Ключевые решения в лечении ВИЧ: оптимизация стратегии лечения для пациентов с вирусной супрессией (2021) /Slides on Key Decisions in HIV Care-Optimizing Switch Strategies for Patients With Viral Suppression.2021

Key Decision in HIV Care: Optimizing Switch
Strategies for Patients With Viral Suppression
This program is supported by educational grants from Gilead Sciences, Inc.;
Janssen Therapeutics, Division of Janssen Products, LP; and ViiV Healthcare

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Faculty
Daniel R. Kuritzkes, MD
Chief, Division of Infectious
Diseases
Brigham and Women's Hospital
Harriet Ryan Albee Professor of
Medicine
Harvard Medical School
Boston, Massachusetts
Chloe Orkin, MBChB, FRCP, MD
Professor of HIV
Queen Mary, University of London
Consultant Physician
Lead for HIV Research
Barts Health NHS Trust
The Royal London Hospital
London, United Kingdom

Faculty Disclosures
Daniel R. Kuritzkes, MD, has disclosed that he has received funds
for research support from Atea, Gilead Sciences, Merck, Novartis,
and ViiV; consulting fees from Abpro, Atea, Decoy, Gilead Sciences,
GlaxoSmithKline, Merck, Rigel, and ViiV and speaking honorarium
from Janssen.
Chloe Orkin, MBChB, FRCP, MD, has disclosed that she has received
consulting fees, fees for non-CME/CE services, and funds for research
support from Gilead Sciences, GlaxoSmithKline, Janssen, MSD, and ViiV.

Overview: Optimizing Switch Strategies for Patients
With Viral Suppression
 What to Consider When Switching
 Switching to Single-Tablet Regimens
 Recommendations
 2-Drug Regimens
 Doravirine-Based Regimen
 Long-Acting Injectable
 Take-Home Points

Reasons to Consider an ART Switch During Viral
Suppression
Appropriate
 To simplify a regimen (eg, reduce pill
burden or dosing frequency)
 To enhance tolerability or decrease
toxicity
 To prevent or mitigate drug–drug or
drug–food interactions
 To eliminate food/fluid requirements
 To allow for optimal ART use during
pregnancy or where pregnancy may occur
 To reduce costs
Inappropriate
 To use the “newest” regimen
 To reduce costs at the price of a toxicity
or intolerance risk for your patient
DHHS ART. February 24, 2021.

Considerations When Switching Regimens in Virologically
Suppressed Patients
Comorbidity:
 HBV coinfection
 Cardiovascular disease or risk
 Renal function
 Bone mineral density
 Pregnancy
 Other coinfections
Safety:
 Review ART history for intolerance
 Consider drug–drug interactions with
comedications
Drug Resistance:
 Review ART history for possible VF
 Review all available resistance test results
 If earlier resistance uncertain, only consider
switch if new regimen likely to maintain
suppression of resistant virus
 Within-class switches usually maintain virologic
suppression if no resistance to drugs in that class
are present
 Caution when switching from boosted PI to
another class if full treatment/resistance history
not known
 Consult an expert when switching if resistance to
≥ 1 class
DHHS ART. February 24, 2021. Slide credit: clinicaloptions.com

Switching From Suppressive ART to an STR:
Noninferior Efficacy Across Phase III Studies
1. Daar. Lancet HIV. 2018;5:e347. 2. Molina. Lancet HIV. 2018;5:e357. 3. Sax. Clin Infect Dis. 2020 Jul 15:ciaa988. 4. Kityo. CROI 2018. Abstr
500. 5. Johnson. JAIDS. 2019;81:463. 6. Orkin. Lancet HIV. 2017;4:e195. 7. DeJesus. Lancet HIV. 2017;4:e205. 8. Trottier. Antivir Ther.
2017;22:295. 9. Mills. Lancet Infect Dis. 2016;16:43. 10. Orkin. Lancet HIV. 2018;5:e23 11. van Wyk. Clin Infect Dis. 2020;71:1920.
12. Llibre. Lancet. 2018;391:839. 13. Hagins. CROI 2020. Abstr 36. Slide credit: clinicaloptions.com
Key Studies* Switch to† Switch From
380-1878,[1] 380-1844,[2] 380-4030‡,[3] 380-
1961,‡[4] and BRAAVE‡[13] BIC/FTC/TAF
Boosted PI + 2 NRTIs, DTG/ABC/3TC, DTG +
FTC/(TAF or TDF), or EVG/COBI/FTC/(TAF or
TDF), 2 NRTIs + third agent
DRIVE-SHIFT[5] DOR/3TC/TDF Boosted PI, EVG/COBI, or NNRTI + 2 NRTIs
GS-1216[6] and GS-1160[7] RPV/FTC/TAF RPV/FTC/TDF or EFV/FTC/TDF
STRIIVING[8] DTG/ABC/3TC Third agent + 2 NRTIs
GS-109[9] EVG/COBI/FTC/TAF TDF-based regimen
EMERALD‡[10] DRV/COBI/FTC/TAF Boosted PI + FTC/TDF
TANGO[11] DTG/3TC 3-drug or 4-drug TAF-based ART
SWORD-1/2[12] DTG + RPV Third agent + 2 NRTIs
*Listed studies not head to head. †Most recent FDA approvals: for BIC/FTC/TAF, DTG/RPV, DOR/3TC/TDF, and DTG/3TC must have no history of
treatment failure and no resistance to regimen components; for DRV/COBI/FTC/TAF, must have no resistance to DRV, TFV. ‡Patients with
resistance included.

Recommended Regimen Switch Strategies in the Setting
of Viral Suppression
EACS 20203
 Within-class or between-class switches are
usually of low virological risk if
components are of equal potency and in
the absence of resistance
 TDF or TAF should not be discontinued in
persons with chronic HBV
 Dual therapies supported for switch by
large RCTs or meta-analysis:
– DTG + RPV
– DTG + 3TC
– DRV/b + 3TC
– ATV/b + 3TC
 Dual therapies supported only by small
trials:
– DRV/b + RPV
– DRV/b + DTG
IAS-USA 20202
 Maintenance of viral suppression has been
demonstrated after switching to a single-
tablet regimen for most fixed-dose
combination regimens, compared with
regimens prior to switchingII
 Patients with HIV/HBV coinfection should
continue taking TAF or TDF (Alll) unless these
drugs are contraindicated…
 Switching from a 3-drug to 2-drug regimen is
appropriate to manage toxicities, intolerance,
adherence or patient preference, provided
there is no resistance to either agent (Ala);
recommended regimens include:
– DTG + RPV (Ala)
– DTG + 3TC (Ala)
– CAB + RPV long acting injectable Q4W
(Ala) or Q8W (Bib)
– Pl/b + 3TC (Ala)
DHHS 20191
 Within-class switch strategies studied in
individuals without underlying resistance
include switching from:
– TDF† or ABC‡ to TAF†
– RAL§ to DTG
– DTG, EVG/c, or RAL§ to BIC
– EFV to RPV or DOR
– ATV/c or ATV/r to ATV (with ABC/3TC)
 Between-class switch strategies studied
in individuals without underlying
resistance include switching from:
– Pl/b to INSTI (BIC, DTG, EVG)
– Pl/b to RPV or DOR
– NNRTI to INSTI
– Pl/b with MVC
IIAmong people who have been receiving treatment and have at least 6 months of viral suppression, no history of treatment failure, and no evidence of archived mutations.
1. Department of Health and Human Services. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/AdultandAdolescentGL.pdf. Accessed May 2021.
2. Saag. JAMA. 2020;324:1651-1669.
3. Adapted from EACS guidelines version 10.1 October 2020. https://eacs.sanfordguide.com/art/switch-strategies. Accessed May 2021.

Recommended Monitoring After Switching
EACS 20203
 People living with HIV should
be seen soon (eg, 4 weeks)
after treatment switches to
check for maintenance of
suppression and possible
toxicity or tolerability issues
of the new regimen
IAS-USA 20202
 HIV viral load assessment is
recommended 1 month
after switching regimens
(evidence rating: BlII)
DHHS 20191
 After a treatment switch, patients
should be evaluated closely for 3
months (eg, a clinic visit or phone call
1 to 2 weeks after the change and a
viral load test to check for rebound
viremia 4 to 8 weeks after the switch)
(evidence rating: Alll)
1. Adapted from DHHS ART. February 24, 2021. https://clinicalinfo.hiv.gov/sites/default/files/guidelines/documents/AdultandAdolescentGL.pdf.
Accessed May 2021; 2. Adapted from Saag. JAMA. 2020;324:1651-1669; 3. Adapted from EACS . https://eacs.sanfordguide.com/art/switch-
strategies. Accessed May 2021.

Key Secondary Endpoint
(HIV-1 RNA < 50 c/mL)
DTG/3TC noninferior to
continued TAF-based ART
TANGO: Switch to DTG/3TC vs Continuing TAF-Based
3-Drug Regimen
0.5
Patients
(%)
100
80
40
60
20
0
HIV-1 RNA
≥ 50 c/mL
HIV-1 RNA
< 50 c/mL
No Virologic
Data
0.3
93.2 93.0
6.5 6.5
Switch to DTG/3TC
(n = 369)
Continue TAF-based ART
(n = 372)
Virologic Outcomes by FDA Snapshot (ITT-E) at Wk 48 Adjusted Treatment Difference (95% CI)*
Primary Endpoint
(HIV-1 RNA ≥ 50 c/mL)
DTG/3TC noninferior to
continued TAF-based ART
*Adjusted for baseline third agent class.
Difference (%)
-3.4
0.2
-8 -6 -4 -2 0 2 4 6 8
3.9
-8% NI
margin
TAF-Based ART
DTG/3TC
TAF-Based ART DTG/3TC
-1.2 0.7
-0.3
-8 -6 -4 -2 0 2 4 6 8
4% NI
margin
van Wyk. IAS 2019. Abstr WEAB0403LB.
 No CVW in DTG/3TC arm, CVW in 1 (< 1%) patient in
TAF-based ART arm; no resistance detected at failure
 All 7 patients (4 in DTG/3TC group, 3 in TAF-based ART
group) with proviral M184V/I mutation at baseline
maintained HIV-1 RNA < 50 c/mL at Wk 48
 International, randomized, open-label phase III noninferiority study in adults with HIV-1 RNA < 50 c/mL for > 6 mos
on TAF-based ART

TANGO: Changes in Lipids, HbA1c, Fasting Glucose, and
Fasting Insulin at Wk 48
 In analysis excluding those with BL lipid-modifying agent use, lipid changes favored
switch to DTG/3TC (n = 275) vs continued TAF-based ART (n = 263) in overall
population
‒ Significant reductions in total cholesterol, LDL, triglycerides, and TC:HDL ratio
with DTG/3TC
 When stratified by previous use of boosting agents, statistically favorable changes
with DTG/3TC vs TAF-based ART persisted in boosted subgroup
‒ Significant reductions in total cholesterol, LDL, triglycerides, and TC:HDL ratio
with DTG/3TC
 A1C and fasting glucose changes minimal, comparable between treatment arms;
fasting insulin changes statistically favored switch to DTG/3TC vs continued
TAF-based ART in boosted subgroup (P = .006), with trend for unboosted subgroup
van Wyk. Clin Infect Dis. 2020;71:1920. van Wyk. AIDS 2020. Abstr OAB0606.

TANGO: Weight Change at Wk 48
 Overall weight gains minimal, comparable between treatment arms
van Wyk. AIDS 2020. Abstr OAB0606.
Weight Parameter
DTG/3TC
(n = 343)
TAF-Based ART
(n = 343)
Adjusted mean weight change from BL, kg (SE)
 Prior TAF duration < 1 yr*
 Prior TAF duration ≥ 1 yr†
 Boosted baseline regimen
 Unboosted baseline regimen
0.81 (0.23)
1.45 (0.46)
0.60 (0.26)
0.81 (0.27)
0.81 (0.45)
0.76 (0.22)
1.35 (0.47)
0.60 (0.25)
0.88 (0.25)
0.40 (0.44)
Weight increase ≥ 10% from BL, n (%) 11 (3) 13 (4)
*DTG/3TC, n = 83; TAF-based ART, n = 76. †DTG/3TC, n = 260; TAF-based ART, n = 267.

SWORD-1 and -2: Switch to DTG + RPV vs Continuation
of Baseline ART in Virologically Suppressed Adults
 Parallel, randomized, open-label, multicenter phase III noninferiority studies in adults on stable ART (INSTI,
NNRTI, or PI + 2 NRTIs) with HIV-1 RNA < 50 copies/mL for ≥ 6 mos[1,2]
 Primary endpoint: HIV-1 RNA < 50 copies/mL maintained in 95% of patients in each arm at Wk 48; adjusted
treatment difference: -0.2% (95% CI: -3.0 to 2.5)[2]
 10/990 (1%) confirmed virologic withdrawals through Wk 100[1]
‒ Treatment-emergent NNRTI resistance mutations documented in 3/10, all from early switch arm*
Time of
Failure
Previous
Regimen
Mutations at Baseline
Mutations at
Confirmed Virologic Withdrawal
NNRTI INSTI NNRTI INSTI
Wk 36 EFV/FTC/TDF None None K101K/E None
Wk 88 DTG/ABC/3TC None None E138E/A None
Wk 100 EFV/FTC/TDF K101E, E138A G193E
K101E, E138A,
M230M/L
Assay failure
*For these 3 patients, HIV-1 RNA at last measurement: < 50 copies/mL, 55 copies/mL, 300 copies/mL, respectively.
1. Aboud. AIDS 2018. Abstr THPEB047. 2. Llibre. Lancet. 2018;391:839.

DRIVE-SHIFT: DOR/3TC/TDF, Immediate-Switch vs
Delayed-Switch
 International, randomized, open-label phase III noninferiority study[1,2]
Baseline ART†
(n = 223)
Wk 48
Wk 24
*DOR/3TC/TDF dosing: 100/300/300 mg QD.
†2 NRTIs + boosted PI (ATV, DRV, or LPV), EVG/COBI, or NNRTI (EFV, NVP, or RPV).
DOR/3TC/TDF*
(n = 209)
DOR/3TC/TDF*
(n = 447)
DOR/3TC/TDF*
(n = 427)
Adults with HIV-1 RNA
< 40 c/mL, stable ART
for ≥ 6 mos, and eGFR
≥ 50 mL/min; no prior
VF or resistance to
study drugs
(N = 670)
Wk 144
DOR/3TC/TDF*
DOR/3TC/TDF*
Base Study Extension Phase
 Primary endpoint: HIV-1 RNA < 50 copies/mL at Wk 48 in immediate switch arm vs
Wk 24 in delayed switch arm[2]
Kumar. J Acquir Immune Defic Syndr. 2021;87:801.

DRIVE-SHIFT: Efficacy of Switch to DOR/3TC/TDF at
Wks 24, 48, and 144 vs Continued BL ART
DSG, delayed-switch group (n = 209); ISG, immediate-switch group (n = 447)
100
80
40
60
20
0
ISG Week 0-48
DSG Week 24-48
ISG Week 24-48
DSG Week 24-144
Virologic Nonresponse
(≥ 50 c/mL)
90.8
94.7
80.1
83.7
Virologic Success
(< 50 c/mL)
1.6 2.9 2.7 4.8
No Virologic Data
7.6
2.4
17.1
11.5
Patients
(%)
Kumar. J Acquir Immune Defic Syndr. 2021;87:801. Slide credit: clinicaloptions.com

DRIVE-SHIFT: Post-Switch Mean Weight Change
*Adjusted for weight at switch, race (black vs nonblack), ethnicity (Hispanic vs other), sex, age, BL CD4+ cell count, and HIV-1 RNA.
Mean Weight
Δ,* kg (95% CI)
Immediate
Switch
Delayed
Switch
Wk 24
0.7
(0.4 to 0.9)
NA
Wk 48
0.7
(0.4 to 1.1)
0.5
(0 to 1.0)
Wk 96
1.1
(0.7 to 1.6)
0.8
(0.2 to 1.5)
Wk 144
1.4
(0.8 to 1.9)
1.2
(0.4 to 2.0)
Wk
Immediate Switch
Delayed Switch
Mean
Weight
Δ,*
kg
(95%
CI)
2.5
2.0
1.5
1.0
0.5
0.0
-0.5
2.5
2.0
1.5
1.0
0.5
0.0
-0.5
144
0 4 12 2428 36 48 64 80 96 112 128
Kumar. J Acquir Immune Defic Syndr. 2021;87:801.

ATLAS and FLAIR: Long-Acting Intramuscular CAB + RPV
After Initial Virologic Suppression With Oral Therapy
 Multicenter, randomized, open-label phase III noninferiority trials
 Primary endpoint for both trials: HIV-1 RNA ≥ 50 copies/mL at Wk 48 by FDA Snapshot in ITT-E
LA CAB 400 mg + LA RPV 600 mg IM Q4W
(n = 303)
Continue Baseline ART
(n = 308)
Adults on stable ART (either
first or second regimen) with
HIV-1 RNA < 50 copies/mL for
≥ 6 mos with no previous VF
(N = 616)
Comparator arm
patients eligible to
receive CAB + RPV
in extension phase
after Wk 52
(ATLAS-2M study)
Wk 48 Primary Endpoint
ATLAS
LA CAB 400 mg +
LA RPV 600 mg IM Q4W
(n = 278)
Continue DTG/ABC/3TC PO QD
(n = 283)
ART-naive patients with
HIV-1 RNA ≥ 1000 copies/mL,
HBsAg negative, no NNRTI RAMs
but K103N permitted
(N = 629)
CAB 30 mg +
RPV 25 mg PO QD
(n = 283)
Wk 48 Primary Endpoint
Wk 4
DTG/ABC/3TC PO QD
Wk 96
Day 0
Wk 20
FLAIR
1. Swindells. NEJM. 2020;382:1112. 2. Orkin. NEJM. 2020;382:1124.
CAB 30 mg +
RPV 25 mg PO QD
(n = 308)
Wk 4
Day 0

-1.2 2.5
0.6
-10 -8 -6 -4 -2 0 2 4 6 8 10
ATLAS: Switch to Long-Acting CAB + RPV vs Continued
3-Drug ART in Virologically Suppressed Adults
Patients
(%)
Difference (%)
Difference (%)
100
80
40
60
20
0
1.6 1.0
92.5 95.5
5.8 3.6
LA CAB + LA RPV
(n = 308)
Continued BL ART
(n = 308)
-6.7
-3.0
-10 -8 -6 -4 -2 0 2 4 6 8 10
0.7
Adjusted Treatment Difference (95% CI)*
Key Secondary Endpoint
(HIV-1 RNA < 50 copies/mL)
LA CAB + LA RPV noninferior
to continued BL ART
Primary Endpoint
(HIV-1 RNA ≥ 50 copies/mL)
LA CAB + LA RPV noninferior
to continued BL ART
6% NI
margin
-10% NI
margin
*Adjusted for sex and
BL third agent class.
Virologic Outcomes at Wk 48
Virologic
Nonresponse
(≥ 50 c/mL)
Virologic
Success
(< 50 c/mL)
No Virologic
Data
Continued ART
LA CAB + LA RPV
Continued ART LA CAB + LA RPV
Swindells. NEJM. 2020;382:1112.

Difference (%)
Difference (%)
FLAIR: Efficacy at Wk 96 in ITT-E Population
Patients
(%)
100
80
40
60
20
0
Virologic
Nonresponse
(≥ 50 c/mL)
Virologic
Success
(< 50 c/mL)
No
Virologic
Data
3.2 3.2
86.6
89.4
10.2 7.4
CAB LA + RPV LA
(n = 283)
DTG/ABC/3TC
(n = 283)
-10% NI
margin
Difference (%)
-8.2
-2.8
-10 -8 -6 -4 -2 0 2 4 6 8 10
2.5
-2.9 2.9
0
6% NI
margin
-10 -8 -6 -4 -2 0 2 4 6 8 10
Virologic Outcomes (FDA Snapshot) Adjusted Treatment Difference (95% CI)*
DTG/ABC/3TC
CAB LA + RPV LA
DTG/ABC/3TC CAB LA + RPV LA
*Adjusted for sex, BL HIV-1
RNA (< vs ≥ 100,000 c/mL).
Orkin. CROI 2020; abstr 482.
HIV-1 RNA ≥ 50 copies/mL
CAB LA + RPV LA noninferior
to DTG/ABC/3TC
HIV-1 RNA < 50 copies/mL
to DTG/ABC/3TC

ATLAS and FLAIR: Treatment-Emergent Resistance With
Long-Acting CAB + RPV
 In the FLAIR trial, at Wk 96, there were no additional cases of treatment-emergent
resistance3
1. Swindells. CROI 2019. Abstr 139. 2. Orkin. CROI 2019. Abstr 140LB. 3. Orkin. CROI 2020. Abstr 482LB. Slide credit: clinicaloptions.com
Study Sex Country
HIV-1
Subtype
Wk of
Failure
NNRTI RAMs INSTI RAMs
Baseline Failure Baseline Failure
ATLAS1
F Russia A6 8 E138E/A E138A None None
F France A6 12 V108V/I, E138K V108I, E138K None None
M Russia A6 20 None E138E/K None N155H
FLAIR2
F Russia A6 20 None E138E/A/K/T None Q148R
M Russia A6 28 None K101E None G140R
F Russia A6 48 None E138K None Q148R

ATLAS-2M: Cabotegravir + Rilpivirine IM Q8W vs Q4W
Overton. Lancet. 2021;396:1994.
 Multicenter, randomized, open-label phase III noninferiority trial
CAB LA 600 mg + RPV LA 900 mg IM Q8W
(n = 522)
CAB LA 400 mg + RPV LA 600 mg IM Q4W
(n = 523)
2 populations: adults from
ATLAS receiving either CAB LA
+ RPV LA Q4W* or SoC ART
and patients receiving SoC
ART outside of ATLAS†
(N = 1045)
*Participants transitioning from ATLAS must have been on CAB LA + RPV LA Q4W or a current ART regimen through at least Wk 52 and had HIV-1 RNA <50 c/mL
at screening. †SoC participants not transitioning from ATLAS study on uninterrupted current regimen (initial or second combined ART) for ≥6 mo prior to
screening and documented evidence of ≥2 plasma HIV-1 RNA <50 c/mL in 12 mo prior to screening (one 6-12 mo and one within 6 mo prior to screening).
Participants excluded if history of VF or if prior genotype results show any major INSTI or NNRTI mutations (except K103N).
Option to
continue
CAB LA +
RPV LA
Q4W or
Q8W after
Wk 100
Oral CAB
30 mg +
RPV 25
mg QD
(except ATLAS
participants
on LA tx)
Wk 48 Primary
Endpoint
Wk 4 Wk 96 Wk 100
 Primary endpoint: HIV-1 RNA ≥50 copies/mL at Wk 48 by FDA snapshot in ITT-E
 Secondary endpoints: HIV-1 RNA <50 copies/mL at Wk 48 by FDA snapshot in ITT-E,
safety and tolerability, VF, resistance, and treatment preference
Stratified by prior
CAB + RPV exposure

ATLAS-2M: Virologic Outcomes at Wk 96 in ITT-E by
FDA Snapshot
Q4W
Q8W
Difference (%)
-0.6 2.5
1.0
4% NI
margin
Difference (%)
-2.8 4.3
0.8
Q8W
Q4W
-10% NI
margin
CAB LA + RPV LA Q8W
(n = 522)
CAB LA + RPV LA Q4W
(n = 523)
Adjusted Treatment Difference at Wk 96 (95% CI)*
Virologic Outcomes
*Based on Cochran-Mantel-Haenszel analysis adjusting for prior CAB + RPV exposure.
100
80
60
40
20
0
Participants
(%)
Virologic
Nonresponse
(≥50 c/mL)
Virologic
Success
(<50 c/mL)
No Virologic
Data
1.1
8.6
91.0 90.2
-10 -8 -6 -4 -2 0 2 4 6 8 10
-10 -8 -6 -4 -2 0 2 4 6 8 10
2.1
6.9
Jaeger. CROI 2021. Abstr 401. NCT03299049.
HIV-1 RNA ≥ 50 copies/mL
to DTG/ABC/3TC
HIV-1 RNA < 50 copies/mL
to DTG/ABC/3TC

 CAB LA + RPV LA well tolerated
‒ 98% of ISRs were grade 1/2; median
duration was 3 days
 Patients preferred CAB LA +
RPV LA over oral therapy
 Patients previously receiving CAB LA
+ RPV LA preferred Q8W dosing over
Q4W dosing
ATLAS-2M: Virologic Failure, ISRs, Patient Preferences
Overton. Lancet. 2021;396:1994.
Outcome
CAB LA + RPV
LA Q8W
(n = 522)
CAB LA + RPV
LA Q4W
(n = 523)
CVF, n (%) 8 (1.5) 2 (0.4)
CVF with RPV
RAMs,* n/N
6/8 1/2
Treatment-
emergent RPV
RAMs
K101E, E138E/K,
E138A, Y188L
K101E, M230L
CVF with INSTI
RAMs,* n/N
5/8 2/2
Treatment-
emergent INSTI
RAMs
Q148R, N155H† E138E/K,Q148R,
N155N/H
*Post hoc BL PBMC HIV-1 DNA testing. †Or a mixture.

Long-Acting CAB + RPV Approved in Europe, US, Canada
 FDA indication:
‒ As complete regimen for treatment of HIV-1 infection in adults who are
virologically suppressed on a stable ART regimen
‒ No history of treatment failure and no known or suspected resistance to either
CAB or RPV
 Requires oral CAB + RPV lead-in dosing for ~1 mo to assess tolerability
 Initiate IM gluteal injection of CAB 600 mg + RPV 900 mg on last day of oral lead-in
period and continue with injections of CAB 400 mg + RPV 600 mg every mo
thereafter
 In Europe approved for Q4W and Q8W dosing
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212888s000lbl.pdf. Slide credit: clinicaloptions.com

Long-Acting CAB + RPV: DHHS Statement on Use
 CAB and RPV intramuscular injections can be used as an optimization strategy for
people with HIV currently on oral antiretroviral therapy with documented viral
suppression for at least 3 mo (although optimal duration is not defined) (AI), who:
‒ have no baseline resistance to either medication,
‒ have no prior virologic failures,
‒ do not have active hepatitis B virus (HBV) infection (unless also receiving an oral HBV
active regimen),
‒ are not pregnant and are not planning on becoming pregnant, and
‒ are not receiving medications with significant drug interactions with oral (during lead-in
or bridging therapy) or injectable CAB or RPV
https://clinicalinfo.hiv.gov/en/guidelines/adult-and-adolescent-arv/hhs-adults-and-adolescents-antiretroviral-guidelines-panel Slide credit: clinicaloptions.com
Cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension PI.

“Direct to Inject”: Switching to CAB/RPV Without an
Oral Lead-in
 FLAIR extension study
‒ Participants on DTG/ABC/3TC
arm achieving virologic
suppression (HIV-1 RNA
<50 copies/mL) in 20-wk
induction phase could switch
to monthly CAB/RPV at Wk 100
‒ Switchers randomized to groups
with (n = 121) or without
(n = 111) an oral CAB + RPV
lead-in
D’Amico. J Int AIDS Soc. 2020;23(suppl 7):15.
Patients
(%)
99.1
93.4
0.9 0.8 0
5.8
Virologic Outcomes at Wk 124 Following
Switch to CAB/RPV at Wk 100
No lead-in
Lead-in
Virologic
Nonresponse
Virologic
Suppression
No Virologic
Data
100
80
40
60
20
0

Factors That May Contribute to Risk of Treatment
Failure With Long-Acting CAB/RPV
 Post hoc analysis of phase III data (Wk 48)
‒ ATLAS and FLAIR (Q4W dosing)
‒ ATLAS-2M (Q4W and Q8W dosing)
 Backwards elimination model (10 covariates)
 Factors associated with increased odds of
confirmed virologic failure:
‒ RPV RAMs at baseline (OR: 40.36;
P <.001)
‒ Log2 of post hoc Wk 8 RPV trough concentration
(OR: 5.00; P = .002)
‒ Baseline HIV-1 subtype A6 (OR: 5.92;
P = .008)
‒ BMI ≥30 kg/m2 at baseline (OR: 1.13; P = .020)
 Q8W dosing was not a significant factor
Cutrell. AIDS. 2021;[Epub].
Baseline
Factors
Patients,
% (n)*
CVF,
% (n)
HIV-1 RNA
<50 c/mL, % (n)
None 70.5 (732) 0.41 (3) 94.8 (694)
1 26.2 (272) 0.37 (1) 96.0 (261)
≥2 3.37 (35) 25.71 (9) 71.4 (25)
*For CVF analysis, N = 1039

Special Considerations for Switching During the
Pandemic
 If possible, postpone changes to the regimen
 If prompt switching is necessary, choose medications which require
less frequent monitoring
 Consider the timing and logistics of the switch

Take-Home Points
 Patients with viral suppression and no history of drug resistance have many options
for switching therapy—risk of virologic failure low
‒ For those not experiencing AEs, it is critical that the switch strategy offers some safety,
convenience, or cost benefit
‒ Certain 2-drug regimens appear to be as effective as 3-drug strategies, although long-
term data are not yet available
‒ Monotherapy should be avoided
 Patients with viral suppression and a history of single-class resistance have
treatment simplification options
‒ It is critical to review all available resistance tests to ensure that the new regimen has
at least 2 fully active agents
‒ Viable switch strategies can be inferred from studies of second-line therapy

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