hygiene and Tropical Medicine, United Kingdom. 12. Desmond Tutu Tuberculosis Centre, Department of Paediatrics and Child Health, Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa. 13. Department of Medicine, Imperial College London and Imperial College National Institute for Health Research Biomedical Research Centre, United Kingdom.
Abstract
BACKGROUND: There have been concerns about reduced adherence and human immunodeficiency virus (HIV) virological suppression (VS) among clinically well people initiating antiretroviral therapy (ART) with high pre-ART CD4 cell counts. We compared virological outcomes by pre-ART CD4 count, where universal ART initiation was provided in the HIV Prevention Trials Network 071 (PopART) trial in South Africa prior to routine national and international implementation. METHODS: This prospective cohort study included adults initiating ART at facilities providing universal ART since January 2014. VS (<400 copies/mL), confirmed virological failure (VF) (2 consecutive viral loads >1000 copies/mL), and viral rebound were compared between participants in strata of baseline CD4 cell count. RESULTS: The sample included 1901 participants. VS was ≥94% among participants with baseline CD4 count ≥500 cells/µL at all 6-month intervals to 30 months. The risk of an elevated viral load (≥400 copies/mL) was independently lower among participants with baseline CD4 count ≥500 cells/µL (3.3%) compared to those with CD4 count 200-499 cells/µL (9.2%) between months 18 and 30 (adjusted relative risk, 0.30 [95% confidence interval, .12-.74]; P = .010). The incidence rate of VF was 7.0, 2.0, and 0.5 per 100 person-years among participants with baseline CD4 count <200, 200-499, and ≥500 cells/µL, respectively (P < .0001). VF was independently lower among participants with baseline CD4 count ≥500 cells/µL (adjusted hazard ratio [aHR], 0.23; P = .045) and 3-fold higher among those with baseline CD4 count <200 cells/µL (aHR, 3.49; P < .0001). CONCLUSIONS: Despite previous concerns, participants initiating ART with CD4 counts ≥500 cells/µL had very good virological outcomes, being better than those with CD4 counts 200-499 cells/µL. CLINICAL TRIALS REGISTRATION: NCT01900977.
BACKGROUND: There have been concerns about reduced adherence and human immunodeficiency virus (HIV) virological suppression (VS) among clinically well people initiating antiretroviral therapy (ART) with high pre-ART CD4 cell counts. We compared virological outcomes by pre-ART CD4 count, where universal ART initiation was provided in the HIV Prevention Trials Network 071 (PopART) trial in South Africa prior to routine national and international implementation. METHODS: This prospective cohort study included adults initiating ART at facilities providing universal ART since January 2014. VS (<400 copies/mL), confirmed virological failure (VF) (2 consecutive viral loads >1000 copies/mL), and viral rebound were compared between participants in strata of baseline CD4 cell count. RESULTS: The sample included 1901 participants. VS was ≥94% among participants with baseline CD4 count ≥500 cells/µL at all 6-month intervals to 30 months. The risk of an elevated viral load (≥400 copies/mL) was independently lower among participants with baseline CD4 count ≥500 cells/µL (3.3%) compared to those with CD4 count 200-499 cells/µL (9.2%) between months 18 and 30 (adjusted relative risk, 0.30 [95% confidence interval, .12-.74]; P = .010). The incidence rate of VF was 7.0, 2.0, and 0.5 per 100 person-years among participants with baseline CD4 count <200, 200-499, and ≥500 cells/µL, respectively (P < .0001). VF was independently lower among participants with baseline CD4 count ≥500 cells/µL (adjusted hazard ratio [aHR], 0.23; P = .045) and 3-fold higher among those with baseline CD4 count <200 cells/µL (aHR, 3.49; P < .0001). CONCLUSIONS: Despite previous concerns, participants initiating ART with CD4 counts ≥500 cells/µL had very good virological outcomes, being better than those with CD4 counts 200-499 cells/µL. CLINICAL TRIALS REGISTRATION: NCT01900977.
Authors: Rolf H H Groenwold; A Rogier T Donders; Kit C B Roes; Frank E Harrell; Karel G M Moons Journal: Am J Epidemiol Date: 2011-12-23 Impact factor: 4.897
Authors: Matt A Price; Carole L Wallis; Shabir Lakhi; Etienne Karita; Anatoli Kamali; Omu Anzala; Eduard J Sanders; Linda-Gail Bekker; Rogers Twesigye; Eric Hunter; Pontiano Kaleebu; Kayitesi Kayitenkore; Susan Allen; Eugene Ruzagira; Mary Mwangome; Gaudensia Mutua; Pauli N Amornkul; Gwynn Stevens; Sergei L K Pond; Malinda Schaefer; Mary A Papathanasopoulos; Wendy Stevens; Jill Gilmour Journal: AIDS Res Hum Retroviruses Date: 2010-11-23 Impact factor: 2.205
Authors: Jienchi Dorward; Richard Lessells; Paul K Drain; Kogieleum Naidoo; Tulio de Oliveira; Yogan Pillay; Salim S Abdool Karim; Nigel Garrett Journal: Lancet HIV Date: 2018-06-05 Impact factor: 12.767
Authors: Jean B Nachega; Michael Hislop; David W Dowdy; Richard E Chaisson; Leon Regensberg; Gary Maartens Journal: Ann Intern Med Date: 2007-04-17 Impact factor: 25.391
Authors: Mark J Siedner; Courtney K Ng; Ingrid V Bassett; Ingrid T Katz; David R Bangsberg; Alexander C Tsai Journal: Clin Infect Dis Date: 2014-12-16 Impact factor: 9.079
Authors: Olga Tymejczyk; Ellen Brazier; Constantin Yiannoutsos; Kara Wools-Kaloustian; Keri Althoff; Brenda Crabtree-Ramírez; Kinh Van Nguyen; Elizabeth Zaniewski; Francois Dabis; Jean d'Amour Sinayobye; Nanina Anderegg; Nathan Ford; Radhika Wikramanayake; Denis Nash Journal: PLoS Med Date: 2018-03-23 Impact factor: 11.069
Authors: Richard Hayes; Helen Ayles; Nulda Beyers; Kalpana Sabapathy; Sian Floyd; Kwame Shanaube; Peter Bock; Sam Griffith; Ayana Moore; Deborah Watson-Jones; Christophe Fraser; Sten H Vermund; Sarah Fidler Journal: Trials Date: 2014-02-13 Impact factor: 2.279
Authors: Lauren Jennings; Tracy Kellermann; Matthew Spinelli; Zukiswa Nkantsu; Dolphina Cogill; Marije van Schalkwyk; Eric Decloedt; Gert van Zyl; Catherine Orrell; Monica Gandhi Journal: AIDS Res Hum Retroviruses Date: 2021-12-29 Impact factor: 1.723
Authors: Dathan M Byonanebye; Fred C Semitala; Jackson Katende; Alex Bakenga; Irene Arinaitwe; Peter Kyambadde; Patrick Musinguzi; Irene Andia Biraro; Pauline Byakika-Kibwika; Moses R Kamya Journal: Afr Health Sci Date: 2020-03 Impact factor: 0.927
Authors: Lucas E Hermans; Sergio Carmona; Monique Nijhuis; Hugo A Tempelman; Douglas D Richman; Michelle Moorhouse; Diederick E Grobbee; Willem D F Venter; Annemarie M J Wensing Journal: PLoS Med Date: 2020-02-25 Impact factor: 11.069