Early initiation of antiretroviral therapy (ART) has been shown to reduce mortality in resource-
rich settings, but the complexity, toxicity and interactions of these drugs when given
concurrently with chemotherapy or radiation make the simultaneous use of ART and cancer-
directed therapy challenging. For the original “AIDS-Defining Cancers” (Kaposi sarcoma, non-
Hodgkin lymphoma, and cervical cancer), concurrent ART and chemoradioation has well-proven
survival benefit. Non-AIDS-defining cancers (NADCs) are a more heterogeneous group, some of
which are provoked by chronic infections and immunodeficiency, while others occur at similar
frequency as in the HIV-negative population. What is the optimal timing of initiation of ART vis
a vis chemotherapy in HIV-1 seropositive patients newly diagnosed with cancer and HIV? While
this question has been answered in studies evaluating therapy for opportunistic infections and
ART, it has not been addressed in patients with malignancy. This issue is especially urgent in
sub-Saharan Africa, where the burden of both HIV and malignancy is high and the ancillary
management of side effects of chemotherapy is less well defined. We propose to investigate
concurrent vs. sequential ART and cancer-directed therapy at the Uganda Cancer Institute
(UCI). We will first perform a cross-sectional study to evaluate HIV status, CD4 T-cell count, and
HIV treatment history of all new patients presenting for care at the Uganda Cancer Institute.
We will then randomize new ART naïve HIV-infected patients with NADCs to concurrent vs.
sequential ART and cancer-directed therapy and evaluate one year survival and risk of drug
toxicities and opportunistic infections.