The contribution of immune activation and accelerated aging in multiple myeloma occurring in HIV-infected population

: The widespread use of antiretroviral treatment results in a significant improvement in immunological condition of people living with HIV (PLWH) who nevertheless experience a significantly increased risk to develop non-Hodgkin lymphoma compared with the general population. Despite many literature observations regarding multiple myeloma in PLWH, a consensus on its relevance in HIV infection does not exist. A number of large population studies on multiple myeloma in PLWH gave contrasting results, fluctuating from increased standardized incidence ratios to the lack of observed cases of multiple myeloma. Use of antiretroviral treatment, in this context, seems to induce a slight reduction of standardized incidence ratio, although with a partial effect, especially in young patients. However, a high variability in clinical onset has been described in different reports: the only common feature of multiple myeloma in PLWH is an atypical presentation as compared with general population, with a worse prognosis in case of uncontrolled HIV infection. We identified three pathogenetic steps in the complex scenario of multiple myeloma in PLWH: first, antigenic trigger; second, persistent T cell deficiency/dysfunction; third, altered regulation of B cells. All these pathogenetic steps play a role in immunological dysregulation, leading to B cell abnormalities and hyperactivation and, finally, resulting in the development of lymphoid malignancies. HIV has a role in each one of these three steps, due to its ability to trigger and dysregulate immune system. We hypothesize that HIV could be closely implicated in the multiple myeloma development in PLWH by accelerating the carcinogenesis events in a complex and only partially understood early aging process.