HIV Cases “What to Start” Dr Anton Pozniak Chelsea and Westminster Hospital London
Dec 24, 2015
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 Regimen 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
1. DHHS Guidelines, March 2012. 2. T. JAMA. 2012;304:321-333. 3. EACS Guidelines, November 2011.
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
2.5%2.9%
5.0%
8.9%
0.8%0.4%
0%
2%
4%
6%
8%
10%
12%
Any class NRTI NNRTI PI Multi DrugRestistance (2
classes)
Multi DrugResistance (3
classes)
pre
vale
nce
of
mu
tati
on
s
Eacs 2011 SPREAD
If you decide to give a boosted PIDrug Interactions
• What Drugs have significant interactions with a boosted PI?
1 St Johns Wort 2 Fluticasone 3 Amlodopine 4 None5 all
Difficulties in choice of NRTI
• AZT-– lipodystrophy– BD
• ABC– High Viral load– Cardiovascular risk(smoker and diabetic and BP)
• TDF– Renal changes,– Bone changes
CVD – Do drugs matter? D:A:D: Recent and/or cumulative ARV exposure and risk of MI
Adapted from Lundgren JD, et al. CROI 2009. Oral presentation 44LB.
RR
of
cum
ula
tive
e
xpo
sure
/ye
ar
95
%C
I
# PYFU: 138,109 74,407 29,676 95,320 152,009 53,300 39,157# MI: 523 331 148 405 554 221 139
RR
of
rece
nt*
exp
osu
reye
s/n
o9
5%
CI
1.9
1.5
1.2
1.0
0.8
0.6ZDV ddI ddC d4T 3TC ABC TDF
# PYFU: 68,469 56,529 37,136 44,657 61,855 58,946# MI: 298 197 150 221 228 221
IDV NFV LPV/RTV SQV NVP EFV
PI† NNRTI1.2
1.13
1.0
1.1
0.9
1.9
1.5
1.2
1.0
0.8
0.6
*Current or within past 6 months; †Approximate test for heterogeneity: p=0.02; **not shown due to low number of patients receiving ddC
RR
of
cum
ula
tive
e
xpo
sure
/ye
ar
95
%C
I
NRTI
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
**
0.27
0.21
0.51
1.16
-0.26
-0.43
-0.45
-0.53
0.008
-0.11
0.03
0.31
-0.8 -0.4 0 0.4 0.8 1.2
Mantel-Haenszel Risk Difference % (95% CI)
All Trials n=26
GSK Trials n=16
NIH Trials n=5
Academic Trials n=5
Created from Ding X, et al. CROI 2011. Poster presentation 808.
• 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: Do drugs matter?
FDA meta-analysis of abacavir and MI
CVD=cardiovascular disease; FDA=Food and Drug Administration; MI=myocardial infarction; RCTs=randomised controlled trials; CV=cardiovascular; PI=protease inhibitor
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+
Adapted from Mocroft A, et al. AIDS. 2010;24:1667–8.
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% p
rogr
e ss e
d t o
CK
D
Incidence: 1.05 (0.91–1.18)/100 PYFU
MonthsART=antiretroviral therapy; PYFU=patient years follow up; IRR=incidence rate ratio
1. Adapted from McComsey G, et al. JID. 2011;203:1791–801.
ACTG 5224 & SMART: BMD loss with ART initiation ~2-4% at 1-2 yrs1
Low bone density/fracture: Relationship to ART
NRTI ComponentPrimary Analysis
NNRTI/PI ComponentSecondary Analysis
TDF/FTCABC/3TC
p=.004*
0-1
-2-3
-4-5
Spi
ne B
MD
per
cent
cha
nge
from
wee
k 0
0 24 48 96 144 192
Visit Week from RandomizationNo. of subjects
TDF/FTC 128 111 105 97 87 53130ABC/3TC 122 106 101 80 53
* - two-sample t-testNo significant interaction of NRTI and NNRTI/PI components (p=0.63)
Visit Week from RandomizationNo. of subjects
EFVATV/rtv
133 117 109 107 86 58125 116 102 91 81 48
EFVATV/rtv
p=.035*
0-1
-2-3
-4-5
0 24 48 96 144 192
p=.004*
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
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