Transcript Antiretroviral Therapy

Antiretroviral Therapy 2015
Paul A. Pham Pharm.D. BCPS
Conflict of Interest
MADAP consultant
CDC OI guidelines committee member
HIV renal guidelines member
Janssen Advisory Board 2014
Objectives
Updated 2015 DHHS guidelines
Rationale for recommendations on
1) when to start, 2) what to start with,
3) what to change to
Pharmacology of Antiretrovirals
– Adverse Drug Reactions
– Drug-drug Interactions
– Resistance Mutations
When to Start ART
Current 2015 DHHS recommendation: ART
is for ALL HIV-infected patients.
CD4 Count
(cells/µL)
Data
Benefit
<350
RCT
Mortality and
Morbidity Benefit
350-500
non-RCT, Cohort
Morbidity benefit
Studies, secondary and perhaps
analysis of RCT
mortality
>500
Cohort Studies
RCT ongoing
Morbidity benefit and
perhaps mortality.
NA-ACCORD
94% increase in
relative risk of death
w/ deferred ART
Urgency of ART
– HIV-associated nephropathy
– Rapidly declining CD4 count (>100 cell/mm3 per year)
and high viral load (>100,000 c/mL)
– HBV and HCV co-infection
– Acute HIV
– Pregnancy
– AIDS defining conditions (ex. HIV-associated dementia)
– Acute OI
Importance of ART during an acute OI
282 pts randomized to early (within 14 days) vs.
deferred
Median time to ART 12d vs. 45 d
PCP-63%, Crypto meningitis-12%, Bacterial
Infection-12%
Fewer AIDS progression/deaths (OR = 0.51;
95% CI = 0.27-0.94) with
early ART
Zolopa AR Plos one 2009
Goals of therapy
HIV RNA below limit of detection (ie, <20-75
copies/mL, depending on assay)
1) reduce HIV-associated morbidity and mortality
2) restore and preserve immunologic function
3) prevent HIV transmission.
Expected Virologic Response*
Time
Viral Load
1 week
Decrease 0.75-1.0 log10/mL
4 weeks
Decrease 1.3-2.0 log10/mL; <5000
c/mL
8-16 weeks
<5000 c/mL
24**
<20 c/mL
*Faster VL response in the first month observed with InSTI-based regimens
** Most patient should be undetectable at 24 weeks. VL response rate may
be slower with higher baseline VL and low CD4 count
Monitoring Before and During ART
Test
Baseline
ART
initiation
Week
2-8
Every 3-6
months
CD4 count
+
+
q3-6 mo first 2 years of ART
-viremia on ART; CD4 <200
q12h mo if CD4 300-500
If CD4 >500 VL <20 c/ml: optional
+
VL
+
+
Q4-8 weeks
until VL <20
then q3-6mo
+
Genotype*
+
+
+
Viral
failure/Clinically
indicated
+
*Transmitted resistance in 6-16%
In absence of therapy (selective pressure), resistance mutations may
decline over time and become undetectable, but may persist and
cause treatment failure when ART is started
Treatment history is very important when off ART
26 FDA Approved ARVs
ARVs Mechanism of Action
NRTIs ADRs
Class black box warning for lactic acidosis (but only w/ ddI, d4T, AZT)
NRTIs
ADRs
Comments
Zidovudine (AZT)
Bone marrow suppression;
GI intolerance; headache,
myopathy; lipoatrophy.
Antagonism with d4t
Didanosine (ddI)
GI intolerance, mitochondrial Low potency
toxicity, PN, pancreatitis,
non-cirrhotic portal HTN
Stavudine (d4T)
Mitochondrial toxicity; PN;
Lipoatrophy
Abacavir (ABC)
HSR, possible increased risk Fatalities w/ HSR
of MI (debated)
rechallenge
Tenofovir (TDF)
Nephrotoxicity; Decrease in
bone density
HBV flare w/ d/c
Lamivudine (3TC)
Well tolerated
HBV flare w/ d/c
Emtricitabine (FTC)
Well tolerated; skin
hyperpigmentation
HBV flare w/ d/c
Antagonism with AZT
Protease
Inhibitors
ADRs
Class adverse events: GI intolerance, hepatitis, hyperlipidemia
PIs
ADRs*
Comments
Saquinavir (SQV)
PR and QTc prolongation (avoid w/ QTc
>450 ms); fat accumulation
Low potency; low
absorption
Indinavir (IDV)
Nephrolithiasis; fat accumulation
Avoid
Nelfinavir (NFV)
Secretory diarrhea; fat accumulation
Low potency
Fosamprenavir
(FPV)
Rash; nephrolithiasis (rare); fat
accumulation
Cross-resistance with DRV
Lopinavir/r (LPV/r)
GI (n/v/d); PR and QTc prolongation; fat
accumulation.
Higher rates of GI
intolerance compared to
ATV/r and DRV/r
Atazanavir (ATV)
Indirect bilirubin elevation; nephrolithiasis;
PR prolongation; rash
Lipid friendly
Tipranavir (TPV/r)
GI intolerance; hepatitis; intracranial
hemorrhage; rash
Sulfa moiety
Darunavir/r (DRV/r)
Rash
Lipid friendly; Sulfa moiety
NNRTIs ADRs
Class ADRs: rash; hepatitis
NNRTIs
ADRs
Comments
Nevirapine
(NVP)
Severe rash (SJS, TEN) and
hepatitis
Women CD4>250 and men
CD4 >400 are at increased
risk
Delavirdine
(DLV)
Rash
Low potency
Efavirenz
(EFV)
CNS side effects (insomnia,
dizziness, confusion,
depression); hyperlipidemia
False+ THC and Benzo;
teratogenic (first 8 weeks)
Etravirine
(ETR)
Generally well tolerated; HSR
(rash, hepatitis)
Must d/c with HSR
Rilpivirine
(RPV)
Dose dependent QTc
Monitor drug-drug
prolongation; CNS side effects interaction with CYP3A4
inhibitors.
Integrase Inhibitors ADRs
Generally well tolerated w/ lower discontinuation than PI/r- and EFV-based ART
InSTI
ADRs
Comments
Raltegravir (RAL)
CK elevation (+/rhabdomyolysis); rash; LFT
elevation; GI intolerance
Must d/c w/ increased
LFTs and rash
Elvitegravir (EVG)
GI intolerance
Scr elevation (0.14+/0.13 mg/dL with COBI
boosting with no
change in GFR
Dolutegravir (DTG) CK elevation; insomnia
Scr elevation w/ no
change in GFR by
iohexal
Entry Inhibitors ADRs
• Enfuvirtide (T-20): injection site reaction
(induration, pain, erythema). Rotate
injection sites.
• Maraviroc (MVC): Generally well tolerated.
CK elevation; myalgia; orthostatic
hypotension (CrCL <30ml/min and CYP3A
inhibitor)
Not Recommended Due to Toxicity
 AZT-GI intolerance, bone marrow suppression,
mitochondrial toxicity
 d4T-mitochondrial toxicity, peripheral
neuropathy
 ddI-mitochondrial toxicity, peripheral
neuropathy, pancreatitis
 NVP-rash (including TEN and SJS) and
hepatitis
 IDV/r-nephrolithiasis
 RTV 600 mg twice-daily-severe GI intoleranceN/V/D
ADRs due to Drug-Drug Interactions
“statin”
PIs
Effect of on “statin” PK
Simvastatin
SQV/RTV
NFV
AUC Increased by 3059%
AUC increased by 506%
Lovastatin
All PI
May significantly increase
lovastatin
• Equivalent to giving simvastatin 600mg/d !!
• Atorvastatin (up to 40 mg), rosuvastatin (up to 20 mg), or
pitavastatin (up to 4 mg) can be given to PIs
Gerber JG et al. CROI 2004 abst.603; Hsyu PH et al. ICAAC 2000 abst
425
Beneficial CYP3A4 Inhibition
LPV/r single-dose pharmacokinetics
LPV 400mg alone
LPV400mg +100mg RTV
Drug concentration (mg/mL)
10
1
0.1
0.01
0.001
0
6
12
18
24
30
Time (hours)
Data on File
36
42
48
PIs Drug Interactions
PIs
Interacting Drug
Comments
Saquinavir (SQV)
Indinavir (IDV)
Nelfinavir (NFV)
Fosamprenavir (FPV)
Lopinavir/r (LPV/r)
Tipranavir (TPV/r)
Darunavir(DRV/r or /c)
Atazanavir(ATV/r or /c)
Amiodarone, quinidine,
dofetilide, propafenone,
bepridil
Pimozide,
fentanyl,
oral midazolam, triazolam
Significant increase of the
interacting drugs.
Contraindicated
PPI, H2 blocker, antacid
Avoid ATV
All substrate and
inhibitor of 3A4
Rifampin
Contraindicated. Use rifabutin
Rifabutin
Rifabutin 150 mg once daily
(higher than FDA approved
dose). Monitor RBT levels.
RTV=COBI >>LPV/r=DRV/r= TPV/r>IDV=NFV=APV=ATV>>SQV
NNRTIs Drug Interactions
NNRTIs
Interacting Drug
Nevirapine
(NVP)
3A4
Efavirenz
(EFV)
2B6>3A4
Tacrolimus, sirolimus
Comments
Tacrolimus, sirolimus, cyclosporine
Simvastatin
Simvastatin AUC 58%. Titrate to effect
Methadone
Methadone
Etravirine
(ETR)
3A4,
2C9,2C19
Clopidogrel
Conversion to active clopidogrel
metabolite may be inhibited by ETR. Avoid
if possible.
Rilpivirine
(RPV)
3A4
Macrolide, PI/r
May significantly increase RPV. Monitor
QTc
Antacid, PPI, H2
blockers
Decreased RPV levels. Avoid
up to 50%. Must titrate.
InSTI Drug Interactions
InSTI
Interacting Drug
Comments
Raltegravir (RAL)
Glucuronidation
Rifampin
Increase RAL to 800 mg BID
Dolutegravir (DTG) Rifampin, EFV, FPV, Must increase DTG 50 mg bid
Glucuronidation>> TPV
Use only if no InSTI mutations
CYP3A4
Elvitegravir/c
(EVG/c or /r)
CYP3A4
Etravirine
DTG and ETR can only be coadministered in if given with
PI/r.
CYP3A4 substrate
All interactions with PIs apply
Al and Mg antacid: EVG, RAL, DTG: decreased by ~5070%. Give EVG or DTG >2hrs before antacid
NRTIs, MVC, T-20 Drug Interactions
NRTIs
Interacting drug
Comments
Zidovudine (AZT)
Didanosine (ddI)
Stavudine (d4T)
Abacavir (ABC)
Lamivudine (3TC)
Emtricitabine (FTC)
PI/r and COBI
Increased TDF levels
EFV, ETR, phenytoin,
phenobarbital,
carbamazepine
Increase MCV to 600
mg bid
PI/r, macrolides, azoles
Decrease MCV to 150
mg bid
Tenofovir (TDF)
Maraviroc
CYP3A4
T-20
No significant
interaction
Food-drug Interactions w/ ARVs
Antiretrovirals
Food Effect
Recommendation
Rilpivirine
AUC ~40% lower in a fasted state
Administer wth food (BUT not protein shake
50% lower)
Etravirine
Improves absorption. Fasted state: AUC
decreased 50%
Administer with food
Nelfinavir
AUC 2- to 5-fold higher when given with
food.
Administer with a minimum of 500 Kcal with
20% fat meal.
Tipranavir/r
AUC increased by 31% with high fat
meal.
Administer with food
Atazanavir
(+rtv or cobi)
AUC increased by 70% (w/unboosted),
33 (w/rtv), and 28% (w/cobi) with light
meal.
Administer with food.
Darunavir (+ rtv or
cobi)
Administer with food
AUC increased by 30% (w/rtv) and 70%
(w/cobi)
EVG/Cobi/TDF/FTC
EVG AUC increased 34%
Administer with food
Efavirenz
AUC increased by 22% and 50% with low
fat and high fat meals.
Take on empty stomach during the first 2 weeks
to minimize the risk of CNS side effects.
IDV/r, LPV/r, FPV/r,
SQV/r,, MVC, NVP;
RAL; DTG; All
NRTIs (except ddI);
No significantly affected
Administer with or without food.
DHHS Guidelines, April 2015:
What to Start
INSTI based 


DTG (QD) + TDF/FTC (AI)
RAL + TDF/FTC (AI)
EVG/COBI/TDF/FTC; only if pre-ART CrCl >70
mL/min (AI)
PI based

DTG/ABC/3TC; only if HLA-B*5701 negative (AI)

DRV/r (QD) + TDF/FTC (AI)
Demoted: EFV- and ATV/r-based regimen
DHHS Guidelines for Antiretroviral Therapy in Adults and Adolescents, April 2015.
SINGLE: Dolutegravir + ABC/3TC vs.
EFV/TDF/FTC
100
DTG+ABC/3TC: 88%
Proportion (%) with <50 c/mL
90
80
EFV/TDF/FTC: 81%
70
WK 48 difference in response (95% CI):
+7.4% (+2.5% to +12.3%); p=0.003
60
50
40
30
20
10
DTG 50 mg + ABC/3TC QD
EFV/TDF/FTC QD
0
BL 2
4
8
12
16
24
Week
32
● DTG + ABC/3TC QD superior to EFV/TDF/FTC at Wk 48 (1o endpoint)
Walmsley S, et al. N Engl J Med 2013;369:1807-18
40
48
SINGLE: DTG + ABC/3TC vs. EFV/TDF/FTC:
Disposition
DTG 50 mg +ABC/3TC
n=411
n (%)
EFV/TDF/FTC
(N=419)
n (%)
364 (88)
338 (81)
21 (5)
26 (6)
Data in window not <50 c/mL
6 (1)
5 (1)
Discontinued for lack of efficacy
7(2)
9 (2)
Discontinued for other reason while not <50 c/mL
8 (2)
12 (3)
29 (7)
55 (13)
Discontinued because of AE or death*
9 (2)
40 (10)
Discontinued for other reasons
20 (5)
14 (3)
0
1 (<1)
Outcome (snapshot) at Week 48
Virologic success
Virologic nonresponse
No virologic data at Week 48
Missing data during window but on study
*Deaths: n=2, both on EFV/TDF/FTC: n=1 primary cause of death (sepsis) judged unrelated to study drug but
complicated by renal failure judged possibly related to EFV/TDF/FTC; n=1 not related to EFV/TDF/FTC (pneumonia).
Walmsley S, et al. N Engl J Med 2013;369:1807-18
ACTG A5257
ATV/r vs. DRV/r vs. RAL (+TDF/FTC)
Virologic failure at 96 weeks
(equivalent):
RAL 10%
ATV 13%
DRV 15%
High incidence of
discontinuation due to
toxicity in ATV/r-treated
patients (16% vs. 1% RAL
and 5% /DRV/r)
Landovitz RL et al. CROI 2015
Comparing the Integrase Inhibitors
Agent
Advantages
Disadvantages
Raltegravir
• Longest experience
• Fewest drug interactions
• Twice daily dosing
• No coformulation
Elvitegravir
• Single-tablet regimen
(EVG/cobi/TDF/FTC)
• Once-daily dosing
• Requires COBI or RTV
boosting
• Multiple COBI drug
interactions (similar to RTV)
• Not recommended with CrCL
<70 ml/min
Dolutegravir
• Single-table regimen
(DTG/ABC/3TC)
• Potency demonstrated with
ABC/3TC
• Once-daily dosing
• Higher barrier to resistance
(compared to RAL)
• Few drug interactions
• Active against some RALand EVG-resistant virus
• Coformulated only with
ABC/3TC
FLAMINGO: DTG superior to DRV/r
VL <50 c/mL at Week 48, Snapshot analysis
Proportion (%)
100
90
DTG 50 mg QD (N=242)
DRV/r 800/100 mg QD (N=242)
83
95% CI for differencea
Favors Favors
DRV/r DTG
80
60
0.9 7.1 13.2
40
20
6
7
4
10
0
Virologic
success
Virologic
non-response
No Week 48
data
-20% -12%
0
20%
Test for superiority:
P=0.025
Feinberg et al. ICAAC 2013; Denver, CO. Abstract H-1464a.
FLAMINGO: Proportion with VL <50
Snapshot Outcomes
Virologic success
Virologic non-response
Data in window not <50 c/mL
Discontinued for lack of efficacy
Discontinued for other reason while not <50 c/mL
Change in ART
No virologic data at Week 48
Discontinued due to AE or death
Discontinued for other reasons
Missing data during window but on study
DTG 50 mg QD
(N=242)
DRV/r
800 mg/100 mg QD
(N=242)
217 (90%)
15 (6%)
6 (2%)
1 (<1%)
3 (1%)
5 (2%)
10 (4%)
3 (1%)
6 (2%)
1 (<1%)
200 (83%)
18 (7%)
11 (5%)
1 (<1%)
5 (2%)
1 (<1%)
24 (10%)
9 (4%)
11 (5%)
4 (2%)
Feinberg et al. ICAAC 2013; Denver, CO. Abstract H-1464a.
When Should DRV/r + TDF/FTC
be used?
• Must start ART before resistance test
available (e.g setting of an acute OI)
• Patients with a history of non-adherence
and possible resistance. Re: higher barrier
to resistance.
Lesson Learned from
SWITCHMRK
ART-experienced pts w/ VL <50 c/mL on a stable LPVrbased regimen. Pts had median of 5 previous ARVs.
Randomized to switch LPV/r to RAL (n=350) or continue on
LPV/r (n=352) while remaining on same background ART,
which included at least 2 NRTI.
At week 24, RAL (84.4%) vs LPV (90.6%) pts had HIV RNA
<50; treatment difference -6.2 % (95%CI -11.2 to -1.3)
Teaching point: Before switching to a regimen with lower
barrier to resistance, get a complete ART and resistance
history.
Enron JJ et al. Lancet 2010
DHHS Guidelines, April 2015:
Alternatives (2nd line)
NNRTI based 

EFV/TDF/FTC (BI)
RPV/TDF/FTC; only if pre-ART HIV RNA
<100,000 copies/mL and CD4 >200 cells/µL (BI)
PI based

ATV/c + TDF/FTC; only if pre-ART CrCl >70
mL/min (BI)


ATV/r + TDF/FTC (BI)
(DRV/c or DRV/r) + ABC/3TC (BIII for DRV/c,
BII for DRV/r)

DRV/c + TDF/FTC; only if pre-ART CrCl >70
mL/min (BII)
Cobicistat vs. RTV boosting
Pros: co-formulation with DRV, ATV, EVG
Cons:
– Not recommended with CrCL <30 ml/min
– Unable to overcome induction properties of
EFV, ETR, NVP (compared to RTV).
DRV/cobi not recommended with EFV, ETR, NVP
ATV/cobi not recommended with ETR or NVP
Must increase ATV to 400mg with cobi when given
with EFV (treatment-naïve patients only);
Initial Regimens:
INSTI based

rd
3
Line “other”
RAL + ABC/3TC (CII)
NNRTI based  EFV + ABC/3TC; only if pre-ART HIV RNA
<100,000 copies/mL (C1)
PI based

(ATV/c or ATV/r)a + ABC/3TC; only if pre-ART
HIV RNA <100,000 copies/mL (CIII for ATV/c and CII
for ATR/r)

LPV/r (QD or BID) + ABC/3TC; only if HLAB*5701 negative (C1)

LPV/r (QD or BID) + TDF/FTC (C1)
ACTG 5202
TDF/FTC vs. ABC/3TC + EFV OR ATV/r
Early termination by DSMB in the ≥100,000 c/mL group due to
higher rate of virologic failure in ABC/3TC treated pts (14% among
ABC/3TC recipients vs. 7% among TDF/FTC recipients) (hazard
ratio [HR] = 2.33; p = .0003).
No difference between ABC/3TC and TDF/FTC in pts w/ baseline
VL <100K.
No difference between ATV/r and EFV arm
Choosing “backbone”: Dual-NRTI Pairs
TDF/FTC
ABC/3TC
 Once-daily dosing
 Coformulated with EVG/c
and EFV
 Superior efficacy at RNA
>100,000 copies/mL w/
ATV/r or EFV
 Active against HBV;
potential HBV flare with
discontinuation
 Potential for renal toxicity;
caution in patients w/ renal
insufficiency
 Once-daily dosing
 Coformulated with DTG
 Inferior efficacy if baseline HIV
RNA >100,000 copies/mL when
combined with ATV/r or EFV, but
efficacy with DTG.
 3TC active against HBV; potential
for flare.
 Possible risk of MI; caution in
patients with CV risk factors
 Use only for patients who are
negative for HLA-B*5701 (risk of
hypersensitivity reaction if positive
HLA-B*5701 and fatalities with
rechallenge)
What to give a Pt w/ a recent MI
and CrCL 20ml/min?
DRV/r + RAL; only if pre-ART HIV RNA
<100,000 copies/mL and CD4 >200 cells/µL
(C1) (Raffi F et al. NEAT001/ANRS143 CROI abstract 84LB, 2014)
DRV/r + RAL vs. DRV/r + TDF/FTC
-Treatment failure at 96 weeks: RAL 17.8% and TDF/FTC
13.8%,(difference 4·0%, 95% CI -0·8 to 8·8).
-With CD4 <200, RAL+DRV/r was inferior to
TDF/FTC+DRV/r (p=0.02).
-With VL >100K , RAL+DRV/r did not do as well (p = 0.09).
LPV/r (BID) + 3TC (BID) (C1)
Most would use DRV/r+RAL+3TC or FTC
Virologic Failure, Definitions
Virologic failure:
Inability to achieve or maintain and
undetectable HIV viral load
Virologic “blip”:
An isolated detectable HIV RNA level (
between 20-200 copies/mL) that is
followed by a return to virologic
suppression
No evolution of resistance during a
“blip”
Management of Virologic Failure
Causes for virologic failure:
– 1) Adherence (with or without resistant mutations);
sub therapeutic ARV levels (drug-drug interactions,
absorption)
– 2) transmitted drug resistance
Best time to obtain resistance test
– While patient is taking the failing regimen (selective
pressure), or within 4 weeks of treatment
discontinuation
– If >4 weeks since ARV discontinuation, resistance
testing may still provide useful information (if
mutations detected). Not helpful if no mutations
detected.
NRTIs Resistant Mutations
3TC 65R,184VI
ABC 65R/E/N, 74V, 115F, 184V
AZT 41L, 67N, 70R, 210W, 215Y/F, 219Q/E
d4T 41L, 65R/E/N, 67N, 70R, 210W, 215Y/F, 219Q/E
ddI 65R/E/N, 74V
FTC 65R/E/N, 184V/I
TDF 65R/E/N, 70E
multi-NRTI resistance (TAMS) 41L, 67N, 70R, 210W, 215Y/F, 219Q/E (Pan resistance)
multinucleoside Q151m plus 62V, 75I, 77L, 116Y, 151M (TDF susceptibility retained)
multinucleoside 69 insertion 41L, 62V, 69 insert, 70R, 210W, 215Y/F, 219Q/E
(Pan
resistance)
184V-high level 3TC and FTC resistance; ABC-decreased susceptibility; TDF-hyper
susceptibility
K65R-intermediate resistance to ddI, TDF (improved w/184V), 3TC, and FTC.
ABC (worse w/ 184V)
L74V-intermediate resistance to ddI, low level resistance to ABC (worse w/ 184V),
PIs Resistant Mutations
• No single mutation causes high level resistance
• Cross resistance between PIs: 82A/F/T/S, 84V, 90M
• DRV mutation score
With 0-2, 3, or ≥ 4 of 47V, 54M, 74P & 84V DRV mutations at baseline, the virologic
response (< 500 c/mL at 24 weeks) was 50%, 22%, and 10% respectively.
NNRTIs Resistant Mutations
K103N-high level resistance to EFV and NVP; ETR and RPV susceptible
ETR mutation score (based on DUET)
3 points: 181I/V; 2.5 points: 101P, 100I, 181C, 230L; 1.5 points: 138A, 106I,
190S, 179F; 1 point: 90I, 179D, 101E, 101H, 98G, 179T, 190A. 0-2 points:
74% response; 2.5-3.5 points: 52% response; 4+ points: 38% response
With RPV resistance, there is 89% cross-resistance to ETR
InSTIs Resistant Mutations
DTG associated with less resistance in clinical trials.
The most common DTG-resistance mutation is T97A. Other mutations are
E138K/A, G140S/A, Q148H/R/K
RAL: 3 pathways to resistance with mutations in integrase gene:
(1) N155H + (E92Q,V151I, T97A, G163R, L74M) and
(2) Q148K/R/H + (G140S/A, E138K)
(3) Y143R/H/C
Cross-resistance between RAL and EVG; cross-resistance w/ DTG if
Q148H or G140S (+ L74I/M, E92Q, T97A, E138A/K, G140A, N155H)
Entry Inhibitors Resistant Mutations
MVC: R5 tropism shifts with disease
progression 80/20 vs. 50/50
Check tropism when ready to start MVC
ART in TreatmentExperienced Patients
New regimen should contain at least 2
(preferably 3) fully active agents
– Based on ARV history, resistance testing
– Consider new ARV in a different class
It is a SIN to add 1 active drug to a failing
regimen-resistance will develop quickly.
Consult with experts
Factors Affecting ARV Selection
The
Perfect
ARV
regimen
ARV
-Good Potency
-Minimal Side Effects
-Manageable Drug-Drug
Interactions
-High Barrier to
resistance
VIRUS
-Viral load (>100K vs. <100K)
-Resistance Mutations
-CCR5 vs. CXCR4 tropic
PATIENT
-Adherence (social
support, IVDU ect)
-CD4 count
-Acute OI
-HCV and HBV coinfection
-Co-morbidities
(CV risk factor,
renal function,
concurrent
medications ect)
-HLA*B5701
Summary
All HIV-infected should receive ART
Urgent treatment needed in setting of Acute OI
Know your patient’s ARV treatment history,
genotype, level of adherence before choosing
“the perfect ART regimen”
The first regimen is the best regimen (choose
wisely)
Clinical trials are favoring InSTI-based
regimens
The Good News
June 5, 1981
Today
The Bad News
The Continuum of HIV Care - US
100
%
75%
80
%
50%
77
%
66
%
25%
89
%
77
%
US- 850,000 (72%) have detectable HIV
MMWR (60), 2011
Role of the Clinical Pharmacist
Adherence counseling
Side effects and drug-drug interactions
management
ART selection and dosing based on renal
function, concurrent medications, and
resistance profile