Contemporary HIV Treatment and Prevention 2022:

Cutting-Edge Concepts in HIV Care

This program is supported by ViiV Healthcare.

Long-Acting Therapies
Case Patient 1: Long-Acting ART
 A 37-yr-old woman has been virologically suppressed on BIC/FTC/TAF
for 2 yr
 Previously she was on several different ART regimens, but she does not
remember their names
 She struggled with medication adherence in past but has done
significantly better over past 2 yr
 She is interested in switching to long-acting injectable cabotegravir +
rilpivirine
 Long-Acting Cabotegravir + Rilpivirine
 Approved as monthly injections since January 2021
 Approved as every-2-mo injections since February 2022
 Challenges
‒ Frequency of in-clinic injections
‒ Concerns about elevated BMI
‒ Logistics and operationalizing rollout and uptake

fda.gov/news-events/press-announcements/fda-approves-first-extended-release-injectable-drug-regimen-adults-living-hiv.
Cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension PI. Slide credit: clinicaloptions.com
 Guidance on Use of LA CAB + RPV
 Optimal candidates:
‒ Virologically suppressed on oral regimen
for 3-6 mo
‒ Any renal function
‒ Engaged with their healthcare
‒ Agree to make frequent clinic visits
DHHS ART guidelines.
 Contraindications:
‒ Prior INSTI or NNRTI resistance
(except K103N)
‒ Prior virologic failure
‒ Chronic HBV infection (active or occult)
Slide credit: clinicaloptions.com
 ATLAS-2M: LA CAB + RPV Q8W vs Q4W
 Multicenter, randomized, open-label phase IIIb noninferiority trial
Stratified by prior Wk 4 Wk 48 Primary Endpoint Wk 96 Wk 152
CAB + RPV exposure

2 populations: adults from Oral CAB LA CAB 600 mg + LA RPV 900 mg IM Q8W Option to
ATLAS receiving either LA CAB 30 mg + (n = 522) continue
+ LA RPV Q4W or SoC ART and RPV LA CAB +
patients receiving SoC ART 25 mg QD LA RPV
outside of ATLAS (except ATLAS LA CAB 400 mg + LA RPV 600 mg IM Q4W Q4W or
participants (n = 523) Q8W
(N = 1045) on LA tx)

 Primary endpoint: HIV-1 RNA ≥50 c/mL at Wk 48 by FDA snapshot in ITT-E

‒ Q8W found to be noninferior to Q4W at Wk 48
 Secondary/other Wk 152 endpoints: plasma HIV-1 RNA ≥50 or <50 copies/mL at Wk 152 by
FDA snapshot in ITT-E, CVF incidence, viral resistance in patients with CVF, safety and
tolerability, treatment satisfaction
Overton. Lancet. 2021;396:1994. Overton. CROI 2022. Abstr 479. NCT03299049. Slide credit: clinicaloptions.com
 ATLAS-2M: Wk 152 Outcomes
100 87.4 85.9 88.2 86.9  LA CAB + RPV well tolerated
Q8W CAB + RPV LA ITT-E
Participants (%)

80
(n = 522)
Q4W CAB + RPV LA ITT-E
‒ 99% of ISRs were grade 1/2;
60 (n = 523)
Q8W CAB + RPV LA PP
median duration was 3 days
40 (n = 510)
20 Q4W CAB + RPV LA PP
(n = 513)
‒ 8 (2%) Q8W and 13 (3%) Q4W
0 withdrew due to ISRs
Virologic Success
(<50 c/mL)  Patient satisfaction scores
Outcome
Q8W Q4W significantly favored Q8W vs
(n = 522) (n = 523)
Q4W dosing at
CVF, n (%) 11 (2) 2 (<1)
Wk 24, 48, and 152
RPV RAMs, n/N 9/11 1/2
INSTI RAMs, n/N 8/11 2/2

Overton. Lancet. 2021;396:1994. Overton. CROI 2022. Abstr 479. Slide credit: clinicaloptions.com
 Risk Factors for Virologic Failure With LA CAB + RPV:
Wk 48 Data
 Post hoc analysis of Wk 48 phase III data1 Factors Associated With CVF OR
‒ ATLAS and FLAIR (Q4W dosing) RPV RAS(s) at baseline 40.36
‒ ATLAS-2M (Q4W and Q8W dosing) Wk 8 RPV trough concentration 5.00
 13/1039 (1.25%) participants had CVF in ATLAS, Baseline HIV-1 subtype A6/A1 5.92
FLAIR, ATLAS-2M
BMI (kg/m2) at baseline 1.13
 Among 96.7% with 0 or 1 risk factor for CVF,
0.4% had CVF No. of Baseline Factors HIV-1 RNA
CVF, %
Associated With CVF <50 c/mL, %
 Q8W dosing was not a significant factor
associated with CVF None 0.4 95
1 0.4 96
≥2 26 71
Total 1.3 94

1. Cutrell. AIDS. 2021;35:1333. 2. Injectable CAB+RBV PI. Slide credit: clinicaloptions.com

 Combined Clinical Trials of LA CAB + RPV:
Efficacy by BMI Class
 Data from participants naive to CAB + RPV Virologic Outcome (<50 copies/mL)
who received LA CAB + RPV Q8W or Q4W in 100 94 92.7 91.5 92.2
phase III ATLAS, FLAIR, and ATLAS-2M Q8W
studies pooled 80 Q4W

Participants (%)
‒ Participants categorized by 60

‒ Dosing regimen: Q8W vs Q4W 40

‒ BMI category: <30 vs >30 kg/m2 20

 Results: Among participants with BMI ≥30 0

kg/m2 as only risk factor (n = 153), none BMI <30 kg/m2 BMI >30 kg/m2
(n = 1032) (n = 213)
met criterion for confirmed virologic failure
 CAB and RPV trough levels remained above  Use of 2-inch needles resulted in higher
target PA-IC90 values regardless of dosing median CAB trough concentrations in
schedule or BMI people with BMI >30 kg/m2
Eliot. EACS 2021. Abstr BPD1/8. Slide credit: clinicaloptions.com
 Practical Considerations for LA CAB + RPV

Administration
 Recommended to be administered only by HCP
 Optional oral CAB + RPV lead-in dosing for ~1 mo to assess tolerability; initiate injections on
last day of oral lead-in period
 Initiate Q1M injections with a loading dose (CAB 600 mg/3 mL + RPV 900 mg/3 mL) followed
by monthly continuation doses (CAB 400 mg/2 mL + RPV 600 mg/2 mL)
 For Q2M dosing schedule: Initiate injections of CAB 600 mg and RPV 900 mg monthly for the
first 2 mo, and then every 2 mo thereafter2
 23-gauge, 1.5-inch intramuscular needle recommended (use 2-inch needle if BMI >30 kg/m2)
 Give ventrogluteal IM injections on opposite sides when possible or ≥2 cm apart if given on
same side

DHHS Guidelines. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV.
Cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension PI. Slide credit: clinicaloptions.com
 CUSTOMIZE: Implementation of LA CAB + RPV
 Phase IIIb implementation-effectiveness study  Key strategies for successful clinic
of LA CAB + RPV implementation
‒ Data collected July 2019 to October 2020 from ‒ Good staff communication
26 providers (physicians, injectors, admin) and
‒ Teamwork
109 patients from 8 clinics
‒ Use of a web-based treatment planner
Virologic Outcome at Mo 12, n (%) Patients
(N = 115)  Key implementation strategies for patient
Virologic success (<50 copies/mL) 101 (88) adherence
Virologic nonresponse (≥50 copies/mL) 0 ‒ Good communication about dosing window
‒ Effective appointment reminder systems
No virologic data 14 (12)
 Discontinued due to AE or death 5 (4)* ‒ Designated staff for appointment tracking
 Discontinued for other reasons 8 (7)
 On study but missing data in window 1 (1)†  Duration of visit length decreased over time
Scheduling injection visits 2 ‒ Mo 1: median 57 min

*2 deaths, both unrelated to study treatment. †Due to COVID-19.

‒ Mo 11: median 34 min

Czarnogorski. IAS 2021. Abstr OAD0705. Slide credit: clinicaloptions.com

 Practical Considerations for LA CAB + RPV
Monitoring and Missed Doses
Monthly Dosing
 HIV-1 RNA: 4-8 wk after switch to LA CAB + RPV and after unplanned missed
visits/delayed dosing
 If viremia develops, test for resistance (including INSTI resistance)
 Oral-bridging therapy should be made available for planned missed doses
 If <2 mo since last injections, resume prior continuation dosing schedule
 If >2 mo since last injections, administer loading dose, followed by monthly
continuation dosing
 When stopping, transition to suppressive oral regimen within 4 wk of last IM doses
 To switch to every-2-mo dosing, administer CAB 600 mg and RPV 900 mg 1 mo after
last dose, followed by every-2-mo injections thereafter

DHHS Guidelines. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Slide credit: clinicaloptions.com
 Practical Considerations for LA CAB + RPV
Monitoring and Missed Doses
Every-2-Mo Dosing
 HIV-1 RNA: 4-8 wk after switch to LA CAB + RPV and after unplanned missed
visits/delayed dosing
 If viremia develops, test for resistance (including INSTI resistance)
 Oral-bridging therapy should be made available for planned missed doses
 If <3 mo since last every-2-mo injections, resume prior dosing schedule
 If >3 mo since last every-2-mo injections, initiate dose, followed by another dose
1 mo later, then resume every-2-mo dosing
 When stopping, transition to suppressive oral regimen within 8 wk of last IM doses

DHHS Guidelines. Guidelines for the Use of Antiretroviral Agents in Adults and Adolescents Living with HIV. Slide credit: clinicaloptions.com
 “Direct to Inject”: Switching to LA CAB + RPV Without
an Oral Lead-in
 FLAIR extension study1
‒ Participants receiving DTG/ABC/3TC achieving virologic suppression (HIV-1 RNA <50 copies/mL)
could switch to monthly LA CAB + RPV at Wk 100
‒ Switchers elected to start with (n = 121) or without (n = 111) oral CAB + RPV lead-in
Outcome, n (%)
Direct to Inject Oral Lead-in  As of March 2022, the oral
(n = 111) (n = 121)
lead-in is optional according
HIV-1 RNA <50 copies/mL 110 (99.1) 113 (93.4)
to the FDA approved
HIV-1 RNA ≥50 copies/mL 1 (0.9) 1 (0.8) prescribing information.2
 Discontinued for lack of efficacy 1 (0.9) -
 Data in window not below threshold -- 1 (0.8)

No virologic data 0 7 (5.8)

 Discontinued due to AE -- 2 (1.7)
 Discontinued for other reason -- 5 (4.1)*
*Burden of travel, prohibited medication use, participant relocation, burden of
procedures/intolerability of injections, and pregnancy.
1. Orkin. Lancet HIV. 2021;8:e668.
2. Cabotegravir extended-release injectable suspension; rilpivirine extended-release injectable suspension PI. Slide credit: clinicaloptions.com
 Supporting Candidates for Long-Acting ART
 Primary populations: those wanting or needing long-acting ART
Virologically suppressed patients Patients with suboptimal
desiring an ART switch adherence to oral therapy
(current FDA approved indication) LATITUDE (ACTG A5359)1
Strategies to Monitor and Circumvent Barriers to Long-Acting ART
 Shot clinics in clinical programs  Incentives
 Pharmacies administer shots  Mobile vans
 Constant supply of oral CAB and
RPV at home for “bridges”
 Additional population: those needing injectable therapy because they are
unable to take oral medications, studied under compassionate use 2
1. NCT03635788. 2. D’Amico. IAS 2020. Abstr PEB0263 Slide credit: clinicaloptions.com
 Implementation Study for LA CAB + RPV in Patients With
Challenges to Oral ART Adherence in San Francisco
 Observational study of PWH with challenges adhering to oral ART who were started
on LA CAB + RPV monthly
‒ Diverse and marginalized population with barriers (substance use, unstable housing)
 Of 132 patients referred, 39 received ≥2 follow-up injections (the analysis population):
‒ 24 with viral suppression All maintained suppression
at time of initiation of LA ART
‒ 15 without viral suppression 12 (80%) achieved viral suppression
at time of initiation of LA ART
‒ Of 3 patients who did not achieve viral
suppression, all had 2-log decline in
viral load at a median of 22 days
 87% injections on-time (28 ± 7 days from last injection)
 No discontinuations due to AEs
Christopoulos. AIDS 2022. Abstr EPB286. Christopoulos. Clin Infect Dis. 2022;ciac631. Slide credit: clinicaloptions.com
Future Long-Acting Therapy
 Lenacapavir: Investigational Long-Acting HIV Capsid
Inhibitor
 CAPELLA1: Lenacapavir in heavily ART–  CALIBRATE2: Lenacapavir in treatment-naive
experienced PWH PWH with HIV-1 RNA >200 c/mL, CD4+ >200
− 83% (30/36) achieved HIV-1 RNA <50 c/mL by cells/mm3, no active HCV/HBV coinfection
52 wk overall − Randomization: LEN + FTC/TAF for 28 wk, then
LEN + TAF or BIC if HIV-1 RNA <50 c/mL
Efficacy According to Active Agents in OBR (n = 36) Virologic Outcomes by FDA Snapshot (ITT) at Wk 54
94
100
100 92
79 90

Patients With HIV-1 RNA <50

Patients With HIV-1 RNA

85 85
80 Group 1: LEN SC + FTC/TAF (→ TAF)
67 80 Group 2: LEN SC + FTC/TAF (→ BIC)
<50 c/mL (%)

Group 3: LEN PO + FTC/TAF

60
Group 4: BIC/FTC/TAF

c/mL (%)
60

40
40

20
20
4/6 11/14 15/16
0 4/6 47/52 45/53 44/52 23/25
11/14 15/16 0
0 1 ≥2
1. Ogbuagu. CROI 2022. Abstr 491. 2. Gupta. CROI 2022. Abstr 138. Slide credit: clinicaloptions.com
 Lenacapavir Resistance From
CAPELLA and CALIBRATE Studies
 CAPELLA1,2: LEN in HTE PWH  CALIBRATE3,4: LEN in treatment-naive
‒ 83% (30/36) achieved HIV-1 RNA <50 PWH
copies/mL by 52 wk in randomized cohort ‒ 90% (47/52) and 85% (45/53) in LEN SC +
‒ LEN RAMs emerged in 8/72 from FTC/TAF groups achieved HIV-1 RNA
randomized and nonrandomized cohorts <50 copies/mL by 54 wk
Participants First Visit
CA RAMs
No. of Fully Reason for LEN ‒ LEN RAMs emerged in 2/157
With CA-R2 With CA-R Active Agents Monotherapy
1 Wk 26 M66I 3 First Visit
Lack of Participant CA RAMs Adherence
2 Wk 4 M66M/I, K70K/S 2 adherence to With CA-R4 With CA-R
K70H, A105A/S/T, OBR based on
3 Wk 10 2 plasma PK on target for LEN;
T107T/N 1 M184I/V developed
concentrations (LEN SC + Wk 10 Q67H, K70R
4 Wk 4 Q67H, K70R 3 first, suggests poor
FTC/TAF) adherence to FTC/TAF
5 Wk 10 M66I, N74D, A105T 0
6 Wk 4 M66M/I 0 Poor adherence by
No fully active 2 pill counts and low
M66M/I, ARVs in OBR (LEN PO + Wk 54 Q67H
7 Wk 4 Q67Q/H/N, K70K/R 1* LEN and TFV
FTC/TAF) concentrations
8 Wk 4 M66I, T107A 0
*TFV active at BL, inactive at Wk 10
1. Ogbuagu. CROI 2022. Abstr 491. 2. Margot. AIDS 2022. Abstr EPB240.
3. Gupta. CROI 2022. Abstr 138. 4. VanderVeen. AIDS 2022. Abstr EPB239. Slide credit: clinicaloptions.com
 Lenacapavir ISRs in CAPELLA and CALIBRATE Studies
Incidence and Severity of ISRs Related to LEN SC*
No ISR
Capella Calibrate Grade 1
100
After First SC After Second SC 100
After First SC After Second SC Grade 2
Grade 3
80 80
Participants (%)

60 74 76 78 78 79 60
89 88 89 89 90 87 87 86 90 91 90 84 91 92 94 *Only includes
40 40 AEs related to LEN
as determined by
20 20 investigator and
19 15 14 14 excludes those
22
6 1 7 1 7 1 10 1 10 3 8 3
7 10 1 6 11
3 13 11 4 11 9 10 1 15 1 9 7 1 6 not related to it;
0 4 0
ng a n le
Pai odu ratio
n ng a n le
Pai odu ratio
n ng a i n le on ng a
Pai
n l e
tio
n includes >10% in
welli ythem N u welli ythem N u w elli ythem Pa Nodu urati welli ythem du
No dura
S Er Ind S Er Ind S Er Ind S Er In both studies.

Median ISR Duration, CAPELLA CALIBRATE  There were 4 total discontinuations due to ISRs
Days (Q1, Q3) (N = 72) (N = 105)
(1/72 in CAPELLA and 3/103 in CALIBRATE)
Swelling 10 (4, 21) 10 (5, 30)
Erythema 6 (3, 8) 5 (2, 11) ‒ All were grade 1
Pain 3 (1, 6) 4 (1, 9)
Nodule 235 (72, 422) 301 (140, 369)
 Histopathology of biopsied injection sites
Induration 99 (22, 224) 213 (143, 445) points to foreign body reaction not due to
Kumar. AIDS 2022. Abstr EPB184. glass vial Slide credit: clinicaloptions.com
Take Home Points on Long-Acting Injectable ART
 LA CAB + RPV is now approved for monthly and every-2-mo dosing
 Virologic failure occurred in a small number of patients on LA CAB +
RPV despite on time dosing and in numerically more patients on Q8W
dosing compared to Q4W
 Data supports direct to inject with LA CAB + RPV, but this is not yet
approved
 Additional pipeline LA agents have been found to be effective,
including lenacapavir
PrEP
 CDC PrEP Guideline 2021 Updates for Oral PrEP
Updates

Candidates for PrEP Discuss PrEP with all sexually active patients; prescribe to anyone who
asks for it

Medications for PrEP
 FTC/TAF as an FDA-approved PrEP option for sexually active men and TGW
women
 Instructions for off label use of FTC/TDF as “event-driven” or “on-demand”
PrEP option for selected patients, though not fully recommended
– Not studied with FTC/TAF

 HIV Ag/Ab and HIV-1 RNA testing every 3 mo on oral PrEP

 Lipid monitoring at initiation then yearly on FTC/TAF
Laboratory Testing  CrCl monitoring every 6 mo if age ≥50 or eCrCL <90 ml/min, every 12 mo
and Monitoring if age <50 and eCrCl ≥90 mL/min
− Persons with a CrCl <60 mL/min should not take FTC/TDF for PrEP
− Persons with a CrCl <30 mL/min should not take FTC/TAF for PrEP

www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf. Slide credit: clinicaloptions.com

 ANRS IPERGAY: On-Demand Oral FTC/TDF PrEP in MSM
at High Risk for HIV Infection
 Double-blind, randomized study of On-demand regimen for each sexual intercourse3
on-demand FTC/TDF vs placebo as PrEP*  2 FTC*/TDF tablets 2-24 hr before sex; 1 FTC*/TDF tablet
24 hr after the first drug intake, and 1 FTC*/ TDF tablet 24
‒ Men and TG women who have sex with men, hr later
with unprotected anal sex with ≥2 partners in 1 dose 1 dose
≤6 mo In case of Sex
multiple subsequent sexual intercourses3
FTC/TDF FTC/TDF
 1 FTC*/TDF tablet per day until the last sexual
1 dose 1 dose
intercourse,
Sex then 1 FTC*/TDF tablet per day for 2 further
days placebo placebo
Total Median Risk P
Study Phase N Follow- Reduction, *FTC and 3TC considered interchangeable by WHO.
Pills/Mo Value
up, PY %
 AMPrEP study: when MSM offered both daily
Placebo
controlled, 400 431.3 15 86 .002 and on-demand options, they choose both
randomized1 and they alternate between them depending
Open-label
on their circumstances4
361 518 18 97 NR
extension2  On-demand FTC/TDF should not be used for
*On-demand PrEP strategy not FDA approved. PWID or those with HBV infection3
1. Molina. NEJM. 2015;373:2237. 2. Molina. Lancet HIV. 2017;4:e402.
3. WHO. apps.who.int/iris/bitstream/handle/10665/325955/WHO-CDS-HIV-19.8-eng.pdf. 4. Hoornenborg. Lancet HIV. 2019;6:e447. Slide credit: clinicaloptions.com
Case Patient 2: PrEP
 A 54-yr-old cisgender man has been  Data from his last clinic visit with
receiving daily oral FTC/TAF for PrEP you 3 mo ago:
Parameter Result
 He has sex with multiple male BMI 32
partners one weekend each mo and HIV Ag/Ab Negative
does not use condoms Lipids WNL
CrCl, mL/min 79
 He is interested in switching to Syphilis testing Negative
LA CAB Gonorrhea and chlamydia testing,
Negative
(throat, rectum, and urine)
AST/ALT Normal
HBsAg Negative
Anti-HBc, mIU/mL Negative
Anti-HBs, mIU/mL Positive
 CDC PrEP Guideline 2021 Updates for Injectable PrEP
Updates

Candidates for PrEP  Discuss PrEP with all sexually active patients; prescribe to anyone who
asks for it

 Bimonthly injectable CAB for adults and adolescents weighing at least

Medications for PrEP 35 kg
− Does not require refrigeration
− Oral lead in is optional

 HIV Ag/Ab and HIV-1 RNA testing for patients with IM CAB in the last
Laboratory Testing and 12 mo
Monitoring  HIV Ag/Ab and HIV-1 RNA testing every 2 mo on IM CAB
 SCr monitoring not required on IM CAB

www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf. Slide credit: clinicaloptions.com

 HPTN 083 and 084: Efficacy and Safety of LA Injectable
CAB vs Daily Oral FTC/TDF for PrEP
 International, randomized, double-blind phase IIb/III (083) and phase III (084) trials
Wk 5
Step 1 Step 2 Step 3
083: MSM and TGW ≥18 yr of age
at high risk of HIV infection CAB 30 mg PO QD + CAB LA 600 mg IM Q2M† +
(N = 4566)1,2 Placebo PO QD Placebo PO QD for ~3 yr
084: Sexually active cisgender FTC/TDF PO QD
women, 18-45 yr of age, at high for 1 yr
FTC/TDF PO QD + FTC/TDF PO QD +
risk of HIV infection
Placebo PO QD Placebo IM Q2M† for ~3 yr
(N = 3224)3

HPTN 0831,2 HPTN 0843,4

Primary Efficacy Endpoint CAB FTC/TDF CAB FTC/TDF
(n = 2244) (n = 2247) (n = 1614) (n = 1610)
HIV infections, n 13* 39 4* 36
HR for CAB vs FTC/TDF (95% CI) 0.34 (0.18-0.62) 0.11 (0.04-0.32)
*Includes 1 case readjudicated post hoc as a baseline infection

1. Landovitz. NEJM.. 2021 Aug 12;385:595. 2. Landovitz. AIDS 2020. Abstr OAXLB0101.
3. Delany-Moretlwe. HIVR4P 2021. Abstr HY01.02. 4. Marzinke. IAS 2021. Abstr PECLB25. Slide credit: clinicaloptions.com
 HPTN 083: 4 Baseline and 12 Incident HIV Infections in
LA CAB Arm A: 4 baseline infections
B: 5 infections after prolonged delay in CAB dosing
4
A1 C: 3 infections during oral lead-in
5.7 2.9
A2
A3
5 4 D: 4 infections despite on-time CAB dosing
5.4 3.6
A4
5.4 9.9 37.9 20.2 10 53.1
B1
5 98.4 Step 1: Oral CAB lead-in
B2
5.1 6.3 6.9 6.9 31
B3 Step 2: CAB LA 600 mg IM
5.1 3.6 8.3 6.3 11.7 13.1 9
B4 Step 2: CAB LA injection >2 wk overdue
5 44.9
B5 Step 3: Open-label FTC/TDF
1.3
3.9 4 Step 3: Overdue FTC/TDF dispensation
C1
6.6
C2 Annual follow-up
2.7 2.1
C3 Percent adherence to oral lead-in
4.7 4 8 8 7.3 10.7 5.3 8 8 8 CAB LA 600 mg IM
D1
5 4 8 8 8 8 Open-label FTC/TDF dispensed
D2
5.1 3.9 8 8.9 7.1 HIV infection
D3 1.3
5 4 8 6.3 First site positive HIV test
D4

Wk → 10 20 30 40 50 60 70 80 90 100 110 120 130 140

Marzinke. CROI 2021. Abstr 153. Reproduced with permission. Slide credit: clinicaloptions.com
 HPTN 083: 1-Yr Follow-up After Unblinding
1 Yr Unblinded Period Overall Efficacy
HIV Incidence HR (95% CI) HIV Incidence HR (95% CI)
3.5 3.5
31 Infections

HIV Incidence Rate/100 PY

HIV Incidence Rate/100 PY

3 Favors CAB Favors TDF/FTC 3 Favors CAB Favors TDF/FTC

2.5 2.20 2.5
72 Infections

Noninferiority
Noninferiority
2 2

Superiority
Superiority
0.33 0.34
1.5 11 Infections 1.5 1.57
1 0.76 0.17 0.66 1 25 Infections 0.22 0.54
0.5 0.5 0.54
0 1455 PY 1410 PY 0 4660 PY 4596 PY
CAB TDF/FTC 0 0.75 1 1.23 2 CAB TDF/FTC 0 0.75 1 1.23 2
(n = 1662) (n = 1627) NI margin (n = 2244) (n = 2248) NI margin

 13 additional infections identified on CAB

‒ 2 newly identified CAB infections during the blinded period, both with on-time injections
‒ 11 during the unblinded period (1 with on-time injections, 3 with delayed injections, 7 with ≥6 mo after CAB)
 Total of 7 breakthrough infections on CAB despite on-time dosing to date out of a total of
2244 participants randomized to LA CAB
Landovitz. CROI 2022. Abstr 96. Slide credit: clinicaloptions.com
 HPTN 084: Incident HIV Infections With Cabotegravir

4.6 3.9 7.7 8.4 7.7 Infection at baseline

A1
*
10.9
B1
* Infection in the absence
of CAB LA injection
5.1 46.9 5.3
B2
*
5.4 5.7 4.3 8.6 6 15.1 4.9 8.3 16.1
DX *
Wk 0 Wk 10 Wk 20 Wk 30 Wk 40 Wk 50 Wk 60 Wk 70 Wk 80
Step 1: Oral CAB lead-in Blinded CAB dispensed
Step 2: CAB LA 600 mg IM  No major INSTI mutations in CAB arm
CAB LA 600 mg IM
Step 2: CAB LA injection >2 wk overdue
Step 3: Open-label FTC/TDF for pregnancy Open-label FTC/TDF dispensed
Step 3: Overdue FTC/TDF dispensation First positive visit
Annual follow-up
* First site positive visit
Marzinke. IAS 2021. Abstr PECLB25. Slide credit: clinicaloptions.com
 HPTN 084: 1-Yr Follow-up After Unblinding
HIV Incidence in Blinded + 1-Yr Unblinded Periods  3 additional infections identified in CAB
group during 1-yr unblinded period
HR: 0.11; 95% CI: 0.05-0.24
3.5 ‒ 2 without recent CAB injections
3.0
Incidence Rate per 100 PY

56 infections ‒ 1 with no quantifiable CAB during

2.5 3292 PY oral lead-in
2.0 1.70
‒ Received first injection at first positive
1.5 visit
6 infections
1.0 3334 PY ‒ Identified 28 days later
0.5 0.18
 7 HIV infections out of 1614 participants
0
CAB (n = 1613)* FTC/TDF (n = 1610) in CAB arm to date
*Excludes 1 baseline infection from blinded period. ‒ None with injections within 2 wk of
target dose Slide credit: clinicaloptions.com
Delany-Moretlwe. AIDS 2022. Abstr OALBX0107.
 LA CAB for PrEP: Monitoring and Safety
 In HPTN 083, HIV detection with antigen/antibody testing was delayed compared with
qualitative HIV-1 RNA testing1
‒ Cabotegravir delays: 62 days for baseline infections; 98 days for incident infections2
‒ FTC/TDF delays: 34 days for baseline infections; 31 days for incident infections2

 7 participants in HPTN 083 received LA CAB after HIV infection; 5 had INSTI resistance;
2 had no genotyping results because HIV-1 RNA <500 c/mL at all visits3
‒ Single genome assay for integrase resistance showed that a sensitive HIV-1 RNA assay would
have detected infection before development of major INSTI RAMs in most patients4
 In HPTN 084, no participants developed INSTI resistance on LA CAB
 Injection-site reactions were common (81.4% with CAB in HPTN 083; 32% with CAB in HPTN
084), but rarely led to discontinuation (2.4% in HPTN 083, 0 in HPTN 084)
1. Marzinke. CROI 2021. Abstr 153. 2. cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf.
3. Marzinke. J Infect Dis. 2021;224:1581. 4. Eshleman. CROI 2022. Abstr 95 Slide credit: clinicaloptions.com
 Stopping LA CAB for PrEP
 Assess for ongoing risk of
HIV exposure
HIV Resistance and PrEP
 Counsel about the long duration of HIV infection
declining CAB levels and risk of 1.0
Resistant infection

Risk of Resistance (Red)

Zone of
resistance if HIV acquisition occurs • No drug • No infection

HIV Protection (Blue)

• No resistance resistance • No resistance
• Infection risk
 Give oral PrEP if it is indicated:
FTC/TDF or FTC/TAF can begin 0.5

within 8 wk after last CAB injection

 Continue follow-up quarterly for 0.0
12 mo to assess PrEP needs, and Low High

complete HIV testing Adherence/Drug Exposure

www.cdc.gov/hiv/pdf/risk/prep/cdc-hiv-prep-guidelines-2021.pdf. Slide credit: clinicaloptions.com

Take-home Points on PrEP
 CDC guidelines updated in 2021 to recommend that PrEP be discussed
with all sexually active patients
 Injectable cabotegravir was superior to FTC/TDF for PrEP in men and
women and was FDA approved
‒ Some breakthrough infections despite on time dosing
 Due to delays in HIV diagnoses in studies, CDC recommends
HIV-1 RNA testing in addition to Ag/Ab testing for all patients on PrEP
 Instructions for on-demand dosing of FTC/TDF included in CDC
guidelines and data support this dosing in MSM, but it is not yet FDA
approved
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