HIV-Tat protein-accelerated aging

accelerates aging [1]. This effect is expected to become increasingly problematic because currently, in the United States, more than half of those infected with HIV are over 50 years old and thus are subjected to the combined effects of HIV and aging [1]. Antiretroviral therapy (ART) for HIV greatly suppresses viral loads and reduces HIV-related morbidity and mortality, enabling people living with HIV (PLWH) to have a much better quality-of-life and survive into old age. However, ART does not prevent neurological disturbances from developing in PLWH including disruptions in mood and cognitive ability and the development of intractable pain states. These comorbidities reduce quality-of-life and catalyze problematic behaviors including substance use disorders that worsen HIVand age-related outcomes. These sequelae occur in part because ART does not stop HIV reservoirs from synthesizing and releasing toxic proteins such as the transactivator of transcription (Tat) protein, appreciable levels of which are present in the central nervous system during ART (e.g., [2]). In particular, Tat is neurotoxic and it induces neuroinflammation, oxidative stress, and mitochondrial dysfunction (see [3]), effects that also are associated with aging [1].