BACKGROUND: It is unclear whether lack of immunological response despite viral suppression and relatively preserved CD4 T-cell count is associated with increased risk of AIDS or severe non-AIDS events. METHODS: Patients initiating first combination antiretroviral therapy (cART) were studied from first viral load 80 copies/ml or less up to AIDS, serious non-AIDS events (malignancies, severe infections, acute kidney injury, cardiovascular events, liver decompensation) or death. Follow-up was right censored if viral load was more than 500. Immunological nonresponse (INR) was defined as current CD4 cell count less than 120% pre-cART. A Poisson regression analysis was used to investigate the association between INR and the outcome. RESULTS: Three thousand, three hundred and seventy-eight patients were followed for a median of 32 months (interquartile range: 15-67). Two hundred and twenty-two events (32 deaths, 39 AIDS-defining events, 48 malignancies, 32 severe infections, 47 acute kidney injuries, 12 cardiovascular events, 12 other nonfatal events) were observed. The rate of clinical events among INR and immunological responders was 4.41 [95% confidence interval (CI) 3.38-5.74] and 1.84 (95% CI 1.58-2.15) per 100 person years of follow-up, respectively, accounting for a crude rate ratio of 2.39 (95% CI 1.77-3.25; P < 0.001). INR remained an independent predictor of clinical progression after adjusting for baseline characteristics, including pre-cART CD4 cell count (adjusted rate ratio 2.93; 95% CI 2.06-4.16, P < 0.001) or current CD4 cell count (adjusted rate ratio 1.94; 95% CI 1.39-2.72, P < 0.001). The association did not vary by pre-cART CD4 cell counts (P for interaction = 0.93) CONCLUSION: INR are at higher risk of severe clinical events than responders. The association was consistent across different CD4 cell counts at cART initiation and was only partially explained by current CD4 cell count. INR could be a marker of immune system malfunctioning, not completely captured by absolute CD4 cell count.
BACKGROUND: It is unclear whether lack of immunological response despite viral suppression and relatively preserved CD4 T-cell count is associated with increased risk of AIDS or severe non-AIDS events. METHODS:Patients initiating first combination antiretroviral therapy (cART) were studied from first viral load 80 copies/ml or less up to AIDS, serious non-AIDS events (malignancies, severe infections, acute kidney injury, cardiovascular events, liver decompensation) or death. Follow-up was right censored if viral load was more than 500. Immunological nonresponse (INR) was defined as current CD4 cell count less than 120% pre-cART. A Poisson regression analysis was used to investigate the association between INR and the outcome. RESULTS: Three thousand, three hundred and seventy-eight patients were followed for a median of 32 months (interquartile range: 15-67). Two hundred and twenty-two events (32 deaths, 39 AIDS-defining events, 48 malignancies, 32 severe infections, 47 acute kidney injuries, 12 cardiovascular events, 12 other nonfatal events) were observed. The rate of clinical events among INR and immunological responders was 4.41 [95% confidence interval (CI) 3.38-5.74] and 1.84 (95% CI 1.58-2.15) per 100 person years of follow-up, respectively, accounting for a crude rate ratio of 2.39 (95% CI 1.77-3.25; P < 0.001). INR remained an independent predictor of clinical progression after adjusting for baseline characteristics, including pre-cART CD4 cell count (adjusted rate ratio 2.93; 95% CI 2.06-4.16, P < 0.001) or current CD4 cell count (adjusted rate ratio 1.94; 95% CI 1.39-2.72, P < 0.001). The association did not vary by pre-cART CD4 cell counts (P for interaction = 0.93) CONCLUSION: INR are at higher risk of severe clinical events than responders. The association was consistent across different CD4 cell counts at cART initiation and was only partially explained by current CD4 cell count. INR could be a marker of immune system malfunctioning, not completely captured by absolute CD4 cell count.
Authors: Zhenwu Luo; Zhen Li; Lisa Martin; Zhuang Wan; Eric G Meissner; Enrique Espinosa; Hao Wu; Xiaocong Yu; Pingfu Fu; Maria Anna Julia Westerink; J Michael Kilby; Jennifer Wu; Lei Huang; Sonya L Heath; Zihai Li; Wei Jiang Journal: J Infect Dis Date: 2017-07-01 Impact factor: 5.226
Authors: Viviane D Lima; Anja Reuter; P Richard Harrigan; Lillian Lourenço; William Chau; Mark Hull; Lauren Mackenzie; Silvia Guillemi; Robert S Hogg; Rolando Barrios; Julio S G Montaner Journal: AIDS Date: 2015-09-10 Impact factor: 4.177
Authors: Ashwin Balagopal; David M Asmuth; Wei-Teng Yang; Thomas B Campbell; Nikhil Gupte; Laura Smeaton; Cecilia Kanyama; Beatriz Grinsztejn; Breno Santos; Khuanchai Supparatpinyo; Sharlaa Badal-Faesen; Javier R Lama; Umesh G Lalloo; Fatima Zulu; Jyoti S Pawar; Cynthia Riviere; Nagalingeswaran Kumarasamy; James Hakim; Xiao-Dong Li; Richard B Pollard; Richard D Semba; David L Thomas; Robert C Bollinger; Amita Gupta Journal: J Acquir Immune Defic Syndr Date: 2015-10-01 Impact factor: 3.731
Authors: Maria Pino; Susan Pereira Ribeiro; Amélie Pagliuzza; Khader Ghneim; Anum Khan; Emily Ryan; Justin L Harper; Colin T King; Sarah Welbourn; Luca Micci; Sol Aldrete; Keith A Delman; Theron Stuart; Michael Lowe; Jason M Brenchley; Cynthia A Derdeyn; Kirk Easley; Rafick P Sekaly; Nicolas Chomont; Mirko Paiardini; Vincent C Marconi Journal: PLoS Pathog Date: 2021-08-27 Impact factor: 6.823
Authors: Giuseppe Lapadula; Liliane Chatenoud; Andrea Gori; Francesco Castelli; Simona Di Giambenedetto; Massimiliano Fabbiani; Franco Maggiolo; Emanuele Focà; Nicoletta Ladisa; Laura Sighinolfi; Massimo Di Pietro; Angelo Pan; Carlo Torti Journal: PLoS One Date: 2015-05-28 Impact factor: 3.240