Covariates were included into multi-variable models, if univariable analyses showed that they were associated with the outcome variable at the .Significance level. Backward model selection process was applied and the final models kept only those covariates that had P values <.05. For reported models, effects of predictors are described by regression coefficients and their standard errors . A third set of analyses was performed in the subgroup of participants who did not show NCI at baseline. We used Cox proportional hazard models to assess time to NCI. Two models were run: a baseline model, which used values of the VACS Index and baseline covariates; and a time-dependent model, which included time-dependent measures of the VACS Index and covariates. Covariate selection followed the same process as described above. Hazard ratio was used as a measure of effect size for these analyses. Given that the VACS Index was initially developed in HIV-infected persons initiating therapy, we investigated interactions between the VACS Index and ART status for all 3 types of analyses. Based on prior cross-sectional findings showing that HIV infected persons with particularly elevated VACS Index scores might be at highest risk for NCI, we categorized VACS Index scores at each time point based on cutoff scores. These cutoff scores were based on the distribution of the VACS Index at baseline of the current sample . We then performed again the main analyses described above using these categories of the VACS Index . P values for pairwise comparisons of the groups were adjusted for multiple testing using Tukey and false discovery rate methods, and Cohen’s d was computed to measure effect sizes of group differences. All analyses were carried with the statistical software R and used 2-sided tests and a significance level of .05, unless stated otherwise. Sample sizes vary by model, because complete data were not available for some of the covariates .

For a subset of participants ,growing cannabis outdoors the baseline visit for current analyses was their first time to complete neurocognitive assessments. This allowed us to investigate neurocognitive change based on published summary regression-based change scores in this subset of participants. Following methods outlined elsewhere, we determined overall neurocognitive change and performed again core analyses presented above. Results were comparable to previous findings; that is, the VACS Index was significantly associated with neurocognitive decline in time-dependent models after adjustment for significant covariates.We also investigated whether lifetime history of intravenous drug use affected the association of the VACS Index with neurocognitive change in the subset of participants for whom data were available, as well as whether CNS penetration effectiveness affected this association among persons on ART. Findings from all core models showed that the association between the VACS Index and neurocognitive change was substantially similar to that of prior analyses.The present longitudinal study adds to the evolving scientific literature on the VACS Index and NCI by showing that changes in VACS Index scores correspond to changes in neurocognitive function over time in a large, well-characterized HIV-infected cohort. Baseline VACS Index scores were not significantly associated with change in global neurocognitive function during the overall follow-up period of up to 6 years . This suggests that the VACS Index might not be a good predictor of subsequent neurocognitive change over the span of a number of years. However, we found statistically significant associations in time-dependent analyses, indicating that changes in the VACS Index correspond to concurrent changes in global neurocognitive function. These significant associations, albeit relatively small, were found across multiple neurocognitive domains, and remained significant after adjusting for the effect of potential covariates, suggesting an independent effect of the VACS Index. Analyses of a subset of participants who were neurocognitively normal at baseline yielded a similar pattern of results. Baseline VACS Index scores were not significantly associated with incident NCI in adjusted analyses.

However, time-dependent analyses showed that increases in VACS Index scores significantly increased the probability of becoming neurocognitively impaired. Because the VACS Index was initially developed in samples of HIV-infected persons initiating ART, we investigated whether ART status modified the association between the VACS Index and neurocognitive change. We found that this was the case for the memory domain in time-dependent analyses, where there was a significant association between VACS Index scores and memory decline among untreated participants but not among participants receiving ART. Other biomarkers not included in the VACS Index might be important for memory decline in participants on ART. In line with this, effect sizes of analyses by VACS Index group tended to be smaller for learning and memory. Memory problems are the hallmark of neurocognitive conditions of aging, such as Alzheimer’s disease. Considering biomarkers of these other age-related conditions might assist in developing an index that fully encompasses the neurocognitive changes observed among persons aging with HIV infection. We have also found that the association of learning and memory to NCI was not significant among Hispanics. Unfortunately, we did not have enough Hispanic participants with longitudinal data to examine ethnic/racial differences in the current study. Prior findings had indicated that it is valuable to categorize the VACS Index to better understand its association with NCI. In the current study, we found that participants who scored high on the VACS Index were significantly more likely to experience global neurocognitive decline, with effect sizes indicating a relatively strong effect. Among participants who were neurocognitively normal at baseline, those who scored within the high VACS Index range were twice as likely to develop incident NCI as those in the low VACS Index group, and 76% more likely than those in the middle group. Overall, results from these analyses on categorized VACS Index scores support the notion that those with particularly higher VACS Index values are indeed at risk for worse neurocognitive outcomes. Our study had several limitations. Our group of participants was relatively young. Including older participants with higher rates of medical comorbid conditions might strengthen the association between the VACS Index and neurocognitive change.

Most baseline assessments in the present study were completed in the early 2000s and the median duration of HIV infection was 9 years. Thus, many of the participants were diagnosed with HIV infection in the era before combination ART era, and findings might differ in more recently infected cohorts. A relatively small proportion of participants in our sample were of Hispanic origin. Given recent findings, future studies including more Hispanic subjects would better address whether longitudinal associations between the VACS Index and neurocognitive change differ by ethnic group. It has also yet to be established whether other biomarkers not included in the VACS Index might increase its predictive utility for detecting NCI. Some covariates examined in present analyses were unexpectedly associated with neurocognitive change; for example, cannabis use and being off ART were associated with better neurocognitive performance in some models. Although these potentially interesting associations warrant further investigation,microgreens shelving our models were not constructed to investigate their impact on neurocognitive change, and thus caution is warranted in interpreting these findings. Most relevant for the purpose of the current study, the VACS Index was significantly associated with neurocognitive change, even after adjustment for multiple covariates. Another future direction is to investigate whether the combination of the VACS Index and NCI might help improve predictive power for mortality risk among HIV infected persons. Some of the strengths of the study include the use of a comprehensive neurocognitive battery that has been validated in persons with HIV infection and enabled the examination of domains based on composite scores. Overall, baseline VACS Index scores may not be a good predictor of neurocognitive change in the longer term. Changes in VACS Index scores, however, correspond to changes in neurocognition. Although the strength of this association is relatively weak in analyses using continuous scores of the VACS Index, results from categorized VACS Index scores indicate that having very high VACS Index scores might indicate a notable increased risk for neurocognitive decline and for incident NCI. These findings support the VACS Index as a simple tool for identifying HIV-infected patients who are at high risk for NCI and might warrant further neurocognitive follow-up.One -fifth of new HIV diagnoses in the United States are in young people aged 13 to 24 years. Youth are more likely than other age groups to engage in behaviors, such as unprotected sex, substance use, and having multiple sexual partners that place them at higher risk for infection with HIV; however, youth are less likely than older Americans to receive HIV testing.

After infection, adolescents and young adults are also less likely than other age groups to be connected with HIV-related health care, and have low rates of viral suppression. Risk of HIV transmission is greatly elevated for the many young people involved in the U.S. justice system. In 2016, over 850,000 youth under age 18 were arrested. At any given time, nearly 50,000 youth are incarcerated or detained in residential settings. Prevalence of other sexually transmitted infections among youth with justice involvement is significantly higher than what is observed in the general adolescent population,ranging from 9% and 13% chlamydia diagnosis among newly arrested males and females, respectively to 20 to 42% infection rates in studies of detained females. Yet prevalence rates of HIV among the juvenile justice population remain largely unknown and challenging to accurately measure, particularly since many youth are not screened for HIV when entering the juvenile justice system. However, behavioral risk data are clear. Nearly 90% of youth in juvenile detention are sexually active. Thirty -five percent of boys and over 40% of girls report unprotected sex in the past month prior to detention, and 20% of boys and 10% of girls report ever having sex with a high-risk partner. Substance use is often a catalyst for risky behavior: approximately a third of detained youth report having had unprotected sex while drunk or high. As formerly detained youth age into young adulthood, HIV/STI risk behaviors and substance use remain substantially higher than those experienced by youth in the general population, pointing to the enduring influence of incarceration and criminal justice involvement in long-term public health outcomes. Young adults ages 20–-29 years had the highest rates of new HIV infection in the US in 2014, accounting for 36% of new HIV diagnoses, with the vast majority occurring among racial/ethnic minorities. The vast majority of juveniles involved in the justice system return to their communities following arrest, typically within 2 weeks, where they have opportunities to engage in risky substance use and sexual behaviors that increase HIV vulnerability. Individuals supervised by the justice system living in the community may be at higher risk of HIV acquisition and have more difficulty accessing treatment than those incarcerated. These populations often struggle with lack of health insurance, increased rates of sexually transmitted infections, and housing instability, all factors associated with increased risk of HIV acquisition. This is critical to consider for youth involved in the justice system, as legal policies over the past decade have increasingly emphasized diverting justice-involved youth from detention to the community. Diversion programs are an effective way to reduce recidivism. However, fewer youth may receive STI/HIV screening and treatment when not in supervised settings. Congruent with juvenile justice policy changes , recent research examining the interrelationships among HIV/STI risk and substance use has expanded from focusing on detained youth to communitysupervised . For example, in 2010, when our group published a comprehensive rigorous review of any published HIV -prevention interventions for justice involved youth, 16 studies were identified and of these, four were conducted with non-detained or community-supervised justice-involved populations. Five years later, Hong and colleagues published a comprehensive review of HIV/STI -prevention interventions among detained and delinquent youth, of which only 1 of 15 identified studies focused on non-detained youth. To advance public health priorities in line with shifting juvenile justice policy changes, clinicians, researchers, and policymakers must gain a better understanding of justice-involved youths’ intersecting HIV and substance use risks, particularly in their natural environments. We summarize recent main themes of this area of research using data from published reports and provide future directions to guide the field as to requisite next clinical, research, and policy steps regarding HIV prevention and substance use for justice-involved youth. In order to capture all relevant, published studies addressing this broad topic, a comprehensive search strategy was employed, using multiple online search tools.