Personal narrative writing workshops for medical students and patients with HIV: narrative medicine in the post-HAART era

Since the advent of highly active antiretroviral therapy(HAART) in the mid-1990's, HIV in the United States has become a chronic and largely controllable disease. Adherence to therapy is one of the most crucial aspects of HIV treatment and control due to the high risk of viral resistance. The main barriers to successful treatment are now psychosocial and structural, including social stigma and the high burden of disease in vulnerable communities. To improve clinical outcomes, physicians today must learn to engage with their patients on the level of their lived experiences, which include their social backgrounds and personal values and priorities. In 2016, supported by a Narrative Medicine Fellowship from Columbia University, we piloted a novel narrative medicine-based medical education intervention in which patients with HIV and medical students from the Keck School of Medicine of the University of Southern California wrote and shared personal narratives with each other. Nine medical students and five patients participated in one of two five-week long workshop series. Patients were recruited from the Maternal, Child, and Adolescent/Adult Clinic at Los Angeles County General.Mixed methods were used to evaluate the feasibility and effectiveness of the intervention. This included the development of a grounded theory of participants’ experiences of the workshop series. Participants articulated how the workshop series expanded their sense of agency, humanity, and empathy toward others, enabling them to explore new ideals for therapeutic physician-patient relationships. The results of the study, as well as the workshop series method and syllabus, will be presented.

Impact of medications prescribed for treatment of attention-deficit hyperactivity disorder on physical growth in children and adolescents with HIV.

OBJECTIVE: To examine the relationships between physical growth and medications prescribed for symptoms of attention-deficit hyperactivity disorder in children with HIV. METHODS: Analysis of data from children with perinatally acquired HIV (N = 2251; age 3-19 years), with and without prescriptions for stimulant and nonstimulant medications used to treat attention-deficit hyperactivity disorder, in a long-term observational study. Height and weight measurements were transformed to z scores and compared across medication groups. Changes in z scores during a 2-year interval were compared using multiple linear regression models adjusting for selected covariates. RESULTS: Participants with (n = 215) and without (n = 2036) prescriptions were shorter than expected based on US age and gender norms (p \u3c .001). Children without prescriptions weighed less at baseline than children in the general population (p \u3c .001) but gained height and weight at a faster rate (p \u3c .001). Children prescribed stimulants were similar to population norms in baseline weight; their height and weight growth velocities were comparable with the general population and children without prescriptions (for weight, p = .511 and .100, respectively). Children prescribed nonstimulants had the lowest baseline height but were similar to population norms in baseline weight. Their height and weight growth velocities were comparable with the general population but significantly slower than children without prescriptions (p = .01 and .02, respectively). CONCLUSION: The use of stimulants to treat symptoms of attention-deficit hyperactivity disorder does not significantly exacerbate the potential for growth delay in children with HIV and may afford opportunities for interventions that promote physical growth. Prospective studies are needed to confirm these findings

Sertraline Pharmacokinetics in HIV-Infected and Uninfected Children, Adolescents, and Young Adults

Objective: Due to potential disease and drug interactions, the appropriate sertraline starting dose and titration range may require adjustment in pediatric patients living with HIV. This is the first report of sertraline pharmacokinetics in HIV-infected youth.Methods: IMPAACT P1080 was a multicenter pilot study describing psychiatric medication pharmacokinetics in HIV-infected and uninfected youth. Participants were stable on sertraline, >6 to <25 years old, and (1) HIV-uninfected (HIV(–)), (2) HIV-infected taking efavirenz (EFV), or (3) HIV-infected taking boosting ritonavir/protease inhibitor (PI/r). Sampling occurred at pre-dose, 2, 4, 6, 12, and 24-h post-dose. Analyses were performed for sertraline and N-desmethylsertraline, and CYP2D6 phenotyping was completed with dextromethorphan.Results: Thirty-one participants (16 HIV(-), 12 PI/r, and 3 EFV) had median (range) weight, age, and dose of 69.5 (31.5–118.2) kg, 21.8 (9.1–24.7) years, and 75.0 (12.5–150.0) mg once daily. Sertraline exposure was highest for HIV(–) and lowest for EFV cohorts; median dose-normalized AUC0−24 was 1176 (HIV(–)), 791 (PI/r) and 473 (EFV) ng*hr/mL, and C24 was 32.7 (HIV(–)), 20.1 (PI/r), and 12.8 (EFV) ng/mL. The urinary dextromethorphan/dextrorphan (DXM/DXO) ratio was higher in HIV(–) vs. PI/r cohorts (p = 0.01). Four HIV(–) participants were CYP2D6 poor metabolizers (ln(DXM/DXO) of >-0.5).Conclusions: HIV(–) cohort had the highest sertraline exposure. Sertraline exposure was ~40% lower in the PI/r cohort than in HIV(–); the need to alter sertraline dose ranges for PI/r participants is not clear. The impact of efavirenz on sertraline needs further investigation due to limited numbers of EFV participants

Effect of Cytomegalovirus Co-Infection on Normalization of Selected T-Cell Subsets in Children with Perinatally Acquired HIV Infection Treated with Combination Antiretroviral Therapy

Background: We examined the effect of cytomegalovirus (CMV) co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+) children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART)-algorithm study. Methods: Participants were categorized as CMV-naïve, CMV-positive (CMV+) viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+), activated (CD38+HLA-DR+) and terminally differentiated (CD62L-CD45RA+; CD95+CD28-) CD4+ and CD8+ T-cells were measured by flow cytometry. Results: Of the 107 participants included in the analysis, 14% were CMV+ viremic; 49% CMV+ aviremic; 37% CMV-naïve. In longitudinal adjusted models, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L+CD45RA+% and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets. Conclusions: In this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system

Mental Health Diagnoses, Symptoms, and Service Utilization in US Youth with Perinatal HIV Infection or HIV Exposure

Youth perinatally HIV infected (PHIV) or HIV exposed, but uninfected (PHEU), are aging into adolescence and adulthood with multiple complex risk factors for mental health (MH) problems and poor MH treatment utilization. Our aims were to estimate prevalence of MH diagnoses, clinically significant symptoms, and MH treatment utilization among youth with PHIV and among PHEU youth, 10-22 years old. We also aimed to identify correlates of diagnoses and treatment utilization. Analyses of data from standardized interviews, behavioral assessments, and chart review of 551 youth revealed that 36% had a previous or current MH diagnosis, with no significant HIV status group differences. Prevalence of clinically significant symptoms was 15% for both groups, of whom a third had no diagnosis, and half were not receiving treatment. Among youth with a current MH diagnosis, those with PHIV had greater utilization of services than PHEU youth (67% vs. 51%; p = 0.04). Factors associated with MH diagnoses and/or treatment utilization included caregiver characteristics, age and sex of child, HIV status, and stressful life events. Prevalence of MH diagnoses was higher than in the general population, but lower than in similar perinatally HIV-exposed cohorts, with some unmet service needs, particularly in PHEU youth. Family characteristics warrant careful consideration in early diagnosis and treatment of MH problems among youth affected by HIV

Sertraline Pharmacokinetics in HIV-Infected and Uninfected Children, Adolescents, and Young Adults.

Objective: Due to potential disease and drug interactions, the appropriate sertraline starting dose and titration range may require adjustment in pediatric patients living with HIV. This is the first report of sertraline pharmacokinetics in HIV-infected youth. Methods: IMPAACT P1080 was a multicenter pilot study describing psychiatric medication pharmacokinetics in HIV-infected and uninfected youth. Participants were stable on sertraline, >6 to <25 years old, and (1) HIV-uninfected (HIV(-)), (2) HIV-infected taking efavirenz (EFV), or (3) HIV-infected taking boosting ritonavir/protease inhibitor (PI/r). Sampling occurred at pre-dose, 2, 4, 6, 12, and 24-h post-dose. Analyses were performed for sertraline and N-desmethylsertraline, and CYP2D6 phenotyping was completed with dextromethorphan. Results: Thirty-one participants (16 HIV(-), 12 PI/r, and 3 EFV) had median (range) weight, age, and dose of 69.5 (31.5-118.2) kg, 21.8 (9.1-24.7) years, and 75.0 (12.5-150.0) mg once daily. Sertraline exposure was highest for HIV(-) and lowest for EFV cohorts; median dose-normalized AUC 0-24 was 1176 (HIV(-)), 791 (PI/r) and 473 (EFV) ng*hr/mL, and C24 was 32.7 (HIV(-)), 20.1 (PI/r), and 12.8 (EFV) ng/mL. The urinary dextromethorphan/dextrorphan (DXM/DXO) ratio was higher in HIV(-) vs. PI/r cohorts (p = 0.01). Four HIV(-) participants were CYP2D6 poor metabolizers (ln(DXM/DXO) of >-0.5). Conclusions: HIV(-) cohort had the highest sertraline exposure. Sertraline exposure was ~40% lower in the PI/r cohort than in HIV(-); the need to alter sertraline dose ranges for PI/r participants is not clear. The impact of efavirenz on sertraline needs further investigation due to limited numbers of EFV participants

Relationships between markers of vascular dysfunction and neurodevelopmental outcomes in perinatally HIV-infected youth

To examine the relationship between markers of vascular dysfunction and neurodevelopmental status in pediatric HIV disease. A cross-sectional design within a prospective, 15-site cohort study conducted in the United States. Nine vascular biomarkers were examined in 89 HIV-infected children: soluble P-selectin/sCD62P, fibrinogen, adiponectin, monocyte chemoattractant protein-1/CCL-2, interleukin-6, C-reactive protein, soluble vascular cell adhesion molecule-1/sCD106, sE-selectin/sCD62E, and soluble intercellular adhesion molecule-1/sCD54. The Wechsler Intelligence Scale for Children-Fourth edition (WISC-IV) was administered yielding indices for verbal comprehension, perceptual reasoning, working memory and processing speed, and overall composite Full-Scale IQ score. Linear regression models were used to evaluate neurodevelopmental status (measured by WISC-IV scores) as a function of each biomarker while adjusting for demographics, disease severity, and receipt of HAART. Biomarker levels were evaluated in quartiles to evaluate trends in WISC-IV responses. Among the 89 HIV-infected children (median age = 12 years), 56% were girls, 71% black, 16% Hispanic, and 43% had yearly household income below US $20,000. Log (soluble P-selectin) was significantly correlated with all WISC-IV scores; adjusted slopes showed 6-11-point average decrease in scores for each one log unit increase in soluble P-selectin. Final linear regression models for log (fibrinogen) adjusted for sociodemographic and disease characteristics also indicated a negative correlation with all WISC-IV scores (13-30-point decrease for each one log unit increase in fibrinogen); these decreases were significant in the verbal comprehension, perceptual reasoning, and Full-Scale IQ scores. Proinflammatory microvascular and immunologic mechanisms may be involved in neurodevelopmental impairment in children with perinatally acquired HIV disease