Personalizing prevention: Advances in pharmacotherapy for HIV prevention.

The HIV epidemic continues to pose a significant burden on the healthcare system. Although the incidence of annual new infections is decreasing, health disparities persist and most new infections remain concentrated into different racial, ethnic, and minority groups. Pre-exposure prophylaxis (PrEP), which involves those at high risk of acquiring HIV to take chronic medications to prevent acquisition of the virus, is key to preventing new HIV infections. The purpose of this article is to review medication therapies for PrEP and examine their role in personalizing PrEP in different patient populations. Additionally, new medications currently under development for PrEP are reviewed, as well as treatment as prevention (TasP) and post-exposure prophylaxis (PEP). There are currently four medications available for PrEP: the oral options of co-formulated emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or emtricitabine/tenofovir alafenamide (FTC/TAF); injectable long-acting cabotegravir (CAB-LA); and the vaginal ring dapivirine (DPV-VR). FTC/TAF is not currently indicated for persons at risk for HIV through vaginal sex due to lack of studies, but trials are currently ongoing. DPV-VR is available in Zimbabwe and South Africa and has been endorsed by the World Health Organization but is not currently available in the United States. Several agents are also in development for use in PrEP: the novel long-acting injectable lenacapavir, a first-in-class capsid inhibitor, which has no cross-resistance to any existing HIV drug class; the subdermal implant islatravir, a first-in-class translocation inhibitor; and VRC01, a broadly neutralizing antibody (bnAb) which has been evaluated in proof-of-concept studies that may lead to the development of more potent bnAbs. Overall, PrEP is highly effective at preventing HIV infection in high-risk populations. Identifying optimal PrEP regimens in different patient populations is complex and must consider patient-specific factors and medication cost and access considerations. Lastly, providers should consider individual patient preferences with regard to prevention to improve access, retention in care, and adherence

Personalizing prevention: Advances in pharmacotherapy for HIV prevention.

The HIV epidemic continues to pose a significant burden on the healthcare system. Although the incidence of annual new infections is decreasing, health disparities persist and most new infections remain concentrated into different racial, ethnic, and minority groups. Pre-exposure prophylaxis (PrEP), which involves those at high risk of acquiring HIV to take chronic medications to prevent acquisition of the virus, is key to preventing new HIV infections. The purpose of this article is to review medication therapies for PrEP and examine their role in personalizing PrEP in different patient populations. Additionally, new medications currently under development for PrEP are reviewed, as well as treatment as prevention (TasP) and post-exposure prophylaxis (PEP). There are currently four medications available for PrEP: the oral options of co-formulated emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) or emtricitabine/tenofovir alafenamide (FTC/TAF); injectable long-acting cabotegravir (CAB-LA); and the vaginal ring dapivirine (DPV-VR). FTC/TAF is not currently indicated for persons at risk for HIV through vaginal sex due to lack of studies, but trials are currently ongoing. DPV-VR is available in Zimbabwe and South Africa and has been endorsed by the World Health Organization but is not currently available in the United States. Several agents are also in development for use in PrEP: the novel long-acting injectable lenacapavir, a first-in-class capsid inhibitor, which has no cross-resistance to any existing HIV drug class; the subdermal implant islatravir, a first-in-class translocation inhibitor; and VRC01, a broadly neutralizing antibody (bnAb) which has been evaluated in proof-of-concept studies that may lead to the development of more potent bnAbs. Overall, PrEP is highly effective at preventing HIV infection in high-risk populations. Identifying optimal PrEP regimens in different patient populations is complex and must consider patient-specific factors and medication cost and access considerations. Lastly, providers should consider individual patient preferences with regard to prevention to improve access, retention in care, and adherence

Second asymptomatic carotid surgery trial (ACST-2) : a randomised comparison of carotid artery stenting versus carotid endarterectomy

Background: Among asymptomatic patients with severe carotid artery stenosis but no recent stroke or transient cerebral ischaemia, either carotid artery stenting (CAS) or carotid endarterectomy (CEA) can restore patency and reduce long-term stroke risks. However, from recent national registry data, each option causes about 1% procedural risk of disabling stroke or death. Comparison of their long-term protective effects requires large-scale randomised evidence. Methods: ACST-2 is an international multicentre randomised trial of CAS versus CEA among asymptomatic patients with severe stenosis thought to require intervention, interpreted with all other relevant trials. Patients were eligible if they had severe unilateral or bilateral carotid artery stenosis and both doctor and patient agreed that a carotid procedure should be undertaken, but they were substantially uncertain which one to choose. Patients were randomly allocated to CAS or CEA and followed up at 1 month and then annually, for a mean 5 years. Procedural events were those within 30 days of the intervention. Intention-to-treat analyses are provided. Analyses including procedural hazards use tabular methods. Analyses and meta-analyses of non-procedural strokes use Kaplan-Meier and log-rank methods. The trial is registered with the ISRCTN registry, ISRCTN21144362. Findings: Between Jan 15, 2008, and Dec 31, 2020, 3625 patients in 130 centres were randomly allocated, 1811 to CAS and 1814 to CEA, with good compliance, good medical therapy and a mean 5 years of follow-up. Overall, 1% had disabling stroke or death procedurally (15 allocated to CAS and 18 to CEA) and 2% had non-disabling procedural stroke (48 allocated to CAS and 29 to CEA). Kaplan-Meier estimates of 5-year non-procedural stroke were 2·5% in each group for fatal or disabling stroke, and 5·3% with CAS versus 4·5% with CEA for any stroke (rate ratio [RR] 1·16, 95% CI 0·86-1·57; p=0·33). Combining RRs for any non-procedural stroke in all CAS versus CEA trials, the RR was similar in symptomatic and asymptomatic patients (overall RR 1·11, 95% CI 0·91-1·32; p=0·21). Interpretation: Serious complications are similarly uncommon after competent CAS and CEA, and the long-term effects of these two carotid artery procedures on fatal or disabling stroke are comparable