Background: As adult brain structure is primarily established in early life, genetic and environmental exposures in infancy and childhood influence the risk for Alzheimer disease (AD). In this systematic review, we identified several early life risk factors and discussed the evidence and underlying mechanism for each. Summary: Early risk factors for AD may alter brain anatomy, causing vulnerability to AD-related dementia later in life. In the perinatal period, both genes and learning disabilities have been associated with the development of distinct AD phenotypes. During early childhood, education and intellect, as well as body growth, may predispose to AD through alterations in cognitive and brain reserve, though the specific mediators of neural injury are disputed. Childhood socioeconomic status (SES) may predispose to AD by influencing adult SES and cognition. Association of these risk factors with underlying AD pathology (rather than just clinical diagnosis) has not been sufficiently examined. Key Messages: Factors that impede or alter brain growth during early life could render certain brain regions or networks selectively vulnerable to the onset, accumulation or spread of AD-related pathology during later life. Careful life-course epidemiology could provide clues as to why the brain systematically degenerates during AD.

Introduction In 2004, the U.S. President’s Emergency Plan for AIDS Relief (PEPFAR), with CDC as a major U.S. government implementing agency, began providing HIV antiretroviral therapy (ART) worldwide. Through suppression of HIV viral load, effective ART reduces morbidity and mortality among persons with HIV infection and prevents vertical and sexual transmission. Methods To describe program impact, data were analyzed from all PEPFAR programs and from six countries that have conducted nationally representative Population-based HIV Impact Assessment (PHIA) surveys, including PEPFAR programmatic data on the number of persons with HIV infection receiving PEPFAR-supported ART (2004–2022), rates of viral load coverage (the proportion of eligible persons with HIV infection who received a viral load test) and viral load suppression (proportion of persons who received a viral load test with <1,000 HIV copies per mL of blood) (2015–2022), and population viral load suppression rates in six countries that had two PHIA surveys conducted during 2015–2021. To assess health system strengthening, data on workforce and laboratory systems were analyzed. Results By September 2022, approximately 20 million persons with HIV infection in 54 countries were receiving PEPFAR-supported ART (62% CDC-supported); this number increased 300-fold from the 66,550 reported in September 2004. During 2015–2022, viral load coverage more than tripled, from 24% to 80%, and viral load suppression increased from 80% to 95%. Despite increases in viral load suppression rates and health system strengthening investments, variability exists in viral load coverage among some subpopulations (children aged <10 years, males, pregnant women, men who have sex with men [MSM], persons in prisons and other closed settings [persons in prisons], and transgender persons) and in viral load suppression among other subpopulations (pregnant and breastfeeding women, persons in prisons, and persons aged <20 years). Conclusions and implications for public health practice Since 2004, PEPFAR has scaled up effective ART to approximately 20 million persons with HIV infection in 54 countries. To eliminate HIV as a global public health threat, achievements must be sustained and expanded to reach all subpopulations. CDC and PEPFAR remain committed to tackling HIV while strengthening public health systems and global health security.

No abstract