HIV infection in adolescents

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

An increasing number of HIV-infected children who acquired HIV infection through perinatal transmission are now surviving into adolescence. They generally have had a long clinical course and extensive ARV treatment history. Adolescents with behaviorally acquired infection (i.e., infection acquired via sexual activity or intravenous substance use) generally follow a clinical course similar to that in adults. Because behaviorally infected adolescents are at an early stage of HIV infection, they are potential candidates for early intervention and treatment.

Chapter Outline

The following chapter is outlined as follows:

• Treatment
  • Dosing
  • Specific issues in antiretroviral therapy
    • Contraception
    • Pregnancy
    • Adherence
      • Adherence assessment and monitoring
      • Strategies to improve and support adherence
• Transition of Adolescent into Adult: Changes needed in HIV Care Settings
• Recommendations

Treatment

Dosing

• Many ARV medications (e.g., abacavir, emtricitabine, lamivudine, tenofovir, and some protease inhibitors [PIs]) are administered to children at higher weight- or surface area-based doses than would be predicted by direct scaling of adult doses, based upon reported PK data indicating more rapid drug clearance in children.
• Continued use of these pediatric weight- or surface area-based doses as a child grows during adolescence can result in medication doses that are higher than the usual adult doses.
• Many factors may affect the transition from pediatric to adult doses. In addition to toxicity, pill burden, adherence, and virologic and immunologic parameters, factors may include social determinants, such as housing, family support, employment, and recent discharge from the foster care system.

Specific issues in antiretroviral therapy for HIV-infected adolescents

Adolescent Contraception

• Adolescents with HIV infection, regardless of mode of acquisition, may be sexually active. Contraception methods and safer sex techniques for prevention of HIV transmission should be discussed with them regularly.
• Several PI and non-nucleoside reverse transcriptase inhibitor (NNRTI) drugs interact with oral contraceptives, resulting in possible decreases in ethinyl estradiol or increases in estradiol or norethindrone levels. These changes may decrease the effectiveness of the oral contraceptives or potentially increase the risk of estrogen- or progestin-related side effects.
• Providers should be aware of these drug interactions and consider alternative or additional contraceptive methods for patients receiving ARV drugs with such interactions.
• Whether interactions with ARV drugs would compromise the contraceptive effectiveness of progestogen-only injectable contraceptives (such as depot methoxyprogesterone acetate - DMPA) is unknown because these methods produce higher blood hormone levels than other progestogen-only oral contraceptives and combined oral contraceptives.
  • In one study, the efficacy of DMPA was not altered among women receiving concomitant nelfinavir-, efavirenz-, or nevirapine-based treatment, with no evidence of ovulation during concomitant administration for 3 months, no additional side effects, and no clinically significant changes in ARV drug levels.
• Intrauterine device (IUD) use while on ART is not restricted by current guidelines; however, IUD users with AIDS should be closely monitored for pelvic infection.
• Adolescents who desire to become pregnant should be referred for preconception counseling and care, including discussion of special considerations with ART use during pregnancy.

Adolescent Pregnancy

• The possibility of planned or unplanned pregnancy should be considered when selecting an ARV regimen for the adolescent female.
• The most vulnerable period in fetal organogenesis is early in gestation, often before pregnancy is recognized. Therefore sexual activity, reproductive plans including preconception care, and use of effective contraception should be discussed with the patient.
• Pregnancy should not preclude the use of optimal therapeutic regimens. However, because of considerations related to prevention of perinatal transmission and to maternal and fetal safety, timing of initiation of treatment and selection of regimens may be different for pregnant women than for nonpregnant adults or adolescents.

Adherence

• Medication adherence is fundamental to successful ART. Adherence is a major factor in determining the degree of viral suppression achieved in response to ART. Poor adherence can lead to virologic failure.
• Prospective adult and pediatric studies have shown the risk of virologic failure to increase as the proportion of missed doses increases.
• Several studies have identified pill burden as well as lifestyle issues (i.e., not having medications on hand when away from home, change in schedule) as barriers to complete adherence.
• Adolescents’ denial and fear of their HIV infection is common, especially in recently diagnosed youth; this may lead to refusal to initiate or continue ART.
• Distrust of the medical establishment, misinformation about HIV, and lack of knowledge about the availability and effectiveness of ARV treatments can all be barriers to linking adolescents to care and maintaining successful ART.
• Perinatally infected youth are familiar with the challenges of taking complex drug regimens and with the routine of chronic medical care; nevertheless, they may have long histories of inadequate adherence.
• Regimen fatigue has also been identified as a barrier to adherence in adolescents.
• Regardless of the mode of acquisition of HIV infection, HIV-infected adolescents may suffer from low self-esteem, may have unstructured and chaotic lifestyles and concomitant mental illnesses, or may cope poorly with their illness because of a lack of familial and social support.
• Depression, alcohol or substance abuse, poor school attendance, and advanced HIV disease stage all correlate with nonadherence.
• In a study of 833 HIV-infected Medicaid beneficiaries 12–17 years of age, youth diagnosed with a psychiatric comorbidity (substance abuse, conduct disorder, or emotional disorder) were less likely to be receiving combination therapy; however, for those on therapy, only a conduct disorder diagnosis was associated with poorer adherence.
• In a cross-sectional study of youth with perinatal HIV infection, no significant differences in the frequency of mental health disorders were found between adherent and nonadherent participants.
• A review of published papers on adherence among HIV-infected youth, however, suggests that depression and anxiety have been consistently associated with poorer adherence.
• Adherence to complex regimens is particularly challenging at a time of life when adolescents do not want to be different from their peers. Further difficulties face adolescents who live with parents or partners to whom they have not yet disclosed their HIV status and adolescents who are homeless and have no place to store medicine.
• When recommending treatment regimens for adolescents, clinicians must balance the goal of prescribing a maximally potent ARV regimen with realistic assessment of existing and potential support systems to facilitate adherence.
• Interventions to promote long-term adherence to ARV treatment have not been rigorously evaluated in adolescents. In clinical practice, reminder systems, such as beepers and alarm devices, are well accepted by some youth.
• Small, inconspicuous pillboxes may be useful for storing medications in an organized fashion. In a pilot study evaluating peer support and pager messaging in an adult population, peer support was associated with greater self-reported adherence post-intervention; however, the effect was not sustained at follow-up. Although pager messaging was not associated with reported adherence, improved biologic outcomes were measured.
• Another study evaluating the efficacy of a four-session, individual, clinic-based motivational interviewing intervention targeting multiple risk behaviors in HIV-infected youth demonstrated an association with lower viral load at 6 months among youth taking ART. However, reduction in viral load was not maintained at 9 months.

Adherence assessment and monitoring

The process of adherence preparation and assessment should begin before therapy is initiated or changed. Adherence is difficult to assess accurately; different methods of assessment have yielded different results, and each approach has limitations.

Steps involved in assessment

• A routine adherence assessment should be incorporated into every clinic visit.
• A comprehensive assessment should be instituted for all children in whom ARV treatment initiation or change is considered.

Evaluation

Evaluations should include nursing, social, and behavioral assessments of factors that may affect adherence by the child and family and can be used to identify individual needs for intervention.

Preparation

• Adherence preparation should focus on establishing a dialogue and a partnership with the child and family regarding medication management.
• Specific, open-ended questions should be used to elicit information about past experience as well as concerns and expectations about treatment.
• When assessing readiness and preparing to begin treatment, it is important to obtain the patient’s explicit agreement with the treatment plan, including strategies to support adherence.
• It is also important to alert patients to the minor side effects of ARV drugs, such as nausea, headaches, and abdominal discomfort, that may recede over time or respond to change in diet or method and timing of medication administration.

Monitoring

• Both caregivers and health care providers often overestimate adherence. Use of multiple methods to assess adherence is recommended.
  • Viral load response to a new regimen is often the most accurate indication of adherence, but it may be a less valuable measure in children with long treatment histories and multidrug-resistant virus.
  • Other measures include quantitative self-report of missed doses by caregivers and children or adolescents (focusing on recent missed doses during a 3-day or 1-week period), descriptions of the medication regimens, and reports of barriers to administration of medications.
  • Caregivers may report number of doses taken more accurately than doses missed. Also, targeted questions about stress, pill burden, and daily routine are recommended.
    • Pharmacy refill checks and pill counts can identify adherence problems not evident from self-reports.
    • Electronic monitoring devices, such as Medication Event Monitoring System (MEMS) caps, which are equipped with a computer chip that records each opening of a medication bottle, have been shown to be useful tools to measure adherence in some settings.
    • Home visits can play an important role in assessing adherence.
  • In some cases, suspected nonadherence is confirmed only when dramatic clinical responses to ART occur during hospitalizations or in other supervised settings.
  • Preliminary studies suggest that monitoring plasma concentrations of PIs, or therapeutic drug monitoring (TDM), may be a useful method to identify nonadherence.

Interpersonal relationship & Psychological support

• It is important for clinicians to recognize that nonadherence is a common problem and that it can be difficult for patients to share information about missed doses or difficulties adhering to treatment. Furthermore, adherence can change over time.
• An adolescent who was able to strictly adhere to treatment upon initiation of a regimen may not be able to maintain complete adherence over time.
• A nonjudgmental attitude and trusting relationship foster open communication and facilitate assessment. To obtain information on adherence in older children, it is often helpful to ask both the HIV-infected child and caregivers about missed doses and problems. Their reports may differ significantly; therefore, clinical judgment is required to best interpret adherence information obtained from the multiple sources.

Strategies to improve and support adherence

• Intensive follow-up is required, particularly during the critical first few months after therapy is started.
• Patients should be seen frequently, as often as weekly during the first month of treatment, to assess adherence and determine the need for strategies to improve and support adherence.
• Strategies include development of patient-focused treatment plans to accommodate specific patient needs, integration of medication administration into the daily routines of life (e.g., associating medication administration with daily activities such as brushing teeth), and use of social and community support services.

Transition of Adolescent into Adult: Changes needed in HIV Care Settings

• Transition is described as “a multifaceted, active process that attends to the medical, psychosocial, and educational or vocational needs of adolescents as they move from the child-focused to the adult-focused health-care system”
• Facilitating a smooth transition of adolescents with chronic health conditions from their pediatric/adolescent medical home to adult care can be difficult and is especially challenging for adolescents infected with HIV.
• Care models for children and adolescents with perinatally acquired HIV tend to be family centered, consisting of a multidisciplinary team that often includes pediatric or adolescent physicians, nurses, social workers, and mental health professionals. These providers generally have long-standing relationships with patients and their families, and care is rendered in discreet, more intimate settings.
• Although expert care is also provided under the adult HIV care medical model, the adolescent may be unfamiliar with the more individual-centered, busier clinics typical of adult medical providers and uncomfortable with providers who often do not have a long-standing relationship with the adolescent.
• Providing the adolescent and the adult medical care provider with support and guidance regarding expectations for each partner in the patient-provider relationship may be helpful. In this situation, it may also be helpful for the pediatric and adult provider to share joint care of the patient for a period of time.
• Providers should also have a candid discussion with the transitioning adolescent to understand what qualities the adolescent considers most important in a provider (e.g., confidentiality, small clinic size, after-school appointments).
• Pediatric and adolescent providers should have a formal plan to transition adolescents to adult care.

Recommendations

Adherence to antiretroviral therapy in HIV-infected children and adolescents

• Strategies to maximize adherence should be discussed before initiation of antiretroviral therapy (ART) and again prior to changing regimens (AIII).
• Adherence to therapy must be stressed at each visit, along with continued exploration of strategies to maintain and/or improve adherence (AIII).
• At least one method of measuring adherence to ART (e.g., quantitative and/or qualitative self-report, pharmacy refill checks, pill counts) should be used in addition to monitoring viral load (AII).
• When feasible, once-daily antiretroviral (ARV) regimens should be prescribed (AI*).
• To improve and support adherence, providers should maintain a nonjudgmental attitude, establish trust with the patient/caregiver, and identify mutually acceptable goals for care (AII*).

Related Chapter

HIV infection in infants

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