Immune checkpoint inhibition with anti-PD1 and anti PD-L1 therapy is revolutionizing cancer management. There are 6 monoclonal antibodies targeting PD-1 or PD-L1 that have been approved for 15 distinct cancers. Cancer is a leading cause of death for the 37 million people living with HIV (PLWH) worldwide. Anti-PD1 therapy is indicated for several cancers associated with HIV, including lung cancer, head and neck cancer, liver cancer, cervical cancer and Hodgkin lymphoma. There is an ongoing study evaluating pembrolizumab in Kaposi sarcoma. Recent clinical trials and observational cohort studies suggest the safety profile of immune check point inhibitors for use in people with HIV and cancer is acceptable for those with a CD4 count >100 cells/uL. Meaningful responses were noted in Kaposi sarcoma, primary effusion lymphoma, lung cancer and liver cancer in Cancer Immunotherapy Trials Network-12. CD4 counts tend to increase in HIV infected patients receiving anti-PD1 therapy and HIV remains controlled in people on concurrent ART. Oncologists using this class of agents should be knowledgeable about managing immune related adverse events. Special consideration is required for people with concurrent infections, as tuberculosis immune reconstitution syndrome and KSHV lymphoproliferation has been observed. Safety and feasibility studies of check- point inhibitors are warranted in sub-Saharan. Unique and new indications may exist for immune checkpoint inhibitors in HIV infected and HIV uninfected cancer patients in this setting.

In resource-rich settings, Kaposi sarcoma (KS) is a diagnosis first suspected on clinical grounds and confirmed by biopsy and pathologic interpretation. Microscopically, KS features varying combinations of spindle cells, inflammatory infiltrate, and abnormal vasculature. In resource-limited settings, such as sub-Saharan Africa, the paucity of pathology capacity often results in KS being diagnosed on clinical visualization alone. This is despite research showing that the positive predictive value of clinical suspicion of KS is estimated to be only 80%. Even where pathology is available in sub-Saharan Africa, turnaround time is often slow, and accuracy, compared to experienced dermatopathologists in the U.S., is sub-optimal. In one study, concordance was only 69%. The ramifications of this current imperfect approach to KS diagnosis in Africa are manifold: some KS diagnoses are missed, sometimes with fatal consequences, and other instances of non-KS are falsely called KS and sometimes subsequently treated with potentially toxic chemotherapy. To ameliorate this, our group has hypothesized that the central dogma of KS — that a herpesvirus, Kaposi’s sarcoma-associated herpesvirus, is a necessary but not sufficient cause of KS — can be taken advantage to allow for diagnosis of KS simply based on quantification of KSHV DNA in suspicious skin or mucosal lesions. Working in Uganda, we have performed biopsies on over 500 patients referred to our skin biopsy service because of, at least some, suspicion of KS by their health care providers. In addition to pathologic evaluation in Africa, all biopsies received at least two pathologic interpretations in the U.S. In testing done in carefully controlled U.S. laboratories, quantification of lesional KSHV DNA content by either polymerase chain reaction (PCR) or loop-mediated isothermal amplification (LAMP), performed in a novel portable device called TINY, revealed very good diagnostic performance compared to gold standard U.S.-derived pathology determinations. For PCR, sensitivity for KS diagnosis was 96% and specificity 94%; for LAMP in TINY, sensitivity was 93% and specificity 94%. The next step in this work is validation of the performance of KSHV DNA quantification for KS diagnosis in real-world conditions in Africa. If the initial inferences hold, it is possible to envision a future in which KS is diagnosed within a few hours with a point-of-care device.