Ashwini Shete1, Sampada Dhayarkar1, Shashikala Sangale2, Uttam Medhe3, Narayan Panchal1, Girish Rahane1, Rajendra Yelgate1, Ashwini Dhamanage1, Raman Gangakhedkar4. 1. ICMR-National AIDS Research Institute, Bhosari, Pune, India. 2. B.J. Medical College and Sassoon General Hospital, Pune, India. 3. Yashwantrao Chavan Memorial Hospital, Sant Tukaram Nagar, Pimpri, Pune, India. 4. ICMR-National AIDS Research Institute, Bhosari, Pune, India; Indian Council of Medical Research, V. Ramalingaswami Bhawan, Ansari Nagar, New Delhi, India. Electronic address: rgangakhedkar@nariindia.org.
Abstract
BACKGROUND: Immunological non-responders (INR) represent a unique category of HIV-infected patients on antiretroviral therapy. These patients have suppressed viremia but a suboptimal increase in CD4 cell count, which might have opposing effects on functional immune reconstitution. Hence, the extent of immune reconstitution in INR patients was investigated in order to determine their susceptibility to opportunistic infections. METHODS: Twenty-three INR patients (CD4 increase <50 cells/mm3, viral load <40 copies/ml), 40 age-, sex-, and baseline CD4 count-matched responders (CD4 increase >100 cells/mm3, viral load <40 copies/ml), and 18 treatment failures defined as per the national guidelines were enrolled at 1year of antiretroviral therapy. The following examinations were performed: haemogram, phenotypic characterization by flow cytometry, and assessment of functional immune status by ELISPOT and intracellular cytokine assays. RESULTS: A higher percentage of INR patients had clinically symptomatic infections than the responders. CD8+ activation and innate immune parameters, including the absolute neutrophil count and natural killer (NK) cell frequency and functionality, were restored in the INR patients. They had significantly higher non-HIV antigen-specific T-cell responses and activated CD4+ cells, but significantly compromised T-cell functionality, as assessed after anti-CD3 stimulation, and lower CD31+ and CD62L+CD4+ cells. CONCLUSIONS: INR patients showed lower thymic output, incomplete functional T-cell reconstitution, higher responses to HIV co-pathogens, and higher symptomatic events, indicating the need for close monitoring and intervention strategies to overcome their continuing immunocompromised status.
BACKGROUND: Immunological non-responders (INR) represent a unique category of HIV-infectedpatients on antiretroviral therapy. These patients have suppressed viremia but a suboptimal increase in CD4 cell count, which might have opposing effects on functional immune reconstitution. Hence, the extent of immune reconstitution in INR patients was investigated in order to determine their susceptibility to opportunistic infections. METHODS: Twenty-three INR patients (CD4 increase <50 cells/mm3, viral load <40 copies/ml), 40 age-, sex-, and baseline CD4 count-matched responders (CD4 increase >100 cells/mm3, viral load <40 copies/ml), and 18 treatment failures defined as per the national guidelines were enrolled at 1year of antiretroviral therapy. The following examinations were performed: haemogram, phenotypic characterization by flow cytometry, and assessment of functional immune status by ELISPOT and intracellular cytokine assays. RESULTS: A higher percentage of INR patients had clinically symptomatic infections than the responders. CD8+ activation and innate immune parameters, including the absolute neutrophil count and natural killer (NK) cell frequency and functionality, were restored in the INR patients. They had significantly higher non-HIV antigen-specific T-cell responses and activated CD4+ cells, but significantly compromised T-cell functionality, as assessed after anti-CD3 stimulation, and lower CD31+ and CD62L+CD4+ cells. CONCLUSIONS: INR patients showed lower thymic output, incomplete functional T-cell reconstitution, higher responses to HIV co-pathogens, and higher symptomatic events, indicating the need for close monitoring and intervention strategies to overcome their continuing immunocompromised status.