Use of a High Resolution Melting (HRM) Assay to Compare Gag, Pol, and Env Diversity in Adults with Different Stages of HIV Infection

Cross-sectional assessment of HIV incidence relies on laboratory methods to discriminate between recent and non-recent HIV infection. Because HIV diversifies over time in infected individuals, HIV diversity may serve as a biomarker for assessing HIV incidence. We used a high resolution melting (HRM) diversity assay to compare HIV diversity in adults with different stages of HIV infection. This assay provides a single numeric HRM score that reflects the level of genetic diversity of HIV in a sample from an infected individual.HIV diversity was measured in 203 adults: 20 with acute HIV infection (RNA positive, antibody negative), 116 with recent HIV infection (tested a median of 189 days after a previous negative HIV test, range 14-540 days), and 67 with non-recent HIV infection (HIV infected >2 years). HRM scores were generated for two regions in gag, one region in pol, and three regions in env.Median HRM scores were higher in non-recent infection than in recent infection for all six regions tested. In multivariate models, higher HRM scores in three of the six regions were independently associated with non-recent HIV infection.The HRM diversity assay provides a simple, scalable method for measuring HIV diversity. HRM scores, which reflect the genetic diversity in a viral population, may be useful biomarkers for evaluation of HIV incidence, particularly if multiple regions of the HIV genome are examined

The evolution of virus diseases: their emergence, epidemicity, and control

The evolution of virus diseases, both their emergence and disappearance, involves complex interactions between the agent, the host, and the environment. These themes are illustrated by three examples, poliomyelitis of humans, bovine spongiform encephalopathy of cattle, and AIDS of humans. Emergence may be due to evolution of the virus genome, such as probably occurred in parvovirus infection of dogs and human immunodeficiency virus infection of humans. However, emergence of some new viral diseases can be traced to host or environmental factors with no change in the agent. Poliomyelitis, an enteric infection, probably emerged as an epidemic disease due to improvements in personal hygiene and public sanitation which led to a delay in the occurrence of initial infections from the perinatal period (when maternal antibody protected against paralysis) to later childhood when passive immunity had waned. Bovine spongiform encephalopathy is a common source epidemic which was transmitted through nutritional supplements which became contaminated due to a change in the method of production of bone meal supplements in rendering plants. The reduction or disappearance of virus diseases usually involves human intervention, as exemplified by immunization for smallpox and other virus diseases of humans and animals. Naturally occurring immunity may lead to fadeout of a virus as seen with measles in isolated island populations. Evolution of a virus can also result in waning of a disease as seen with myxomatosis among rabbits in Australia. The evolution of virus diseases is a provocative scientific topic and carries lessons relevant to the control of important diseases of humans, animals, and plants

Methodology for Evaluating a Partially Controlled Longitudinal Treatment Using Principal Stratification, With Application to a Needle Exchange Program

We consider studies for evaluating the short-term effect of a treatment of interest on a time-to-event outcome. The studies we consider are partially controlled in the following sense: (1) Subjects’ exposure to the treatment of interest can vary over time, but this exposure is not directly controlled by the study; (2) subjects’ follow-up time is not directly controlled by the study; and (3) the study directly controls another factor that can affect subjects’ exposure to the treatment of interest as well as subjects’ follow-up time. When factors (1) and (2) are both present in the study, evaluating the treatment of interest using standard methods, including instrumental variables, does not generally estimate treatment effects. We develop the methodology for estimating the effect of treatment in this setting of partially controlled studies under explicit assumptions using the framework for principal stratiŽ cation for causal inference. We illustrate our methods by a study to evaluate the efŽ cacy of the Baltimore Needle Exchange Program to reduce the risk of human immunodeŽ ciency virus (HIV) transmission, using data on distance of the program’s sites from the subjects

Impact of interventions to reduce Alzheimer's disease pathology on the prevalence of dementia in the oldest-old.

IntroductionThe number of persons aged >90 years will grow significantly in coming decades. This group has the highest rates of dementia, most commonly Alzheimer's disease (AD).MethodsUsing The 90+ Study, we developed a statistical model for dementia risk based on brain pathologies. Intervention scenarios which reduce or eliminate AD pathology were considered, and the numbers of dementia cases among the U.S. oldest-old that could be prevented were estimated.ResultsThe U.S. dementia prevalence among the oldest-old will increase from 1.35 million in 2015 to 4.72 million in 2050. If interventions eliminate AD pathology, dementia prevalence would be reduced by approximately 50%, averting nearly 2.4 million cases in 2050. However, large numbers of dementia cases would still remain.DiscussionReducing AD pathology would significantly decrease the public health burden of dementia. However, other interventions are needed to address the burden associated with other dementing pathologies prevalent in the oldest-old

Racial and Ethnic Disparities in Years of Potential Life Lost Attributable to COVID-19 in the United States: An Analysis of 45 States and the District of Columbia.

The coronavirus disease 2019 (COVID-19) epidemic in the United States has disproportionately impacted communities of color across the country. Focusing on COVID-19-attributable mortality, we expand upon a national comparative analysis of years of potential life lost (YPLL) attributable to COVID-19 by race/ethnicity (Bassett et al., 2020), estimating percentages of total YPLL for non-Hispanic Whites, non-Hispanic Blacks, Hispanics, non-Hispanic Asians, and non-Hispanic American Indian or Alaska Natives, contrasting them with their respective percent population shares, as well as age-adjusted YPLL rate ratios-anchoring comparisons to non-Hispanic Whites-in each of 45 states and the District of Columbia using data from the National Center for Health Statistics as of 30 December 2020. Using a novel Monte Carlo simulation procedure to perform estimation, our results reveal substantial racial/ethnic disparities in COVID-19-attributable YPLL across states, with a prevailing pattern of non-Hispanic Blacks and Hispanics experiencing disproportionately high and non-Hispanic Whites experiencing disproportionately low COVID-19-attributable YPLL. Furthermore, estimated disparities are generally more pronounced when measuring mortality in terms of YPLL compared to death counts, reflecting the greater intensity of the disparities at younger ages. We also find substantial state-to-state variability in the magnitudes of the estimated racial/ethnic disparities, suggesting that they are driven in large part by social determinants of health whose degree of association with race/ethnicity varies by state

Racial and Ethnic Disparities in Years of Potential Life Lost Attributable to COVID-19 in the United States: An Analysis of 45 States and the District of Columbia.

The coronavirus disease 2019 (COVID-19) epidemic in the United States has disproportionately impacted communities of color across the country. Focusing on COVID-19-attributable mortality, we expand upon a national comparative analysis of years of potential life lost (YPLL) attributable to COVID-19 by race/ethnicity (Bassett et al., 2020), estimating percentages of total YPLL for non-Hispanic Whites, non-Hispanic Blacks, Hispanics, non-Hispanic Asians, and non-Hispanic American Indian or Alaska Natives, contrasting them with their respective percent population shares, as well as age-adjusted YPLL rate ratios-anchoring comparisons to non-Hispanic Whites-in each of 45 states and the District of Columbia using data from the National Center for Health Statistics as of 30 December 2020. Using a novel Monte Carlo simulation procedure to perform estimation, our results reveal substantial racial/ethnic disparities in COVID-19-attributable YPLL across states, with a prevailing pattern of non-Hispanic Blacks and Hispanics experiencing disproportionately high and non-Hispanic Whites experiencing disproportionately low COVID-19-attributable YPLL. Furthermore, estimated disparities are generally more pronounced when measuring mortality in terms of YPLL compared to death counts, reflecting the greater intensity of the disparities at younger ages. We also find substantial state-to-state variability in the magnitudes of the estimated racial/ethnic disparities, suggesting that they are driven in large part by social determinants of health whose degree of association with race/ethnicity varies by state

Impact of interventions to reduce Alzheimer's disease pathology on the prevalence of dementia in the oldest-old.

IntroductionThe number of persons aged >90 years will grow significantly in coming decades. This group has the highest rates of dementia, most commonly Alzheimer's disease (AD).MethodsUsing The 90+ Study, we developed a statistical model for dementia risk based on brain pathologies. Intervention scenarios which reduce or eliminate AD pathology were considered, and the numbers of dementia cases among the U.S. oldest-old that could be prevented were estimated.ResultsThe U.S. dementia prevalence among the oldest-old will increase from 1.35 million in 2015 to 4.72 million in 2050. If interventions eliminate AD pathology, dementia prevalence would be reduced by approximately 50%, averting nearly 2.4 million cases in 2050. However, large numbers of dementia cases would still remain.DiscussionReducing AD pathology would significantly decrease the public health burden of dementia. However, other interventions are needed to address the burden associated with other dementing pathologies prevalent in the oldest-old

Chronic lymphocytic leukemia and acquired disorders affecting the immune system: A case-control study

The relationship of a number of subacute or chronic infectious diseases, connective tissue or autoimmune disorders, allergic conditions, and surgical excision of lymphoid tissue with chronic lymphocytic leukemia (CLL) was examined in a case-control study involving 342 cases and 342 matched controls. In both analyses of all matched pairs and those pairs in which both subjects were respondents, no statistically significant association was found between a history of subacute viral infections or subacute and chronic bacterial infections and CLL. Connective tissue or autoimmune disorders also were found not to be associated with CLL. Examination of the association between several allergic conditions and CLL suggested a protective effect as did a doseresponse analysis, although none of the individual disorders showed a statistically significant relationship; however, a test for linear trend was significant (P=.04). Similarly, examination of the relationship between surgical excision of lymphoid tissue in several anatomic locations and CLL showed a protective effect, statistically significant for tonsillectomy-adenoidectomy (odds ratio = 0.69; 95% confidence interval = 0.48, 0.98). A statistically significant negative dose-response relationship, substantiating the protectiveness of the effect, was found. © 1986, Oxford University Press. All rights reserved