Predictors of immunological non-response despite virological suppression in people living with HIV on antiretroviral therapy: A systematic review and meta-analysis
12 affiliations
- 1Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- 2Division of Tropical Medicine and Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- 3Master of Medical Sciences in Clinical Investigation, Harvard Medical School, Boston, Massachusetts, United States of America
- 4Master of Public Health Program, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
- 5Center for Tropical Medicine, Faculty of Medicine, Universitas Gadjah Mada, Yogyakarta, Indonesia
- 6Institute of Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
- 7Department of Physiology and Medical Biochemistry, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- 8Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya, Indonesia
- 9Universitas Airlangga Hospital, Surabaya, Indonesia
- 10Division of Global and Environmental Health Sciences, Department of Future Social Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
- 11Division of Gastroenterohepatology, Department of Internal Medicine, Faculty of Medicine, Dr. Soetomo Teaching Hospital, Universitas Airlangga, Surabaya, Indonesia
- 12Helicobacter pylori and Microbiota Study Group, Institute Tropical Disease, Universitas Airlangga, Surabaya, Indonesia
Abstract
Immunological Nonresponse (INR) in people living with HIV (PLWH) is characterized by inadequate CD4+ T-cell recovery despite effective viral suppression through antiretroviral therapy (ART). This systematic review and meta-analysis identify key clinical, demographic, and molecular predictors of INR to optimize immune recovery strategies. A comprehensive literature search was conducted in accordance with PRISMA 2020 guidelines, yielding 59 eligible studies, with a total of 19,511 individuals with INR. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and pooled effect estimates were calculated as odds ratio (OR), mean difference (MD), or standardized mean difference (SMD). Significant predictors of INR included male sex [OR 1.33 (1.12–1.58)], older age [MD 2.61 (1.42–3.81)], intravenous drug use [OR 1.67 (1.15–2.42)], hepatitis B coinfection [OR 1.30 (1.08–1.57)], hepatitis C coinfection [OR 1.85 (1.50–2.28)], tuberculosis [OR 1.77 (1.41–2.21)], advanced HIV stage [OR 2.66 (2.34–3.02)], and lower baseline and nadir CD4+ counts [SMD −3.82 (−4.94-(−2.70)), SMD −1.69 (−2.69-(−0.68))], respectively. Additionally, 57 biomarkers were identified as potential predictors of INR, implicating several immunological pathways. These findings underscore the multifactorial nature of INR and the need for personalized approaches among ART-treated individuals.
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BibTeX
@article{rachman2026predictors,
title = {{Predictors of immunological non-response despite virological suppression in people living with HIV on antiretroviral therapy: A systematic review and meta-analysis}},
author = {Brian Eka Rachman and Yehuda Tri Nugroho Supranoto and Fitri Revita Nurannisa and Siti Mei Saroh and Siti Qamariyah Khairunisa and Citrawati Dyah Kencono Wungu and Dian Paramita Kartikasari and Nasronudin Nasronudin and Masanori Kameoka and Muhammad Miftahussurur and Retno Pudji Rahayu and Afif Nurul Hidayati},
journal = {PLOS One},
year = {2026},
month = oct,
doi = {10.1371/journal.pone.0358793},
url = {https://doi.org/10.1371/journal.pone.0358793},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Predictors of immunological non-response despite virological suppression in people living with HIV on antiretroviral therapy: A systematic review and meta-analysis
AU - Brian Eka Rachman
AU - Yehuda Tri Nugroho Supranoto
AU - Fitri Revita Nurannisa
AU - Siti Mei Saroh
AU - Siti Qamariyah Khairunisa
AU - Citrawati Dyah Kencono Wungu
AU - Dian Paramita Kartikasari
AU - Nasronudin Nasronudin
AU - Masanori Kameoka
AU - Muhammad Miftahussurur
AU - Retno Pudji Rahayu
AU - Afif Nurul Hidayati
PY - 2026
DA - 2026/10/12
JO - PLOS One
DO - 10.1371/journal.pone.0358793
UR - https://doi.org/10.1371/journal.pone.0358793
AB - Immunological Nonresponse (INR) in people living with HIV (PLWH) is characterized by inadequate CD4+ T-cell recovery despite effective viral suppression through antiretroviral therapy (ART). This systematic review and meta-analysis identify key clinical, demographic, and molecular predictors of INR to optimize immune recovery strategies. A comprehensive literature search was conducted in accordance with PRISMA 2020 guidelines, yielding 59 eligible studies, with a total of 19,511 individuals with INR. Study quality was assessed using the Newcastle-Ottawa Scale (NOS), and pooled effect estimates were calculated as odds ratio (OR), mean difference (MD), or standardized mean difference (SMD). Significant predictors of INR included male sex [OR 1.33 (1.12–1.58)], older age [MD 2.61 (1.42–3.81)], intravenous drug use [OR 1.67 (1.15–2.42)], hepatitis B coinfection [OR 1.30 (1.08–1.57)], hepatitis C coinfection [OR 1.85 (1.50–2.28)], tuberculosis [OR 1.77 (1.41–2.21)], advanced HIV stage [OR 2.66 (2.34–3.02)], and lower baseline and nadir CD4+ counts [SMD −3.82 (−4.94-(−2.70)), SMD −1.69 (−2.69-(−0.68))], respectively. Additionally, 57 biomarkers were identified as potential predictors of INR, implicating several immunological pathways. These findings underscore the multifactorial nature of INR and the need for personalized approaches among ART-treated individuals.
SN - 1932-6203
ER -