Современное лечение ВИЧ: индивидуализация стартовой АРТ /Contemporary Management of HIV: Individualizing First-line ART (2021)

Contemporary Management of HIV:
Individualizing First-line ART
Supported by an educational grant from ViiV Healthcare.

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Core Faculty
Daniel R. Kuritzkes, MD
Harriet Ryan Albee Professor of Medicine
Harvard Medical School
Chief, Division of Infectious Diseases
Brigham and Women’s Hospital
Boston, Massachusetts

Program Directors
Joseph J. Eron, Jr., MD
Professor of Medicine and
Epidemiology
University of North Carolina
School of Medicine
Director, AIDS Clinical Trials Unit
University of North Carolina
Chapel Hill, North Carolina
Princy N. Kumar, MD, FIDSA,
MACP
Professor of Medicine and
Microbiology
Chief, Division of Infectious Diseases
and Travel Medicine
Senior Associate Dean of Students
Georgetown University School of
Medicine
Washington, DC

Faculty Disclosures
Daniel R. Kuritzkes, MD, has reported that he has received funds for
research support from Atea, Gilead Sciences, Merck, Novartis, and ViiV
Healthcare and consulting fees from Abpro, Atea, Decoy, Gilead Sciences,
GlaxoSmithKline, Merck, Rigel, and ViiV Healthcare.

Faculty Disclosures
Joseph J. Eron, Jr., MD, has disclosed that he has received consulting fees
from Gilead Sciences, Janssen, Merck, and ViiV Healthcare and funds for
research support from Gilead Sciences, Janssen, and ViiV Healthcare.
Princy N. Kumar, MD, FIDSA, MACP, has disclosed that she has received
consulting fees from Amgen, Gilead Sciences, GlaxoSmithKline, Merck,
and Theratechnologies; has received funds for research support from
Gilead Sciences, GlaxoSmithKline, Merck, and Theratechnologies; and has
ownership interest in Gilead Sciences, GlaxoSmithKline, Johnson &
Johnson, Merck, and Pfizer.

Program Overview
 Program Overview
 Case-Based Discussion
‒ Initiating ART in a newly diagnosed MSM
‒ Initiating ART in a newly diagnosed woman trying to conceive
‒ Initiating ART in a newly diagnosed person who is overweight with active
hepatitis B infection
 Question and Answer Session

Case 1: Man Newly Diagnosed With HIV

Patient Case: Newly Diagnosed MSM
 23-yr-old MSM newly diagnosed
with HIV infection
‒ Discontinued use of FTC/TDF
PrEP 4 yrs ago
 Wants a single-tablet regimen
Parameter Result
CD4+ cell count, cells/mm3 340
HIV-1 RNA, copies/mL 67,000
HBV status Immune
HCV status Negative
HLA-B*5701 status Positive
BMI, kg/m2 21
HIV resistance genotype No RAMs
ALT, U/L 14
AST, U/L 12
Other labs Normal

DHHS, IAS-USA Guidelines:
Recommended First-line ART Regimens for Most PWH
DHHS[1] IAS-USA[2]
Recommended (rating AI, unless otherwise
specified) initial regimens for most PWH:
 BIC/FTC/TAF
 DTG/3TC/ABC if HLA-B*5701 negative
 DTG + (FTC or 3TC) + (TAF or TDF)
 DTG/3TC†
 RAL + (FTC or 3TC) + (TAF or TDF)
Recommended (rating A1a) initial regimens
for most PWH:
 BIC/FTC/TAF
 DTG + FTC/(TAF or TDF)
 DTG + 3TC/TDF
 DTG/3TC†‡
1. DHHS Guidelines. December 2019. 2. Saag. JAMA. 2020; 324:1651.
†Except for individuals with baseline HIV-1 RNA > 500,000 copies/mL, with HBV, or for whom results of HIV genotypic resistance testing or HBV
testing are not yet available. ‡Possibly not suitable for individuals with baseline CD4+ cell count < 200 cells/mm3.

Clinical Studies of Recommended First-line INSTIs
 Rates of discontinuation for AEs numerically lower with INSTIs vs PIs or NNRTIs and no BIC
or DTG resistance detected in these trials
Trial INSTI Regimen Comparator Wks Outcome vs Comparator
GS-1489[1] BIC/FTC/TAF DTG/3TC/ABC 96 Noninferior
GS-1490[2] BIC/FTC/TAF DTG + FTC/TAF 96 Noninferior
SINGLE[3] DTG + 3TC/ABC EFV/FTC/TDF 144 Favors INSTI
FLAMINGO[4] DTG + 2 NRTIs DRV + RTV + 2 NRTIs 96 Favors INSTI
SPRING-2[5] DTG + 2 NRTIs RAL + 2 NRTIs 96 Noninferior
ARIA[6] DTG/3TC/ABC ATV + RTV + FTC/TDF 48 Favors INSTI
GEMINI-1/2[7] DTG + 3TC DTG + FTC/TDF 96 Noninferior
ACTG A5257[8] RAL + FTC/TDF ATV or DRV + RTV + FTC/TDF 96 Favors INSTI
STARTMRK[9] RAL + FTC/TDF EFV + FTC/TDF 240 Favors INSTI
1. Wohl. Lancet HIV. 2019;6:e355.2. Stellbrink.Lancet HIV. 2019;6:e364. 3. Walmsley.JAIDS. 2015;70:515.
4. Molina. Lancet HIV. 2015;2:e127.5. Raffi.Lancet Infect Dis. 2013;13:927. 6. Orrell. Lancet HIV. 2017;4:e536.
7. Cahn. JAIDS. 2020;83:310. 8. Lennox. Ann Intern Med. 2014;161:461. 9. Rockstroh. JAIDS. 2013;63:77. Slide credit: clinicaloptions.com

Choosing Among Integrase Inhibitors for First-line ART
Agent[1,2] Advantages Disadvantages
Bictegravir
 STR once daily with FTC/TAF
 Few drug or food interactions
 High barrier to resistance
 Least amount of data
 Only available as an STR
 Limited safety data in pregnancy
Dolutegravir
 STR once daily with 3TC or 3TC/ABC
 Also available as a single agent (eg, can be
combined with other NRTIs)
 High barrier to resistance
 A preferred option for pregnant women in
every trimester[3]
 ABC coformulation requires HLA-B*5701
testing
 Increases metformin levels
 Limited safety data at conception[3]
Raltegravir
 Longest experience
 A preferred option for pregnant women
 Multiple pills (ie, no STR)
 Lower barrier to resistance than BIC or DTG
 Limited safety data at conception
1. DHHS ART Guidelines. December 2019. 2. Saag. JAMA. 2020; 324:1651. 3. DHHS Perinatal Guidelines. December 2020.

Single-Tablet Regimens Available for Initial ART
Class Agent Components Caveats[1]
INSTI
BIC/FTC/TAF INSTI + dual NRTI
DTG/3TC INSTI + single NRTI
Do not use if HIV-1 RNA > 500,000 c/mL,
HBV coinfection, or without resistance
testing results
DTG/3TC/ABC INSTI + dual NRTI Only if HLA-B*5701 negative
EVG/COBI/FTC/(TAF or TDF) Boosted INSTI + dual NRTI
NNRTI
DOR/3TC/TDF NNRTI + dual NRTI
EFV (400 or 600 mg)/3TC/TDF NNRTI + dual NRTI
EFV/FTC/TDF NNRTI + dual NRTI
RPV/FTC/(TAF or TDF) NNRTI + dual NRTI
Only if HIV-1 RNA < 100,000 c/mL and
CD4+ cell count > 200 cells/mm3
Boosted PI DRV/COBI/FTC/TAF Boosted PI + dual NRTI
1. DHHS Guidelines. December 2019. Slide credit: clinicaloptions.com

AMBER: DRV/COBI/FTC/TAF vs DRV/COBI + FTC/TDF in
Treatment-Naive Adults at Wk 96
 Virologic response at Wk 96 consistent
across subgroups
‒ BL VL >/≤ 100,000 copies/mL,
BL CD4+ ≥/< 200 cells/mm3,
age >/≤ 50 yrs, sex, race
 Resistance analysis in 9/15 patients with
PDVF with DRV/COBI/FTC/TAF vs 8/19 in
control arm through Wk 96
‒ 1 patient with M184V/I in each arm
‒ No evidence of emergent DRV, primary
PI, or TFV RAMs
4% 6%
4% 9%
DRV/COBI/FTC/TAF (n = 362)
Wk 48
3% 4%
8% 12%
DRV/COBI + FTC/TDF (n = 363)
Wk 48
Wk 96 Wk 96
HIV-1 RNA ≥ 50 c/mL
No virologic data
HIV-1
RNA
<
50
copies/mL
(%)
FDA Snapshot Analysis at Wks 48 and 96
91 85 84
0
20
40
60
80
100 88
Orkin. AIDS. 2020;34:707.
 Multicenter, randomized, double-blind, noninferiority
phase III trial in ART-naive adults over 48 wks
‒ Patients could continue on or switch to DRV/COBI/FTC/TAF
in an open-label extension phase until Wk 96

73.1
66.0
DRV + RTV
+ 2 NRTIs
(n = 383)
DOR
+ 2 NRTIs
(n = 383)
DOR/3TC/
TDF
(n = 364)
77.5 73.6
EFV/FTC/
TDF
(n = 364)
DOR + 2 NRTIs vs EFV or (DRV + RTV) + 2 NRTIs
in Treatment-Naive Adults
 Resistance analyses at Wk 96
‒ DRIVE-AHEAD:
1.6% with DOR-R vs 3.8%
with EFV-R; NRTI-R in 1.4%
vs 1.6%, respectively
‒ DRIVE-FORWARD:
DOR + NRTI resistance,
n = 2; NRTI resistance but no
PI resistance, n = 1; lipid
changes more favorable
with DOR vs DRV + RTV
HIV-1
RNA
<
50
copies/mL
at
Wk
96
(%)
0
20
40
60
80
100
1. Orkin. Clin Infect Dis. 2020;[Epub]. 2. Molina. Lancet HIV. 2020;7:e16.
DRIVE-AHEAD[1] DRIVE-FORWARD[2]
Treatmentdifference:
3.8% (95% CI: -2.4% to 10.0%)
Treatmentdifference:
7.1% (95% CI: 0.5% to 13.7%)

GEMINI-1 and -2: DTG + 3TC in ART-Naive Adults
 Parallel, international, randomized, double-blind phase III noninferiority studies in ART-naive adults
with HIV-1 RNA 1000-500,000 copies/mL
 DTG + 3TC met criteria for noninferior efficacy vs DTG + FTC/TDF at Wk 96; no treatment-emergent
resistance observed in patients with CVW
*Adjusted for BL HIV-1 RNA, BL CD4+ cell count, and study.
Endpoint, % (n)
DTG + 3TC
(n = 716)
DTG + FTC/TDF
(n = 717)
Difference,* %
(95% CI)
Responders 86.0 (616) 89.5 (642) -3.4 (-6.7 to 0)
HIV-1
RNA
<
50
copies/mL,
%
(95%
CI)
100
80
60
40
20
0
0 4 8 12 16 24 36 48 60 72 84 96
Wk
87.0
93.2 91.5 87.2 86.0
89.5
89.4
93.3
93.4
84.4
Cahn. JAIDS. 2020;83:310.

INSTI vs Boosted PIs as First-line ART:
Current Role of Boosted PIs
Settings where boosted PI
regimens might be considered[1]
 If starting ART before availability of
resistance data
 If high risk for poor adherence
Challenges with boosted PI use
 Drug–drug interactions[2,3]
 GI intolerance[2,3]
 Hyperlipidemia[3]
 CV risk with some PIs[4]
 ATV not part of fully coformulated
regimen
1. DHHS ART Guidelines. December 2019. 2. ATV PI. 3. DRV/COBI/FTC/TAFPI. 4. Worm. J Infect Dis. 2010;201:318. Slide credit: clinicaloptions.com

NNRTIs vs INSTIs as First-line ART:
Possible Role of NNRTIs Today
Possible role for NNRTIs[1]
 Patient experiencing adverse event(s)
with INSTIs
 In women desiring pregnancy
 If patient is experiencing weight gain
with INSTIs[2]
Challenges with NNRTI use
 Low barrier to resistance at VF with EFV,
RPV[3,4]
 Neuropsychiatric AEs with EFV[3]
 Higher rates of VF in RPV patients with
HIV-1 RNA > 100,000 copies/mL and
CD4+ cell counts < 200 cells/mm³[5]
 RPV must be taken with a meal[4]
 Fixed-dose combination with DOR
includes TDF not TAF[6]
 Lipid increases with EFV[3]
 Drug-drug interactions with EFV, RPV[3,4]
1. DHHS ART Guidelines. December 2019. 2. McCann. EACS 2019. Abstr PS3/3.
3. EFV PI. 4. RPV PI. 5 Cohen. AIDS. 2014;28:989. 6. DOR/TDF PI. Slide credit: clinicaloptions.com

Is There Still a Role for TDF in Today’s First-line
Regimens?
Supporting TDF
 Longer experience with greater number
of patients with TDF vs TAF
 Coformulations with many regimens
 Lipid decreases of uncertain clinical
significance seen with use of TDF
regimens
 Weight gain signal with TAF[1,2]
 A preferred NRTI in pregnancy[3]
 Available as generic NRTI combinations
with 3TC and FTC
Supporting TAF
 At Wk 144, TAF superior to TDF[4]
 TAF had less impact than TDF on
bone mineral density (comparable to
ABC)[5]
 Less impact on markers of renal
tubular dysfunction
 Low dose allows small tablet
(co)formulations
1. NAMSAL ANRS 12313 Study Group. NEJM;2019;381:816. 2. McCann. EACS 2019. Abstr PS3/3.
3. DHHS Perinatal Guidelines. December 2020. 4. Arribas. JAIDS. 2017;75:211. 5. Sax. Lancet. 2015;385:2606. Slide credit: clinicaloptions.com

Is There Still a Role for ABC in Today’s First-line
Regimens?
Supporting ABC
 Coformulated with DTG in first-line
regimen
 Long history of use
 Not renally cleared
Opposing ABC
 HLA-B*5701 test required before use
 ACTG 5202 demonstrated higher rate
of VF in patients with HIV-1 RNA
> 100,000 copies/mL when paired
with EFV and ATV/RTV[1]
 Continuing evidence of association of
ABC with increased risk of MI[2-6]
 More subjective AEs vs TDF[1] and
TAF[7]
1. Sax. NEJM. 2009;361:2230. 2. D:A:D Study Group. Lancet. 2008;371:1417. 3. Worm. J Infect Dis.
2010;201:318. 4. Sabin. BMC Med. 2016;14:61. 5. Elion. JAIDS. 2018;78:62. 7. Wohl. Patient. 2018;11:561. Slide credit: clinicaloptions.com

Key Take-home Points
 All preferred initial regimens contain an unboosted INSTI plus NRTIs
‒ DTG and BIC have a higher resistance barrier than RAL
‒ FTC/TAF has improved safety, tolerability vs FTC/TDF and ABC/3TC, but
appears to be associated with greater weight gain
‒ DTG/3TC now recommended alongside 3-drug ART options
 Potential AEs with INSTIs include weight gain, CNS AEs, and possible
small potential risk to newborn if taken at the time of conception
 Several single-tablet regimens available, now representing all ARV drug
classes

Outcomes Case
 You are seeing a 23-yr-old MSM newly diagnosed with HIV who
discontinued use of FTC/TDF PrEP 4 yrs ago
 He is HLA-B*5701 positive, with no HIV-1 drug resistance mutations
 His CD4+ cell count is 340 cells/mm3 and his HIV-1 RNA is 67,000
copies/mL
 He is HBV immune and HCV negative; his other laboratory work is
normal
 You would like to select first-line ART recommended for most patients

Assessment 1: If selecting a DHHS-recommended first-line
regimen for this patient, you could consider any of the
following, EXCEPT:
A. BIC/FTC/TAF
B. DOR/3TC/TDF
C. RAL + FTC/TAF
D. DTG/3TC
E. Unsure

Answer: If selecting a DHHS-recommended first-line regimen for
this patient, you could consider any of the following, EXCEPT:
A. BIC/FTC/TAF
B. DOR/3TC/TDF
C. RAL + FTC/TAF
D. DTG/3TC
E. Unsure
Correct answer: This regimen is not recommended as first-
line ART for most patients: DHHS recommends an unboosted
INSTI plus NRTI(s) as first-line for most patients with HIV

Case 2: Woman Newly Diagnosed With HIV and
Trying to Conceive

Patient Case: Newly Diagnosed Female
 23-yr-old woman newly
diagnosed with HIV infection
 Has been trying to conceive, still
interested in becoming pregnant
 Eager to start ART to minimize
perinatal transmission risk
Parameter Result
HBV status Immune
HCV status Negative
HLA-B*5701 status Negative
BMI, kg/m2 24
ALT, U/L 25
AST, U/L 20
Other labs Normal

Tsepamo Birth Outcomes Surveillance Study in
Botswana: Background
 In May 2018, unplanned analysis of Tsepamo birth outcomes surveillance study
found increase in NTD incidence among Botswanan women who conceived on
DTG[1]
‒ DTG vs non-DTG ART: 0.94% (95% CI: 0.37-2.4) vs 0.12% (95% CI: 0.07-0.21)
‒ Prevalence difference: 0.82% (95% CI: 0.24-2.3)
 Analysis of data through March 2019 found NTD prevalence among women who
received DTG at conception lower than previous analysis, but still higher than other
exposure groups[2]
‒ DTG vs non-DTG ART: 0.30% (95% CI: 0.13-0.69) vs 0.10% (95% CI: 0.06-0.17)
‒ Prevalence difference: 0.20% (95% CI: 0.01-0.59)
 Most recent analysis reports data from Tsepamo through April 2020[3]
1. Zash. NEJM. 2018; 379:979. 2. Zash. IAS 2019. Abstr MOAX0105LB. 3. Zash. AIDS 2020. Abstr OAXLB0102. Slide credit: clinicaloptions.com

Tsepamo Update: Prevalence of NTDs by ARV Exposure
Zash. AIDS 2020. Abstr OAXLB0102. Slide credit: clinicaloptions.com
Parameter
Conception Pregnancy
HIV Negative
(n = 119,630)
DTG
(n = 3591)
Non-DTG
(n = 19,361)
EFV
(n = 10,958)
DTG
(n = 4581)
Total NTDs per exposures, n/N 7/3591 21/19,361 8/10,958 2/4581 87/119,630
NTD prevalence, % (95% CI)
 March 2019
 April 2020
0.30
(0.13-0.69)
0.19
(0.09-0.40)
0.10
(0.06-0.17)
0.11
(0.07-0.17)
0.04
(0.01-0.11)
0.07
(0.03-0.17)
0.03
(0.0-0.15)
0.04
(0.01-0.16)
0.08
(0.06-0.10)
0.07
(0.06-0.09)
Prevalence diff. for DTG at
conception, Apr 2020, % (95% CI)
Ref
0.09
(-0.03 to 0.30)
0.12
(0.0 to 0.32)
0.15
(0.0 to 0.36)
0.12
(0.01 to 32)
NTDs per exposures between
March 2019 and April 2020, n/N
2/1908* 6/4569 5/2999 1/741 17/30,258
*Includes 1 lumbosacral myelomeningocele (spina bifida) and 1 encephalocele.

Current Guidance on DTG Use in Treatment-Naive
Women of Childbearing Potential
 DTG can be prescribed for adult
women and adolescent girls of
childbearing age or potential who
wish to become pregnant or who are
not otherwise using or accessing
consistent and effective contraception
if they have been fully informed of
the potential increase in the risk of
neural tube defects (at conception
and until the end of the first
trimester)
 DTG a “preferred” ARV for women
trying to conceive and for pregnant
women, irrespective of trimester
‒ Based on higher rate of virologic
suppression, faster rate of HIV-1 RNA
decline, and higher genetic barrier of
DTG vs other ARVs
1. WHO ARV Policy Update. July 2019. 2. DHHS Perinatal Guidelines. December 2020. Slide credit: clinicaloptions.com
WHO Guidance[1] DHHS Guidance[2]

IMPAACT 2010: Safety and Efficacy of DTG vs EFV and
TDF vs TAF in Pregnancy
 Randomized, open-label phase III trial:
pregnant WHIV randomized to DTG +
FTC/TAF (n = 217) vs DTG + FTC/TDF
(n = 215) vs EFV/FTC/TDF (n = 211) at
14-28 wks of gestational age
‒ Median gestational age: 21.9 wks
‒ Median maternal HIV-1 RNA:
903 c/mL
‒ HIV-1 RNA < 50 c/mL: 16%
‒ Median CD4+ count: 466 cells/mm3
‒ ART before entry: 83% (median
6 days)
 2 infants diagnosed with HIV in
DTG-containing arms at < 14 days
(0 in EFV-containing arm)
‒ 1 in DTG + FTC/TAF arm: maternal
delivery HIV-1 RNA 58,590 c/mL
‒ 1 in DTG + FTC/TDF arm: maternal
delivery HIV-1 RNA < 40 c/mL
Chinula. CROI 2020. Abstr 130LB. Slide credit: clinicaloptions.com
Delivery HIV-1 RNA
< 200 c/mL, n/N (%)
DTG
Arms
EFV/FTC/
TDF
Est. Risk
Difference,
% (95% CI)
P
Value
ITT 395/405
(97.5)
182/200
(91.0)
6.5
(2.0-10.7)
.005
Per protocol 389/399
(97.5)
171/187
(91.4)
6.0
(1.6-10.3)
.008

IMPAACT 2010: Adverse Pregnancy Outcomes
 No spontaneous abortions occurred
Chinula. CROI 2020. Abstr 130LB. Slide credit: clinicaloptions.com
Women
(%)
40
35
30
25
20
15
10
5
0
DTG + FTC/TDF
DTG + FTC/TAF EFV/FTC/TDF
Any Adverse
Pregnancy Outcome
Preterm Delivery Small for
Gestational Age
Stillbirth
P = .047
P = .023
P = .28
P = .26
P = .043 P = .97
P = .16 P = .38
P = .12 P = .63
P = .46 P = .067
24.1
32.9 32.7
5.8
9.4
12.1
16.3
22.5
20.5
3.7
5.2
1.9

Adverse Pregnancy Outcomes With DTG vs EFV:
Meta-analysis of 5 Clinical Trials
 Meta-analysis of 5 recent trials that have included pregnant women:
DolPHIN-1, DolPHIN-2, NAMSAL, ADVANCE, and IMPAACT 2010 (N = 1074)
Asif. AIDS 2020. Abstr OABLB0105. Slide credit: clinicaloptions.com
DTG-based ART EFV-based ART
Mothers With ≥ 1 AE
Outcome
Participants
(%)
Infants With ≥ 1 AE
100
80
60
40
20
0
Viral Suppression Stillbirth Neonatal Deaths MTCT
n/N = 547/605 271/378 26/659 9/415 10/659 12/415 5/659 0/415 141/649 73/403 130/590 105/370
P = .001
P = .06 P = .68 P = .18
P = .73
P = .06
90
72
22 18
22
28
4 2 2 3 1 0

Pregnancy Outcomes After RAL Exposure
 RAL manufacturer Adverse Event Review and Reporting System (MARRS):
961 prospective, 520 retrospective reports through May 27, 2019
‒ No evidence of increased rate of spontaneous abortion, stillbirth, or congenital
anomalies in pregnant women exposed to RAL vs background population
‒ No NTDs in prospective reports of RAL exposure at conception/during first
trimester as of 9/6/2019; 1 case of anencephaly following second trimester
RAL initiation, considered unrelated to RAL exposure
 No NTDs reported among 222 periconception exposures to RAL in UK
National Study of HIV in Pregnancy and Childhood
 No NTDs reported among 218 periconception exposures to RAL in ANRS-
French Perinatal Cohort
Shamsuddin. IDWeek 2019. Abstr 886.

INSTI Use During Pregnancy and Birth Outcomes
1. http://www.apregistry.com/forms/interim_report.pdf. 2. Vannappagari. EACS 2019. PS1/2.
 Antiretroviral pregnancy registry (APR) data reported through July 2020[1]
 Increased risk of birth defects not demonstrated with any first-line INSTI above the
population expected rate of defects (2.72‐4.17/100 live births from MACDP and
TBDR, respectively)[1,2]
INSTI
Total
Outcomes
Live Births Defect Cases CNS Defects NT Defects
Encephalocele
Defects
Any BIC exposure
 Periconception
91
56
85
51
2
2
1
1
0
0
0
0
Any DTG exposure
 Periconception
915
479
842
420
33
13
4
2
1
1
0
0
Any RAL exposure
 Periconception
953
392
891
350
30
11
1
0
0
0
0
0

 Preferred regimens: Dual NRTI backbone plus INSTI or boosted PI
 Alternative regimens: Dual NRTI backbone plus NNRTI
DHHS Recommendations on ART in Pregnancy and in
Non-Pregnant Women Who Are Trying to Conceive
Preferred
 3TC/ABC
 FTC/TDF
 3TC/TDF
Alternative
 FTC/TAF*
 3TC/ZDV
Preferred
 DTG
 RAL BID
Preferred
 ATV/RTV
 DRV/RTV BID
DHHS Perinatal Guidelines. December 2020. Slide credit: clinicaloptions.com
NRTI Backbone
NNRTIs
Alternative
 EFV
 RPV
 BIC, DOR, IBA, FTR: insufficient data
 EVG/COBI, ATV/COBI, and DRV/COBI: pharmacokinetic
concerns
Not Recommended
INSTI Boosted PIs
*TAF: data support continuation
in pregnancy; insufficient data to
support initiation in pregnancy.

Assessment 2: According to DHHS guidance, all of the following
are recommended for women with HIV trying to conceive,
EXCEPT:
A. BIC/FTC/TAF
B. DTG + FTC/TDF
C. DRV/RTV + 3TC/TDF
D. RAL + FTC/TDF
E. Unsure

Answer: According to DHHS guidance, all of the following are
recommended for women with HIV trying to conceive, EXCEPT:
A. BIC/FTC/TAF
B. DTG + FTC/TDF
C. DRV/RTV + 3TC/TDF
D. RAL + FTC/TDF
E. Unsure
Correct answer: There are insufficient data to recommend
bictegravir or TAF in women trying to conceive

 Most recent data reassuring that DTG likely does not increase the risk of
neural tube defects as compared with non-DTG ART taken at time of
conception
 DTG during pregnancy more likely to achieve viral suppression at time of
delivery as compared with EFV
 DTG now preferred regimen in women regardless of desire to conceive or
pregnancy status
 TAF appears to be safe and potentially advantageous compared to
TDF during pregnancy
‒ Data only for initiation in second trimester; insufficient data in first trimester or
periconception

Case 3: Older Woman Newly Diagnosed With HIV

Patient Case: Newly Diagnosed Black Female
 54-yr-old black woman newly
diagnosed with HIV infection
‒ Moderate glucose intolerance,
hypertension
 HBV DNA positive
Parameter Result
HBV status Core Ab +
HCV status Negative
HLA-B*5701 status Negative
BMI, kg/m2 32
ALT, U/L 60
AST, U/L 55
Other labs Normal

*
*
Multivariate Analysis of Weight Gain After ART Start
 Pooled analysis of 8 phase III RCTs of first-line ART initiation during 2003-2015 (N = 5680)
‒ Baseline factors associated with weight gain: lower CD4+ cell count, higher HIV-1 RNA level, no IDU,
female sex, black race, symptomatic HIV, younger age (< 50 vs ≥ 50 yrs), and higher BMI
Sax. Clin Infect Dis. 2020;71:1379.
*Color-coded to match respective comparators, denoting P ≤ .05 vs NNRTI (first panel), EVG/COBI (second panel), or ZDV (third panel).
TAF
ABC
TDF
ZDV
BIC
DTG
EVG/COBI
INSTI
PI
NNRTI
1
0
4
3
LS
Mean
Weight
Δ,
kg
(95%
CI)
Wks
12 24 36 48 60 72 84 96
2
*
*
* *
* *
*
*
LS
Mean
Weight
Δ,
kg
(95%
CI)
Wks
12 24 36 48 60 72 84 96
6
0
5
4
3
2
1
LS
Mean
Weight
Δ,
kg
(95%
CI)
Wks
12 24 36 48 60 72 84 96
6
0
5
4
3
2
1
*
*
*
*
*
*
*
*
*
* *
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*
*

ADVANCE: Mean Weight Change in South Africa by Sex
 N = 1053, 99% black, 59% female, mean age 32 yrs (range: 13-62)
 Greater weight increase with first-line DTG vs EFV, with first-line TAF vs TDF, and in
women vs men
Men Women
0 4 12 24 36 48
0
2
4
6
Mean
Weight
Change
(kg)
Wk
8
4.7 kg
3.0 kg
0.5 kg
6.4 kg
3.2 kg
1.7 kg
Venter. NEJM. 2019;381:803.
1
3
7
5
-1
0 4 12 24 36 48
0
2
4
6
Mean
Weight
Change
(kg) Wk
8
1
3
7
5
-1
DTG + FTC/TAF
DTG + FTC/TDF
EFV/FTC/TDF

OPERA: Weight Change With Switch From TDF to TAF
While Maintaining Other ARVs by Class of Anchor Agent
 Longitudinal cohort analysis of routine EHR data collected from ~ 8% of US PWH receiving
care (> 115,000 individuals across 65 cities in 19 states and Puerto Rico)
 Current analysis restricted to adults receiving TDF-containing 3-drug ART at BL with
≥ 2 consecutive HIV-1 RNA < 200 copies/mL who switched TDF to TAF
Mallon. AIDS 2020. Abstr OAB0604. Slide credit: clinicaloptions.com
Estimated Weight
Δ by Time From
TDF to TAF
Switch, kg/yr
(95% CI)
INSTI
(n = 3281)
NNRTI
(n = 1452)
Boosted PI
(n = 746)
-60 to 0 mos
0.42 (0.26 to
0.59)
0.66 (0.51 to
0.81)
0.31 (-0.02
to 0.64)
0 to 9 mos
2.64 (2.26 to
3.01)
2.25 (1.78 to
2.71)
1.98 (1.13 to
2.83)
9+ mos
0.29 (0.08 to
0.51)
0.20 (-0.14
to 0.54)
-0.11 (-0.57
to -0.35)
Weight
(kg)
92
90
88
86
84
82
80
78
0
-60-54-48-42-36-30-24-18-12-6 0 6 12 1824 30 36 4248
NNRTI
bPI
INSTI

OPERA: Weight Change With Switch From TDF to TAF
While Also Switching to an INSTI
Mallon. AIDS 2020. Abstr OAB0604. Slide credit: clinicaloptions.com
Mos From Switch
Weight
(kg)
92
90
88
86
84
82
80
78
0
-60-54-48-42-36-30-24-18-12 -6 0 6 12 18 24 30 36 42 48
EVG/c
BIC
DTG
Estimated Weight
Δ by Time From
TDF to TAF Switch,
kg/yr (95% CI)
EVG/c
(n = 1120)
DTG
(n = 174)
BIC
(n = 129)
-60 to 0 mos
0.24
(0.04 to 0.43)
0.22
(-0.08 to
0.52)
0.01
(-0.38 to
0.39)
0 to 9 mos
2.55
(1.86 to 3.24)
3.09
(1.26 to 4.93)
4.47
(0.81 to 8.13)
9+ mos
0.26
(-0.10 to
0.61)
-0.23
(-1.62 to
1.16)
-9.97
(-23.79 to
3.85)

Assessment 3: How do you counsel patients regarding
what is known about weight gain with ART?
A. ART is associated with similar levels of weight gain regardless of
drugs/regimen
B. ART is associated with weight gain that appears to be higher for INSTIs
vs boosted PIs or NNRTIs
C. ART is associated with reversible weight gain that is lost when the
problematic drug is discontinued
D. ART is associated with weight gain that appears to be higher for
boosted PIs vs INSTIs or NNRTIs
E. Unsure

Answer: How do you counsel patients regarding what is
known about weight gain with ART?
A. ART is associated with similar levels of
weight gain regardless of drugs/regimen
B. ART is associated with weight gain that
appears to be higher for INSTIs vs
boosted PIs or NNRTIs
C. ART is associated with reversible weight
gain that is lost when the problematic
drug is discontinued
D. ART is associated with weight gain that
appears to be higher for boosted PIs vs
INSTIs or NNRTIs
E. Unsure
INSTIs and TAF associated with greater
weight gain vs other ARVs
Reversibility of weight gain unknown
Multivariate analysis of weight gain following
ART initiation in RCTs demonstrated higher
weight gain with INSTIs vs boosted PIs or
NNRTIs
Correct answer:
As demonstrated by multivariate analysis of
weight gain following ART initiation in RCTs

HBV Suppression in Patients With HIV/HBV Coinfection
Hafkin. J Viral Hepatitis. 2014;21:288.
 Retrospective cohort study in
US of 133 patients with HIV/HBV
coinfection and HBV viremia
 Tenofovir-based ART initiated;
HBV DNA measured at 1 yr
 54% (95% CI: 46% to 63%)
had incomplete HBV DNA
suppression at 1 yr
‒ Incomplete suppression
associated with BL HBV DNA
level > 8 IU/mL (adjusted OR:
3.21; 95% CI: 1.39-7.43)
Time to HBV Suppression
by BL HBV DNA
Time to HBV
Suppression by Age
Proportion
Unsuppressed
Days
600
0 200 400
0.20
1.00
0.80
0.60
0.40 HBV DNA < 8
log IU/mL
HBV DNA
≥ 8 log IU/mL
Log-rank
P < .001
Days
600
0 200 400
0.20
1.00
0.80
0.60
0.40
Age > 43 yrs
Age ≤ 43 yrs
Log-rank
P < .03
 Shorter time to suppression associated with
age > 43 yrs and BL HBV DNA < 8 log IU/mL

HBV Seroconversion With HBV-Active ART
 Noninterventional, retrospective
cohort from 7 HIV care centers in
Germany
 359 patients with HIV/HBV coinfection
receiving HBV-active ART with TAF or
TDF
 At baseline:
‒ 73% receiving FTC/TDF
‒ 18% receiving 3TC/TDF
‒ 3% receiving FTC/TAF
 53% switched to TAF during follow-up
 HBsAg loss occurred in 66 patients (18.4%)
Follow-up Characteristics Value
Median follow-up, yrs 11 (IQR: 10-12)
Median CD4+ cell gain, cells/mm3 188 (IQR: 130-229)
Median time to HBsAg loss, mos 41 (IQR: 33-60)
Parameters Negatively
Associated With HBsAg Loss
P Value
CDC category C HIV ≤ .001
Lower CD4+ cell gain .043
Not receiving FTC/TDF .008
Boesecke. CROI 2019. Abstr 627.

Guidance on HBV-HIV Coinfection
Terrault. Hepatology. 2018;67:1560. EASL. J Hepatol. 2017;67:370.
AASLD[1] EASL[2]
 All persons with HIV-HBV coinfection should start
ART irrespective of CD4+ cell count
 All ART regimens should include 2 drugs active
against HBV
 TDF* or TAF† plus 3TC or FTC
 Patients already on ART without anti-HBV activity
should switch to include TDF or TAF with 3TC or FTC
 Alternatively, ETV‡ may be added to current ART
if ART fully suppressive
 Drugs with anti-HBV activity should not be
discontinued without substituting another anti-HBV
drug
 All persons with HIV-HBV coinfection should start ART
irrespective of CD4+ cell count
 Recommended for persons with HIV-HBV coinfection:
TDF-(evidence level I) or TAF-based (evidence level II-1)
ART regimen
 Avoid stopping TFD-or TAF-containing regimens
due to high risk of severe hepatitis flares
 ETV an alternative regimen, due to lack of
strong activity against HIV
ETV, TAF, and TDF have favourable safety and resistance profiles; 3TC has low barrier to resistance[1,2]
*Regimens including TDF/FTC require dose-adjustment for creatine clearance < 50 mL/min. † Regimens including TAF/FTC not recommended for
patients with creatinine clearance < 30 mL/min.

 Most individuals gain weight in the mos following ART initiation; those who start
TAF gain more than those who start TDF, and those who start an INSTI (especially
DTG or BIC) gain more than those who start an NNRTI or PI
 Other factors associated with more pronounced weight gain reflect trends in the
general population and social determinants of health
 Consistent association between switching TDF to TAF or switching NNRTI to INSTI
(especially DTG or BIC) and weight gain; most in the first 9 mos post switch
 Mechanism of weight gain unclear
‒ Adverse effect of TAF or the INSTI or removal of weigh-suppressive effects of TDF and
NNRTIs?
 In patients with HBV-HIV coinfection, regimens containing 3TC or FTC should
include TDF or TAF

Современное лечение ВИЧ: индивидуализация стартовой АРТ /Contemporary Management of HIV: Individualizing First-line ART (2021)

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Современное лечение ВИЧ: индивидуализация стартовой АРТ /Contemporary Management of HIV: Individualizing First-line ART (2021)