The strength of recommendation (A-C) and quality of evidence (I-V) grading scales are defined at the end of the "Major Recommendations" field.
Entry into and Retention in Human Immunodeficiency Virus (HIV) Medical Care
The associations between entry into and retention in HIV medical care and both individual health outcomes and HIV transmission dynamics mediated by antiretroviral therapy (ART) have been well-established in retrospective, prospective, and mathematical modeling studies. Accordingly, individual-level monitoring of entry and retention is essential to the development and evaluation of cost-effective interventions required to improve these critical components of clinical care.
Recommendation 1: Systematic monitoring of successful entry into HIV care is recommended for all individuals diagnosed with HIV (II A).
Recommendation 2: Systematic monitoring of retention in HIV care is recommended for all patients (II A).
Recommendation 3: Brief, strengths-based case management for individuals with a new HIV diagnosis is recommended (II B).
Recommendation 4: Intensive outreach for individuals not engaged in medical care within 6 months of a new HIV diagnosis may be considered (III C).
Recommendation 5: Use of peer or paraprofessional patient navigators may be considered (III C).
Monitoring ART Adherence
Monitoring adherence is necessary to assess the effect of interventions and also to inform providers of the need to implement interventions. Measurement methods include self-reports, pharmacy refill data, pill counts, electronic drug monitors (EDMs), and drug concentrations from biological samples; each has unique strengths and weaknesses. Many of the studies reviewed combined measures to improve sensitivity and specificity, but because of the large variability in these approaches, these guidelines will not address these potential combinations here. Regardless of measurement method, adherence is a factor that varies with time and therefore must be repeatedly assessed.
Recommendation 6: Self-reported adherence should be obtained routinely in all patients (II A).
Recommendation 7: Pharmacy refill data are recommended for adherence monitoring when medication refills are not automatically sent to patients (II B).
Recommendation 8: Drug concentrations in biological samples are not routinely recommended (III C).
Recommendation 9: Pill counts performed by staff or patients are not routinely recommended (III C).
Recommendation 10: EDMs are not routinely recommended for clinical use (I C).
Interventions to Improve ART Adherence
Important determinants of ART adherence and the related construct of ART persistence, or uninterrupted receipt of treatment, include dosing schedule, pill count, tolerability, and toxicity profiles of ART. Advances in ART now allow simplification of dosing schedules and reduction of pill burden for a majority of patients while maintaining excellent viral suppression. Additional factors to be considered in initiating or changing ART include transmitted or emergent viral resistance, individual ART treatment history, medical and psychosocial comorbid conditions, concomitant medications, and patient preference.
Recommendation 11: Among regimens of similar efficacy and tolerability, once-daily regimens are recommended for treatment-naive patients beginning ART (II B).
Recommendation 12: Switching treatment-experienced patients receiving complex or poorly tolerated regimens to once-daily regimens is recommended, given regimens with equivalent efficacy (III B).
Recommendation 13: Among regimens of equal efficacy and safety, fixed-dose combinations are recommended to decrease pill burden (III B).
Adherence Tools for Patients
Many commonly used self-management adherence tools, including pillboxes and medication planners or calendars, have been associated with improved adherence and HIV-1 ribonucleic acid (RNA) suppression. It is common for adherence tools to be combined with behavioral and structural interventions. Given their simplicity and observational data supporting their use, they are considered the standard of care despite limited comparative research to establish efficacy. Recommendations regarding use of these tools are limited because of this lack of evidence.
Recommendation 14: Reminder devices and use of communication technologies with an interactive component are recommended (I B).
Recommendation 15: Education and counseling using specific adherence-related tools is recommended (I A).
Education and Counseling Interventions
Several systematic syntheses of behavioral interventions targeting ART adherence are available and report generally positive modest effect sizes, but the effect on HIV-1 RNA is less consistent. Recommendations are limited to those appropriate for general clinic populations; interventions targeting behavioral determinants of adherence in specific subgroups are included in other sections. Because of the volume and breadth of data supporting these recommendations, individual study results are not reviewed in detail, but Appendix Table 2 in the original guideline document describes studies and outcomes. Across recommendations, pertinent issues exist with regard to best structure, deliverer, training, duration, timing, frequency, and targets of educational and counseling interventions, as well as optimal modalities for dissemination and implementation.
Recommendation 16: Individual one-on-one ART education is recommended (II A).
Recommendation 17: Providing one-on-one adherence support to patients through one or more adherence counseling approaches is recommended (II A).
Recommendation 18: Group education and group counseling are recommended; however, the type of group format, content, and implementation cannot be specified on the basis of the currently available evidence (II C).
Recommendation 19: Multidisciplinary education and counseling intervention approaches are recommended (III B).
Recommendation 20: Offering peer support may be considered (III C).
Health System and Service Delivery Interventions
The authors focused on interventions targeting factors believed to be related to adherence and ones that are also associated with systems of care or service delivery (for example, transportation to clinic and food supplements, staffing and service modifications, co-location of services) or influence social determinants, such as HIV-associated stigma.
Recommendation 21: Using nurse- or community counselor–based care has adherence and biological outcomes similar to those of doctor- or clinic counselor–based care and is recommended in under resourced settings (II B).
Recommendation 22: Interventions providing case management services and resources to address food insecurity, housing, and transportation needs are recommended (III B).
Recommendation 23: Integration of medication management services into pharmacy systems may be considered (III C).
Recommendation 24: Directly administered ART is not recommended for routine clinical care settings (I A).
More than 50% of the 37.2 million adults with HIV in the world are women, and most are of childbearing age. Optimal ART adherence during pregnancy and the postpartum period remains a challenge globally. The evidence regarding ART adherence interventions during pregnancy comes predominantly from resource-limited settings and is focused only on short-term prevention of mother-to-child transmission (PMTCT) rather than on ART adherence throughout pregnancy and afterward.
Recommendation 25: Targeted prevention of mother-to-child transmission (PMTCT) treatment (including HIV testing and serostatus awareness) improves adherence to ART for PMTCT and is recommended compared with an untargeted approach (treatment without HIV testing) in high HIV prevalence settings (III B).
Recommendation 26: Labor ward–based PMTCT adherence services are recommended for women who are not receiving ART before labor (II B).
Substance Use Disorders
Individuals with alcohol and other substance use disorders are at increased risk for poor retention in care, poor adherence, and virologic failure. Several adherence strategies not recommended for general clinic populations are effective among those with substance use disorders.
Recommendation 27: Offering buprenorphine or methadone to opioid-dependent patients is recommended (II A).
Recommendation 28: Directly administered ART (DAART) is recommended for individuals with substance use disorders (I B).
Recommendation 29: Integration of DAART into methadone maintenance treatment for opioid-dependent patients is recommended (II B).
Mental health disorders may predispose individuals to acquiring HIV, are common among individuals living with HIV, and present serious challenges for HIV treatment adherence. A meta-analysis of 95 studies found a significant relationship between depression and ART nonadherence that was consistent across patients in resource-rich and resource-limited settings. Research has linked depressive symptoms to poor HIV care engagement and health outcomes, including impaired immunologic response and mortality.
Recommendation 30: Screening, management, and treatment for depression and other mental illnesses in combination with adherence counseling are recommended (II A).
HIV and acquired immune deficiency syndrome (AIDS) prevalence is higher among incarcerated populations in low-, middle-, and high-income countries. Globally, incarceration negatively affects continuity of care; development of trust; and, ultimately, optimal adherence. Incarceration provides a public health opportunity to provide ART to HIV-infected persons; however, barriers to ART delivery and adherence exist, and unintended ART interruptions sometimes occur after release. Key challenges to ART adherence among criminal justice populations include identifying successful strategies for medication distribution that preserve confidentiality and avoid stigma and maintaining persistent ART use during transitions from correctional facilities to the community.
Recommendation 31: DAART is recommended during incarceration (III B) and may be considered upon release to the community (II C).
Homeless and Marginally Housed Individuals
In communities where stable housing is a societal norm, homeless persons represent a special population with respect to ART adherence because of the multiple and often interrelated adherence challenges in this population (such as unstable housing, mental illness, substance use disorders, food insecurity, mistrust of the health care system, incarceration, and inconsistent provider–patient relationships). Homelessness itself often disrupts daily routines, including medication taking, and can make medication storage difficult. In highly resourced countries, many homeless people have concomitant mental illness or substance use disorders that are associated with incomplete adherence. Mistrust of the health system and inconsistent provider–patient relationships can contribute to delayed entry into care. The homeless have competing survival needs, including food access, which have been associated with incomplete adherence and poor viral suppression. Excellent adherence and reliable viral suppression can, however, be achieved despite these multiple barriers.
Recommendation 32: Case management is recommended to mitigate multiple adherence barriers in the homeless (III B).
Recommendation 33: Pillbox organizers are recommended for persons who are homeless (II A).
Children and Adolescents
HIV-infected young people between birth and 24 years of age are a developmentally diverse group, including those perinatally and behaviorally infected. For perinatally infected children, adherence to medications is determined largely by their caregivers, who often have many challenges, including HIV infection. Unique medication-related factors associated with nonadherence for children include difficulty swallowing pills, bad taste of medications, and difficulty timing medication administration around meals. Perinatally infected teens often experience deterioration in medication adherence during adolescence, as do their peers with other chronic diseases. Transition from pediatric to adult care settings may create additional adherence barriers because of disruptions in comprehensive services and insurance issues. Adolescents and young adults are less likely than their older counterparts to be retained in care and receive prescriptions for ART, and they have worse clinical outcomes.
Recommendation 34: Intensive youth-focused case management is recommended for adolescents and young adults living with HIV to improve entry into and retention in care (IV B).
Recommendation 35: Pediatric- and adolescent-focused therapeutic support interventions using problem-solving approaches and addressing psychosocial context are recommended (III B).
Recommendation 36: Pill-swallowing training is recommended and may be particularly helpful for younger patients (IV B).
Recommendation 37: DAART improves short-term treatment outcomes and may be considered in pediatric and adolescent patients (IV C).
Quality of the Body of Evidence
- Randomized controlled trial (RCT) evidence without important limitations
- Overwhelming evidence from observational studies
- RCT evidence with important limitations
- Strong evidence from observational studies
- RCT evidence with critical limitations
- Observational study evidence without important limitations
- Observational study evidence with important or critical limitations
Strength of Recommendations
||Almost all patients should receive the recommended course of action.
||Most patients should receive the recommended course of action. However, other choices may be appropriate for some patients.
||There may be consideration for this recommendation on the basis of individual patient circumstances. Not recommended routinely.