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Background  Adolescents living with perinatal HIV often experience difficult living circumstances that can impact educational achievement and thus their transition to adult life. We explored their school trajectories and evaluated the contribution of perinatal HIV-infection, in Thailand, where education is free and compulsory until the age of 15.    Methods  We used data from the Teens Living with Antiretrovirals (TEEWA) study, a cross-sectional case-control study conducted from 2011 to 2014 in Thailand. Participants were 707 adolescents living with perinatal HIV (ALPHIV, cases) aged 12–19 receiving antiretroviral therapy in 19 hospitals throughout Thailand and 689 HIV-uninfected adolescents (controls) living in the same institutions or, for those living in family settings, randomly selected from the general population and individually matched for sex, age, and place of residence. School trajectory disruption was defined as ≥1 year of academic delay or as early school dropout (before 15 years of age). Logistic regression models were used to assess factors independently associated with disrupted school trajectory and to estimate the proportion of school disruption attributable to HIV-infection. We used multivariate imputations by chained equations (MICE) to manage missing data and performed two sensitivity analyses to evaluate the main model’s reliability.    Results  The study population’s median age was 14.5 years (58% female). School trajectory disruption was experienced by 37% of ALPHIV and 12% of the controls. After adjusting for sociodemographic factors, ALPHIV were 5 times more likely to experience disruption than controls (  ORA    =5.2 [3.7–7.2]). About 50% of school trajectory disruption was attributable to HIV-infection. Males and adolescents living in institutions were more likely to experience school trajectory disruption (  ORA    =1.8 [1.3–2.4] and   ORA    =11.0 [7.7–15.8], respectively). Among ALPHIV, neurocognitive difficulties and growth delay were significantly associated with disruption (  ORA    =3.3 [2.1–5.2] and   ORA    =1.8 [1.3–2.6], respectively). For those living in families, disruption was also associated with having a caregiver who had less than a secondary-level education (  ORA    =2.1 [1.1–3.9]) or having experienced stigmatization (  ORA    =1.9 [1.2–3.1]).    Conclusions  HIV and contextual factors combine to aggravate the educational disadvantage among ALPHIV. The impact of this disadvantage on their life prospects, especially regarding access to higher education and professional achievement, should be further explored.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12889-021-10189-x.

School trajectory disruption among adolescents living with perinatal HIV receiving antiretroviral treatments: a case-control study in Thailand