Development of a multiassay algorithm (MAA) to identify recent HIV infection in newly diagnosed individuals in Indonesia

Abstract

Background: Ongoing HIV transmission is a public health priority in Indonesia, the 4th most populous country in the world. Efforts to control transmission are hindered by the lack of knowledge of HIV incidence. We developed a new multiassay algorithm (MAA) to identify recent HIV infection among newly diagnosed antiretroviral (ARV) naïve individuals for use in estimating HIV incidence in Indonesia.Methods: The MAA incorporated biomarkers consisting of CD4+ T cell count, plasma viral load (pVL), avidity of antibody, and ambiguity rate of HIV-1 pol gene to identify recent HIV infection. Plasma from 140 HIV-infected adults participating in a multicentred cohort from 19 hospitals across Indonesia (January 2018 – June 2020) was studied. A training set (N = 60) of longstanding infection (≥12-months) was used to identify the performance characteristics of a 2-well avidity index enzymatic immunoassay (AI EIA). The test set (N = 80) of newly diagnosed (≤1-month) ARV naïve individuals was assessed for antibody avidity using the newly established 2-well AI EIA as a screening for potential recent infection, with those screened were subjected for population sequencing to determine the proportion of ambiguous bases in pol gene, subtypes, and antiretroviral drug resistance mutations (DRMs). Recent infection was inferred from a sequential decision tree starting from CD4+ T cells >200/µl, followed by plasma viral load (pVL) >1,000 copies/ml, AI <0·7 and ended by pol ambiguity <0·47%.Findings: Ten of eighty (10/80; 12·5%) newly diagnosed individuals were classified as recent infections by the MAA. DRMs were identified in two individuals: one infected with HIV subtype C (K219Q, V179T) and the other with CRF01_AE (V179D).Interpretation: The MAA demonstrates that the rate of HIV transmission, including infections with DRMs, are substantial in Indonesia.Funding: Ministry of Health Indonesia; the Intramural Research Program, National Institutes of Health; National Cancer Institute, Center for Cancer Research, National Institutes of Health, under Contract No ZIA BC 010819.Declaration of Interests: The authors declare no conflict of interest.Ethics Approval: The study was conducted in accordance with the Declaration of Helsinki and approved by the Ethics Committee of The Faculty of Medicine, Universitas Indonesia – Cipto Mangunkusumo Hospital (Number KET-1499 / UN2.F1 / ETIK / PPM.00.02 / 2020 dated 28 December 2020). Written informed consent were obtained from all participants.

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