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Open Access Publications from the University of California

Scholarly Works (14 results)

  • Thesis
  • Peer Reviewed
UC San Diego Electronic Theses and Dissertations (2024)

Rationale: HIV and aging are associated with an increased risk for HIV-associated neurocognitive disorders (HAND) and Alzheimer’s disease (AD). Cross-sectional research among people with HIV (PWH) has shown that the apolipoprotein e4 (APOE-e4) allele and family history of dementia (FHD+) are independently associated with worse neurocognition. However, these cross-sectional data do not address the potential additive effect of FHD and APOE-e4 on rates of global and domain-specific neurocognitive decline among older PWH.Design: This study utilized longitudinal data from the CNS HIV Antiretroviral Therapy Effects Research programs (N=283 PWH; ages 45-69). Aim 1 used a 2x2 factorial analysis of covariance to model independent and interactive effects of FHD and APOE-e4 status. Aim 2 used linear mixed-effects modeling to examine global- and domain-specific neurocognitive trajectories (average follow-up = 7.0 visits over 5.4 years) in the four FHD/APOE-e4 groups linearly and non-linearly. The exploratory aim examined if demographic, neuropsychiatric, substance use, daily functioning factors, comorbidities, and HIV disease characteristics impact neurocognitive trajectories by FHD and APOE-e4 status, using linear mixed-effects modeling. Results: Cross-sectional analyses revealed lower executive functioning (p = .03) and motor skills (p = .04) T-scores among FHD+. Global T-scores trended towards significance (p = .07), with lower scores among FHD+. Mean differences in motor skills trended towards significance by APOE-e4 status (p = .08), with worse scores among APOE-e4 carriers. Longitudinal analyses revealed significant and trend-level differences in curvilinear trajectories between the FHD-/APOE-e4- and FHD+/APOE-e4+ groups in global performance (p = .01), executive functioning (p = .08), learning (p = .02), delayed recall (p = .07), and motor skills (p = .004). Lastly, demographics, depression, substance use history, cardiovascular conditions, and HIV-disease characteristics significantly predicted poorer neurocognitive outcomes, with worse global- and domain-specific trajectories in the FHD+/APOE-e4+ compared to the FHD-/APOE-e4- group. Conclusions: FHD+ and APOE-e4 jointly heighten risk of cognitive decline among middle-to-older age PWH with compounding medical and psychiatric burdens. Additional research is needed to clarify whether domain-specific differences in curvilinear cognitive trajectories between FHD+/APOE-e4+ and FHD-/APOE-e4- reflect HAND or early-stages of AD, considering there were limited sample sizes in follow-up visits and the possibility that cohorts may have been too young to detect expected neurocognitive decline.  

    Cover page: Family history of dementia and APOE e4 status predict neurocognitive trajectories among persons with HIV
    • Article
    • Peer Reviewed
    UC San Diego Previously Published Works (2021)
      Cover page: Using health technology to capture digital phenotyping data in HIV-associated neurocognitive disorders.
      • Article
      • Peer Reviewed
      UC San Diego Previously Published Works (2020)

      Background

      Heavy alcohol use negatively impacts neurocognition, but some studies report neurocognitive benefits associated with light drinking among HIV-seronegative (HIV-) older persons, suggesting a nonlinear or an inverted "J-shaped" association of alcohol consumption on neurocognition. Alcohol use is common among people with HIV (PWH); however, the association between recent "low-risk" alcohol consumption and neurocognition among PWH is poorly understood.

      Methods

      Participants included 310 PWH and 89 HIV- older (≥50 years) adults who reported alcohol abstinence or "low-risk" drinking, defined per the National Institute on Alcohol Abuse and Alcoholism criteria (i.e., ≥15 drinks/wk or ≥5 drinks/d for men; ≥8 drinks/wk or ≥4 drinks/d for women). Neurocognition was measured using global and domain-specific demographically corrected T-scores. Multiple linear regressions examined the interaction between total drinks in the last 30 days (linear and quadratic terms) and HIV serostatus on neurocognition, covarying for age, sex, lifetime major depressive disorder, lifetime nonalcohol substance use disorders, and lifetime alcohol use disorder.

      Results

      Total drinks consumed in the last 30 days did not differ by HIV serostatus (p = 0.202). Among HIV- older adults, quadratic effects of total drinks on neurocognition occurred such that optimal neurocognition (i.e., global function, executive function, learning, delayed recall, and motor skills) was detected at intermediate levels of "low-risk" drinking (~20 to 40 drinks), with poorer performance at the lower and higher ranges of "low-risk" consumption. In PWH, total drinks did not exhibit linear or quadratic associations with neurocognition.

      Conclusions

      In HIV- "low-risk" drinkers, intermediate levels of recent alcohol use were associated with better neurocognition, consistent with the inverted J-shaped association. The same nonlinear effect of recent alcohol consumption on neurocognition was absent in PWH, indicating there may be no beneficial or deleterious effects of low-risk alcohol consumption on neurocognition among PWH. Future research is warranted to examine associations between alcohol consumption and HIV-related biopsychosocial disadvantages that may supersede the neurocognitive benefits of alcohol.
        Cover page: The Effects of Low‐Risk Drinking on Neurocognition Among Older Persons Living With HIV as Compared to Those Without HIV
        • Article
        • Peer Reviewed
        UC San Diego Previously Published Works (2020)

        Background

        Methamphetamine use poses a barrier to antiretroviral therapy (ART) adherence. Black and Hispanic men who have sex with men living with HIV (PLWH) shoulder much of the health burden resulting from the methamphetamine and HIV syndemic. Smartphones are nearly ubiquitous in the USA and may be promising vehicles for delivering interventions for ART adherence and drug use cessation. However, the acceptability of using applications to collect sensitive information and deliver feedback in this population has not been adequately explored.

        Objective

        This study examined minority PLWH's appraisals of the risks of participating in smartphone-based research to promote ART adherence in the context of methamphetamine use and explored their views on appropriate steps to mitigate perceived risks of participation.

        Methods

        Three focus groups were conducted among Black and Hispanic PLWH who use methamphetamine. Of the 13 participants, 5 had previously participated in a smartphone-based observational study of ART adherence and substance use. Discussants provided feedback on smartphone-based research, including receiving probes for HIV medication adherence, mood, and substance use as well as feedback on passive location-tracking for personalized messages. Transcribed audio-recordings were thematically coded and analyzed using the qualitative software MAXQDA.

        Results

        Participants expressed confidentiality concerns related to potential unintentional disclosure of their HIV status and methamphetamine use and to possible legal consequences. They additionally expressed concerns around the invasiveness of daily assessments and the potential of methamphetamine use questions to trigger cravings. To mitigate these concerns, they suggested maintaining participant privacy by indirectly asking sensitive questions, focusing on positive behaviors (e.g., number of days sober), allowing user-initiated reporting of location to tailor messages, and ensuring adequate data protections. In addition to financial compensation, participants cited altruism (specifically, continuing a tradition of volunteerism in HIV research) as a motivator for potentially engaging in such research.

        Conclusions

        Minority PLWH have concerns regarding the use of smartphones for ART adherence and methamphetamine sobriety intervention research. However, minority PLWH are likely to participate if studies include appropriate protections against risks to confidentiality and experimental harm and are designed to offer future benefit to themselves and other PLWH.
          Cover page: Perceived risks and amelioration of harm in research using mobile technology to support antiretroviral therapy adherence in the context of methamphetamine use: a focus group study among minorities living with HIV
          • Article
          • Peer Reviewed
          UC San Diego Previously Published Works (2023)
            Cover page: Daily self-report of substance use via text message corresponds to retrospective assessment in people with HIV who use methamphetamine
            • Article
            • Peer Reviewed
            UC San Diego Previously Published Works (2023)
            Positive psychological attributes are associated with better health outcomes, yet few studies have identified their underlying constructs and none have examined their temporal trajectories in clinical vs. non-clinical samples. From data collected over 4 years from people with HIV (PWH) and HIV-uninfected (HIV-) participants, we identified two latent factors (internal strengths; socioemotional support) based on responses to seven positive psychological attributes. Internal strengths increased over 4 years for PWH, but not for HIV- comparisons. Socioemotional support did not change significantly in either group. Lower internal strengths and worse socioemotional support were related to greater depressive symptoms. We speculate that improvement in internal strengths in PWH could reflect their being in care, but this requires further study to include PWH not in care. Given the apparent malleability of internal strengths and their association with improved health outcomes, these attributes can serve as promising intervention targets for PWH.
              Cover page: Four-Year Trajectories of Internal Strengths and Socioemotional Support Among Middle-Aged and Older Adults with HIV
              • Article
              • Peer Reviewed
              UC San Diego Previously Published Works (2020)
              The co-occurrence of HIV and alcohol use disorder (AUD) amplifies risk for neural injury and neurocognitive deficits. However, the substantial neurocognitive heterogeneity across HIV+/AUD+ individuals suggests inter-individual differences in vulnerability to the neurotoxicity of comorbid HIV/AUD. Genetic variation in alcohol dehydrogenase (ADH), which metabolizes ethanol, may contribute to inter-individual neurocognitive variability. We evaluated associations between five ADH single-nucleotide polymorphisms (SNPs) and neurocognition in men stratified by HIV and lifetime AUD status. Neurobehavioral assessments were administered to 153 men. Three-way ANOVAs examined the interaction of HIV, AUD, and ADH SNPs on global and domain-specific demographically corrected T scores. Follow-up ANCOVAs adjusted for age, estimated verbal IQ, depression, and remote non-alcohol substance use disorders. HIV/AUD groups differed globally and for verbal fluency, working memory, executive function, and processing speed T scores specifically, with HIV+/AUD+ exhibiting the poorest performance. ADH4 (rs1126671) was associated with large effects on working memory (d = - 1.16, p = .001) and executive function (d = - 0.77, p = .028) selectively in HIV+/AUD+, which remained significant in ANCOVA models. ADH1A (rs3819197) moderated the deleterious effects of HIV+/AUD+ on processing speed such that HIV+/AUD+ related to slower information processing in A allele carriers but not GG homozygotes (ps < 0.03). Preliminary findings suggest genetic variation in the ADH pathway moderates the deleterious neurocognitive effects of comorbid HIV/AUD. Differential metabolism of heavy ethanol exposure may compromise neurocognition under conditions of neurobiological stress, such as in HIV infection. The functional effects on ethanol metabolism of ADH SNPs examined in this study remain poorly understood, warranting further examination of pharmacokinetic mechanisms mediating ADH gene-neurobehavior relationships in HIV.
                • Article
                • Peer Reviewed
                UC San Diego Previously Published Works (2020)
                The co-occurrence of HIV and alcohol use disorder (AUD) amplifies risk for neural injury and neurocognitive deficits. However, the substantial neurocognitive heterogeneity across HIV+/AUD+ individuals suggests inter-individual differences in vulnerability to the neurotoxicity of comorbid HIV/AUD. Genetic variation in alcohol dehydrogenase (ADH), which metabolizes ethanol, may contribute to inter-individual neurocognitive variability. We evaluated associations between five ADH single-nucleotide polymorphisms (SNPs) and neurocognition in men stratified by HIV and lifetime AUD status. Neurobehavioral assessments were administered to 153 men. Three-way ANOVAs examined the interaction of HIV, AUD, and ADH SNPs on global and domain-specific demographically corrected T scores. Follow-up ANCOVAs adjusted for age, estimated verbal IQ, depression, and remote non-alcohol substance use disorders. HIV/AUD groups differed globally and for verbal fluency, working memory, executive function, and processing speed T scores specifically, with HIV+/AUD+ exhibiting the poorest performance. ADH4 (rs1126671) was associated with large effects on working memory (d = - 1.16, p = .001) and executive function (d = - 0.77, p = .028) selectively in HIV+/AUD+, which remained significant in ANCOVA models. ADH1A (rs3819197) moderated the deleterious effects of HIV+/AUD+ on processing speed such that HIV+/AUD+ related to slower information processing in A allele carriers but not GG homozygotes (ps < 0.03). Preliminary findings suggest genetic variation in the ADH pathway moderates the deleterious neurocognitive effects of comorbid HIV/AUD. Differential metabolism of heavy ethanol exposure may compromise neurocognition under conditions of neurobiological stress, such as in HIV infection. The functional effects on ethanol metabolism of ADH SNPs examined in this study remain poorly understood, warranting further examination of pharmacokinetic mechanisms mediating ADH gene-neurobehavior relationships in HIV.
                  Cover page: Genetic variation in alcohol dehydrogenase is associated with neurocognition in men with HIV and history of alcohol use disorder: preliminary findings
                  • Article
                  • Peer Reviewed
                  UC San Diego Previously Published Works (2022)

                  Objective

                  Given the aging population of people with HIV (PWH), along with increasing rates of binge drinking among both PWH and the general older adult population, this study examined the independent and interactive effects of HIV, binge drinking, and age on neurocognition.

                  Method

                  Participants were 146 drinkers stratified by HIV and binge drinking status (i.e., ≥4 drinks for women and ≥5 drinks for men within approximately 2 h): HIV+/Binge+ (n = 30), HIV-/Binge+ (n = 23), HIV+/Binge- (n = 55), HIV-/Binge- (n = 38). All participants completed a comprehensive neuropsychological battery measuring demographically-corrected global and domain-specific neurocognitive T scores. ANCOVA models examined independent and interactive effects of HIV and binge drinking on neurocognitive outcomes, adjusting for overall alcohol consumption, lifetime substance use, sex, and age. Subsequent multiple linear regressions examined whether HIV/Binge group moderated the relationship between age and neurocognition.

                  Results

                  HIV+/Binge+ participants had worse global neurocognition, processing speed, delayed recall, and working memory than HIV-/Binge- participants (p's < .05). While there were significant main effects of HIV and binge drinking, their interaction did not predict any of those neurocognitive outcomes (p's > .05). Significant interactions between age and HIV/Binge group showed that HIV+/Binge+ participants demonstrated steeper negative relationships between age and neurocognitive outcomes of learning, delayed recall, and motor skills compared to HIV-/Binge- participants (p's < .05).

                  Conclusions

                  Results showed adverse additive effects of HIV and binge drinking on neurocognitive functioning, with older adults demonstrating the most vulnerability to these effects. Findings support the need for interventions to reduce binge drinking, especially among older PWH.
                    Cover page: Binge Drinking Relates to Worse Neurocognitive Functioning Among Adults Aging with HIV
                    • Article
                    • Peer Reviewed
                    UC San Diego Previously Published Works (2020)
                    Many factors can influence perceptions of successful aging (SA), including social isolation and poor physical health. We hypothesized that social support attenuates the negative effect of plasma D-dimer, a correlate of HIV and aging, on SA. Participants included 230 adults (134 people with HIV; PWH, 96 HIV-), ages 36-65, segregated into age cohorts with up to 5 yearly visits. Multilevel modeling examined longitudinal within-person associations between D-dimer, social support, and SA. Social support moderated the relationship between D-dimer and SA and was significant among PWH and older individuals (ages 56-65), but not HIV- or younger cohorts. This association was significant only at extreme levels of social support, with significant decreases in social support potentiating the negative impact of D-dimer on SA and significant increases in social support facilitating increased SA. Despite declining health, high social support may improve SA in PWH and older adults, and low support may be especially problematic for older adults.
                      Cover page: Social support moderates D-dimer and self-rated successful aging within people with HIV and older adults
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