Association Between Antiretroviral Therapy Initiation and Malignancies among Children Living with HIV in Sub-Saharan Africa: A Multicenter Case-Control Study

Background: Currently only 43% of children living with HIV worldwide receive antiretroviral therapy (ART). Among adults, ART has been shown to decrease risk of HIV-related malignancies; however, few studies have described the association among children living with HIV, especially in resource-limited settings. Our objective is to determine the association between age at ART initiation and the incidence of malignancies in children with HIV infection. Methods: We conducted a multicenter case-control study at five pediatric HIV centers in Botswana, Malawi, Tanzania, and Uganda from 2003-2016. Cases were defined as children living with HIV ages 0-21 years with a cancer diagnosis. Controls were defined as children with HIV but no cancer with 5:1 matching based on sex, country, and age of enrollment in HIV care. We conducted a longitudinal cohort analysis for a subset of incident cancer cases, defined as malignancy diagnosis >3 months after enrollment in care. Data were extracted from electronic and paper medical records at each site and analyzed using Stata 15.1 to describe associations between ART and malignancies. Results: There were 451 total cases of malignancies (of which 136 were incident cases) among children living with HIV and 2,175 controls. Cases were 41% female, with a median age of 7 years (IQR 3-11) at time of HIV diagnosis. Of the 451 cancer diagnoses, 83.8% were Kaposi sarcoma, 10.7% were non-Hodgkin lymphoma, 2.0% were Hodgkin lymphoma, and 3.6% were other malignancies. Histopathological diagnosis was obtained for 69.9% of incident cases. There was no significant increased cancer risk for males compared to females (OR 1.12, p=0.55). Compared to children that initiated ART at under 2 years of age, there were increased odds of developing incident cancer in children who began ART between ages 2-6 years (OR 3.85, p=0.001) and over 7 years (OR 4.98, p=0.001). Conclusion: Early diagnosis of HIV and prompt initiation of ART may decrease the incidence of some malignancies. Further efforts to improve early infant diagnosis and prompt initiation of ART may reduce malignancies among children living with HIV.