ibalizumab
Sources réglementaires consultées
Indications approuvées
- Traitement des adultes avec VIH-1 multirésistant en échec du schéma actuel, toujours avec traitement de fond optimisé.
Contre-indications
Absolues
- Hypersensibilité à l’ibalizumab.
Mises en garde cliniques
- Mise en garde majeure · Il peut provoquer hypersensibilité, réactions de perfusion et syndrome de restauration immunitaire. — DailyMed, set_id c548ad82-9d1f-4d16-95b6-4e6106badf43
Effets indésirables
Communs (≥1%)
Diarrhée, vertiges, nausées et éruption
Rares mais graves
Hypersensibilité sévère et syndrome de restauration immunitaire
Grossesse et allaitement
L’exposition pendant la grossesse peut entraîner une immunosuppression néonatale réversible. Demander un avis spécialisé avec phénotypage des lymphocytes CD4 et B et tenir compte de l’incertitude concernant les vaccins vivants. Les personnes vivant avec le VIH ne doivent pas allaiter.
Bibliographie récente (PubMed)
To date, more than 30 antiretroviral drugs have been approved by the Food and Drug Administration for the treatment of HIV infection. As new drugs with better efficacy and safety profile become available for clinical practice, older drugs are either withdrawn from the market or become no longer actively prescribed. We review hepatotoxicity associated with contemporary antiretroviral drugs, with emphasis on data from the past 3 years. Although less robust data exists for side effects of contemporary antiretroviral medications recently approved for the management of HIV (i.e., doravirine, ibalizumab, fostemsavir, cabotegravir), the risks of substantial hepatotoxicity appears to be minimal with these agents. Although newer antiretroviral drugs are better tolerated than their earlier counterparts, they are not completely devoid of adverse drug reactions, including hepatotoxicity. Monitoring patients on antiretroviral therapy for treatment-emergent liver injury should continue to be part of routine clinical care.
Sustained viral suppression in patients with multidrug-resistant (MDR) HIV infection remains difficult; accordingly, agents targeting different steps in the HIV life cycle are needed. Ibalizumab, a humanized immunoglobulin G4 monoclonal antibody, is a cluster of differentiation (CD4)-directed postattachment inhibitor. In this phase 2b study, 113 patients with MDR HIV-1 and limited treatment options were assigned an optimized background regimen (OBR) and randomized to either 800 mg ibalizumab every 2 weeks (q2wk; n = 59) or 2000 mg ibalizumab every 4 weeks (q4wk; n = 54) up to week 24. Viral loads (VL) below the detection limit were achieved in 44% and 28% of patients in the 800 mg q2wk and 2000 mg q4wk groups, respectively, at week 24. Mean (SD) VL (log 10 copies/mL) decreased from Baseline [4.6 (0.8), 800 mg q2wk; 4.7 (0.7), 2000 mg q4wk] to week 2, with the reduction maintained through week 24 [2.9 (1.5), 800 mg q2wk; 3.2 (1.4), 2000 mg q4wk]. Baseline CD4 + counts were 80.5 and 54.0 cells/μL in the 800 mg q2wk and 2000 mg q4wk groups, respectively. Mean CD4 + T-cell count was increased at week 24 in both groups. No serious adverse events were related to ibalizumab. In heavily treatment-experienced patients with HIV (PWH) at a more advanced baseline disease severity, clinically significant response rates at week 24 were achieved with ibalizumab plus OBR. Ibalizumab's unique mechanism of action and lack of cross-resistance to other antiretroviral agents make it an important component of combination treatment regimens for PWH with limited treatment options.
Long-acting cabotegravir/rilpivirine (LA-CAB/RPV) was approved for use in virally suppressed patients with human immunodeficiency virus (HIV) in January 2021. While this was a paradigm shift for many patients living with HIV, as LA-CAB/RPV was the first injectable complete regimen for the treatment of HIV, several patient populations, including those lacking virologic suppression, have not been able to easily access this advance in science and care. In this article, we provide an update on 2 patients from our previous report and describe one further patient who experienced treatment failure following initiation of LA-CAB/RPV. Additionally, we review reports published to date of the clinical outcomes of patients with viremia who have accessed LA-CAB/RPV in the setting of baseline resistance-associated mutations (RAMs) to either component and any resulting RAMs at virologic failure. On the basis of this evidence, we recommend that hybrid or all-injectable regimens be considered for patients who have struggled with adherence to oral antiretroviral therapy or have partial or full resistance to one component of LA-CAB/RPV. The case series reported here adds to literature supporting the notion that LA-CAB/RPV can be successfully used in patients who are viremic.
Objective: The objective of this review is to compare ibalizumab, fostemsavir, and lenacapavir, present the clinical trials evaluating each agent, and provide guidance on their use in highly-treatment experienced (HTE) population living with HIV (PWH). Data sources: A search of PubMed and clinicaltrials.gov was conducted using the search terms: ibalizumab, fostemsavir, and lenacapavir. Study selection and data extraction: English-language, clinical publications were included. Data synthesis: Ibalizumab, fostemsavir, and lenacapavir, are each first-in-class agents, that have major differences in mechanism of action, route and frequency of administration, pharmacokinetic parameters, including elimination half-life, potential for drug-drug interactions, safety profiles, and cost. Each has been shown, when combined with an optimized background regimen (OBR) with at least one other active agent, to achieve virologic suppression in HTE-PWH. Conclusion: In HTE-patients, adding ibalizumab, fostemsavir, and/or lenacapavir to at least one other active agent can lead to virologic suppression in this difficult to treat population. Monotherapy with any of these agents is not recommended and will lead to a high likelihood of drug resistance. Selection of which agent(s) to include with an OBR will depend on other patient factors including concomitant medications, acceptance of formulations (oral vs. subcutaneous vs. intravenous infusion), and potential access (both insurance-based and transportation). Adherence to all agents in the regimen is paramount to successful outcomes.