Antiretroviral Treatment Efficacy and Safety in Older HIV‐Infected Adults

Abstract

Highly active antiretroviral therapy (ART) and its widespread availability have revolutionized the landscape of HIV care and patient outcomes, transforming infection with HIV into a manageable chronic condition rather than a life-limiting disease. This transformation has created an older patient demographic. The effect that older age has on the outcomes of ART is not completely understood. Limited data are available in older individuals due to underrepresentation in clinical trials. To better understand this relationship, we conducted a literature search to assess the impact of older age on the outcomes of ART in the older HIV-infected population, including immunologic and virologic outcomes, mortality, disease progression, toxicity of ART, and pharmacokinetic considerations. In addition, package inserts of antiretroviral (ARV) medications were reviewed for efficacy, safety, and pharmacokinetic information pertaining to the older population. Most studies in older adults (50 yrs or older) demonstrated slower and blunted CD4 immune recovery but better virologic suppression in response to ART. Higher rates of mortality and faster disease progression have been observed in adults 50 years and older, particularly during the first year after ART initiation. HIV-infected patients aged 50 years and older appear to be at greater risk for certain ART-associated toxicities including nephrotoxicity, decline in bone mineral density and bone fracture, symptomatic peripheral neuropathy, and cardiovascular disease including myocardial infarction. The available literature suggests that clinicians should consider avoiding agents such as tenofovir disoproxil fumarate (TDF) in older patients with risk factors for renal impairment and/or osteoporosis. If TDF is used in patients aged 50 years or older, more frequent monitoring should be considered. Older age was a significant predictor for higher atazanavir exposure and higher lopinavir trough concentration at 24 weeks. The clinical implications of these findings are unknown. It is imperative that future development of novel ARV drug therapies includes a greater proportion of older subjects in clinical trials.

Impact of comorbidity on the risk and cost of hospitalization in HIV-infected patients: real-world data from Abruzzo Region

“… 34 Moreover, it is well known that aging with HIV is a complex clinical problem, as CMs in HIV infection increase with age. 16 , 17 , 35 , 36 In fact, HIV patients have documented accelerated aging at the vascular level; they often present with increased levels of blood atherogenic lipids due to antiretrovirals and frequently suffer from renal and bone toxicities due to both HIV and HAART drugs. 9 – 12 , 37 – 40 Chronic pulmonary diseases have been lately documented as frequent CMs in people aging with HIV, and end-stage liver disease, often associated with HCV coinfection, is definitely more recurrent and severe among these patients.…”

“…In line with many other reports showing that the burden of CMs is on the rise in the aging HIV population, this evidence indicates that health care resources will still be necessary in the near future, likely in growing amount, to assist PWLHIV in the ordinary settings of care. 35 , 36 , 40 , 42 , 47 …”

Achieving the fourth 90

“…Management of HIV and other health conditions can be more complex in older PLWH [ 53 ]. ART side effects may be more severe, and ART may exacerbate or increase the risk of other conditions such as kidney disease, declines in bone mineral density and bone fracture, symptomatic peripheral neuropathy, and cardiovascular disease including myocardial infarction [ 54 , 55 ]. In addition, older PLWH are likely to already have comorbid conditions such as cardiovascular, renal, and liver disease, which has the potential to complicate the management of HIV disease because of challenges related to polypharmacy and drug–drug interactions [ 56 , 57 ].…”

The good, the Bad and the Ugly: Determinants of antiretroviral-associated Toxicities

“…Older age is a risk factor for chronic kidney disease, regardless of HIV status; if we add the impact of possibly nephrotoxic drugs (such as tenofovir) this risk of toxicity may increase exponentially [22]. These findings were observed often in the current literature, therefore, a cautious clinical approach in aging HIV-infected patients has to be warranted in order to avoid kidney disease occurrence.…”