The impact of age on antiretroviral drug pharmacokinetics in the treatment of adults living with HIV

Calcagno, Andrea; Trunfio, Mattia; D’Avolio, Antonio; Perri, Giovanni Di; Bonora, Stefano

doi:10.1080/17425255.2021.1915285

Cited by 10 publications

(11 citation statements)

References 113 publications

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“…The only factor associated with an increased risk of discontinuation in their cohort was female gender (HR 2.53 (95% CI: 1.10–5.82); female gender was associated with an increased risk of discontinuation also in our study, independently from the type of treatment (RR 1.18, 95%CI 1.02–1.37). In our cohort, there was an high interruption of DTG in the first year for adverse events, in part due to SNC adverse events, already described in many studies [ 17 , 42 , 43 , 44 ]. However, DTG interruptions due to AEs were counterbalanced by lower proportion of discontinuations due to other causes and rapidly declined over the study period, thus resulting in the RRs and HRs showed in Table 3 , Table 4 , Table 5 and Table 6 .…”

Section: Discussionmentioning

confidence: 53%

Causes of HIV Treatment Interruption during the Last 20 Years: A Multi-Cohort Real-Life Study

Vito

Ricci

Menzaghi

et al. 2023

Viruses

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In the last years, many antiretroviral drugs (ART) have been developed with increased efficacy. Nowadays, the main reasons for treatment switches are adverse events, proactive strategy or simplification. We conducted a retrospective cohort study to investigate the reason for treatment interruption in the last 20 years. We merged data of eight cohorts of the SCOLTA project: lopinavir/r (LPV), atazanavir/r (ATV), darunavir/r or /c (DRV), rilpivirine (RPV), raltegravir (RAL), elvitegravir/c (EVG), dolutegravir (DTG) and bictegravir (BIC). We included 4405 people with HIV (PWH). Overall, 664 (15.1%), 489 (11.1%), and 271 (6.2%) PWH interrupted the treatment in the first, second, and third years after starting a new ART. Looking at the interruption in the first year, the most frequent causes were adverse events (3.8%), loss to follow-up (3.7%), patients’ decisions (2.6%), treatment failure (1.7%), and simplification (1.3%). In the multivariate analysis regarding experienced patients, treatment with LPV, ATV, RPV or EVG/c, having less than 250 CD4 cells/mL, history of intravenous drug use, and HCV positivity were associated with an increased risk of interruption. In naive people, only LPV/r was associated with an increased risk of interruption, while RPV was associated with a lower risk. In conclusion, our data on more than 4400 PWH show that adverse events have represented the most frequent cause of treatment interruptions in the first year of ART (3.84%). Treatment discontinuations were more frequent during the first year of follow-up and decreased thereafter. First-generation PI in both naïve and experienced PWH, and EVG/c, in experienced PWH, were associated with a higher risk of treatment interruptions.

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Section: Discussionmentioning

confidence: 53%

Causes of HIV Treatment Interruption during the Last 20 Years: A Multi-Cohort Real-Life Study

Vito

Ricci

Menzaghi

et al. 2023

Viruses

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“…It is therefore difficult to determine differences in response between younger and older (including elderly) individuals – a factor which could potentially limit the generalizability of LAI-ART's efficacy and rate of failure to older populations [60]. The median age of participants in noninferiority randomized control trials (ATLAS, FLAIR, LATTE-2) has ranged from 34–42 years (Table 3) [42,43,1–63]. Two trials (ATLAS-2 M, LATTE-2) did not report the number of enrolled participants aged 50 years or older; of other trials that did, only 228 patients enrolled were 50 years old or older, and of these, 99 were randomized to receive LAI-ART [42–45,61–63].…”

Section: Long-acting Injectable- Antiretroviral Therapy Biologic Chal...mentioning

confidence: 99%

Considerations for long-acting antiretroviral therapy in older persons with HIV

O'Shea,

Cholli,

Heil

et al. 2023

Aids

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People with HIV (PWH) can now enjoy longer, healthier lives due to safe and highly effective antiretroviral therapy (ART), and improved care and prevention strategies. New drug formulations such as long-acting injectables (LAI) may overcome some limitations and issues with oral antiretroviral therapy and strengthen medication adherence. However, challenges and questions remain regarding their use in aging populations. Here, we review unique considerations for LAI-ART for the treatment of HIV in older PWH, including benefits, risks, pharmacological considerations, implementation challenges, knowledge gaps, and identify factors that may facilitate uptake of LA-ART in this population.

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“…Participant age, however, may be important; the ability to absorb, distribute, metabolize, and excrete medications may become less effective, which may affect the relationship between CPE and neurocognitive functioning. Additionally, older HIV+ patients tend to have more comorbidities, and may be taking a larger number of medications overall, which increases the likelihood of side effects and other interactions [51].…”

Section: Global Functioningmentioning

confidence: 99%

HIV Antiretroviral Medication Neuropenetrance and Neurocognitive Outcomes in HIV+ Adults: A Review of the Literature Examining the Central Nervous System Penetration Effectiveness Score

Arentoft

Troxell

Alvarez

et al. 2022

Viruses

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This literature review summarizes the existing research examining the CNS penetration effectiveness (CPE) score and neurocognitive outcomes (i.e., neuropsychological assessment and neurocognitive screening) in HIV+ individuals. Despite the effectiveness of Combined Antiretroviral Therapy (CART) in reducing mortality and morbidity in HIV and controlling viral replication, HIV often persists in the Central Nervous System (CNS), and rates of neurocognitive impairment remain higher than predicted in the post-CART era. The CPE score was developed to rank antiretroviral regimens on their ability to penetrate the CNS and potency in inhibiting the virus, and it has been examined in relation to neurocognitive functioning for over a decade. Based on the results of 23 studies, we conclude that CPE is not as strongly associated with neurocognitive outcomes as initially hypothesized, although higher CPE ARV regimens may be associated with modest, improved outcomes in global neurocognitive functioning, and to a lesser extent attention/working memory and learning/memory. Conclusions, however, are limited by the heterogeneity in study design and methods, and the lack of a more recent CPE metric update. It is recommended that future research in this area employ comprehensive, standardized neuropsychological test batteries and examine domain-level performance, and use the newer 2010 CPE metric, although an updated CPE ranking is urgently needed.

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The impact of age on antiretroviral drug pharmacokinetics in the treatment of adults living with HIV

Cited by 10 publications

References 113 publications

Causes of HIV Treatment Interruption during the Last 20 Years: A Multi-Cohort Real-Life Study

Causes of HIV Treatment Interruption during the Last 20 Years: A Multi-Cohort Real-Life Study

Considerations for long-acting antiretroviral therapy in older persons with HIV

HIV Antiretroviral Medication Neuropenetrance and Neurocognitive Outcomes in HIV+ Adults: A Review of the Literature Examining the Central Nervous System Penetration Effectiveness Score

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