Defining and Predicting HIV Immunological Non-Response: A Multi-Definition Analysis from an Indonesian Cohort

Rachman, Brian Eka; Supranoto, Yehuda Tri Nugroho; Iskandar, Soraya Isfandiary; Asmarawati, Tri Pudy; Khairunisa, Siti Qamariyah; Arfijanto, Muhammad Vitanata; Hadi, Usman; Miftahussurur, Muhammad; Nasronudin, Nasronudin; Kameoka, Masanori; Rahayu, Retno Pudji; Hidayati, Afif Nurul

doi:10.3390/v17121581

Open AccessArticle

Defining and Predicting HIV Immunological Non-Response: A Multi-Definition Analysis from an Indonesian Cohort

by

Brian Eka Rachman

^1,2,3

,

Yehuda Tri Nugroho Supranoto

⁴

,

Soraya Isfandiary Iskandar

⁵,

Tri Pudy Asmarawati

^3,6

,

Siti Qamariyah Khairunisa

²,

Muhammad Vitanata Arfijanto

³,

Usman Hadi

³,

Muhammad Miftahussurur

^3,7

,

Nasronudin Nasronudin

^3,6,

Masanori Kameoka

^8,9

,

Retno Pudji Rahayu

^2,10 and

Afif Nurul Hidayati

^6,11,*

¹

Doctoral Program of Medical Science, Faculty of Medicine, Universitas Airlangga, Surabaya 60131, Indonesia

²

Institute of Tropical Disease, Universitas Airlangga, Surabaya 60115, Indonesia

³

Department of Internal Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60131, Indonesia

⁴

Harvard Medical School, Boston, MA 02115, USA

⁵

Department of Public Health and Preventive Medicine, Faculty of Medicine, Universitas Airlangga, Surabaya 60131, Indonesia

⁶

Universitas Airlangga Hospital, Surabaya 60116, Indonesia

⁷

Helicobacter pylori and Microbiota Study Group, Institute of Tropical Medicine, Universitas Airlangga, Surabaya 60115, Indonesia

⁸

Center for Infectious Diseases, Graduate School of Medicine, Kobe University, Kobe 650-0017, Japan

⁹

Department of Public Health, Graduate School of Health Sciences, Kobe University, Kobe 654-0142, Japan

¹⁰

Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, Universitas Airlangga, Surabaya 60132, Indonesia

¹¹

Department of Dermatology Venereology and Aesthetics, Faculty of Medicine, Universitas Airlangga, Surabaya 60131, Indonesia

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^*

Author to whom correspondence should be addressed.

Viruses 2025, 17(12), 1581; https://doi.org/10.3390/v17121581

Submission received: 6 November 2025 / Revised: 29 November 2025 / Accepted: 2 December 2025 / Published: 4 December 2025

(This article belongs to the Special Issue Cascade of Care for HIV, Hepatitis and Sexually Transmitted Infections)

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Abstract

Immunological non-response (INR) to antiretroviral therapy (ART) is a critical concern for PLHIV, characterized by inadequate CD4⁺ T-cell recovery despite virological suppression. This retrospective study analyzed medical records of virologically suppressed adult PLHIV on ART (2004–2024) at two hospitals in Surabaya, Indonesia, using four operational categories to identify clinical and demographic determinants of INR. Patients were classified as immunological responders (IRs) or non-responders (INRs) based on four definitions: INR1 (CD4⁺ gain < 100 cells/mm³), INR2 (CD4⁺ < 350 cells/mm³), INR3 (meeting of either criterion), and INR4 (meeting of both criteria). Of 464 patients, 382 were analyzed. Baseline CD4⁺ < 200 cells/mm³ strongly predicted INR2 (aOR = 5.60, 95% CI: 2.95–10.62) and INR3 (aOR = 4.46, 95% CI: 2.39–8.29), while anal sexual transmission was protective against INR2 (aOR = 0.42, 95% CI: 0.19–0.92) and INR3 (aOR = 0.41, 95% CI: 0.19–0.89). By month 12, IR groups had over 350 CD4⁺ cells/mm³, with faster recovery slopes in months 0–6 (IR: >20 vs. INR: <10 cells/mm³/month). INR1 and INR4 had flat or negative slopes at 12–24 months, while IR groups had positive slopes. Baseline CD4⁺ was the strongest INR predictor, suggesting the value of early ART and individualized care for Indonesian PLHIV.

Keywords: HIV infections; immune reconstitution; anti-retroviral agents; risk factors; immunological nonresponse

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MDPI and ACS Style

Rachman, B.E.; Supranoto, Y.T.N.; Iskandar, S.I.; Asmarawati, T.P.; Khairunisa, S.Q.; Arfijanto, M.V.; Hadi, U.; Miftahussurur, M.; Nasronudin, N.; Kameoka, M.; et al. Defining and Predicting HIV Immunological Non-Response: A Multi-Definition Analysis from an Indonesian Cohort. Viruses 2025, 17, 1581. https://doi.org/10.3390/v17121581

AMA Style

Rachman BE, Supranoto YTN, Iskandar SI, Asmarawati TP, Khairunisa SQ, Arfijanto MV, Hadi U, Miftahussurur M, Nasronudin N, Kameoka M, et al. Defining and Predicting HIV Immunological Non-Response: A Multi-Definition Analysis from an Indonesian Cohort. Viruses. 2025; 17(12):1581. https://doi.org/10.3390/v17121581

Chicago/Turabian Style

Rachman, Brian Eka, Yehuda Tri Nugroho Supranoto, Soraya Isfandiary Iskandar, Tri Pudy Asmarawati, Siti Qamariyah Khairunisa, Muhammad Vitanata Arfijanto, Usman Hadi, Muhammad Miftahussurur, Nasronudin Nasronudin, Masanori Kameoka, and et al. 2025. "Defining and Predicting HIV Immunological Non-Response: A Multi-Definition Analysis from an Indonesian Cohort" Viruses 17, no. 12: 1581. https://doi.org/10.3390/v17121581

APA Style

Rachman, B. E., Supranoto, Y. T. N., Iskandar, S. I., Asmarawati, T. P., Khairunisa, S. Q., Arfijanto, M. V., Hadi, U., Miftahussurur, M., Nasronudin, N., Kameoka, M., Rahayu, R. P., & Hidayati, A. N. (2025). Defining and Predicting HIV Immunological Non-Response: A Multi-Definition Analysis from an Indonesian Cohort. Viruses, 17(12), 1581. https://doi.org/10.3390/v17121581

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Defining and Predicting HIV Immunological Non-Response: A Multi-Definition Analysis from an Indonesian Cohort

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