1. LONG-ACTING CABOTEGRAVIR AND
RILPIVIRINE AFTER ORAL INDUCTION FOR
HIV-1 INFECTION
CHAIRMAN : DR. S M BIRADAR
MODERATOR : DR K BHEMASHANKAR
PRESENTOR : DR GAURAV SOMANI
2. • NAME OF JOURNAL – NEW ENGLAND JOURNAL OF
MEDICINE
• PUBLISHED ON MARCH 4, 2020, AT NEJM.ORG
3. • INTRODUCTION
• CABOTEGRAVIR AND RILPIVIRINE
• AIM OF STUDY
• MATERIALS AND METHOD
• RESULT
• DISSCUSION
• CONCLUSION
• TAKE HOME MESSAGE
4. INTRODUCTION
• HIV is retrovirus. It is of two types HIV 1 and HIV 2.
• HIV 1 is more common.
• In India for diagnosis and treatment NACO guidelines
follow.
• For diagnosis
• Strategy I for screening
• Strategy II (a) for surveillance purposes
• Strategy II (b) and Strategy III for diagnosis in
symptomatic and asymptomatic persons, respectively.
5.
6. • Currently irrespective of CD4 count and stage of HIVwe
have to start treatment.
• Preferred first line art is-
Tenofovir (tdf 300 mg) + Lamivudine (3tc 300 mg) +
Dolutegravir (dtg 50 mg) regimen (tld) as FDC in a single
pill once a day (at a fixed time every day as per patient’s
convenience)
7. CABOTEGRAVIR
• It is integrase inhibitior
• Avilable in oral and injectable form
• Uses- HIV1 treatment and HIV1 pre exposure
prophylaxis
• Dose – oral – 30mg tablet
Injection- 600 mg 1st dose f/b 400mg subsequent
dose
• Route - Intramascular
9. RILPIVIRINE
• It is non nucleoside reverse transcriptase inhibitor
• Available in oral and injectble form
• Use – for HIV1 infection
• Dose- oral 25mg tablet
injection- 900mg 1st dose f/b 600mg subsequent dose
• Route - Intramascular
10. • Adverse reaction- hypersensitivity reaction, depressive
disorder
• Contraindication-
• Anticonvulsants carbamazepine, oxcarbazepine,
phenobarbital, phenytoin
• Antimycobacterials rifabutin, rifampin, rifapentine
• Proton pump inhibitors
• The glucocorticoid systemic dexamethasone (more than a
single dose)
11. AIM OF STUDY
• To assess the efficacy of long acting cabotegravir and
rilpivirine once a month injection in comparison to daily
oral regimen.
12. MATERIALS AND METHOD
• Inclusion criteria
1. Age more than 18 years
2. Not previously received antiretroviral therpy
3. Plasma HIV1 RNA level of 1000 copies per mm of
higher at screening
13. • Exclusion criteria-
1.Pregnant or will be pregnant or breatfeeding woman
2.Moderate to sever hepatic impairment patient
3.Sucidal risk patient
4. Seizure disorder patient
5. HBV co-infection patient
14. • Trail design – phase 3, randamosized, multicenter, open
label, non inferiorty trail to have screening, induction,
maintenance, extension and long term follow up phases
• During the induction phase, a single-tablet regimen of
dolutegravir, abacavir, and lamivudine (dtg–abc–3tc) was
administered once daily for 20 weeks; those who had side
effects in association with this therapy or were positive for
HLAb*5701 received dolutegravir plus two nucleoside
re- verse-transcriptase inhibitors other than abacavir.
15. • During randomization, participants were randomly assigned
to continue the current oral therapy or switch to longacting
therapy during the maintenance phase in 1:1 ratio.
• Participants in the long acting therapy group received oral
lead-in therapy with cabotegravir (cab) plus rilpivirine
(rpv), followed by injections of long-acting formulations:
initial loading injections of 600 mg of cabotegravir and 900
mg of rilpivirine were administered at week 4, and
subsequent injections of 400 mg of cabotegravir and 600 mg
of rilpivirine were administered every 4 weeks beginning at
week 8.
16.
17.
18. • The primary end point was percentage of participants who
had a plasma HIV 1 RNA level of 50 copies per milliliter or
higher at week 48 of the maintenance phase, determined
with the use of the food and drug administration (FDA)
snapshot algorithm.
• The key secondary end point was the percentage of
participants who had a plasma HIV 1 RNA level of less than
50 copies per milliliter at week 48 (FDA snapshot
algorithm)
• Treatment satisfaction was measured with the use of the
HIV treatment satisfaction questionnaire, change version
(hivtsqc), at week 48
19. RESULT
• At week 48, an HIV-1 RNA level of 50 copies per
milliliter or higher was found in 6 participants (2.1%)
who received long-acting therapy and in 7 participants
(2.5%) who received oral therapy.
• The key secondary end point of the percentage of
participants with an HIV-1 RNA level of less than 50
copies per milliliter at week 48, in long acting therpy is
93.5%(260 out of 278) and in oral therpy is 93.3%(264
out of 282)
• At week 48, the HIVTSQc total score for satisfaction
with current treatment as compared with induction
treatment was higher in the long-acting–therapy group
than oral therapy.
20.
21.
22. DISCUSSION
• In this trial after viral suppression was achieved with a
standard oral regimen, the simplified injectable regimen,
which consisted of long acting formulations of cabotegravir
and rilpivirine, was non inferior to continued oral therapy
with regard to maintaining suppression through week 48.
• At baseline, HIV 1subtype A1 was present in 8 participants
in the long-acting–therapy group, 5 of whom maintained
viral suppression and 3 of whom had virologic failure.
• All 3 of the participants who had virologic failure during
long-acting therapy also had a body-mass index of more
than 30, plasma drug levels in the lowest quartile, and HIV
1 with the L74i integrase polymorphism.
23. • However, the l74i integrase polymorphism does not confer
resistance to cabotegravir by itself: 51 of 54 participants in
the long-acting–therapy group who had the l74i integrase
polymorphism did not have virologic failure at week 48.
• Efficacy results with long-acting therapy in this trial were
similar to those seen in the atlas trial.
• Major side effect is injection site reaction , their incidence
from 71% to 20% during trial.
• The incidences of some adverse events other than injection-
site reactions were higher in the long-acting–therapy group
than in the oral-therapy group.
24. • The long-acting regimen was preferred over the previous
oral therapy by 91% of recipients, even after 12 monthly
injections.
25. CONCLUSION
• Monthly two-drug long-acting therapy was
noninferior to standard three-drug oral therapy with
regard to maintaining viral suppression for 48 weeks
in adults with hiv-1 infection who had not previously
received antiretroviral therapy, with greater reported
treatment satisfaction
26. TAKE HOME MESSAGE
• In clinical practice, the long-acting regimen is a
therapeutic option that patients can select according
to their preference.
• https://www.who.int/publications/i/item/9789240054
097
• https://www.accessdata.fda.gov/scripts/cder/daf/index
.cfm?event=overview.process&varApplNo=212888
