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Choosing ART in Older Patients
Selecting First-line Antiretroviral Therapy in Older Patients: New Data, New Options, Key Considerations

Released: December 16, 2015

Expiration: December 14, 2016

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No currently available HIV guidelines focus primarily on the management of older HIV-infected patients, mainly due to limited information on the efficacy and safety of antiretroviral therapy (ART) regimens in this population. Most recently, regulatory agencies such as the FDA and European Medicines Agency have requested age stratification older or younger than 50 years of age in the analysis of results for registration clinical trials. However, because many such trials exclude patients with comorbidities, the included elderly population may not be representative of most older HIV-infected patients, who typically experience a complex pattern of multimorbidity. Moreover, anagraphic age is not always a good predictor of aging as a health condition. Host factors and duration of HIV infection are associated with increased risk of multimorbidity compared with the HIV-uninfected general population, placing people aging with HIV at substantially higher risk for multimorbidity compared with people who acquired HIV at an older age.

At present, treatment guidelines advise that recommended ART choices for the elderly are the same as for the general HIV-Infected population. However, 3 main considerations should be taken into account when choosing therapy for individual older patients: comorbid conditions, greater medication use, and age-related changes in pharmacokinetics and pharmacodynamics.

Comorbid Conditions
Bone, kidney, metabolic, and cardiovascular disease are more frequent in older adults with HIV, and all patients starting ART should undergo careful risk screening. Treatment guidelines produced by the European AIDS Clinical Society include a detailed screening algorithm to be performed before starting ART with specific issues to be addressed in older treatment-naive patients. Similarly, DHHS treatment guidelines include a section on considerations for ART use in older patients, in which ART-associated common or severe adverse events relevant to the treatment of older patients at higher risk of comorbidities are reviewed.

Greater Medication Use
Polypharmacy for treatment of multimorbidity in both the general older population and in patients with HIV infection is very common. Data from the Swiss HIV Cohort demonstrate that of HIV-infected patients 65 years of age and older, 14% received 4 or more non-HIV comedications. Lipid-lowering agents were the most commonly prescribed non-ART medication in this subgroup, used by 42%. Statin use has important bearing on ART selection because of the potential for drug–drug interactions with ART. In clinical practice, I recommend an annual medication reconciliation, which entails patients listing all current medications and any associated symptoms and assessing their level of adherence. The drug name, dose, frequency, and last fill date should be verified for all current medications. Therapeutic duplication and continued indication should be evaluated prior to each renewal. If electronic fill/refill data are available, medication possession ratios can provide an unbiased estimate of adherence. The process of medication reconciliation might be facilitated by a clinical pharmacist working in conjunction with the clinic or primary care provider.

Age-Related Changes in Pharmacokinetics and Pharmacodynamics
Pharmacokinetic changes associated with aging include a reduction in renal and hepatic clearance and an increase in volume of distribution of lipid-soluble drugs, leading to a prolonged elimination half-life. Pharmacodynamic changes involve altered (usually increased) sensitivity to several classes of drugs, such as anticoagulants, cardiovascular, and psychotropic drugs.

The Table provides an empirical summary of the impact of different ART classes on clinical principles of ART selection in older patients. Integrase inhibitors appear to have some advantages in this setting, whereas NRTIs may have some drawbacks, such as the increased risk of kidney and bone toxicities associated with tenofovir DF or the apparent association between abacavir and risk of myocardial infarction.

Table. Considerations for ART Use in Older Patients

Selection of ART requires particular thought in postmenopausal women or women entering menopause. Menopause is a physiological time frame where rapid hormonal, biochemical, anthropometric, and psychological changes occur, making women more vulnerable to ART toxicities. The most relevant comorbidity in this category is osteoporosis. DHHS guidance recommends that clinicians should consider avoiding tenofovir DF in patients with osteoporosis.

Use of NRTI-limiting strategies intended to avoid use of tenofovir DF and abacavir has been investigated in a number of studies. At the recent 15th European AIDS Conference (EAC), Pedro Cahn presented interim findings from PADDLE, a pilot, open-label, single-arm phase IV trial assessing use of dolutegravir plus lamivudine as initial therapy in 20 ART-naive patients. All 20 patients achieved HIV-1 RNA < 50 copies/mL at Week 24 of treatment. PADDLE is the first study exploring an INSTI/lamivudine-based regimen in treatment-naive patients, and longer follow-up is required to confirm these encouraging initial results. Unfortunately, this study did not include a significant number of older HIV patients, and the median age was 34 years.

The availability of tenofovir alafenamide in clinical practice may rapidly change the need for NRTI-sparing regimens. Tenofovir alafenamide produces tenofovir concentrations in serum that are considerably lower than those produced by tenofovir DF, and exposure is more concentrated in the intracellular lymphocyte cytoplasm. This results in improved bone and kidney safety, which suggests this may be a useful NRTI option for the aging patient. A subanalysis of the 104/111 studies comparing elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide with elvitegravir/cobicistat/emtricitabine/tenofovir DF in treatment-naive patients reported outcomes in patients aged 50 years and older. Loss of bone mineral density at the hip and spine was significantly lower with the tenofovir alafenamide regimen.

The management of ART in patients aging with HIV requires clinicians to maintain a detailed knowledge of physical and psychological patient health in order to tailor the most appropriate ART regimen. It has been proposed that frailty may be assessed as a marker of vulnerability among individuals aging with chronic HIV infection. Future research should investigate the relationship between frailty and ART choice in HIV-infected patients. In this context, frailty may be useful either as inclusion criteria or as a clinical endpoint for randomized clinical trials comparing ART treatment regimens in elderly patients with HIV.

Your Thoughts
What is your approach to assessing baseline comorbidity risk in older HIV-infected patients, and how do you apply screening information when choosing ART for this population? I encourage readers to share their experience below.

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