Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV
The information in the brief version is excerpted directly from the full-text guidelines. The brief version is a compilation of the tables and boxed recommendations.
Considerations for Antiretroviral Use in Special Patient Populations
HIV and the Older Patient
Last Updated: January 28, 2016; Last Reviewed: January 28, 2016
|Key Considerations When Caring for Older Patients With HIV|
|Rating of Recommendations: A = Strong; B = Moderate; C = Optional
Rating of Evidence: I = Data from randomized controlled trials; II = Data from well-designed nonrandomized trials or observational cohort studies with long-term clinical outcomes; III = Expert opinion
Effective antiretroviral therapy (ART) has increased survival in individuals with HIV, resulting in an increasing number of older individuals living with HIV. In the United States, among persons living with HIV at year-end 2013, 42% were age 50 years or older, 6% were age 65 or older, and trends suggest that these proportions will increase steadily.1 Care of patients with HIV increasingly will involve adults 60 to 80 years of age, a population for which data from clinical trials or pharmacokinetic (PK) studies are very limited.
There are several distinct areas of concern regarding the association between age and HIV disease.2 First, older patients with HIV may suffer from aging-related comorbid illnesses that can complicate the management of HIV infection. Second, HIV disease may affect the biology of aging, possibly resulting in early manifestations of clinical syndromes generally associated with advanced age. Third, reduced mucosal and immunologic defenses (such as postmenopausal atrophic vaginitis) and changes in risk related-behaviors (e.g., decrease in condom use because of less concern about pregnancy or more high-risk sexual activity with increased use of erectile dysfunction drugs) in older adults could lead to increased risk of acquisition and transmission of HIV.3,4 Finally, because older adults are generally perceived to be at low risk of acquiring HIV, screening for this population remains low.
HIV Diagnosis and Prevention in the Older Adult
In older adults, failure to consider a diagnosis of HIV likely contributes to later initiation of ART.5 The Centers for Disease Control and Prevention (CDC) estimates that in 2013, 37% of adults aged 55 years or older at the time of HIV diagnosis met the case definition for AIDS. The comparable CDC estimates are 18% for adults aged 25 to 34 years and 30% for adults aged 35 to 44 years.6 In one observational cohort, older patients (defined as those ≥35 years of age) appeared to have lower CD4 T lymphocyte (CD4) cell counts at seroconversion, steeper CD4 count decline over time,7 and tended to present to care with significantly lower CD4 counts.8 When individuals >50 years of age present with severe illnesses, AIDS-related opportunistic infections (OIs) need to be considered in the differential diagnosis of the illness.
Although many older individuals engage in risk behaviors associated with acquisition of HIV, they may see themselves or be perceived by providers as at low risk of infection and, as a result, they are less likely to be tested for HIV infection than younger persons.9,10 Despite CDC guidelines recommending HIV testing at least once in individuals aged 13 to 64, and more frequently for those at risk,11 HIV testing prevalence remains low (<5%) among adults aged 50 to 64, and decreased with increasing age.12 Clinicians must be attuned to the possibility of HIV infection in older adults, including those older than 64 years of age and especially in those who may engage in high-risk behaviors. Sexual history taking is therefore an important component of general health care for older adults who do not have HIV, together with risk-reduction counseling, and screening for HIV and sexually transmitted infections (STIs), if indicated.
Impact of Age on HIV Disease Progression
HIV infection presents unique challenges in aging adults and these challenges may be compounded by ART:
- HIV infection itself is thought to induce immune-phenotypic changes akin to accelerated aging,13 but recent laboratory and clinical data provide a more nuanced view of these changes. Some studies have shown that patients with HIV may exhibit chromosomal and immunologic features similar to those induced by aging.14,15 However, other studies show the immunologic changes to be distinct from age-related changes.16 In addition, although data on the increased incidence and prevalence of age-associated comorbidities in patients with HIV are accumulating,17,18 the age of diagnosis for myocardial infection and non-AIDS cancers in patients who have HIV and those who do not is the same.18,19
- Older patients with HIV have a greater incidence of complications and comorbidities than adults of a similar age who do not have HIV, and may exhibit a frailty phenotype—defined clinically as a decrease in muscle mass, weight, physical strength, energy, and physical activity,20 although the phenotype is still incompletely characterized in people with HIV.
Initiating Antiretroviral Therapy in the Older Patient with HIV
ART is recommended for all individuals with HIV (AI; see Initiation of Antiretroviral Therapy section). Early treatment may be particularly important in older adults in part because of decreased immune recovery and increased risk of serious non-AIDS events in this population. In a modeling study based on data from an observational cohort, the beneficial effects of early ART were projected to be greatest in the oldest age group (patients between ages 45 and 65 years).21 No data support a preference for any one of the Panel’s recommended initial ART regimens (see What to Start) on the basis of patient age. The choice of regimen should instead be informed by a comprehensive review of the patient’s other medical conditions and medications. The What to Start section (Table 7) of these guidelines provides guidance on selecting an antiretroviral regimen based on an older patient’s characteristics and specific clinical conditions (e.g., kidney disease, elevated risk for cardiovascular disease, osteoporosis). In older patients with reduced renal function, dosage adjustment of nucleoside reverse transcriptase inhibitors (NRTIs) may be necessary (see Appendix B, Table 7). In addition, ARV regimen selection may be influenced by potential interaction of antiretroviral medications with drugs used concomitantly to manage comorbidities (see Tables 18a-19b). Adults age >50 years should be monitored for ART effectiveness and safety similarly to other populations with HIV (see Table 3); however, in older patients, special attention should be paid to the greater potential for adverse effects of ART on renal, liver, cardiovascular, metabolic, and bone health (see Table 14).
HIV, Aging, and Antiretroviral Therapy
The efficacy, PKs, adverse effects, and drug interaction potentials of ART in the older adult have not been studied systematically. There is no evidence that the virologic response to ART differs in older and younger patients. In a recent observational study, a higher rate of viral suppression was seen in patients >55 years old than in younger patients.22 However, ART-associated CD4 cell recovery in older patients is generally slower and lower in magnitude than in younger patients.8,23-25 This observation suggests that starting ART at a younger age may result in better immunologic response and possibly clinical outcomes.
Hepatic metabolism and renal elimination are the major routes of drug clearance, including the clearance of ARV drugs. Both liver and kidney functions decrease with age and may result in impaired drug elimination and increased drug exposure.26 Most clinical trials have included only a small proportion of participants over 50 years of age, and current ARV dosing recommendations are based on PK and pharmacodynamic data derived from participants with normal organ function. Whether drug accumulation in the older patient may lead to greater incidence and severity of adverse effects than seen in younger patients is unknown.
Patients with HIV and aging-associated comorbidities may require additional pharmacologic interventions that can complicate therapeutic management. In addition to taking medications to manage HIV infection and comorbid conditions, many older patients with HIV also are taking medications to relieve discomfort (e.g., pain medications, sedatives) or to manage adverse effects of medications (e.g., anti-emetics). They also may self-medicate with over-the-counter medicines or supplements. In older patients who do not have HIV, polypharmacy is a major cause of iatrogenic complications.27 Some of these complications may be caused by medication errors (by prescribers or patients), medication nonadherence, additive drug toxicities, and drug-drug interactions. Older patients with HIV are probably at an even greater risk of polypharmacy-related adverse consequences than younger or similarly aged patients with HIV. When evaluating any new clinical complaint or laboratory abnormality in patients with HIV, especially in older patients, clinicians should always consider the possible role of adverse drug reactions from both ARV drugs and other concomitantly administered medications.
Drug-drug interactions are common with ART and can be easily overlooked by prescribers.28 The available drug interaction information on ARV agents is derived primarily from PK studies performed in small numbers of relatively young participants with normal organ function who do not have HIV (see Tables 18a-19b). Data from these studies provide clinicians with a basis to assess whether a significant interaction may exist. However, the magnitude of the interaction may be greater in older patients with HIV than in younger patients with HIV.
Nonadherence is the most common cause of treatment failure. Complex dosing requirements, high pill burden, inability to access medications because of cost or availability, limited health literacy including misunderstanding of instructions, depression, and neurocognitive impairment are among the key reasons for nonadherence.32 Although many of these factors associated with nonadherence may be more prevalent in older patients, some studies have shown that older patients with HIV may actually be more adherent to ART than younger patients.29-31 Clinicians should regularly assess older patients to identify any factors, such as neurocognitive deficits, that may decrease adherence. To facilitate medication adherence, it may be useful to discontinue unnecessary medications, simplify regimens, and recommend evidence-based behavioral approaches including the use of adherence aids such as pillboxes or daily calendars, and support from family members (see Adherence to the Continuum of Care).
Non-AIDS HIV-Related Complications and Other Comorbidities
Among persons treated effectively with ART, as AIDS-related morbidity and mortality have decreased, non-AIDS conditions constitute an increasing proportion of serious illnesses.33-35 Neurocognitive impairment, already a major health problem in aging adults, may be exacerbated by the effect of HIV infection on the brain.36 In a prospective observational study, neurocognitive impairment was predictive of lower retention in care among older persons.37 Neurocognitive impairment probably also affects adherence to therapy. Social isolation and depression are also particularly common among older adults with HIV and, in addition to their direct effects on morbidity and mortality, may contribute to poor medication adherence and retention in care.38,39 Heart disease and cancer are the leading causes of death in older Americans.40 Similarly, non-AIDS events such as heart disease, liver disease, and cancer have emerged as major causes of morbidity and mortality in patients with HIV receiving effective ART. The presence of multiple non-AIDS comorbidities coupled with the immunologic effects of HIV infection may add to the disease burden of aging adults with HIV.41-43 HIV-specific primary care guidelines have been updated with recommendations for lipid and glucose monitoring, evaluation and management of bone health, and management of kidney disease, and are available for clinicians caring for older patients with HIV.44-48
Switching, Interrupting, and Discontinuing Antiretroviral Therapy in Older Patients
Given the greater incidence of comorbidities, non-AIDS complications and frailty among older patients with HIV, switching one or more ARVs in an HIV regimen may be necessary to minimize toxicities and drug-drug interactions. For example, expert guidance now recommends bone density monitoring in men aged ≥50 years and postmenopausal women, and suggests switching from tenofovir disoproxil fumarate or boosted protease inhibitors to other ARVs in older patients at high risk for fragility fractures.45
Few data exist on the use of ART in severely debilitated patients with chronic, severe, or non-AIDS terminal conditions.49,50 Withdrawal of ART usually results in rebound viremia and a decline in CD4 cell count. Acute retroviral syndrome after abrupt discontinuation of ART has been reported. In severely debilitated patients, if there are no significant adverse reactions to ART, most clinicians would continue therapy. In cases where ART negatively affects quality of life, the decision to continue therapy should be made together with the patient and/or family members after a discussion on the risks and benefits of continuing or withdrawing ART.
Healthcare Utilization, Cost Sharing, and End-of-Life Issues
Important issues to discuss with aging patients with HIV are living wills, advance directives, and long-term care planning, including related financial concerns. Out-of-pocket health care expenses (e.g., copayments, deductibles), loss of employment, and other financial-related factors can cause temporary interruptions in treatment, including ART, which should be avoided whenever possible. The increased life expectancy and the higher prevalence of chronic complications in aging populations with HIV can place greater demands upon HIV services.51 Facilitating a patient’s continued access to insurance can minimize treatment interruptions and reduce the need for other services to manage concomitant chronic disorders.
HIV disease can be overlooked in aging adults who tend to present with more advanced disease and experience accelerated CD4 loss. HIV induces immune-phenotypic changes that have been compared to accelerated aging. Effective ART has prolonged the life expectancy of patients with HIV, increasing the number of patients >50 years of age living with HIV. However, unique challenges in this population include greater incidence of complications and comorbidities, and some of these complications may be exacerbated or accelerated by long term use of some ARV drugs. Providing comprehensive multidisciplinary medical and psychosocial support to patients and their families (the “Medical Home” concept) is of paramount importance in the aging population. Continued involvement of HIV experts, geriatricians, and other specialists in the care of older patients with HIV is warranted.
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