Αντιρετροϊκά Φάρμακα υπό δοκιμή

Ιούλιος 2014

Ως το 2024, η αντιρετροϊκή θεραπεία (ART) μπορεί να είναι τόσο διαφορετική από εκείνη που χρησιμοποιείται σήμερα ως τριπλή θεραπεία, όσο ήταν το 1997 όταν το ΑΖΤ ήταν το μόνο φάρμακο το 1987, ή όπως δραματικά εξελίχθηκαν τα σχήματα του ενός χαπιού μία φορά την ημέρα το 2014 σε σύγκριση με τις πολλαπλές δόσεις των κοκτέηλ του 1997. Πολλά μπορούν να γίνουν σε 10 χρόνια, αν και οι νέες εξελίξεις εν τέλει εξαρτώνται από φιλόδοξους στόχους και επαρκείς πόρους ώστε να μπορέσουν να καρποφορήσουν.

Ματιές στο μέλλον της ART προσφέρουν τα αντιρετροϊκά (ARV) που βρίσκονται φέτος υπό δοκιμή, όπως η άφιξη του συνδυαστικού χαπιού με το νέο αναστολέα ιντεγκράσης dolutegravir και το νέο NNRTI rilpivirine, η δυνατότητα λήψης δύο φαρμάκων μακράς δράσης που θα φέρει επανάσταση στη δοσολογία της θεραπείας και μια ήπια εκδοχή του tenofovir.

Compound

Class/Type

Comments

elvitegravir

INSTI

In November 2013, European Commission approved elvitegravir for use in combination with ritonavir-boosted PIs for individuals without evidence of resistance to elvitegravir

darunavir plus cobicistat
(co-formulation)

PI plus PK booster

EMA application filed October 2013; NDA filed April 2014

atazanavir plus cobicistat
(co-formulation)

PI plus PK booster

NDA filed April 2014

darunavir plus abacavir plus 3TC (co-formulation)

INSTI plus two NRTIs

U.S. and E.U. applications filed in October 2013

tenofovir alafenamide (TAF, GS-7340)

NtRTI (tenofovir prodrug)

In development as FDC component with elvitegravir, cobicistat, and FTC for treatment-naive and –experienced patients. Also as a component of FDC with darunavir, cobicistat, and emtricitabine. FDC with emtricitabine, as follow-up to Truvada, also in development

raltegravir (once-daily formulation)

INSTI

PK data from phase I once-daily formulation (2 x 600 mg tablets) studies presented at EACS 2013 and CROI 2014. A phase III study is expected to begin in 2014

dolutegravir plus
rilpivirine(co-formulation)

INSTI plus NNRTI

Clinical trials evaluating the safety and efficacy of the FDC as two-drug maintenance therapy are expected to begin in early 2015.

darunavir plus cobicistat plus FTC plus TAF
(co-formulation)

PI plus PK booster plus NtRTI and NRTI

Phase II study has been completed. A phase III study of the FDC has not yet been announced

apricitabine

NRTI

3TC-like molecule, stalled at phase IIb with no new studies listed since a phase III study was halted in 2009. A potential role for multiclass-resistant HIV. Partnership announced in December 2013 with NextPharma

BMS-663068

Attachment inhibitor (gp120)

Phase II data presented at CROI 2014

cenicriviroc
(TBR-652)

CCR5 inhibitor (also active against CCR2)

Phase II study results reported at EACS 2013. Tobira plans to study FDC of cenicriviroc plus 3TC in combination with third drug in phase III program

doravirine
(MK-1439)

NNRTI

Phase II data reported at CROI 2014

PRO 140

CCR5-specific humanized monoclonal antibody

No new data since 2010. Phase III trials, including treatment substitution protocol, are planned by CytoDyn

ibalizumab (TMB-355; formerly TNX-355)

CD4-specific humanized IgG4 monoclonal antibody

No data from treatment studies in several years; potential as long-acting preexposure prophylaxis

S/GSK1265744 oral and long-acting parenteral (LAP) formulations

INSTI (follow-up to dolutegravir)

Preliminary data supporting daily oral dosing as maintenance therapy, paired with oral rilpivirine, presented at CROI 2014. Demonstrates potential for once-monthly dosing with rilpivirine-LA

rilpivirine-LA (long-acting formulation)

NNRTI

Preliminary data supporting daily oral dosing as maintenance therapy, paired with oral S/GSK1265744, presented at CROI 2014. Demonstrates potential for once-monthly dosing with S/GSK1265755 LAP

OBP-601 (formerly BMS-986001)

NRTI

d4T-like molecule in phase II, with no new clinical data reported since 2012. Licensing agreement between Oncolys and BMS has been terminated and the compound returned to Oncolys for continued development

albuvirtide

Long-acting
fusion inhibitor

No new data or studies announced since 2013 Pipeline Report

CMX157

NtRTI (similar to TAF)

No new data or studies announced since 2013 Pipeline Report



Lancet

Πρόσφατες δημοσιεύσεις στο περιοδικό The Lancet HIV

Potential for broadly neutralising antibodies as PrEP

Globally, an estimated 40 million people live with HIV. Although 30Β·7 million of the people living with HIV have access to antiretroviral therapy, there were still 1Β·3 million new infections in 2022.1 There is an urgent need to prevent HIV acquisition through effective prevention programmes, including pre-exposure prevention (PrEP) or, ideally, a prophylactic vaccine.

Improving quality of interpersonal care in HIV programmes

The response to the HIV epidemic has shifted from providing care primarily for individuals who are severely ill to a more inclusive approach aimed at expanding access to HIV services.1 Poor quality care, resulting from inefficiencies in clinic systems, staff shortages, and stigmatising or discriminatory behaviours from health-care workers,2–5 can negatively affect client engagement, whereas respect, dignity, empathy, compassion, and clear communication can improve engagement.3,6,7 Although differentiated service delivery models have addressed some structural barriers,8 interventional studies are needed to show how to improve the quality of interpersonal interactions between clients and health-care workers and whether this improvement affects HIV treatment outcomes.

Injectable antiretrovirals: real world or ideal world?

Following on the results of formal randomised clinical trials, real-world data can provide important insights into the safety and efficacy of a new drug regimen when it is used among a more diverse patient population and in a less controlled clinical setting. As Jongen and colleagues1 point out in The Lancet HIV, available real-world data for long-acting injectable cabotegravir and rilpivirine are largely limited to retrospective analyses with small sample sizes.1 The authors aim to address this issue using data from the well established ATHENA cohort, which includes comprehensive data for almost all people living with HIV receiving medical care in the Netherlands.

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