Bone mineral density among children living with HIV failing first-line anti-retroviral therapy in Uganda: A sub-study of the CHAPAS-4 trial

Abstract

Background Children living with perinatally acquired HIV (CLWH) survive into adulthood on antiretroviral therapy (ART). HIV, ART, and malnutrition can all lead to low bone mineral density (BMD). Few studies have described bone health among CLWH in Sub-Saharan Africa. We determined the prevalence and factors associated with low BMD among CLWH switching to second-line ART in the CHAPAS-4 trial (ISRCTN22964075) in Uganda. Methods BMD was determined using dual-energy X-ray Absorptiometry (DXA). BMD Z-scores were adjusted for age, sex, height and race. Demographic characteristics were summarized using median interquartile range (IQR) for continuous variables and proportions for categorical variables. Logistic regression was used to determine the associations between each variable and low BMD. Results A total of 159 children were enrolled (50% male) with median age (IQR) 10 (7–12) years, median duration of first -line ART 5.2(3.3–6.8) years; CD4 count 774 (528–1083) cells/mm3, weight—for–age Z-score -1.36 (-2.19, -0.65) and body mass index Z-score (BMIZ) -1.31 (-2.06, -0.6). Low (Z-score≤ -2) total body less head (TBLH) BMD was observed in 28 (18%) children, 21(13%) had low lumbar spine (LS) BMD, and15 (9%) had both. Low TBLH BMD was associated with increasing age (adjusted odds ratio [aOR] 1.37; 95% CI: 1.13–1.65, p = 0.001), female sex (aOR: 3.8; 95% CL: 1.31–10.81, p = 0.014), low BMI (aOR 0.36:95% CI: 0.21–0.61, p<0.001), and first-line zidovudine exposure (aOR: 3.68; 95% CI: 1.25–10.8, p = 0.018). CD4 count, viral load and first- line ART duration were not associated with TBLH BMD. Low LS BMD was associated with increasing age (aOR 1.42; 95% CI: 1.16–1.74, p = 0.001) and female sex: (aOR 3.41; 95% CI: 1.18–9.8, p = 0.023). Conclusion Nearly 20% CLWH failing first-line ART had low BMD which was associated with female sex, older age, first-line ZDV exposure, and low BMI. Prevention, monitoring, and implications following transition to adult care should be prioritized to identify poor bone health in HIV+adolescents entering adulthood.