Of the 1162 eligible youth who were approached, 582 participated (323 PHIV and 259 Controls, 49% and 52% of eligible, respectively) (Fig. 1). Over half of the sites (16 of 29, 55%) enrolled more than half of their eligible contacted youth, with 5 sites enrolling more than 90% of their eligible candidates. Among the 580 youth who refused to participate, the primary reasons included difficulties with the time commitment or travel to the site (n = 205, 35%), caregiver concerns about privacy or disclosure of HIV status (n = 123, 21%), active illness preventing participation (n = 10, 2%), and general unwillingness to participate (n = 242, 42%), with no overall difference in the distribution of reasons for refusal between PHIV and Controls.
Participation rates by youth and caregiver characteristics at screening are summarized in Table 2. Participation rates did not differ significantly by gender or by HIV status. Participants were slightly older on average than nonparticipants and participation rates were higher among black non-Hispanic and Hispanic youth than among white non-Hispanic youth (P = 0.01). The older age of participants versus nonparticipants was primarily observed among the PHIV screenees (median 13.1 vs 12.0 years, P < 0.001), whereas there was no age difference for Controls (median 11.2 vs 11.0 years, P = 0.40).
PHIV youth and Controls who enrolled were comparable by gender, race, and ethnicity, as reported previously.9 However, PHIV youth were older on average than Controls, less likely to live with biological parents and more likely living in households with higher household income and caregiver education. At study entry, 83% of the PHIV youth were taking highly active antiretroviral therapy (HAART). At the baseline visit, both groups had a similar prevalence of psychiatric symptoms based on either youth self-report or caregiver assessment (61% with at least one condition), although PHIV youth had slightly higher rates of conduct disorder.8,9
Among the 575 enrolled participants who completed a baseline visit, 506 (88%) attended the 1-year follow-up visit and 465 (81%) attended the 2-year follow-up visit, including 22 youth who missed the Year 1 visit but returned at Year 2 (Fig. 1). The retention rates over the 2-year study were significantly higher for PHIV participants than for Controls (84% vs 77%, P = 0.03). In adjusted logistic regression models for LTFU (Table 3), PHIV participants and those whose primary caregiver was their biological mother had reduced odds of LTFU [adjusted odds ratios (aORs) = 0.45, P = 0.002; aOR = 0.61, P = 0.06, respectively]. In contrast, increased odds of LTFU were observed for youth whose caregivers had at least a high school education (aOR = 2.40, P = 0.003) or higher annual income (aOR = 1.61, P = 0.07). Although Hispanic youth had reduced odds of LTFU in unadjusted models, this finding did not persist after adjustment for other sociodemographic factors. We observed no association of age with LTFU after adjustment for HIV status and no interaction between HIV status and any demographic risk factor.
Our study included 457 families, of which 91 (20%) enrolled 2 or more children and 45 (10%) included at least 1 PHIV and 1 Control youth. However, even after adjusting for within family correlation in LTFU, there remained a significant decrease in LTFU for PHIV as compared with Control youth (aOR = 0.49, 95% confidence interval: 0.32 to 0.75, P = 0.001). Effects of other sociodemographic predictors shown in Table 3 remained similar. Sensitivity analyses accounting for clustering of youth within research sites also yielded very similar estimated associations.
In models adjusting for sociodemographic covariates, youth with at least one self-assessed psychiatric condition compared with those without had a 56% increased odds of LTFU (P = 0.05, Table 3). The rate of LTFU for Controls was fairly similar for those with and without a psychiatric condition (20.9% vs 24.1%), whereas the percent LTFU was twice as high for PHIV youth with versus without psychiatric conditions (23.9% vs 10.9%, P-value for interaction test = 0.011). Although no individual condition was a significant predictor of LTFU, estimated odds ratios were consistently >1. No association with LTFU was observed for any psychiatric condition by caregiver assessment (Table 3). Additional analyses evaluating associations with symptom severity scores indicated greater odds of LTFU for youth with higher self-assessed severity of ADHD or disruptive behavior symptoms (see Table S1, Supplemental Digital Content, http://links.lww.com/QAI/A419).
Within the subset of PHIV youth, associations of demographic measures with LTFU were similar to those for the overall study population (Table 4). In addition, PHIV youth with higher viral load at entry had almost twice the odds of LTFU (aOR = 1.90, P = 0.08), whereas those receiving HAART at entry had reduced odds (aOR = 0.53, P = 0.08). After adjustment for sociodemographic and HIV disease severity measures, youth with any self-assessed psychiatric condition had over 3-fold higher odds of LTFU (aOR = 3.11, P = 0.001). The psychiatric condition associated with the highest odds of LTFU was anxiety disorder (aOR = 2.77, P = 0.003). However, in analyses based on severity scores, youth with higher self-assessed symptom severity had significantly higher odds of LTFU for each of the 4 targeted conditions (see Table S2, Supplemental Digital Content, http://links.lww.com/QAI/A419). In evaluating the association of caregiver-assessed psychiatric conditions with LTFU, we observed marginally increased odds of LTFU for youth with at least one condition (aOR = 1.90, P = 0.07) and for all other specific conditions except anxiety (Table 4). Higher caregiver-assessed severity scores for disruptive behavior were also associated with LTFU (see Table S2, Supplemental Digital Content, http://links.lww.com/QAI/A419).
As PHIV youth are living longer owing to advances in treatment and clinical management, improving our understanding of psychiatric and neurocognitive outcomes and their treatment options has developed into a top research priority. However, observational studies and clinical trials face challenges in enrolling representative samples of participants with HIV and those living in families affected by HIV. These difficulties are exacerbated by both declining participation in health research in the United States owing in part to decreases in volunteerism and a lack of trust in scientific research, particularly in pediatric and underserved populations.49–54
In our study, 50% of eligible youth agreed to participate. This rate is slightly higher than the 42% enrollment rate observed among the HIV-infected pregnant women enrolling into the US-based IMPAACT P1025 perinatal cohort study42 but is slightly lower than a single-visit study of metabolic abnormalities in youth with HIV, in which 60% of screened eligible youth participated.43 We observed similar rates of participation by HIV status, in contrast to the PACTS-HOPE study that reported a much higher enrollment rate in HIV-infected youth than in HIV-exposed uninfected controls (89% vs 22%).49 Pediatric health research studies in non-HIV settings have reported higher response rates for completion of questionnaires but lower response rates for studies that involve a clinical examination or collection of biological samples.51 Our study required no physical examination or collection of biological samples but required completion of an extensive battery of psychiatric questionnaires at the clinical sites, which may have led to decreased participation rates.
After exclusion of ineligible and nonapproached candidates, we observed the highest participation rates among Hispanic families, similar to findings of Freedman et al.49 The P1025 study of HIV-infected pregnant women also observed a higher enrollment rate among Hispanics than non-Hispanic whites (28% vs 20%) and an even lower rate among non-Hispanic blacks (17%).42 In our study, Hispanic participants also had lower odds of LTFU, but this finding did not persist in adjusted models, possibly because of the correlation of Hispanic ethnicity with other demographic measures.
The P1055 study successfully retained more than 80% of enrolled participants over the 2-year follow-up study period, which compares favorably with other studies of youth with HIV infection.35–37 High retention was achieved in part by requiring sites to develop a retention approach as part of their site implementation plan. Most sites attempted to maintain engagement with participants through frequent contact between study visits (eg, telephone, mailings) along with financial incentives or vouchers for meals and transportation costs. However, the retention rate for Controls was lower, which may be partially attributable to their avoidance of the potential stigma associated with being seen at an HIV clinic55 and by the fact that most did not receive routine care at the clinical sites.35
Our study design neglected to take into account household structure, and thus siblings were occasionally in separate blocks and could not be enrolled at the same date. Future studies should consider random ordering in clusters by household to enhance enrollment of multiple family members. Our study strengths included being able to evaluate participation based on characteristics of individual participants. Finally, our study demonstrated the feasibility of maintaining relatively high retention rates over the 2-year follow-up period. Future studies may require creative approaches for engaging the HIV-affected community in research efforts and in promoting retention efforts, particularly for youth with psychiatric conditions.
The authors thank Kimberly Hudgens for her operational support of this study and Janice Hodge for data management. In addition to their contributions to the manuscript, the authors acknowledge the help given by Nagamah Sandra Deygoo in representing the site research staff on the protocol team and Vinnie Di Paolo for representing the community affected by HIV.
Children’s Hospital Boston: Sandra Burchett; UCLA-Los Angeles AIDS Consortium: Karin Nielsen, Nicole Falgout, Joseph Geffen, Jaime Deville; Long Beach Memorial Medical Center: Audra Deveikis; UCLA Medical Center: Margaret Keller; University of Maryland Medical Center: Vicki Tepper; Chicago Children’s CRS: Ram Yogev; UCSF Pediatric AIDS CRS: Diane Wara; UCSD Maternal Child and Adolescent HIV CRS: Stephen Spector, Lisa Stangl, Mary Caffery, Rolando Viani; Duke University Medical Center: Kreema Whitfield, Sunita Patil, Joan Wilson, and Mary Jo Hassett; New York University School of Medicine: Sandra Deygoo, William Borkowsky, Sulachni Chandwani, and Mona Rigaud; Jacobi Medical Center: Andrew Wiznia; University of Washington Children’s Hospital, Seattle: Lisa Frenkel; USF Tampa: Patricia Emmanuel, Jorge Lujan Zilberman, Carina Rodriguez, and Carolyn Graisber; Mt Sinai School of Medicine: Roberto Posada and Mary Dolan; San Juan City Hospital: Midnela Acevedo-Flores, Lourdes Angeli, Milagros Gonzalez, and Dalila Guzman; Yale University School of Medicine: Warren Andiman, Leslie Hurst, and Anne Murphy; SUNY Upstate Medical University: Leonard Weiner; SUNY Stony Brook: Denise Ferraro, Michele Kelly, and Lorraine Rubino; Howard University: Sohail Rana; University of Southern California: Suad Kapetanovic; University of Florida Jacksonville: Mobeen Rathore, Ayesha Mirza, Kathleen Thoma, and Chas Griggs; University of Colorado: Robin McEvoy, Emily Barr, Suzanne Paul, and Patricia Michalek; South Florida Center for Diagnostic Care: Ana Puga; St Jude: Patricia Garvie; Children’s Hospital of Philadelphia: Richard Rutstein; St Christopher’s Hospital for Children: Roberta LaGuerre; Bronx-Lebanon Hospital: Murli Purswani; Metropolitan Hospital Center: Mahrukh Bamji; WNE Maternal Pediatric Adolescent AIDS: Katherine Luzuriaga.
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