HIV Cases
“What to Start”
Dr Anton Pozniak
Chelsea and Westminster Hospital
London
Case-SP
• A 57 year old caucasian man presented to the emergency
department with progressive difficulty in swallowing over
the last 4 weeks.
• He is hypertensive and has diet controlled diabetes and
asthma and takes inhaled B2 agonists and inhaled steroids
• He had seen his family practitioner who saw oral thrush
and thought it was related to his diabetes/ inhalers and
gave him amphotericin lozenges
• He had been diagnosed with HIV a year before but had
not attended any clinics as he “felt well”
Case-SP
• He had extensive oral thrush and had severe dysphagia
• BP 145/90 mmHg
• He was admitted and treated with fluconazole
• Social History
– Lives alone is MSM
– Smokes 15 a day
– Alcohol 20 units a week, no recreational drugs
• Drugs
–
–
–
–
Salbutamol inhaler
Fluticasone Inhaler
Amlodopine
St Johns Wort for depression
Case-SP
•
•
•
•
•
•
•
•
•
•
•
Labs
STD screen negative
FBC,U and Es, LFTs Normal ,
Cr CL 69 mls/min, Urine protein +no glucose
CD4 33 cells/uL
VL 365000 copies/ml
Hep B immune
Hep C negative
STS negative
Resistance test and HLA B5701 awaited
Framingham 10 year risk risk 18%
You decide to start ARVs
DHHS[1]
IAS[2]
EACS[3]
EFV/TDF/FTC
Preferred
Recommended
Recommended
ATV/RTV + TDF/FTC
Preferred
Recommended
Recommended
DRV/RTV + TDF/FTC
Preferred
Recommended
Recommended
RAL + TDF/FTC
Preferred
Recommended
Recommended
LPV/RTV + TDF/FTC
Alternative
Alternative
Recommended
EFV + ABC/3TC
Alternative
Alternative
Recommended
ATV/RTV + ABC/3TC
Alternative
Alternative
Recommended
DRV/RTV + ABC/3TC
Alternative
Alternative
Recommended
NVP + TDF /FTC
Acceptable
Alternative
Recommended
MVC + TDF/FTC
Acceptable
Alternative
Alternative
RPV + TDF /FTC
Alternative
No recommendation
No recommendation
RAL + ABC/3TC
Alternative
No recommendation
No recommendation
Regimen
1. DHHS Guidelines, March 2012. 2. T. JAMA. 2012;304:321-333.
3. EACS Guidelines, November 2011.
You decide to start ARVs
What is your choice of main agent?
• NNRTI
• PI/r
• Integrase
• other
Difficulties in choosing-which 3rd
agent?
• NNRTI– may have transmitted dug resistance
– RPV may not be effective in High viral load
• Integrase
– BD
– and may have NRTI transmitted dug resistance
• PI/r
– drug interactions,
– diabetes, lipids
NNRTI/NRTI and Prevalence of
Transmitted Drug Resistance
12%
10%
prevalence of mutations
8.9%
8%
6%
5.0%
4%
2.9%
2.5%
2%
0.8%
0.4%
0%
Any class
Eacs 2011 SPREAD
NRTI
NNRTI
PI
Multi Drug
Multi Drug
Restistance (2 Resistance (3
classes)
classes)
If you decide to give a boosted PI
Drug Interactions
• What Drugs have significant interactions with a boosted
PI?
1 St Johns Wort
2 Fluticasone
3 Amlodopine
4 None
5 all
What NRTI back bone?
•
•
•
•
•
AZT/3TC
ABC/3TC
TDF/FTC
DDI/3TC
OTHER
Difficulties in choice of NRTI
• AZT– lipodystrophy
– BD
• ABC
– High Viral load
– Cardiovascular risk(smoker and diabetic and BP)
• TDF
– Renal changes,
– Bone changes
1.9
1.5
1.5
1.2
1.2
**
1.0
1.0
0.8
0.6
# PYFU:
# MI:
RR of cumulative
exposure/year
95%CI
NRTI
1.9
0.8
ZDV
ddI
138,109
523
74,407
331
ddC
29,676
148
d4T
95,320
405
3TC
ABC
TDF
152,009
554
53,300
221
39,157
139
PI†
1.2
RR of cumulative
exposure/year
95%CI
RR of recent* exposure
yes/no
95%CI
CVD – Do drugs matter? D:A:D: Recent and/or
cumulative ARV exposure and risk of MI
0.6
NNRTI
1.13
1.1
1.0
0.9
# PYFU:
# MI:
IDV
68,469
298
NFV
56,529
197
LPV/RTV
37,136
150
SQV
44,657
221
NVP
61,855
228
EFV
58,946
221
*Current or within past 6 months; †Approximate test for heterogeneity: p=0.02; **not shown due to low number of patients
receiving ddC
CVD=cardiovascular disease; ARV=antiretroviral; MI=myocardial infarction; RR=relative risk; NRTI=nucleoside reverse
transcriptase inhibitor; PI=protease inhibitor; NNRTI=nonnucleoside reverse transcriptase inhibitor; PYFU=patient years of
follow up
Adapted from Lundgren JD, et al. CROI 2009. Oral presentation 44LB.
CVD: Do drugs matter?
FDA meta-analysis of abacavir and MI
•
•
Meta-analysis of Phase
II–IV RCTs including ABC
– Mean follow up 1.6
person-years per subject
– Patients: 80% male
(mean age=39 years)
Limitations
– Young adults, so
underlying MI risk low
– Other CV risk factors
usually unknown
– Unvalidated MIs
– Some studies had a PI
control group
CVD=cardiovascular disease; FDA=Food and Drug
Administration; MI=myocardial infarction; RCTs=randomised
controlled trials; CV=cardiovascular; PI=protease inhibitor
Created from Ding X, et al. CROI 2011. Poster presentation 808.
Mantel-Haenszel Risk Difference %
(95% CI)
Academic
Trials n=5
-0.53
NIH
Trials
n=5
0.31
-0.45
GSK
Trials
n=16
-0.43
All Trials
n=26
-0.8
0.03
-0.11
-0.26 0.008
-0.4
0
1.16
0.51
0.21
0.27
0.4
0.8
1.2
Chronic renal disease: ART risk factors
• 6,843 patients (5,136 male), median age 43 yrs, 90.1% exposed to
cART, CD4 450 cells/mm3, 21.7% hypertension, 4.9% diabetes
• Median follow up 3.7 years
• 2-fold increased risk if hepatitis C RNA+
Incidence: 1.05 (0.91–1.18)/100 PYFU
Multivariate
analysis
IRR/
year
p
Tenofovir
1.16
<0.0001
Indinavir
1.12
<0.0001
Atazanavir
1.21
0.0003
Lopinavir/r
1.08
0.030
Months
ART=antiretroviral therapy; PYFU=patient years follow up; IRR=incidence rate ratio
Adapted from Mocroft A, et al. AIDS. 2010;24:1667–8.
Low bone density/fracture: Relationship to ART
ACTG 5224 & SMART: BMD loss with ART
initiation ~2-4% at 1-2 yrs1
NNRTI/PI Component
Secondary Analysis
EFV
ATV/rtv
0
0
TDF/FTC
ABC/3TC
p=.004*
p=.035*
-4
-4
-3
-3
-2
-2
-1
-1
p=.004*
-5
-5
Spine BMD percent change from week 0
NRTI Component
Primary Analysis
0
No. of subjects
TDF/FTC 128
ABC/3TC 130
24
111
122
96
144
48
Visit Week from Randomization
105
106
97
101
87
80
192
53
53
0
No. of subjects
EFV 133
ATV/rtv 125
24
48
96
144
117
116
109
102
107
91
86
81
* - two-sample t-test
No significant interaction of NRTI and NNRTI/PI components (p=0.63)
ART=antiretroviral therapy; BMD=bone mineral density; DC=drug conservation; VS=viral suppression;
NRTI=nucleoside reverse transcriptase inhibitor; NNRTI=nonnucleoside reverse transcriptase inhibitor; PI=protease
inhibitor; DXA=dual-energy X-ray absorptiometry
1. Adapted from McComsey G, et al. JID. 2011;203:1791–801.
192
Visit Week from Randomization
58
48
Case-SP
• Resistance was wild type
• He starts EFV TDF FTC
Case AP
•
•
•
•
•
35 year old Asian women presents with
Night sweats, weight loss and cough
CXR - RUL cavity and infiltrates
AAFB - smear positive and started on RZHE
Had an HIV test and was positive CD4 was 35
cells/uL
Case AP
• As her CD4 was<50 cells/uL she was offered
ARVs within 2 weeks of starting and tolerating
her TB meds
What ARV combination would you offer her?
What is your choice of main agent?
•
•
•
•
NNRTI-Efavirenz
PI/r-Lopinavir/r
Integrase-Raltegravir
other
Case AP
• Started Efavirenz but couldn't tolerate it
• What would you offer her?
•
•
•
•
NNRTI-Nevirapine
PI/r-Lopinavir/r
Integrase-Raltegravir
other
Case AP
• What would you offer her?
• NNRTI-Nevirapine-less efficacy ? Drug
interaction
• PI/r-Lopinavir/r major interaction with
rifampicin so switch to rifabutin or double
dose lopinavir/r or high dose ritonavir
400mg bd
• Integrase-Raltegravir 400 or 800mg bd
• Other-4 nucleosides