The Prestigio Registry|| Registro PRESTIGIO

Welcome to Prestigio Registry platform

Purposes of the PRESTIGIO Registry

Aims of the PRESTIGIO Registry are

The assessment

of the long-term efficacy of different antiretroviral regimens in people with HIV infection resistant to 4 drug classes (4DCR PLWH)

The development

of genotypic and phenotypic resistance testing in 4DCR PLWH with virological failure

The evaluation

of ART adherence and patient-related outcomes

The characterization

of 4DCR PLWH in terms of immunological, virological and inflammatory parameters

The determination

of the incidence of AIDS-defining conditions and associated non-AIDS clinical events

To perform

pharmacoeconomic analyses to support management of this vulnerable population.

What we do

Description of the Registry

The PRESTIGIO Registry is the first cohort to include people with 4-drug-class-resistant HIV (4DCR-PWH).
It is an ongoing Italian, observational, prospective, multicenter cohort collecting biological samples and data on clinical, laboratory, treatment, and virological characteristics of 4DCR-PWH.

The Registry was established in December 2017 and currently has 39 participating Infectious Diseases centers, located in 15 different Italian regions.

The PRESTIGIO Registry includes PWH who are:

18 years or older;
harboring a 4DCR virus.

Four-class drug resistance is defined as intermediate or high-level resistance to ≥1 NRTI, ≥1 NNRTI, ≥1 PI, and ≥1 INSTI, according to the Stanford algorithm (version 9.5, https://hivdb.stanford.edu/) and considering cumulative data from all the RNA-based genotypic resistance tests performed for each person; in case of unavailability of any integrase genotype, a documented virological failure (2 consecutive HIV-1 RNA detections ≥50 copies/mL, or 1 detection ≥1000 copies/mL) to an INSTI-containing regimen is accepted as an inclusion criterion.

Currently more than 230 individuals are included in the Registry and more than 10 scientific papers have been accepted for publication on peer-reviewed journals. Open Multicenter National Registry.

Dedicated to People with Multidrug-resistant HIV.
Active Since December 2017.
Readily Available for Research Projects.

infectious diseases
centers

patients
enrolled

Research Activities

Main activities include

The in vivo and in vitro evaluation of the efficacy of new or investigational drugs (e.g. fostemsavir, leronlimab) and drugs already in use (e.g. dolutegravir bis in die (DTG BID); second-generation INSTI);

Evaluating the use of next-generation sequencing (NGS) as a potentially useful tool for predicting virological failure in this population;

The role of simplification strategies in people with HIV infection and resistance to 4 drug classes and the assessment of disease burden in this vulnerable population.

Why the PRESTIGIO Registry

The clinical Problem

The availability of combination antiretroviral therapies has significantly increased the life expectancy of people living with HIV (PLWH) ^1,2.
However, a subgroup of PLWH defined as heavily treatment- experienced (HTE-PLWH) have a history of multiple virological failures on different antiretroviral regimens and limited treatment options due to drug resistance mutations and/or drug intolerance ^3,4.
According to various definitions, HTE individuals have two or fewer classes of antiretroviral drugs available and a reduced number of drugs that can be used within each class ⁵, and thus represent a group of PLWH at high risk of clinical progression.
The management of HTE patients is further complicated by the presence of concomitant factors such as severe immunosuppression and multiple comorbidities, including opportunistic infections, which require specific drug therapies ^6-9.
Thus, in this population, the already limited therapeutic options may be further reduced by the addition of adverse drug events and pharmacokinetic interactions ¹⁰.
Finally, HTE-PLWH usually require complex and inconvenient regimens (combinations of drugs taken once or more than once a day, or combinations of drugs administered orally, subcutaneously, or intravenously) that are often burdened by a high number of tablets to be taken each day.
All these factors can lead to suboptimal adherence, increasing the risk of virological failure ¹¹ and worsening the prognosis of HTE- PLWH ¹².
Within this population with limited therapeutic options, those with a history of resistance to four drug classes - nucleoside (NRTIs) and non-nucleoside (NNRTIs) reverse transcriptase inhibitors, protease inhibitors (PIs) and integrase inhibitors (INSTIs) - represent a subgroup of HTE-PLWH with a significant disease burden and very few therapeutic options ⁷.
To better characterize this vulnerable population, the PRESTIGIO registry was established at the end of 2017.

Bibliografia

1. Wandeler G, Johnson LF, Egger M. Trends in life expectancy of HIV-positive adults on antiretroviral therapy across the globe: comparisons with general population. Curr Opin HIV AIDS. 2016 Sep;11(5):492-500.
2. Antiretroviral Therapy Cohort Collaboration. Survival of HIV-positive patients starting antiretroviral therapy between 1996 and 2013: a collaborative analysis of cohort studies. Lancet HIV. 2017 Aug;4(8):e349-e356.
3. Armenia D, Di Carlo D, Flandre P, et al. HIV MDR is still a relevant issue despite its dramatic drop over the years. J Antimicrob Chemother. 2020 May 1;75(5):1301-1310.
4. Cutrell J, Jodlowski T, Bedimo R. The management of treatment-experienced HIV patients (including virologic failure and switches). Ther Adv Infect Dis. 2020 Jan 20;7:2049936120901395.
5. Spivack S, Pagkalinawan S, Samuel R, et al. HIV: how to manage heavily treatment-experienced patients. Drugs Context. 2022 Mar 1;11:2021-9-1.
6. Priest J, Hulbert E, Gilliam Blet al. Characterization of Heavily Treatment-Experienced People With HIV and Impact on Health Care Resource Utilization in US Commercial and Medicare Advantage Health Plans. Open Forum Infect Dis. 2021 Nov 6;8(12):ofab562.
7. Galli L, Parisi MR, Poli A, et al; PRESTIGIO Study Group. Burden of Disease in PWH Harboring a Multidrug-Resistant Virus: Data From the PRESTIGIO Registry. Open Forum Infect Dis. 2020 Sep 26;7(11):ofaa456.
8. Lataillade M, Lalezari JP, Kozal M,et al. Safety and efficacy of the HIV-1 attachment inhibitor prodrug fostemsavir in heavily treatment-experienced individuals: week 96 results of the phase 3 BRIGHTE study. Lancet HIV. 2020 Nov;7(11):e740-e751.
9. Pelchen-Matthews A, Borges, Reekie J et Prevalence and Outcomes for Heavily Treatment-Experienced Individuals Living With Human Immunodeficiency Virus in a European Cohort. J Acquir Immune Defic Syndr. 2021 Jun 1;87(2):806-817.
10. Pelchen-Matthews A, Ryom L, Borges ÁH,et al; EuroSIDA study. Aging and the evolution of comorbidities among HIV-positive individuals in a European cohort. AIDS. 2018;32:2405-2416.
11. Enriquez M, McKinsey DS. Strategies to improve HIV treatment adherence in developed countries: clinical management at the individual level. HIV AIDS (Auckl). 2011;3:45-51.
12. Zaccarelli M, Tozzi V, Lorenzini P et al. Multiple drug class-wide resistance associated with poorer survival after treatment failure in a cohort of HIV-infected patients. AIDS. 2005 Jul 1;19(10):1081-9.