Jannie J van der Helm1, Ronald Geskus2, Sara Lodi3, Laurence Meyer4, Hanneke Schuitemaker5, Barbara Gunsenheimer-Bartmeyer6, Antonella d'Arminio Monforte7, Ashley Olson8, Giota Touloumi9, Caroline Sabin10, Kholoud Porter8, Maria Prins11. 1. Public Health Service Amsterdam, Amsterdam, Netherlands. Electronic address: jvdhelm@ggd.amsterdam.nl. 2. Public Health Service Amsterdam, Amsterdam, Netherlands; Department of Clinical Epidemiology, Biostatistics and Bioinformatics, Center for Infectious Diseases and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. 3. Instituto de Salud Carlos III, Madrid, Spain. 4. Service d'Epidémiologie et de Santé Publique, Hôpital de Bicêtre, AP-HP; INSERM U1018; Université Paris-Sud, France. 5. Department of Experimental Immunology, Sanquin Research, Landsteiner Laboratory, Center for Infectious Diseases and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. 6. Robert Koch Institute, Berlin, Germany. 7. Department of Infectious Diseases and Tropical Medicine, Università degli Strudi di Milano H S Paolo, Milan, Italy. 8. MRC Clinical Trials Unit, University College London, London, UK. 9. Department of Hygiene, Epidemiology and Medical Statistics, Athens University Medical School, Greece. 10. Research Department of Infection and Population Health, University College London, London, UK. 11. Public Health Service Amsterdam, Amsterdam, Netherlands; Department of Infectious Diseases, Center for Infectious Diseases and Immunity Amsterdam, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
Abstract
BACKGROUND: Some individuals remain AIDS-free with a high and stable CD4 cell count without antiretroviral therapy (ART) for many years. We estimated long-term progression-free survival after HIV seroconversion and aimed to identify factors associated with loss of long-term non-progression (LTNP) status. METHODS: For this cohort study, we used data for individuals with well-estimated dates of HIV-1 seroconversion from the CASCADE Collaboration a network of 28 HIV seroconverter cohort studies in Europe, Australia, Canada, and sub-Saharan Africa. The first cohort began enrolling patients in 1979, and for this analysis we used data pooled in May 1, 2011. We defined non-progression as being HIV-positive without AIDS, ART-naive, and with CD4 counts of 500 cells per μL or higher. We defined LTNP as non-progression during the first 10 years after seroconversion. We used longitudinal methods to characterise LTNP. FINDINGS: Of the 4979 HIV seroconverters in our dataset, 3708 (75%) were men. Median time to progression was 2·07 years (95% CI 1·96-2·17), giving estimated progression-free survivals of 18·4% (17·2-19·6) 5 years, 4·0% (3·6-4·5) 10 years, and 1·4% (0·9-1·5) 15 years after seroconversion. The rate of progression did not change beyond 10 years after seroconversion (0·28 [95%CI 0·26-0·31] per person-year at 10 years after seroconversion, 0·24 [0·19-0·29] per person-year at 15 years, and 0·18 [0·10-0·33] per person-year at 20 years). At 10 years since HIV seroconversion, 283 individuals had LTNP, of whom 202 subsequently lost this status (median time to loss of status 2·49 years [2·05-2·92]). In univariable analyses, loss of LTNP status was associated with CD4 cell count at 10 years after seroconversion (p < 0·0001) and HIV RNA load at 10 years after seroconversion (p = 0·005), but not age (p = 0·544), mode of infection (p = 0·621), sex (p = 0·676), or calendar year of seroconversion (p = 0·397). In the multivariable analyses, loss of LTNP status was associated with lower CD4 counts at 10 years after seroconversion (p < 0·0001). After exclusion of CD4 cell counts from the model, higher HIV RNA load at 10 years after seroconversion was independently associated with loss of LTNP status (p = 0·009). INTERPRETATION: Progression-free survival is rare. Most individuals with LTNP eventually lose immunological and clinical control of HIV infection eventually. FUNDING: European Union Seventh Framework Programme.
BACKGROUND: Some individuals remain AIDS-free with a high and stable CD4 cell count without antiretroviral therapy (ART) for many years. We estimated long-term progression-free survival after HIV seroconversion and aimed to identify factors associated with loss of long-term non-progression (LTNP) status. METHODS: For this cohort study, we used data for individuals with well-estimated dates of HIV-1 seroconversion from the CASCADE Collaboration a network of 28 HIV seroconverter cohort studies in Europe, Australia, Canada, and sub-Saharan Africa. The first cohort began enrolling patients in 1979, and for this analysis we used data pooled in May 1, 2011. We defined non-progression as being HIV-positive without AIDS, ART-naive, and with CD4 counts of 500 cells per μL or higher. We defined LTNP as non-progression during the first 10 years after seroconversion. We used longitudinal methods to characterise LTNP. FINDINGS: Of the 4979 HIV seroconverters in our dataset, 3708 (75%) were men. Median time to progression was 2·07 years (95% CI 1·96-2·17), giving estimated progression-free survivals of 18·4% (17·2-19·6) 5 years, 4·0% (3·6-4·5) 10 years, and 1·4% (0·9-1·5) 15 years after seroconversion. The rate of progression did not change beyond 10 years after seroconversion (0·28 [95%CI 0·26-0·31] per person-year at 10 years after seroconversion, 0·24 [0·19-0·29] per person-year at 15 years, and 0·18 [0·10-0·33] per person-year at 20 years). At 10 years since HIV seroconversion, 283 individuals had LTNP, of whom 202 subsequently lost this status (median time to loss of status 2·49 years [2·05-2·92]). In univariable analyses, loss of LTNP status was associated with CD4 cell count at 10 years after seroconversion (p < 0·0001) and HIV RNA load at 10 years after seroconversion (p = 0·005), but not age (p = 0·544), mode of infection (p = 0·621), sex (p = 0·676), or calendar year of seroconversion (p = 0·397). In the multivariable analyses, loss of LTNP status was associated with lower CD4 counts at 10 years after seroconversion (p < 0·0001). After exclusion of CD4 cell counts from the model, higher HIV RNA load at 10 years after seroconversion was independently associated with loss of LTNP status (p = 0·009). INTERPRETATION: Progression-free survival is rare. Most individuals with LTNP eventually lose immunological and clinical control of HIV infection eventually. FUNDING: European Union Seventh Framework Programme.
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