AUTHOR=Liang Yuanhao , Lin Hongqing , Dzakah Emmanuel Enoch , Tang Shixing 

TITLE=Influence of Combination Antiretroviral Therapy on HIV-1 Serological Responses and Their Implications: A Systematic Review and Meta-Analysis

JOURNAL=Frontiers in Immunology

VOLUME=Volume 13 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.844023

DOI=10.3389/fimmu.2022.844023

ISSN=1664-3224

ABSTRACT=To analyze HIV-1 seroreversion caused by combination antiretroviral therapy (cART) and to explore antibody levels of anti-HIV-1 as alternative biomarker of HIV-1 reservoir. We searched PubMed, Embase, the Cochrane Library and Web of Science up to August, 2021 for publications about the performance of HIV-1 serological assays, or the association between antibody responses against HIV-1 and HIV-1 reservoir. Potential sources of heterogeneity were explored by meta-regression analysis, including year of publication, country, pre-treatment viral load, sample size, timing of treatment, time-on-cART and principle or type of serological assay. Twenty-eight eligible studies with a total population of 1883 were included in the meta-analysis. The pooled frequency of HIV-1 seronegativity is 38.0% (95% CI: 28.0-49.0%) among children with vertical HIV-1 infection and cART initiation at the age of less than 6 months old while the percentage of HIV-1 seronegativity declined to 1.0% (95% CI: 0-3.0%) when cART initiated at the age of >6 months old. For adult patients, 16.0% (95% CI: 9.0%-24.0%) of them were serologically negative when cART initiated at acute/early infection of HIV-1, but seronegative reaction was rarely detected when cART started at chronic HIV-1 infection. Substantial heterogeneity was observed among the studies to estimate the frequency of HIV-1 seronegativity in early-cART population (I2 ≥70%, p<0.05 and all) while mild heterogeneity existed for the deferred-cART subjects. Moreover, anti-HIV-1 antibody response positively correlates with HIV-1 reservoir size with a pooled rho of 0.43 (95% CI: 0.28-0.55), suggesting that anti-HIV antibody level may be a feasible biomarker of HIV-1 reservoir size.