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Transactive response DNA-binding protein 43 kDa (TDP-43) is aberrantly aggregated and phosphorylated in frontotemporal lobar degeneration of the TDP-43 type (FTLD-TDP), and in limbic-predominant age-related TDP-43 encephalopathy neuropathologic change (LATE-NC). We examined data from the National Alzheimer's Coordinating Center to compare clinical features of autopsy-confirmed LATE-NC and FTLD-TDP. A total of 265 LATE-NC and 92 FTLD-TDP participants were included. Cognitive and behavioral symptoms were compared, stratified by level of impairment based on global clinical dementia rating (CDR) score. LATE-NC participants were older at death, more likely to carry APOE ε4, more likely to have Alzheimer disease neuropathology, and had lower (i.e. less severe) final CDR global scores than those with FTLD-TDP. Participants with FTLD-TDP were more likely to present with primary progressive aphasia, or behavior problems such as apathy, disinhibition, and personality changes. Among participants with final CDR score of 2–3, those with LATE-NC were more likely to have visuospatial impairment, delusions, and/or visual hallucinations. These differences were robust after sensitivity analyses excluding older (≥80 years at death), LATE-NC stage 3, or severe Alzheimer cases. Overall, FTLD-TDP was more globally severe, and affected younger participants, whereas psychoses were more common in LATE-NC.

Background Despite high efficacy of oral antiretroviral therapy (ART), viral suppression among adolescents and young adults (AYA) living with HIV in sub-Saharan Africa (SSA) remains low. Compared to daily oral ART, bimonthly long-acting injectable ART (LA-ART) may simplify adherence, improve clinical outcomes, and decrease HIV transmission in this priority population. However, LA-ART will likely cost more than oral ART and the cost threshold at which LA-ART will be cost effective in SSA has not been evaluated. Methods We adapted a mathematical model of HIV transmission and progression in Kenya to include HIV acquisition and viral suppression among AYA (age 10–24). We projected the population-level health and economic impact of providing LA-ART to AYA over a 10-year time horizon assuming oral ART costs of US$233 annually and a two-month duration of viral suppression per LA-ART injection. We calculated the maximum cost at which switching from oral to LA-ART would be considered cost-effective, using thresholds of $500 and $1,508 per disability-adjusted life year averted (WHO's threshold of HIV treatment interventions and Kenya's gross domestic product per capita). Findings Assuming 85% of AYA switch from oral to injectable formulations, LA-ART is estimated to prevent 40,540 infections and 20,480 deaths over 10 years. The maximum increase in the annual per-person cost of receiving LA-ART is estimated to be $89 and $236 for LA-ART to be cost-effective under the thresholds of $500 and $1,508 per DALY averted, respectively. The cost threshold was lower when non-adherent oral ART AYA users were assumed to be less likely to switch to LA-ART. Interpretation Providing LA-ART to AYA can be cost-effective in Kenya if it is less than twice the cost of oral ART. Long-acting injectable ART for priority populations with low viral suppression has the potential to cost-effectively avert disability and death. Funding National Institutes of Health (R01 HD085807; PI: Kohler)