ObjectivesThis study aimed to assess the evolution of body mass index (BMI) of HIV-positive adults on second-line antiretroviral therapy (ART) over time and factors affecting it in north-west Ethiopia.DesignAn institution-based retrospective follow-up study was conducted using data extracted from 1016 patient cards from February 2008 to February 2016.SettingEight referral hospitals from Amhara region, Ethiopia were included.ParticipantsHIV patients who started second-line ART.Outcome measuresChange in BMI since starting second-line ART.ResultsFive hundred and thirty-eight (52.95%) participants were males and the median age of the participants was 33 years (IQR: 28; 39). The median follow-up time was 18 months (IQR: 5.2; 32.2). The average change of BMI showed linear increase over time. The amount of BMI increment or decrement according to each variable was shown as β coefficients. Treatment duration (β=0.013, 95% CI 0.004 to 0.022), isoniazid prophylaxis (β=0.87, 95% CI 0.32 to 1.42), cotrimoxazole prophylaxis (β=0.63, 95% CI 0.08 to 1.19), ambulatory functional status (β=−1.16, 95% CI −1.95 to 1.31), bedridden functional status (β=−1.83, 95% CI −2.47 to 1.21), WHO stage III (β=−0.42, 95% CI −0.65 to 0.20), WHO stage IV (β=−0.62, 95% CI −1.02 to 0.22), CD4 count (β=0.001, 95% CI 0.0008 to 0.0015), and time interaction of variables like tertiary educational status (β=0.02, 95% CI 0.01 to 0.04), ambulatory functional status (β=0.03, 95% CI 0.01 to 0.05) and WHO stages III (β=0.01, 95% CI 0.007 to 0.02) were found to be significant predictors.ConclusionThe BMI of patients has shown linear increment over the treatment time. Factors affecting it have been identified but its effect on cardiovascular disease needs further study.