| |
New HIV Guidelines IAS-USA Panel; Aging, Weight
|
| |
| |
Download the PDF here
Antiretroviral Drugs for Treatment and Prevention of HIV Infection in Adults2022 Recommendations of the International Antiviral Society-USA Panel
December 1, 2022
"There is an ongoing growing burden of neurocognitive dysfunction and frailty in people aging with HIV, which results in decreased quality of life, greater health care utilization, and higher mortality.95,96 Recommendations for screening and management of comorbidities in older people with HIV, assessment of functional impairment and frailty, and evaluation of neurocognitive impairment are unchanged since the previous report.1 Recent studies have shown that accumulation of comorbidities had greater negative effect on neurocognitive performance than did HIV disease parameters.97,98 Intensification of ART with either dolutegravir or maraviroc did not improve cognitive impairment, despite lower cerebrospinal fluid HIV viral loads in the intensified group.99 Aggressive management of comorbidities, rather than ART modification, may be the most beneficial strategy for improving neurocognitive function.
By the end of this decade, the proportion of people with HIV who will be older than 65 years is projected to be almost 25%.100 The aging of people with HIV has highlighted the need for integrated care models, including multidisciplinary teams of geriatricians, HIV specialists, pharmacists, and allied health practitioners (such as physiotherapists) offering holistic patient-centered care.101-103
Abstract
Importance Recent advances in treatment and prevention of HIV warrant updated recommendations to guide optimal practice.
Objective Based on a critical evaluation of new data, to provide clinicians with recommendations on use of antiretroviral drugs for the treatment and prevention of HIV, laboratory monitoring, care of people aging with HIV, substance use disorder and HIV, and new challenges in people with HIV, including COVID-19 and monkeypox virus infection.
Evidence Review A panel of volunteer expert physician scientists were appointed to update the 2020 consensus recommendations. Relevant evidence in the literature (PubMed and Embase searches, which initially yielded 7891 unique citations, of which 834 were considered relevant) and studies presented at peer-reviewed scientific conferences between January 2020 and October 2022 were considered.
Findings Initiation of antiretroviral therapy (ART) is recommended as soon as possible after diagnosis of HIV. Barriers to care should be addressed, including ensuring access to ART and adherence support. Integrase strand transfer inhibitor-containing regimens remain the mainstay of initial therapy. For people who have achieved viral suppression with a daily oral regimen, long-acting injectable therapy with cabotegravir plus rilpivirine given as infrequently as every 2 months is now an option. Weight gain and metabolic complications have been linked to certain antiretroviral medications; novel strategies to ameliorate these complications are needed. Management of comorbidities throughout the life span is increasingly important, because people with HIV are living longer and confronting the health challenges of aging. In addition, management of substance use disorder in people with HIV requires an evidence-based, integrated approach. Options for preexposure prophylaxis include oral medications (tenofovir disoproxil fumarate or tenofovir alafenamide plus emtricitabine) and, for the first time, a long-acting injectable agent, cabotegravir. Recent global health emergencies, like the SARS-CoV-2 pandemic and monkeypox virus outbreak, continue to have a major effect on people with HIV and the delivery of services. To address these and other challenges, an equity-based approach is essential.
Conclusions and Relevance Advances in treatment and prevention of HIV continue to improve outcomes, but challenges and opportunities remain.
https://jamanetwork.com/journals/jama/fullarticle/2799240
Weight Gain and Metabolic Complications With ART
Recommendations are summarized in Box 3. Weight gain is generally observed within the first year following initiation of most ART regimens, but treatment with InSTI- and tenofovir alafenamide-based regimens is associated with greater weight gain than regimens containing tenofovir disoproxil fumarate, efavirenz, or a boosted PI. Weight gain can occur with (1) initiation of InSTI- or tenofovir alafenamide-containing ART in previously ART-naive individuals66; (2) switch to InSTI- or tenofovir alafenamide-containing ART in individuals with viral suppression67; or (3) initiation of tenofovir alafenamide or InSTI for PrEP.68 This weight gain with ART is more likely to occur in women and Black and Hispanic individuals and appears to occur mostly within the first year of ART initiation69 or switch.70 In the ADVANCE trial, most of the weight gain in dolutegravir groups was fat gain in trunk and limbs, and it was higher with concomitant tenofovir alafenamide use.71
Exposure to efavirenz or tenofovir disoproxil fumarate for ART or PrEP is associated with weight suppression, compared with other antiretroviral drugs or no ART exposure.72 This might complicate assessment of weight gain after switching from tenofovir disoproxil fumarate to tenofovir alafenamide or after changing efavirenz to an InSTI.
Weight gain while receiving an InSTI is likely mediated by adipocyte dysfunction, inducing adipogenesis, lipogenesis, oxidative stress, fibrosis, and insulin resistance.73,74 CYP2B6 genotypes have been associated with greater weight gain after switch from efavirenz to InSTI-based ART.75 Mechanism(s) of tenofovir alafenamide-associated weight gain remain incompletely elucidated. A switch from tenofovir disoproxil fumarate to tenofovir alafenamide is associated with increases in lipid levels and cardiovascular risk score, perhaps because tenofovir disoproxil fumarate lowers lipid levels.76
Although decreased in the general population, the risk of cardiovascular disease has not declined among people with HIV.77 In addition to traditional risk factors and the chronic inflammation associated with HIV itself, some ART regimens may contribute to this risk, but more research is needed. Recent cohort studies suggest that InSTI-based ART may be associated with an increased risk of incident cardiovascular disease, new-onset diabetes, hyperglycemia,78-80 elevated blood pressure,80 and de novo hepatic steatosis. These cardiometabolic effects were not observed in other studies, and it remains unclear whether they are transient or sustained or whether InSTI exposure is causative. The retrospective nature and lack of availability of weight measurements in most data make it difficult to ascertain whether this risk (if confirmed) is a direct InSTI toxic effect or the result of InSTI-related weight gain. In one study, the InSTI-diabetes association was attenuated when accounting for 12-month weight change.81 Nonetheless, data suggest that diabetes risk with weight gain at ART initiation is significant.82 Further research is needed to evaluate the role of appetite, caloric intake, and energy expenditure in InSTI- and tenofovir alafenamide-related weight gain.
Whether weight gain is reversible with switch to non-InSTI or non-tenofovir alafenamide regimens is unclear and under investigation (ClinicalTrials.gov Identifier: NCT04636437). Data from the SALSA83 and TANGO39 studies suggest that switching off of tenofovir alafenamide does not lead to weight loss. Until there are data proving benefit, switching regimens because of weight gain is not recommended (evidence rating: BIIa); instead, lifestyle modifications, like exercise and diet intervention, are recommended (evidence rating: AIII). Semaglutide and other glucagon-like peptide 1 analogues that decrease weight in people without HIV are being studied in people with HIV.84,85
HIV and Aging
Recommendations for older people with established HIV are summarized in Box 4. Not only is the prevalence of HIV and diagnoses of new infections in people older than 50 years increasing, but more than half of older people with HIV are diagnosed at a late stage of disease (ie, CD4 cell count <350/μL).86,87 Delayed diagnosis is a lost opportunity to initiate ART early for maximal health benefits and for prevention of transmission.
Early diagnosis and initiation of ART is particularly important in older persons because they are more likely to have a blunted immune response following ART initiation88 and have a higher risk of serious non-AIDS complications. Choice of initial ART requires consideration of the background risk and burden of non-AIDS comorbidity, drug-drug interactions, and polypharmacy to manage multimorbidity in older people with HIV (evidence rating: BIII). Recommended initial ART includes InSTI-based regimens with TAF/FTC or DTG/3TC (see Initiation of ART section). Caution should be exercised in the use of tenofovir disoproxil fumarate because of its associated kidney and bone toxicity.89 Studies of pharmacokinetics of ART are limited in older people with HIV. Whether clinically relevant pharmacokinetic changes and potential increased toxicity associated with aging require dose adjustment in older people with HIV remains unclear and is currently not warranted (evidence rating: AIII).90
Polypharmacy occurs more frequently in older people with HIV and is associated with increased risk of adverse health outcomes such as falls, frailty, hospitalization and mortality, and drug-drug interactions.91 Management of polypharmacy includes (1) optimization of ART, including simplification of ART when possible (see When and How to Switch ART Regimens section), and (2) regular medication review with “pruning” of nonessential medications.92,93 Antiretroviral stewardship programs effectively reduce medication errors, dose antiretroviral drugs appropriately for kidney and liver dysfunction, manage drug-drug interactions, and offer an opportunity to assess and deprescribe potentially inappropriate medication.94
There is an ongoing growing burden of neurocognitive dysfunction and frailty in people aging with HIV, which results in decreased quality of life, greater health care utilization, and higher mortality.95,96 Recommendations for screening and management of comorbidities in older people with HIV, assessment of functional impairment and frailty, and evaluation of neurocognitive impairment are unchanged since the previous report.1 Recent studies have shown that accumulation of comorbidities had greater negative effect on neurocognitive performance than did HIV disease parameters.97,98 Intensification of ART with either dolutegravir or maraviroc did not improve cognitive impairment, despite lower cerebrospinal fluid HIV viral loads in the intensified group.99 Aggressive management of comorbidities, rather than ART modification, may be the most beneficial strategy for improving neurocognitive function.
By the end of this decade, the proportion of people with HIV who will be older than 65 years is projected to be almost 25%.100 The aging of people with HIV has highlighted the need for integrated care models, including multidisciplinary teams of geriatricians, HIV specialists, pharmacists, and allied health practitioners (such as physiotherapists) offering holistic patient-centered care.101-103
|
|
| |
| |
|
|
|
