Table 1.

Published Studies Assessing Factors Associated With Adherence Among HIV-Infected Youth

Reference Study Design	Sample Measures	Major Results and Health/Immune Outcomes
Becker et al, 2002³⁰ Retrospective analysis of pharmacy claims data on nucleoside analogue reverse transcriptase inhibitor prescription refills to estimate adherence	3788 HIV+, treatment-naive youth (ages 18–24 years) Adherence defined as proportion of days on which drugs were taken during first 365 days of therapy	Overall adherence rate, 53%. No differences by sex detected in adherence rates (P = .30). 26% of individuals were 80% adherent or better. Age was associated with adherence by chi-square examination (P = .001)
Belzer et al, 1999³⁹ Explored correlates of adherence to antiretroviral therapy, including reasons for missing doses, medical and mental health histories, and substance use histories	Surveyed 31 HIV+ youth (ages 13–24 years) from adolescent HIV clinic One-time 22-question interview administered to participants. Demographics, mental health, medical history, and substance use gleaned from medical records. Data analyzed to explore correlates of antiretroviral adherence	61% reported > 90% compliance with medications in previous 90 days. Youth who believed medications would “most definitely” improve quality of life were more likely to have ≥ 90% adherence at 3 months. Most commonly reported reason for missing medications: having too many pills to take
Comulada et al, 2003³¹ Examined factors associated with antiretroviral drug use and adherence among young HIV+ people, particularly sexual and substance use transmission acts	Recruited 253 HIV+ youth (mean age, 22.9 years) in Los Angeles, San Francisco, and New York HIV/AIDS clinical care sites 2-hour ACASI interview with each participant; participants queried regarding lifetime and recent behavior, including antiretroviral drug use, health status, sexual behavior, substance use, mental health, quality of life, and social support	54% were currently using antiretroviral drugs; 63% of users adhered to 90% of their medications (n = 85). Adherers were less likely than nonadherers to have been sexually abused, attempt suicide, report a lower life satisfaction, and use depression withdrawal or self-destructive escape coping mechanisms. Frequency of recent drug use was statistically significant predictor of antiretroviral adherence
Dodds et al, 2003³⁷ Analyzed preliminary data from subset of adolescent/ young women from mental health–perinatal HIV care project	Recruited 21 perinatally HIV+ women (ages 20–25 years) from obstetric/gynecologic HIV clinics enrolled in Whole Life project Examined sociodemographic patterns, HIV risk, health status, and mental health status among participants	Central to nonadherence: patient fears about unwanted HIV disclosure, drug adverse effects and their interference with social life, and relationships with partners. Validating and praising small concrete steps proved especially important to help teen mothers Achieving maximum patient adherence required: developmental framework, patient peer culture, meaningful patient-practitioner relationships, careful medication selection, mental health services, substance abuse treatment, and trauma-informed systems for HIV care Suggested program services to these ends: case management, developmental and education services, one-stop/ colocation of key services, home visits, transportation provisions, childcare, food, patient incentives, engaging patient in conversation, buddy systems/peer advocates, reminder phone calls and letters, and support groups
Hosek et al, 2005³⁸ Self-report questionnaire and 1-hour interview. Data examined for correlation with adherence	Recruited 42 HIV+ youth (age 16–25 years; 25 male, 17 female patients) from CORE Center, Chicago, IL Surveys assessed adherence, perceived reasons for nonadherence, factors to consider before starting a new regimen, cognitive ability, negative affective, and substance use. Regression analysis examined associations to adherence	44% reported being 95% adherent. Only 19% of participants always properly took all medication. 40% of male and 35% of female participants indicated depressive symptoms; 33% of all participants exceeded the cutoff for medium-high trait anxiety. Depression/anxiety and age of first marijuana use were statistically significant predictors of nonadherence (P < .05). Most common reason for missing a dose: forgetting
Martinez et al, 2000³⁴ Retrospective analysis of patient charts	Consecutive review of 25 charts of HIV+ youths (ages 13–21 years) from 1/1993 to 5/1998 Measures were sociodemographic factors (eg, age, race/ethnicity, sex, housing stability) and health variables (eg, CD4+ count and viral load, length of time on antiretroviral drugs) associated with adherence	13/18 (72%) of patients on antiretroviral therapy were nonadherent; 67% of females and 80% of males reported missing doses. Housing instability and length (months) of treatment with antiretroviral medications correlated with nonadherence (P < .04). Living situation stability was the most statistically significant correlate of adherence
Murphy et al, 2005²⁹ Longitudinal study of cohort of HIV+ adolescents to investigate long-term antiretroviral therapy adherence and its correlates	231 HIV+ adolescents (mean age, 18.4 years) infected primarily through sexual behaviors Validated self-reported adherence measures by comparison with plasma HIV RNA level; assessed behavioral factors associated with antiretroviral therapy adherence	69% of adolescents reported being adherent. Adolescents in later HIV disease stages were less likely to be adherent. Less alcohol use and being in school were associated with adherence. Median time to nonadherence was 12 months, and failure to maintain adherence was associated with younger age and depression
Murphy et al, 2003²⁸ Structured interviews conducted to determine barriers to adherence; principal component factor analysis performed on scores of 19 barrier variables	114 HIV+ adolescents (ages 12–19 years) prescribed antiretroviral therapy and in REACH Project. All participants infected through risk behaviors Main outcome measures were self-report of adherence and barriers to adherence and plasma HIV RNA level	Only 28% of adolescents reported taking all prescribed antiretroviral medications in previous month. Plasma HIV RNA level was associated with self-report of adherence (P = .02). Medication-related adverse effects and complications in daily routines accounted for largest proportion of variance. Adherence was tied closely with daily routine; working closely with adolescents to improve their organizational skills may improve adherence
Murphy et al, 2001³² Combination of face-to-face interview, ACASI, laboratory analysis, and medical chart review to find associations between self-reported medication adherence, depression, anxiety, social support, and demographics	Recruited 161 HIV+ adolescents (ages 13–18 years) from 13 US cities into REACH Project. All adolescents infected through sexual or injection drug use behaviors Antiretroviral drug adherence investigated. Assessed associations between variables using various statistical methods, including chi-squares, logistic regression, analysis of variance, and Pearson correlation	41% reported consistent adherence. 83% reported taking all medications at least “some of the time,” but only 50% of these subjects reported full adherence. Strong association between adherence and reduced viral load. CD4+ level ≥ 500 cells/μL was associated with adherence. Number of drugs prescribed was inversely associated with adherence, with more drugs associated with lower adherence. Higher levels of depression strongly associated with decreased adherence. Adherence was not associated with age, race, or sex
Naar-King et al, 2006³⁵ Tested predictors of adherence previously identified in adults among youth (self- efficacy, social support, and psychologic distress)	Recruited 24 HIV+ youth (ages 16–24 years) from single clinic site. 79% infected through risk behavior Self-administered questionnaires measured medication adherence, self-efficacy, social support, psychologic distress, and participant plasma HIV RNA level	Self-efficacy and psychologic distress were correlated with adherence. Social support was not, but social support with medications was correlated with self-efficacy. In regression analysis, self-efficacy and psychologic distress were independently related to adherence (accounting for 47% of the variance)
Radcliffe et al, 2006⁴¹ Trained interviewers conducted survey to assess demographic characteristics, sense of connection with care team, trauma history, and traumatic stress responses	Recruited 30 HIV+ youth (ages 18–24 years) from urban pediatric hospital-based HIV clinic Participants asked to identify their “biggest, worst experience” and their next “worst” incident or HIV diagnosis. The PTSD Checklist was used to measure stress responses to both above events	Participants experienced a mean of 6 potentially traumatic events, with HIV diagnosis being traumatic 93% of the time. HIV diagnosis was “biggest, worst experience” 59% of the time. 13% of sample met full criteria for PTSD. Percent of clinic visits kept was correlated with practitioner adherence ratings. No relationship found between adherence and care team connection
Rao et al, 2007³⁶ HIV+ adolescents and young adults were asked to participate in focus groups, which explored attitudes and experiences around medication adherence	Recruited 25 HIV+ youth (mean age, 22 years) from young-adult clinic where they received HIV treatment. Most participants infected during sexual contact Each focus group was recorded and professionally transcribed. Thematic categories were identified and responses coded accordingly. Frequency with which each theme occurred was tabulated	Social factors and HIV stigma represent strong barriers to adherence for youth; 50% of respondents indicated that they skipped doses because of fear that family or friends would discover status. Youthful feelings of “invulnerability” do not seem to be important barriers to HIV medication adherence. 64% of participants indicated side effects did not bother them
Schwartz et al, 2001⁴⁰ HIV+, REACH program adolescents observed for 24 months, assessed every 3 months. Health history, demographics, and laboratory results obtained via patient interviews, ACASI, and medical records	215 HIV+, antiretroviral therapy–naive adolescents (aged 12–18 years at entry into REACH) seen at 15 REACH clinical sites Generalized estimating equations applied to identify associations between demographics, risk behaviors, perceived health, and clinical status with initiation of antiretroviral therapy during first 24 study months	Antiretroviral therapy prescribed for 115 (53%). Statistically significant univariate associations with antiretroviral prescription: lower CD4+ cell count (OR, 1.7; 95% CI, 1.1–2.6), higher plasma HIV RNA level (OR, 2.7; 95% CI, 1.5–5.0), and calendar year of antiretroviral therapy prescription (OR, up to 2.4; 95% CI, 1.1–5.2). Multivariate results: higher plasma HIV RNA level (≤ 10,000 copies/mL), having a high school diploma/General Education Degree but no further education (OR, 2.7; 95% CI, 1.3–5.5), and patient perception of poor health status (OR, 0.99; 95% CI, 0.98 – 0.99) were independently associated with antiretroviral therapy
Williams et al, 2006³³ Cross-sectional evaluation using Pediatric AIDS Clinical Trials Group (PACTG) 219C study data. Medical/clinical histories and sociodemographics obtained via clinic records, reviews, interviews. Follow-up visits held every 3 months	PACTG 219C participants with self-assessed adherence (n = 772; median age, 14.4 years). All participants infected through perinatal exposure Obtained and compared information on past antiretroviral therapy, clinical/neurologic diagnoses, CD4+ count, plasma HIV RNA level, and sociodemographics. Age-adjusted logistic regression models measured possible predictors of nonadherence. “Adherent” defined as ≥ 95%, measured via self-reporting on medication adherence in the 3 days before the visit	78% reported complete adherence over past 3 days. Variables associated with increased risk of nonadherence: female sex, plasma HIV RNA level, depression, and anxiety. Variables associated with decreased risk of nonadherence: having an adult primary care giver other than a biological parent, primary care giver education level, and CD4+ level

ACASI indicates audio computer-assisted self-interviewing; CI, confidence interval; HIV+, HIV seropositive; OR, odds ratio; PTSD, posttraumatic stress disorder.