Strategies to maximize adherence should be discussed before and/or at initiation of antiretroviral therapy (ART) and before changing regimens (AIII).
Adherence to therapy must be assessed and promoted at each visit, and strategies to maintain and/or improve adherence must be continually explored (AIII).
In addition to viral load monitoring, at least one other method of measuring adherence to ART should be used (AIII).
Once-daily antiretroviral regimens and regimens with a low pill burden should be prescribed whenever feasible (AII*).
Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = One or more randomized trials in children† with clinical outcomes and/or validated endpoints;
I* = One or more randomized trials in adults with clinical outcomes and/or validated laboratory endpoints with accompanying data in children† from one or more well-designed, nonrandomized trials or observational cohort studies with long-term clinical outcomes; II = One or more well-designed, nonrandomized trials or observational cohort studies in children† with long-term outcomes; II* = One or more well-designed, nonrandomized trials or observational studies in adults with long-term clinical outcomes with accompanying data in children† from one or more similar nonrandomized trials or cohort studies with clinical outcome data; III = Expert opinion
† Studies that include children or children/adolescents, but not studies limited to postpubertal adolescents
Adherence to antiretroviral therapy (ART) is a principal determinant of virologic suppression. Suboptimal adherence may include missed or late doses, treatment interruptions and discontinuations, and subtherapeutic or partial dosing.1,2 Poor adherence will result in subtherapeutic plasma antiretroviral (ARV) drug concentrations, facilitating the development of resistance to one or more drugs in a given ARV regimen and possible cross-resistance to other drugs in the same class. Multiple factors—including regimen potency, pharmacokinetics, drug interactions, viral fitness, and the genetic barrier to ARV resistance—influence the adherence–resistance relationship.3-5 In addition to compromising the efficacy of the current regimen, suboptimal adherence can limit the options for future effective ARV drug regimens in patients who develop multidrug-resistant HIV; it also can increase the risk of secondary transmission of drug-resistant virus.
Poor adherence to ARV drugs is commonly encountered in the treatment of children and adolescents with HIV. Medication formulation , frequency of dosing, drug toxicities and a child’s age and developmental stage psychosocial, behavioral, and for children and caregivers associated with inadequate adherence. No consistent predictors of either good or poor adherence in children have been identified.6-8 findings from the U.S. Pediatric HIV/AIDS Cohort Study (PHACS) demonstrated that the prevalence of nonadherence increased with age. Among 381 children and adolescents with perinatally acquired HIV, the prevalence of nonadherence increased from 31% to 50% (P < 0.001), and the prevalence of unsuppressed viral loads increased from 16% to 40%(P < 0.001) between pre-adolescence and late adolescence/young adulthood.9 Similarly, in a report initiated on ART maintained viral suppression 3 years after it was first achieved.10 Furthermore, several studies have demonstrated that adherence is not static and can vary with time on treatment.11 inconsistent adherence across the three assessments12. These findings illustrate the difficulty of maintaining high levels of adherence and underscore the need to and their
Specific Adherence Issues in Children
Adherence is a complex health behavior that is influenced by drug regimen, patient and family factors, and the patient–provider relationship.13,14 Despite improvements over the last several years, the availability of once-daily and single-tablet ARV regimens and palatable formulations for infants and young children are limited. Furthermore, infants and children are dependent on others for medication administration; adult caregivers may face barriers that undermine adherence in children, including forgetting doses, changes in routine, being too busy, and child refusal.15,16 Caregivers also may be inadequately prepared to support their child’s adherence. In a study of communication strategies among caretakers of children with perinatally acquired HIV in rural South Africa, many caregivers used coercion and threats of grave consequences of nonadherence as a communication strategy to enforce adherence.17 Furthermore, some caregivers may place too much responsibility for managing medications on older children and adolescents before they are developmentally able to undertake such tasks.18
Adherence also may be jeopardized by social and health issues within a family (e.g., substance use, poor physical or mental health, unstable housing, poverty, violence, involvement with the criminal justice system, limited social support).19-22
Adherence Assessment and Monitoring
Should begin assessing potential barriers to adherence and discussing the importance of adherence with patients changing an ARV regimen. Evaluations should assess psychosocial and behavioral factors that may influence adherence, and should ask patients about their experiences with taking medications, as well as concerns and expectations about treatment. Before beginning treatment, it is important that the patient explicitly agree to the treatment plan, which should include strategies to support adherence. It is also important to alert to potential adverse effects (AEs) of ARV drugs (e.g., nausea, headaches, abdominal discomfort, sleep disturbances), explain how they can be managed, and emphasize the importance of informing the clinical team if they occur.
A routine adherence assessment should be incorporated into every clinical visit. Adherence is difficult to assess accurately; different methods of assessment have yielded different results, and each approach has limitations.23-25 Viral load monitoring is the most useful indicator of adherence and is a routine component of monitoring individuals who are on ART (see Plasma HIV-1 RNA [Viral Load] and CD4 Count Monitoring in the Adult and Adolescent Antiretroviral Guidelines). It also can be used as positive reinforcement to encourage continued adherence.26 In addition to viral load monitoring, providers should use at least one other method to assess adherence,24 Table 1 below includes common approaches to monitoring medication adherence.
Strategies to Improve and Support Adherence
ASHM provides information on interventions to overcome challenges to adherence within the HIV Management Guidelines, chapter: Factors affecting adherence and nursing interventions used to promote adherence.
Clinicians may also refer to the Children’s HIV Association (UK) for fixed dose combination regimens and minimum body weight requirements HERE.
In Australia, advice regarding pill swallowing can be provided by your local pharmacy.
MedicineList+ app has been launched by NPS MedicineWise to support treatment adherence.
Monitoring antiretroviral (ARV) drug concentrations in hair is not routinely available in Australia.
When concerns about adherence emerge, a patient should be seen and/or contacted frequently to assess adherence. Strategies should include simplifying the ARV drug regimen, developing treatment plans that integrate medication administration into daily routines (e.g., associating medication administration with daily activities, such as brushing teeth), and optimizing the use of social and community support services. Multifaceted approaches that include regimen-related strategies; educational, behavioral, and supportive strategies focused on children and families; and strategies that focus on health care providers may be more effective than one specific intervention. Table 1 below summarizes some of the strategies that can be used to support and improve adherence to ARV medications. The Centers for Disease Control and Prevention (CDC) offer Partnership for Health – Medication Adherence to HIV care providers.28 A recent analysis using the Cost-Effectiveness of Preventing AIDS Complications (CEPAC)–Adolescent model of HIV disease and treatment modeled the impact of a 12-month hypothetical adherence intervention (based on an interactive smartphone- based reminder system) among youth with HIV in the United States. Compared with the standard of care, the analysis showed that youth-targeted adherence interventions, even with modest efficacy to improve virologic suppression, could improve life expectancy, prevent onward HIV transmissions, and be cost-effective.29
ARV regimens should be simplified with respect to the number of number of pills or volume of liquid prescribed. Efforts should be made to prescribe once-daily ARV regimens and single-tablet regimens whenever feasible (see Table 1 number of pills or volume of liquid prescribed. Efforts should be made to prescribe once-daily ARV regimens and single-tablet regimens whenever feasible (see Table 1 in Management of Children Receiving Antiretroviral Therapy). Several studies in adults have demonstrated better adherence with once- daily ARV regimens than with twice-daily regimens with single-tablet formulations than with multiple-tablet regimens.30-34 See Appendix A, Table 1. Antiretrovirals Available in Fixed-Dose Combination Tablets or as a Co-packaged Formulation, by Drug Class and Appendix A, Table 2.
Antiretroviral Fixed-Dose Combination Tablets and Co-packaged Formulations: Minimum Body Weights and Considerations for Use in Children and Adolescents for information about using FDC tablets in children. The Drugs in the regimen should be chosen to minimize drug interactions and AEs (see Management of Medication Toxicity or Intolerance).35 When nonadherence is related to the poor palatability of a liquid formulation or crushed pills, the offending taste can sometimes be masked with a small amount of flavoring syrup or food if simultaneous administration of food is not contraindicated (see Appendix A: Pediatric Antiretroviral Drug Information).36 Unfortunately, the taste of lopinavir/ritonavir cannot be masked with flavoring syrup. A small study of children and youth aged 4 years to 21 years found that training children to swallow pills was associated with improved adherence at 6 months post-training.37
Patient and caregiver education is an essential component of establishing good medication adherence in children. Educating families about adherence should begin before initiating or changing ARV medications and should include a discussion of the goals of therapy, the importance of optimizing adherence, and the specific plans for supporting and maintaining a child’s medication adherence. Caregiver adherence education strategies should include written and visual materials; a daily schedule illustrating times and doses of medications; and demonstration of the use of syringes, medication cups, and pill boxes. Additionally, it may be helpful to assess the medication adherence of the caregiver or other household members who currently take ARV drugs or other chronic medications. Several behavioral tools can be used to integrate taking medications into a child’s daily routine. The use of behavior modification techniques, especially the application of positive reinforcements and the use of small incentives (including financial incentives) for taking medications, can be effective tools to promote adherence.38
Mental health disorders (e.g., depression) adherence.
If the child has not been informed of their HIV status, HIV disclosure should be discussed with the caregivers. In a recent review that explored the relationship between ART adherence and disclosure, five studies linked disclosure to improved adherence, four studies found that disclosure led to worse adherence among study participants, and five studies found no association.41 In interviews with caregivers of children with HIV in South Africa, investigators found that caregivers who had disclosed to their child that they (i.e., the child) were living with HIV were truthful in their communications and named the disease as HIV, but communication about HIV was infrequent and focused on pill taking. By comparison, those who had not disclosed used deception, deflection, and coercion in response to health-related questions and to enforce adherence.17 The decision to disclose HIV status should not necessarily be expected to improve adherence but should be based on a comprehensive assessment of psychosocial and the needs of the child and family.
In poorly adherent children who are at risk of disease progression and who have severe and persistent aversion to taking medications, the use of a gastrostomy tube may be considered.42
The evidence is mixed as to the efficacy of programs that are designed to improve adherence through DOT, but DOT may still be a useful strategy for some patients.43-45 Among 50 adolescents on atazanavir-based second-line therapy participating in a study of modified directly administered ART (mDAART), there was a significant increase in self-reported adherence (relative risk [RR] = 0.1; 95% confidence interval [CI], 0.02–0.8; P = 0.023) but a nonsignificant increase in virological suppression to <1,000 copies/mL (P = 0.105) among those randomized to the intervention arm compared to the standard of care arm.46 A recent randomized controlled trial (RCT) of a 12-week multicomponent intervention—including remote coaching, electronic dose monitoring, and tailored outreach (Triggered Escalating Real-Time Adherence)—for viremic youth in the United States demonstrated improved adherence but not viral suppression compared with the standard of care.21
Other strategies to support adherence include using mobile applications (apps) that remind patients to take medications; setting cellphone alarms to go off at medication times; sending text-message reminders; conducting motivational interviews; providing pill boxes, blister packaging, and other adherence support tools; and delivering medications to the home. The CDC has an adherence toolkit, that includes a free mobile app (Every Dose, Every Day (E2D2) Toolkit and App).
Several systematic reviews evaluating the use of mobile phone technologies to improve ART adherence (mHealth) have been published. In a recent review, the authors found what they described as “ambiguous results with high variability” about the effectiveness of mHealth interventions to improve adherence in low- and middle-income countries.47 Of 17 studies, 56% reported a statistically significant positive impact of mHealth on adherence; 44% reported insignificant results. Another systematic review reported that the efficacy of mobile short message service (SMS) interventions varied depending on the specific SMS intervention tested.48 A third systematic review of the effectiveness of using mobile phone interventions to improve adherence to ART also reported mixed results; effectiveness varied depending on the measured outcomes and the specific intervention (e.g., whether the study evaluated the use of texts or the use of phone calls).49 It should be noted, however, that the evidence base for effective adherence interventions in adolescents and young adults who are taking daily ART is limited.50-56
Lowenthal et al. examined the association between medication-specific reactance—an aversive response to perceived threats against personal agency—and treatment failure in a cohort of adolescents with HIV in Botswana. Reactant individuals may hear health messaging as a threat to their perceived freedom and respond by engaging in the opposed behavior. Adolescents, scoring >4 had 2.05-fold (95% CI, 1.23–3.41) greater odds of treatment failure than non- reactant youth (P = 0.043). Psychological reactance needs further study and may provide some insight into adherence behaviors among youth; it also may be important to consider in adherence counseling and in designing interventions.57
Two recently published studies provided evidence of the efficacy of peer-based interventions to improve ART adherence and viral suppression among adolescents and young people living with HIV in Africa. In Project YES! in Ndola, Zambia, 273 youth aged 15 to 24 years receiving HIV care in four health facilities were randomly assigned to monthly meetings with youth peer mentors. At 6 months, viral suppression improved in both study arms, but among participants in care at the pediatric clinic, the rate of viral suppression increased from 37.5% to 70.5% in the intervention arm versus the comparison arm, 60.3% to 59.4% (interaction term odds ratio, 4.66; 95% CI, 1.84–11.78).58 Mavhu et al. tested the efficacy of a peer-led differentiated service delivery intervention on HIV clinical outcomes among adolescents with HIV aged 13 to 19 years in rural Zimbabwe. Sixteen clinics were randomized to standard of care or the enhanced intervention in which adolescents were assigned a community adolescent treatment supporter; attended monthly support group; and received text messages, calls, home visits, and clinic-based counseling. Overall, 212 adolescents were recruited at intervention sites and 284 at control sites, with a median age of 15 years. At 96 weeks, among 479 adolescents with data, 52 (25%) adolescents in the intervention arm versus 97 (36%) in the control arm had viral load >1,000 copies/mL or had died (adjusted prevalence ratio 0.58; 95% CI, 0.36–0.94; P = 0.03). The study reported 28 deaths (17 in the intervention arm, 11 in the control arm) and 57 hospital admissions (20 in the intervention arm, 37 in the control arm). These studies demonstrate that peer-based interventions have the potential to improve adherence and health outcomes among youth with HIV.59
Further evidence of the efficacy of peer-support interventions for people living with HIV comes from a recent systematic review and meta-analysis, including 20 RCTs comprising 7,605 participants from nine countries. The authors found superior retention in care (RR 1.07; 95% CI, 1.02–1.12 at 12 months follow-up) and better ART adherence (RR 1.06; 95% CI, 1.01–1.10 at 3 months follow- up) but no statistically significant difference in viral suppression (RR = 1.02; 95% CI, 0.94–1.11 at 6 months follow-up) among peer-support participants.63
Health Care Provider–Related Strategies
To improve and support ART adherence, should maintain a nonjudgmental attitude, establish trust with patients and caregivers, and identify mutually acceptable goals for care. can improve adherence through their relationships with patients together when they obtain explicit agreement on the medication and treatment plan, as strategies to support adherence. Fostering a trusting relationship and engaging in open communication are particularly important. Focus groups and semi-structured interviews were conducted with adolescents and their caregivers participating in a longitudinal adherence study. Participants who self-reported high adherence but for whom electronically monitored data reflected low adherence were selected. Adolescents described hiding and discarding pills and lying about their adherence. Adolescents and parents considered negative feedback for prior poor adherence as motivation for efforts to hide current poor adherence. The authors suggest that positive feedback for truth-telling may help develop family and staff alliances in support of adherence.27
Provider characteristics that have been associated with improved patient adherence in adults include consistency, willingness to give information and ask questions, technical expertise, and commitment to follow-up. Creating an environment in the health care setting that is child-centered and includes caregivers in adherence support also has been shown to improve treatment outcomes. Providing comprehensive multidisciplinary care (e.g., with nurses, case managers, pharmacists, social workers, psychiatric care providers) also may better serve more complex patient and family needs, including adherence. Provider-initiated education about viral load and counseling targeted at understanding viral load results, the health benefits of undetectable viral load, and the undetectable = untransmittable (U=U) concept are other strategies providers can use.
Table 1. Approaches for Monitoring Medication Adherence
Routine Assessment of Medication Adherence in Clinical Carea
|Monitor viral load.||Viral load monitoring should be done more frequently after initiating or changing medications.a|
|Assess a quantitative self-report of missed doses.||Ask the patient and/or caregiver about the number of missed doses over a defined period (1, 3, or 7 days).|
|Request a description of the medication regimen.||Ask the patient and/or caregiver about the name, appearance, and number of medications and how often the medications are taken.|
|Assess barriers to medication administration.||Engage the patient and caregiver in a dialogue about potential barriers to adherence and strategies to overcome them.|
|Monitor pharmacy refills.||Approaches include a pharmacy-based or clinic-based assessment of on-time medication refills.|
|Employ telemedicine to monitor and support medication administration.||Telemedicine visits allow remote and often face-to-face contact and provide new opportunities to support families; to visualize ART preparation, handling, and swallowing; and to conduct DOT in the home setting.|
|Conduct announced and unannounced pill counts.||Approaches include asking patients to bring medications to the clinic, conducting home visits, or providing referral to community health nursing.|
Targeted Approaches to Monitoring Adherence in Special Circumstances
|Implement DOT in person and via telemedicine.||Include a brief period of hospitalization if indicated.|
|Measure drug concentration in plasma or DBS.||Measuring drug concentrations can be considered for particular drugs.|
Approaches to Monitoring Medication Adherence in Research Settings
|Measure drug concentrations in hair.||Measuring hair drug concentrations can be considered for particular drugs; it provides a good measure of adherence over time.23,64,65|
|Use electronic monitoring devices.||Approaches include MEMS caps and Wisepill.|
|Use mobile phone-based technologies.||Approaches include interactive voice response, text messaging, and mobile apps.|
- Vreeman RC, Nyandiko WM, Liu H, et al. Measuring adherence to antiretroviral therapy in children and adolescents in western Kenya. J Int AIDS Soc. 2014;17:19227. Available at: https://www.ncbi.nlm.nih.gov/pubmed/25427633.
- Hawkins A, Evangeli M, Sturgeon K, Le Prevost M, Judd A, Aalphi Steering Committee. Episodic medication adherence in adolescents and young adults with perinatally acquired HIV: a within-participants approach. AIDS Care. 2016;28 Suppl 1:68-75. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26886514.
- Gardner EM, Burman WJ, Steiner JF, Anderson PL, Bangsberg DR. Antiretroviral medication adherence and the development of class-specific antiretroviral resistance. AIDS. 2009;23(9):1035-1046. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19381075.
- Judd A, Melvin D, Thompson LC, et al. Factors associated with nonadherence to antiretroviral therapy among young people living with perinatally acquired HIV in England. J Assoc Nurses AIDS Care. 2020;31(5):574-586. Available at: https://www.ncbi.nlm.nih.gov/pubmed/32467489.
- Parienti JJ, Fournier AL, Cotte L, et al. Forgiveness of dolutegravir-based triple therapy compared with older antiretroviral regimens: a prospective multicenter cohort of adherence patterns and HIV-RNA replication. Open Forum Infect Dis. 2021;8(7):ofab316. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34307726.
- MacDonell KK, Jacques-Tiura AJ, Naar S, Fernandez MI, Team ATNP. Predictors of self-reported adherence to antiretroviral medication in a multisite study of ethnic and racial minority HIV-positive youth. J Pediatr Psychol. 2016;41(4):419-428. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26498724.
- Gray ME, Nieburg P, Dillingham R. Pediatric human immunodeficiency virus continuum of care: a concise review of evidence-based practice. Pediatr Clin North Am. 2017;64(4):879-891. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28734516.
- Schlatter AF, Deathe AR, Vreeman RC. The need for pediatric formulations to treat children with HIV. AIDS Res Treat. 2016;2016:1654938. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27413548.
- Kacanek D, Huo Y, Malee K, et al. Nonadherence and unsuppressed viral load across adolescence among U.S. youth with perinatally acquired HIV. AIDS. 2019;33(12):1923- 1934. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31274538.
- Kakkar F, Lee T, Hawkes MT, et al. Challenges to achieving and maintaining viral suppression among children living with HIV. AIDS. 2020;34(5):687-697. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31794519.
- Giannattasio A, Albano F, Giacomet V, Guarino A. The changing pattern of adherence to antiretroviral therapy assessed at two time points, 12 months apart, in a cohort of HIV- infected children. Expert Opin Pharmacother. 2009;10(17):2773-2778. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19929700.
- Zhou S, Cluver L, Shenderovich Y, Toska E. Uncovering ART adherence inconsistencies: An assessment of sustained adherence among adolescents in South Africa. J Int AIDS Soc. 2021;24(10):e25832. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34708912.
- Haberer J, Mellins C. Pediatric adherence to HIV antiretroviral therapy. Curr HIV/AIDS Rep. 2009;6(4):194-200. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19849962.
- Shubber Z, Mills EJ, Nachega JB, et al. Patient-reported barriers to adherence to antiretroviral therapy: a systematic review and meta-analysis. PLoS Med. 2016;13(11):e1002183. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27898679.
- Marhefka SL, Koenig LJ, Allison S, et al. Family experiences with pediatric antiretroviral therapy: responsibilities, barriers, and strategies for remembering medications. AIDS Patient Care STDS. 2008;22(8):637-647. Available at: https://www.ncbi.nlm.nih.gov/pubmed/18627275.
- Skovdal M, Campbell C, Madanhire C, Nyamukapa C, Gregson S. Challenges faced by elderly guardians in sustaining the adherence to antiretroviral therapy in HIV-infected children in Zimbabwe. AIDS Care. 2011;23(8):957-964. Available at: https://www.ncbi.nlm.nih.gov/pubmed/21400306.
- Molokwane M, Madiba S. Truth, deception, and coercion; communication strategies used by caregivers of children with perinatally acquired HIV during the pre-disclosure and post-disclosure period in rural communities in South Africa. Glob Pediatr Health. 2021;8:2333794X211022269. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34104705.
- Naar-King S, Montepiedra G, Nichols S, et al. Allocation of family responsibility for illness management in pediatric HIV. J Pediatr Psychol. 2009;34(2):187-194. Available at: https://www.ncbi.nlm.nih.gov/pubmed/18586756.
- Cluver LD, Hodes RJ, Toska E, et al. ‘HIV is like a tsotsi. ARVs are your guns’: associations between HIV-disclosure and adherence to antiretroviral treatment among adolescents in South Africa. AIDS. 2015;29 Suppl 1:S57-65. Available at: https://www.ncbi.nlm.nih.gov/pubmed/26049539.
- Cluver L, Meinck F, Toska E, Orkin FM, Hodes R, Sherr L. Multitype violence exposures and adolescent antiretroviral nonadherence in South Africa. AIDS. 2018;32(8):975-983. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29547438.
- Amico KR, Crawford J, Ubong I, et al. Correlates of high HIV viral load and antiretroviral therapy adherence among viremic youth in the United States enrolled in an adherence improvement intervention. AIDS Patient Care STDS. 2021;35(5):145-157. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33960843.
- Haas AD, Technau KG, Pahad S, et al. Mental health, substance use and viral suppression in adolescents receiving ART at a paediatric HIV clinic in South Africa. J Int AIDS Soc. 2020;23(12):e25644. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33283916.
- Pintye J, Bacchetti P, Teeraananchai S, et al. Brief report: lopinavir hair concentrations are the strongest predictor of viremia in HIV-infected Asian children and adolescents on second-line antiretroviral therapy. J Acquir Immune Defic Syndr. 2017;76(4):367-371. Available at: https://www.ncbi.nlm.nih.gov/pubmed/28825944.
- Al-Hassany L, Kloosterboer SM, Dierckx B, Koch BC. Assessing methods of measuring medication adherence in chronically ill children-a narrative review. Patient Prefer Adherence. 2019;13:1175-1189. Available at: https://www.ncbi.nlm.nih.gov/pubmed/31413546.
- Craker L, Tarantino N, Whiteley L, Brown L. Measuring antiretroviral adherence among young people living with HIV: observations from a real-time monitoring device versus self-report. AIDS Behav. 2019;23(8):2138-2145. Available at: https://www.ncbi.nlm.nih.gov/pubmed/30888573.
- Bonner K, Mezochow A, Roberts T, Ford N, Cohn J. Viral load monitoring as a tool to reinforce adherence: a systematic review. J Acquir Immune Defic Syndr. 2013;64(1):74- Available at: https://www.ncbi.nlm.nih.gov/pubmed/23774877.
- Lowenthal ED, Ohrenshall R, Moshashane N, et al. Reasons for discordance between antiretroviral adherence measures in adolescents. AIDS Care. 2021:1-9. Available at: https://www.ncbi.nlm.nih.gov/pubmed/34424796.
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- Neilan AM, Bangs AC, Hudgens M, et al. Modeling adherence interventions among youth with HIV in the United States: clinical and economic projections. AIDS Behav. 2021;25(9):2973-2984. Available at: https://www.ncbi.nlm.nih.gov/pubmed/33547993.
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- Pham PA. Antiretroviral adherence and pharmacokinetics: review of their roles in sustained virologic suppression. AIDS Patient Care STDS. 2009;23(10):803-807. Available at: https://www.ncbi.nlm.nih.gov/pubmed/19795999.
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- Bucek A, Leu CS, Benson S, et al. Psychiatric disorders, antiretroviral medication adherence and viremia in a cohort of perinatally HIV-infected adolescents and young adults. Pediatr Infect Dis J. 2018;37(7):673-677. Available at: https://www.ncbi.nlm.nih.gov/pubmed/29227462.
- Nichols J, Steinmetz A, Paintsil E. Impact of HIV-status disclosure on adherence to antiretroviral therapy among HIV-infected children in resource-limited settings: a systematic review. AIDS Behav. 2017;21(1):59-69. Available at: https://www.ncbi.nlm.nih.gov/pubmed/27395433.
- Shingadia D, Viani RM, Yogev R, et al. Gastrostomy tube insertion for improvement of adherence to highly active antiretroviral therapy in pediatric patients with human immunodeficiency virus. Pediatrics. 2000;105(6):E80. Available at: https://www.ncbi.nlm.nih.gov/pubmed/10835093.
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- Hart JE, Jeon CY, Ivers LC, et al. Effect of directly observed therapy for highly active antiretroviral therapy on virologic, immunologic, and adherence outcomes: a meta- analysis and systematic review. J Acquir Immune Defic Syndr. 2010;54(2):167-179. Available at: https://www.ncbi.nlm.nih.gov/pubmed/20375848.
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