contemporary management of hiv: modifying art in virologically … · 2021. 4. 21. · ‒switching...
TRANSCRIPT
Saturday, April 24, 2021
10:30 AM ET
Contemporary Management of HIV: Modifying ART in Virologically Suppressed Patients
Supported by an educational grant from ViiV Healthcare.
Provided by Clinical Care Options, LLC.SK3
Speaker and Disclosure Information
David A. Wohl, MDProfessor of MedicineSchool of MedicineSite Leader, AIDS Clinical Trials Unit‐Chapel HillUniversity of North Carolina at Chapel HillDirector, North Carolina AIDS Training and Education CenterChapel Hill, North CarolinaCo‐Director, HIV ServicesNorth Carolina Department of CorrectionRaleigh, North Carolina
David A. Wohl, MD, has disclosed that he has received consulting fees from Gilead Sciences, Janssen, and ViiV Healthcare and funds for research support from Gilead Sciences and ViiV Healthcare.
Let’s Vote!
Poll 1: If you are in practice, what is your degree type?
A. Nurse
B. Nurse practitioner
C. Pharmacist
D. Physician
E. Physician assistant
F. Other healthcare professional
Poll 2: If you are in practice, how do you identify your specialty?A. Infectious disease
B. HIV
C. Family practice/general practice/internal medicine
D. Pharmacy
E. Other
Poll 3: If you treat HIV, how many patients do you provide care for in a typical wk?A. < 10
B. 10‐25
C. 26‐50
D. 51‐100
E. > 100
Poll 4: If you treat HIV, for how many yrs have you done so?A. 0‐2 yrs
B. 3‐5 yrs
C. 6‐10 yrs
D. 11‐15 yrs
E. 16‐20 yrs
F. More than 20 yrs
Presurvey 1: According to the FDA prescribing information, in which of the following patients is LA CAB + RPV indicated?
A. Treatment‐naive or virologically suppressed
B. Treatment naive only
C. Virologically suppressed only
D. Current virologic failure
E. Unsure
JB [2]95
Outcomes Case
You are providing care for a patient with long‐term virologic suppression on first‐line EFV/FTC/TDF who would like to switch to another single‐tablet ART regimen because of neuropsychiatric adverse effects
The patient is at high risk for CVD events and is also receiving a proton pump inhibitor for management of GERD
Presurvey 2: If following current guidelines, which of the following regimens would you recommend as a switch option for this patient?
A. DTG/3TC or BIC/FTC/TAF
B. DTG/ABC/3TC
C. DRV/COBI/FTC/TAF
D. RPV/FTC/TAF or RPV/FTC/TDF
E. Unsure
JB [2]96
Outcomes Case
You are providing care for a patient with a history of drug resistance (M184V and K103N) who is currently virologically suppressed on a 4‐pill twice daily ART regimen
The patient would like to switch to a simpler regimen with fewer pills
Presurvey 3: Based on current DHHS guidelines, how would you counsel this patient?
A. Patients with a history of drug resistance should avoid switching ART except in cases of severe toxicity with the current regimen
B. Switching to a new regimen is recommended only if they are experiencing adverse events (any grade) with their current regimen
C. Switching to a new regimen should be feasible with consideration of their ARV history and resistance testing results
D. Unsure
JB [2]96
Program Overview
Case‐Based Discussion: Modifying ART in Virologically Suppressed Patients
‒ Switching ART in a Patient With Daily Pill Fatigue
‒ Switching ART to Avoid Comorbidities
‒ Simplifying ART in the Context of Known Multidrug Resistance
Question and Answer Session
Switching ART in a Patient With Daily Pill Fatigue
Patient Case 1: Background
39‐yr‐old MSM diagnosed with HIV in 2015 shortly after being found unconscious on the street and brought to hospital by police
Urine toxicology screen positive for cocaine, alcohol, and amphetamines
When he awoke, he acknowledged polysubstance use and selling sex for money
Agreed to HIV testing, which was positive
Laboratory parameters at HIV diagnosis: ‒ CD4+ cell count: 334 cells/mm3
‒ HIV‐1 RNA: 34,000 copies/mL
‒ No HIV drug resistance
‒ Hepatitis serologies negative, including HAV, HBV, HCV
Started on EVG/COBI/FTC/TAF, one pill daily and rapidly achieved viral suppression
Transferred to an inpatient substance use disorder treatment program, has been in recovery since then, with excellent medication adherence
No other medical problems except for intermittent STIs, diagnosed on routine screens
Expresses that he’s tired of taking a daily pill for HIV – reminds him of the time of his diagnosis and difficulties with addiction
Slide credit: clinicaloptions.com
Poll 5: Would you switch this patient to long‐acting injectable CAB + RPV?A. Yes
B. Only after he has completed a hepatitis B vaccine series and shows a response
C. No
D. Unsure
Reasons to Consider an ART Switch During Viral SuppressionAppropriate
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
Slide credit: clinicaloptions.comDHHS Guidelines. December 2019.
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
Slide credit: clinicaloptions.com
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 EndpointATLAS
LA CAB 400 mg +LA RPV 600 mg IM Q4W
(n = 278)
Continue DTG/ABC/3TC PO QD(n = 283)
ART‐naive patients withHIV‐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 EndpointWk 4
DTG/ABC/3TC PO QD
Wk 96Day 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 4Day 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
Slide credit: clinicaloptions.com
Patie
nts (%)
Difference (%)
Difference (%)
100
80
40
60
20
01.6 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% NImargin
‐10% NImargin
*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 ARTLA CAB + LA RPV
Continued ART LA CAB + LA RPV
Swindells. NEJM. 2020;382:1112.
‐2.8 2.1
‐0.46% NImargin
‐10 ‐8 ‐6 ‐4 ‐2 0 2 4 6 8 10Difference (%)
Difference (%)Slide credit: clinicaloptions.com
Patie
nts (%)
100
80
40
60
20
0Virologic
Nonresponse (≥ 50 c/mL)
Virologic Success
(< 50 c/mL)
2.1 2.5
93.6 93.3
4.2 4.2
LA CAB + LA RPV(n = 283)
DTG/ABC/3TC(n = 283)
‐10% NImargin
Difference (%)
‐3.7
0.4
‐10 ‐8 ‐6 ‐4 ‐2 0 2 4 6 8 10
4.5
Virologic Outcomes at Wk 48 Adjusted Treatment Difference (95% CI)*
DTG/ABC/3TCLA CAB + LA RPV
DTG/ABC/3TC LA CAB + LA RPV
Key Secondary Endpoint(HIV‐1 RNA < 50 copies/mL):LA CAB + LA RPV noninferior
to DTG/ABC/3TC
*Adjusted for sex, BL HIV‐1 RNA (< vs ≥ 100,000 c/mL).
FLAIR: Long‐Acting CAB + RPV Maintenance After Oral DTG/ABC/3TC Induction
Primary Endpoint(HIV‐1 RNA ≥ 50 copies/mL)LA CAB + LA RPV noninferior
to DTG/ABC/3TC
No Virologic Data
Orkin. NEJM. 2020;382:1124.
ATLAS and FLAIR: Treatment‐Emergent Resistance With Long‐Acting CAB + RPV
101/483 patients had BL L74I in FLAIR: n = 64 from Russia, n = 60 with subtype A[3]
‒ Presence of this polymorphism did not negatively affect proportion achieving HIV‐1 RNA < 50 copies/mL at Wk 48
1. Swindells. CROI 2019. Abstr 139. 2. Orkin. CROI 2019. Abstr 140LB. 3. Overton. IAS 2019. Abstr MOPEB257. Slide credit: clinicaloptions.com
Study Sex Country HIV‐1 Subtype
Wk of Failure
NNRTI RAMs INSTI RAMs*
Baseline Failure Baseline Failure
ATLAS[1]F Russia A/A1 8 E138E/A E138A L74I L74I
F France AG 12 V108V/I, E138K V108I, E138K None None
M Russia A/A1 20 None E138E/K L74I L74I, N155H
FLAIR[2]F Russia A1 20 None E138E/A/K/T L74I L74I, Q148R
M Russia A1 28 None K101E L74I L74I, G140R
F Russia A1 48 None E138K L74I L74I, Q148R*L74I not considered an INSTI RAM by IAS‐USA guidance; not expected to affect CAB sensitivity.
ATLAS and FLAIR: Patient‐Reported Preference for Drug Delivery in Patients Receiving Long‐Acting CAB + RPV
1. Swindells. CROI 2019. Abstr 139. 2. Swindells. NEJM. 2020;382:1112. 3. Orkin. CROI 2019. Abstr 140LB. 4. Orkin. NEJM. 2020;382:1124. Slide credit: clinicaloptions.com
*Per single question in Wk 48 participant survey.
Study PopulationPreferred Regimen,* % (n/N)
Long‐Acting IM Daily PO
ATLAS[1,2] ITT‐E 86 (266/308) 2 (7/308) Responding participants 97 (266/273) ‐‐
FLAIR[3.4] ITT‐E 91 (257/283) 1 (2/283) Responding participants 99 (257/259) ‐‐
Long‐Acting CAB + RPV Approved by FDA January 21, 2021 FDA indication:
‒ As complete regimen for HIV‐1 infection treatment switch 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 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 injections every mo thereafter
https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/212888s000lbl.pdf. Slide credit: clinicaloptions.com
Assessment 1: According to the FDA prescribing information, in which of the following patients is LA CAB + RPV indicated?
A. Treatment‐naive or virologically suppressed
B. Treatment naive only
C. Virologically suppressed only
D. Current virologic failure
E. Unsure
JB [2]95
Questions to Consider
Which of your patients will be good candidates for this novel treatment?
How would you counsel them about the pros and cons?
What concerns do you have?
Case Report: Acute Hepatitis B in a Patient on CAB/RPV
31‐yr‐old MSM diagnosed with HIV 11/16; started induction ART in 2/17 with DTG, 3TC, and ABC in FLAIR study; no markers of prior HBV infection, no history of HBV vaccination at screening
‒ 4/17: HIV‐1 plasma viral load undetectable
9/17: randomized to 4‐wk oral CAB/RPV, followed by monthly LA CAB/RPV injection
HBV vaccine and HAV vaccine: 7/17, 8/17, 4/18; treated 12/16 and 4/18 for syphilis, urethral and anal chlamydia, and shigellosis
6/18: increased AST (78 IU/L) and ALT (162 IU/L); continued increase in ALT to 594 IU/L
‒ Diagnosis acute HBV infection: HBsAg+, HBsAb‐, HBc IgM+, HBeAg+, HBeAb‐, high HBV DNA level of 229,000,000 IU/mL (8.36 log10)
Retrospective testing of 1/18 serum found no detectable anti‐HBsAb
7/18: switched to TDF,FTC, and DTG; after 3 mos, normal ALT, decreased HBV DNA level to 170 IU/mL (2.23 log10)
Slide credit: clinicaloptions.comPintado. Open Forum Infect Dis. 2020;7:ofaa367.
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)
Logistic regression model (10 covariates)
Factors associated with increased odds of confirmed virologic failure:‒ Rilpirivine RAMs at baseline: OR 37.2 (P < .001)
‒ Log2 of post‐hoc Wk 8 rilpirivine trough concentration: OR 4.2 (P = .004)
‒ Baseline HIV‐1 subtype A1/A6: OR 6.6 (P = .005)
‒ BMI ≥ 30 kg/m2 at baseline: OR 1.1 (P = .001)
Q8W dosing was not a significant factor
Slide credit: clinicaloptions.comMargolis. J Int AIDS Soc. 2020;23(suppl 7):17.
Baseline Factors
Confirmed Virologic Failure (%)
HIV‐1 RNA < 50 Copies/mL (%)
None 0.4 951 0.4 96≤ 2 26 71Total 1.3 94
“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
Slide credit: clinicaloptions.comD’Amico. J Int AIDS Soc. 2020;23(suppl 7):15.
Patie
nts (%)
99.193.4
0.9 0.8 05.8
Virologic Outcomes at Wk 124 Following Switch to CAB/RPV at Wk 100
No lead‐inLead‐in
Virologic Nonresponse
Virologic Suppression
No Virologic Data
100
80
40
60
20
0
Questions for Discussion
Would you still consider injectable CAB/RPV for the case patient if …
‒ He had a history of treatment interruptions?
‒ He had transmitted K103N (resistance to efavirenz)?
‒ This was a woman of childbearing potential?
‒ This was a time with a COVID‐19 surge?
‒ If he was a frequent traveler who spent wks at a time out of the country?
‒ He was not HBV immune?
Switching ART to Avoid Comorbidities
Patient Case 2: Background
66‐yr‐old woman diagnosed with HIV in 2008 when her husband was hospitalized with PJP
Her initial CD4+ cell count was 480 cells/mm3, HIV‐1 RNA 67,000 copies/mL, with no transmitted resistance
Started EFV/FTC/TDF, later switched to ATV/RTV + FTC/TDF because of CNS adverse effects
Ended up on DRV/RTV + FTC/TDF because she needed to take acid‐reducing medication for reflux
Switched to single pill DRV/COBI/FTC/TAF in 2019, which she tolerates well
Additional medical history
‒ HTN
‒ Type 2 DM
‒ Renal impairment (eGFR 45 mL/min/1.73m2)
‒ Obesity
Current other medications: atorvastatin, amlodipine, valsartan, metformin, pantoprazole
Nonsmoker
Strong family history of cardiac disease
Slide credit: clinicaloptions.com
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 Must be HLA‐B*5701 negative if considering ABC 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 Guidelines. December 2019. Slide credit: clinicaloptions.com
Reasons to Consider an ART Switch During Viral SuppressionAppropriate
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
Slide credit: clinicaloptions.comDHHS Guidelines. December 2019.
Data Collection on Adverse Events of Anti‐HIV Drugs (D:A:D) Study: DRV Associated With Increased CVD Risk Prospective, multinational analysis
previously showed that longer, cumulative use of older PIs IDV and LPV/RTV associated with CVD risk[1]
Adequate data available for 35,711 participants; during mean follow‐up of ~ 7 yrs, 1157 developed CVD[1]
‒ 379 stroke
‒ 454 type 1 myocardial infarction
‒ 459 angioplasty
‒ 93 bypass
‒ 15 endarterectomy
‒ 0 sudden cardiac deaths
*After adjustment for potential confounders.
Slide credit: clinicaloptions.com1. Ryom. Lancet HIV. 2018;5:e291. 2. Saag. JAMA. 2020;324:1651.
Cumulative use of RTV‐boosted DRV, but not RTV‐boosted ATV, was independently associated with small, but progressively increasing risk of CVD events[1]
IAS‐USA ART guidelines recommend switching from ABC‐based or PI‐containing regimens (except ATV) in patients with or at high for CVD event[2]
Regimen[1] Incidence Rate Ratio/5 Yrs* (95% CI)
RTV‐boosted DRV 1.59 (1.33‐1.91)
RTV‐boosted ATV 1.03 (0.90‐1.18)
Poll 6: What would you recommend for the case patient’s ART regimen?A. Continue DRV/COBI/FTC/TAF
B. Switch to BIC/FTC/TAF
C. Switch to DTG/3TC
D. Switch to DTG/RPV
E. Switch to long‐acting injectable CAB and RPV
F. Something else
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. IAS 2019. Abstr MOAB0105. 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 permitted.
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 atConfirmed 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
Slide credit: clinicaloptions.com
*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.
Comorbidity, n (%)Treatment Experienced
Suppressed (n = 671)
Not Suppressed (n = 197)
Any 587 (87.5) 159 (80.7)
Autoimmune disease 29 (4.3) 8 (4.1)
Cardiovascular disease 89 (13.3) 20 (10.2)
Invasive cancer 80 (11.9) 15 (7.6)
Endocrine disorder 422 (62.9) 94 (47.7)
Mental health disorder 232 (34.6) 58 (29.4)
Liver disease 115 (17.1) 40 (20.3)
Bone disorder 52 (7.7) 17 (8.6)
Peripheral neuropathy 83 (12.4) 27 (13.7)
Renal disease 198 (29.5) 51 (25.9)
Hypertension 290 (43.2) 77 (39.1)
Substance use 92 (13.7) 31 (15.7)
Real‐World Experience With DTG/RPV in the United States Retrospective analysis of clinical characteristics and
outcomes in PWH switching to DTG/RPV between Jan 2018 and Dec 2018 in OPERA study (N = 880)
BL characteristics: 68% had CD4+ cell count > 500 cells/mm3, 63% initiated ART after 2013
88% remained on drug at 12 mos, virologic failure occurred in 1.5%; of 42 patients who discontinued, 41% were virologically suppressed
Pierone. IDWeek 2019. Abstr 2483. Slide credit: clinicaloptions.com
Region (South)
Age (50+)
Risk Factor (MSM)
Race (Black)
Ethnicity (Hispanic)
Sex (Female)
0 10 20 30 40 50 60 70 80 90 100
Baseline Demographics of Patients Switching to DTG/RPV (N = 880)DTG/RPV switchOverall OPERA population
63%57%
54%38%
35%60%
35%44%
28%25%
18%17%
Rilpivirine and Acid‐reducing Therapies
Agent Effect on RPV Concentration Clinical Comment
Antacids: aluminum or magnesium hydroxide, calcium carbonate
No change if antacid taken ≥ 2 hrsbefore RPV or ≥ 4 hrs after RPV
Use antacid + RPV with caution; may cause decreases in RPV plasma
concentration
H2‐receptor antagonists: cimetidine, famotidine*, nizatidine, ranitidine
No change if famotidine taken ≥ 12 hrs before RPV or ≥ 4 hrs after RPV; decreased RPV if famotidine taken
2 hrs before RPV
Use H2‐receptor antagonists + RPV with caution; may cause decreases
in RPV plasma concentration
Proton pump inhibitors: esomeprazole, lansoprazole, omeprazole, pantoprazole, rabeprazole
Decreases in RPVplasma concentrations may occur
due to gastric pH increase
Do not coadminister proton pump inhibitors with RPV
1. Rilpivirine PI. 2. Crauwels. J Int AIDS Soc. 2008;11(Suppl1:239). Slide credit: clinicaloptions.com
*RPV‐famotidine interaction assessed in a clinical study.[2]
Switch from Boosted PIs to BIC/FTC/TAF
Daar. Lancet HIV. 2018;5:e347.
Multicenter, randomized, open‐label, active‐controlled, phase III noninferiority trial
BIC/FTC/TAF(n = 290)
Continue Baseline Boosted PI (n = 287)
Adults with HIV‐1 infection with eGFR ≥ 50 mL, plasma HIV‐1
RNA < 50 copies/mL ≥ 6 mos; on regimen of boosted PI* (N = 578; 1 randomized participant
was not treated)*ATV or DRV + FTC/TDF or 3TC/ABC.
Wk 48 Primary Endpoint
Slide credit: clinicaloptions.com
Primary endpoint: HIV‐1 RNA ≥ 50 copies/mL at Wk 48 by FDA snapshot algorithm with 4% prespecified noninferiority margin
HIV‐1 RNA ≥ 50 copies/mL at Wk 48: 2% with BIC/FTC/TAF or continued boosted PI
Stratified by use of TDF or ABC at screening
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
Slide credit: clinicaloptions.com
0.5
Patie
nts (%)
100
80
40
60
20
0 HIV‐1 RNA ≥ 50 c/mL
HIV‐1 RNA < 50 c/mL
No Virologic Data
0.3
93.293.0
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% NImargin
TAF‐Based ARTDTG/3TC
TAF‐Based ART DTG/3TC
‐1.2 0.7
‐0.3
‐8 ‐6 ‐4 ‐2 0 2 4 6 8
4% NImargin
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
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‒ When stratified by previous use of boosting agents, statistically favorable changes with
DTG/3TC vs TAF‐based ART persisted in boosted subgroup
TANGO: Lipid Changes at Wk 48
Slide credit: clinicaloptions.comvan Wyk. Clin Infect Dis. 2020;71:1920. van Wyk. AIDS 2020. Abstr OAB0606.
Change From BL to Wk 48, %
Overall Boosted Subgroup Unboosted Subgroup
DTG/3TC (n = 275)
TAF‐Based ART (n = 263)
PValue
DTG/3TC (n = 202)
TAF‐Based ART (n = 203)
PValue
DTG/3TC (n = 97)
TAF‐Based ART (n = 94)
PValue
Total cholesterol ‐4.5 2.3 < .001 ‐5.7 2.2 < .001 ‐0.8 2.0 ‐‐
HDL ‐1.2 1.7 ‐‐ ‐0.8 1.02 ‐‐ ‐2.3 0.1 ‐‐
LDL ‐5.5 2.2 < .001 ‐6.6 2.9 < .001 ‐2.0 ‐0.3 ‐‐
Triglycerides ‐11.2 6.0 < .001 ‐14.1 4.0 < .001 ‐1.6 12.2 ‐‐
TC:HDL ratio ‐3.3 0.5 .017 ‐4.8 0.1 .007 1.4 1.8 ‐‐
TANGO: HbA1c, Fasting Glucose, and Fasting Insulin Changes at Wk 48 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
Slide credit: clinicaloptions.comvan Wyk. AIDS 2020. Abstr OAB0606.
Metabolic Parameter, % DTG/3TC TAF‐Based ARTMedian change from BL in A1C 5.3 5.4Adjusted mean change from BL in fasting glucose* Boosted baseline regimen Unboosted baseline regimen
2.3‐0.2
3.82.1
Adjusted mean change from BL in fasting insulin† Boosted baseline regimen Unboosted baseline regimen
‐11.70.9
‐7.25.1
*DTG/3TC (boosted, n = 222; unboosted, n = 82); TAF‐based ART (boosted, n = 221; unboosted, n = 60).†DTG/3TC (boosted, n = 222; unboosted, n = 83); TAF‐based ART (boosted, n = 218; unboosted, n = 61).
Poll 7: If you switch this patient’s ART regimen to DTG/3TC, would you expect her to lose weight?A. Yes
B. No
C. Not sure
TANGO: Weight Change at Wk 48
Overall weight gains minimal, comparable between treatment arms
Slide credit: clinicaloptions.comvan 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.
The Do IT Study: Doravirine in PWH With Significant Weight Gain on INSTIs + TAF ACTG 5391: randomized, open‐label phase IV trial
Primary endpoint: Differences in weight change over 48 wks
Secondary endpoints: metabolic outcomes, viral load, safety
Overweight/obese (BMI ≥ 27.5 kg/m2) patients on RAL, DTG, or BIC + FTC/TAF (or 3TC/TAF) withunintentional > 10% weight gain
over prior 1‐3 yrs(N = 222) Continuation of entry INSTI + FTC/TAF (or
3TC/TAF)
Wk 48
DOR 100 mg QD +FTC/TAF (or 3TC/TAF)
DOR 100 mg QD +FTC/TDF (or 3TC/TDF)
NCT04636437. Slide credit: clinicaloptions.com
The DEFINE Study: Switch to D/C/F/TAF in PWH With Rapid Weight Gain on INSTI Randomized, open‐label, phase IV trial
Primary endpoint: Percent change from baseline in body weight at Week 24
Secondary endpoints: metabolic outcomes, viral load, safety, antiretroviral resistance, adherence
PWH on INSTI + FTC/TAF with rapid and significant body
weight gain(N = 110)
Wk 48
Darunavir 800 mg/cobicistat 150 mg /emtricitabine 200 mg/tenofovir alafenamide
10 mg (D/C/F/TAF)
D/C/F/TAFContinuation of entry INSTI + FTC/TAF
Wk 24
NCT04442737.
Safety of Full‐Dose Lamivudine in Patients with eGFR < 50 mL/min* Primary end points: mean model‐simulated 3TC AUC (0–24 hr) and mean observed 3TC
concentrations predose (Cmin) and 0.5‐1.5 hours postdose (Cmax)
Observed 3TC Cmax values comparable across CrCl cohorts; simulated 3TC AUC values in participants with impaired renal function consistent with historical data
Lactic acid levels all within normal limits; no adverse effects
Men and nonpregnant, nonlactating women age
≥ 18 yrs with HIV receiving 3TC for ≥ 3 mos
(N = 34)
CrCl > 50 mL/min; 3TC 300 mg daily(n = 5)
CrCl 30‐49 mL/min; 3TC 300 mg daily (n = 16)
Stratified by renal function
CrCl 15‐29 mL/min; 3TC 150 mg daily(n = 4; 1 on dialysis)
Hemodialysis; 3TC 100 mg or 150 mg daily(n = 10)
Slide credit: clinicaloptions.com*As of March 2021, DTG/3TC is indicated for patients with eGFR < 30 mL/min Fischetti. Open Forum Infect Dis. 2018;5:ofy225.
Outcomes Case
You are providing care for a patient with long‐term virologic suppression on first‐line EFV/FTC/TDF who would like to switch to another single‐tablet ART regimen because of neuropsychiatric adverse effects
The patient is at high risk for CVD events and is also receiving a proton pump inhibitor for management of GERD
Assessment 2: If following current guidelines, which of the following regimens would you recommend as a switch option for this patient?
A. DTG/3TC or BIC/FTC/TAF
B. DTG/ABC/3TC
C. DRV/COBI/FTC/TAF
D. RPV/FTC/TAF or RPV/FTC/TDF
E. Unsure
JB [2]96
Simplifying ART in the Context of Known Multidrug Resistance
Patient Case 3: Background
60‐yr‐old man diagnosed with HIV in 1990 when he experienced weight loss, thrush, and dysphagia
Treated with fluconazole and improved rapidly; no HIV‐related complications since then
Initial CD4+ cell count: 110 cells/mm3
Treated with NRTIs (ZDV, ddI, d4T, 3TC) until 1996, when he began various combination regimens that included “recycled” NRTIs plus unboosted PIs (SQV, IDV) and NNRTIs (NVP, EFV)
Never consistently achieved viral suppression
HIV genotype in 2007 while receivingLPV/RTV + ABC/3TC (HIV‐1 RNA: 1200 c/mL; CD4+ cell count: 300 cells/ mm3)
‒ NRTI: M184V, L74V (resistance to 3TC, FTC, ABC)
‒ NNRTI: K103N (resistance to EFV, NVP)
‒ PI: D30N, L90M (resistance to NFV, SQV)
Placed on new regimen of DRV/RTV twice daily + RAL twice daily + etravirine twice daily
Viral suppression since then (2007)
Asks if he can take a simpler regimenSlide credit: clinicaloptions.com
Poll 8: How would you manage this patient’s ART regimen?A. Continue current therapy (4 pills twice daily)
B. Switch to once daily DRV/COBI + DTG + DOR (3 pills once daily)
C. Switch to DRV/COBI/FTC/TAF (1 pill once daily)
D. Switch to BIC/FTC/TAF (1 pill once daily)
E. Switch to long‐acting CAB and RPV (2 injections once a month)
F. Something else
Reasons to Consider an ART Switch During Viral SuppressionAppropriate
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
Slide credit: clinicaloptions.comDHHS Guidelines. December 2019.
DHHS: Switching Regimens in Patients With Viral Suppression and Drug Resistance “Patients with prior drug resistance can be switched to a new regimen based
on their ARV history and resistance testing results”
Some data on within‐class switch from 1 high resistance barrier drug to another (DTG BIC): Study 380‐4030
No direct data on between‐class switch from 1 high resistance barrier drug to another (boosted PI to a BIC or DTG‐containing regimen + fully active NRTI)
‒ Theoretical support from Study 380‐4030
‒ Indirectly supported by superior efficacy of DTG compared with boosted PI in patients with first‐line failure and resistance: DAWNING study
DHHS ART Guidelines. December 2019. Slide credit: clinicaloptions.com
Outcomes Case
You are providing care for a patient with a history of drug resistance (M184V and K103N) who is currently virologically suppressed on a 4‐pill twice daily ART regimen
The patient would like to switch to a simpler regimen with fewer pills
Assessment 3: Based on current DHHS guidelines, how would you counsel this patient?
A. Patients with a history of drug resistance should avoid switching ART except in cases of severe toxicity with the current regimen
B. Switching to a new regimen is recommended only if they are experiencing adverse events (any grade) with their current regimen
C. Switching to a new regimen should be feasible with consideration of their ARV history and resistance testing results
D. Unsure
JB [2]96
Between Class Switching With Underlying Resistance
SWITCHMRK results warned of switching from high barrier to low barrier resistance drug in patients with underlying resistance[1]
Viral suppression can be maintained by boosted PIs and high resistance barrier INSTIs (DTG and BIC) when only 1 accompanying NRTI is fully active, unlike lower resistance barrier drugs (eg, EVG, RAL, NNRTIs)[2]
Switching 1 low barrier drug for another is effective in those with multidrug resistance (eg, EVG for RAL as with switch to DRV + EVG/COBI/FTC/TAF)[3]
What about boosted PI to high barrier INSTI switch with underlying resistance?
1. Eron. Lancet. 2010;375:396. 2. DHHS ART Guidelines. December 2019. 3. Huhn. JAIDS. 2017;74:193. Slide credit: clinicaloptions.com
SWITCHMRK: A Cautionary Tale of Between Class Switches Randomized, double‐blind trials in which virologically suppressed patients continued
LPV/RTV‐based regimen or switched to RAL‐based regimen (N = 702)
Underlying resistance matters: % with HIV‐1 RNA < 50 c/mL for RAL vs LPV/RTV by investigator report of previous virologic failure: no, 89% vs 90%; yes, 77% vs 92%
Switch to RALContinue LPV/RTV
50
60
70
80
90
100
0 4Wks
HIV‐1 RNA < 50
c/m
L (%
)
8 12 24
87%
81%
∆: ‐6.6 (95% CI: ‐14.4 to 1.2)*
SWITCHMRK‐1 94%
88%
*Prespecified noninferiority margin: ‐12%.
Slide credit: clinicaloptions.comEron. Lancet. 2010;375:396.
50
60
70
80
90
100
0 4Wks
HIV‐1 RNA < 50
c/m
L (%
)8 12 24
∆:‐5.8 (95% CI: ‐12.2 to 0.2)*
SWITCHMRK‐2
Evidence of High Resistance Barrier With DTG and BIC
No emergent resistance with virologic failure in either treatment naive or switch studies of DTG or BIC plus 2 NRTIs[1]
Rare reports of emergent resistance in clinical practice or with DTG plus 3TC[2]
DTG superior to RAL and LPV/RTV in treatment‐experienced patients with resistance[1,3]
BIC/FTC/TAF noninferior to DTG + FTC/TAF or FTC/TDF in suppressed patients with NRTI resistance[4,5]
1. Cahn. Lancet. 2013;382:700. 2. Mahomed. South Afr J HIV Med. 2020;21:1062. 3. Aboud. Lancet Infect Dis. 2019;19:253. 4. Acosta. CROI 2019. Abstr 0551. 5. Hagins. CROI 2020. Abstr 36. Slide credit: clinicaloptions.com
DAWNING: Virologic Response at Wk 48
Patients with VF on first‐line NNRTI + 2 NRTIs switched to DTG or LPV/RPV + 2 NRTIs (≥ 1 fully active NRTI per GT resistance testing at screening); no primary resistance to INSTIs or PIs Emergent INSTI and INSTI + NRTI
resistance at CVW with DTG: n = 2
Emergent NRTI resistance but no PI resistance at CVW with LPV/RTV: n = 3
1. Aboud. Lancet HIV. 2019;6(9):e576‐e587. Slide credit: clinicaloptions.com
DTG + 2 NRTIsLPV/RTV + 2 NRTIs
*P < .0001 for superiority.
HIV‐1 RNA < 50
c/m
L(%
)[1]
ITT‐E PP
219/312
84
70
261/312
219/312
246/283
204/274
87
74
100
80
60
40
20
0n/N =
Δ 13.8*(7.3‐20.3)
Δ 12.3(5.8‐18.7)
DTG Arm BL At VF
Patient 1 RT: K70E, M184V
RT: M184V;INSTI: H51H/Y, G118R; E138E/K: R263K
Patient 2 RT: M184V, K219K/E
RT: D67N,* M184V;INSTI: G118R
*Did not confer resistance to either NRTI taken during trial.
DAWNING: Virologic Response by Presence of M184V/I and Use of 3TC or FTC at Wk 48
Slide credit: clinicaloptions.comBrown. CROI 2019. Abstr 144.
DTG + 2 NRTIsLPV/RTV + 2 NRTIs
Virologic Outcomes (ITT‐E)
219/312
85
72
187/220
152/210
33/41
30/42
8071
HIV‐1 RNA < 50
c/m
L(%
)
100
80
60
40
20
0n/N =
Use of3TC or FTC
No use of3TC or FTC
12.6 Δ 9.1
41/51
37/60
Δ 18.7
80
62
No M184V/I
M184V/I Other NRTI Mutations
Study 380‐4030: Switch to BIC/FTC/TAF From DTG + FTC/(TAF or TDF) Randomized, double‐blind, active‐controlled phase III noninferiority trial
Sax. Clin Infect Dis. 2020;[Epub]. Slide credit: clinicaloptions.com
Adults receiving DTG + FTC/(TAF or TDF) with HIV‐1 RNA < 50 copies/mL for ≥ 3‐6 mos,* no known
INSTI resistance,† and no previous VF on INSTI(N = 565)
BIC/FTC/TAF QD(n = 284)
DTG + FTC/TAF QD(n = 281)
Wk 48
*3 mos if no known NRTI resistance mutations, 6 mos with known/suspected resistance. †Documented or suspected NRTI, NNRTI, or PI resistance permitted.
Stratified by known/suspected NRTI resistance at BL (K65R or ≥ 3 TAMS vs other NRTI RAMs vs none)
Primary endpoint: HIV‐1 RNA ≥ 50 c/mL at Wk 48 by FDA Snapshot algorithm
‒ Noninferiority margin: 4%
Study 380‐4030: Virologic Outcomes at Wk 48
Patients with viral suppression on stable triple DTG‐based ART switched to BIC/FTC/TAF or continued DTG‐based ART; documented or suspected NRTI, NNRTI, or PI resistance permitted‒ Preexisting NRTI resistance: 25% in BIC/FTC/TAF arm and 24% in DTG‐based ART arm
Sax. Clin Infect Dis. 2020;[Epub].
HIV‐1 RNA< 50 c/mL
HIV‐1 RNA≥ 50 c/mL
No VirologicData
1/284
3/281
265/284
256/281
22/281
18/284
Virologic Outcomes (FDA Snapshot)
BIC/FTC/TAF (n = 284)DTG + FTC/TAF (n = 281)
Patie
nts (%)
n/N =
100
80
40
60
20
0< 1 1
93 91
6 8
‐4 ‐2 0 2 4
Favors DTG + FTC/TAFFavors BIC/FTC/TAF
‐0.71.0‐2.8
HIV‐1 RNA ≥ 50 copies/mLTreatment Difference, % (95% CI)
Slide credit: clinicaloptions.com
Study 380‐4030: Viral Suppression After Switch From DTG to BIC by Baseline NRTI Resistance HIV‐1 RNA ≥ 50 c/mL not observed in any patient with preexisting NRTI resistance
Sax. Clin Infect Dis. 2020;[Epub]. Slide credit: clinicaloptions.com
Virologic Outcomes at Wk 48 (FDA Snapshot) BIC/FTC/TAF (n = 284)DTG + FTC/TAF (n = 281)
100
80
60
40
20
0Overall K65R or ≥ 3 TAMs Other NRTI Resist. No NRTI Resist. No M184V/I M184VI ± Other
Resist.
91 8694 93
87 87 9185
91 86 87 85
Data suggest switching 1 high‐resistance barrier drug for another may be effective in patients with viral suppression, even in the setting of underlying resistance
HIV‐1 RNA < 20
c/m
L(%
)
257/284
241/281n/N =
15/16
13/14
48/55
46/53
194/213
182/214
216/237
212/247
41/47
29/34
BRAAVE 2020: Impact of BL Resistance on Outcomes Following Switch to BIC/FTC/TAF in Black PLWH 2:1 randomized, open‐label, active‐controlled
phase III study
Evaluated switch from BL regimen (2 NRTIs + third agent) to BIC/FTC/TAF in virologically suppressed black PLWH (N = 495)
Switch to BIC/FTC/TAF noninferior to remaining on BL regimen at Wk 24‒ Wk 24 was primary efficacy endpoint
Patients with BL NRTI resistance remained suppressed at Wk 24
Hagins. CROI 2020. Abstr 36. Slide credit: clinicaloptions.com
BL ARV Resistance, %
BIC/FTC/TAF(n = 330)
Continue BL Regimen(n = 165)
NRTI M184V/I
139
1612
NNRTI 21 19PI 11 15
Wk 24 Virologic Outcomes
HIV‐1 RNA < 50
c/m
L (%
) 100
80
40
60
20
0YesNRTI Resistance
98 96
BIC/FTC/TAFBL regimen
No YesM184V or M184I
No
96 95 97 95 96 95
n = 44 26 269 132 31 20 282 138
99 98 99 100 100
Series 1
Switching to BIC/FTC/TAF in Patients With HIV and Pre‐Existing M184V/I Pooled analysis of 6 phase III studies:
N = 2034
‒ Viral suppression at baseline
‒ M184V/I detected in 10%
HIV‐1 RNA < 50 copies/mL at last visit post‐switch
‒ All patients: 99%
‒ With vs without M184V/I: 99% vs 98%
‒ No treatment‐emergent resistance
Patie
nts (%)
HIV‐1 RNA < 50 Copies/mL at Last Visit
M184V/I*Patients with baseline data.
Andreatta. J Int AIDS Soc. 2020;23(suppl 7):105. Slide credit: clinicaloptions.com
All Patients* (n = 1825)
100
80
40
60
20
0All
(n = 182)+NNRTI‐R (n = 97)
+PI‐R (n = 58)
+INSTI‐R (n = 4)
Poll 9: If you did not have historical genotype data for this patient, would you order a proviral HIV genotype?A. Yes
B. No
C. Not sure
Proviral HIV DNA Genotype: Acquiring Resistance Data
DNA (archive) genotype[1,2]
‒ Sequences mutations in cell‐associated proviral DNA
‒ Can be assessed at any HIV‐1 RNA level, including undetectable
‒ Less sensitive than cumulative RNA genotypes
Concordance between DNA and RNA genotypes varies by study and ARV class (26% to 84%)[2,3]
Study 1824: switch to EVG/COBI/FTC/TAF among virologically suppressed patients with M184V/I mutation on RNA assay[4]
‒ M184V/I detected with DNA assay in only 48% (40/84) of screened patients
1. Delaugerre. HIV Med. 2012;13:517. 2. Wirden. J Antimicrob Chemother. 2011;66:709. 3. Derache. PLoS One. 2015;10:e0117430. 4. Margot. IAS 2019. Abstr MOPEB249. Slide credit: clinicaloptions.com
DHHS Guidelines: Recommendations on Proviral DNA Genotyping Proviral DNA genotyping can be considered for individuals with a suppressed viral load, particularly if complex or semi‐complex preexisting resistance is suspected
Results should be interpreted with caution; proviral genotyping may miss some or all preexisting mutations
“… for individuals who have experienced multiple prior failures, a prolonged history of prior ARV regimens, and/or for whom genotypic resistance test results are not available, it
may be appropriate to utilize proviral DNA genotypic testing.”
Slide credit: clinicaloptions.comDHHS Guidelines. December 2019.
Review of Our 3 Cases and Proposed Switch Strategies
Switching ART in a Patient With Daily Pill Fatigue
‒ Optimal switch: Long‐acting injectable CAB and RPV, monthly
‒ Need to monitor adherence, vaccinate against hepatitis B
Switching ART to Avoid Comorbidities
‒ Optimal switch: DTG/3TC, one pill daily
‒ Not approved for eGFR < 50 mL/min, but likely safe
Simplifying ART in the Context of Known Multidrug Resistance
‒ Optimal switch: BIC/FTC/TAF, one pill daily
‒ Limited data on use of this strategy with multiclass resistance, but encouraging data from switches with active TAF and BIC
Slide credit: clinicaloptions.com
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