Upload
others
View
2
Download
0
Embed Size (px)
Citation preview
*Indicates presenting author.
POSTER PRESENTATIONS
Opportunistic Infections
P142 Low rifampicin and isoniazid concentrations are associated with delayed sputum conversion in HIV-positive patients co-infected with tuberculosis in Uganda Sekaggya, C*; Ledergerber, B; von Braun, A; Lamorde, M; Buzibye, A; Eberhard, N; Scherrer, A; Nakijoba, R; Müller, D; Henning, L; Gutteck, U; Corti, N; Musaazi, J; Kamya, M; Castelnuovo, B; Kambugu, A; Fehr, J (Kampala, Uganda)
P143 Isoniazid preventive therapy is highly cost-effective among TB/HIV co-infected patients in Uganda Wiltshire, C*; Kuznik, A; Lamorde, M (Kampala, Uganda)
P144 Predicting the in-hospital mortality in tuberculous meningitis Jipa, R*; Manea, E; Olaru, I; Merisor, S; Niculae, C; Hristea, A (Bucharest, Romania)
P145 Tuberculosis infection in HIV patients in a Portuguese population Maio, A; Coutinho, D; Nunes, S; Velez, J*; Freitas, F; Oliveira, C (Aveiro, Portugal)
P147 Use of dolutegravir in combination with rifampicin-based TB therapy in HIV/TB co-infected patients: real-world experience from Leeds, UK Cevik, M*; Vincent, R; McGann, H (Edinburgh, UK)
P148 The practice and value of interferon gamma release assay testing for latent tuberculosis infection in people living with HIV: a retrospective review of patients at Leeds Teaching Hospitals Trust Baggott, A*; Cevik, M; McGann, H (Leeds, UK)
P150 Incidence and survival in HIV-infected patients with central nervous system opportunistic infections in the cART era: a 10-year Romanian single-center experience Oprea, C*; Ianache, I; Popa, I; Ene, L; Radoi, R; Tardei, G; Ungureanu, E; Erscoiu, S; Ceausu, E; Calistru, P (Bucharest, Romania)
P151 In spite of international guidelines, vaccine coverage of HIV-infected patients remains low Gagneux-Brunon, A*; Frésard, A; Detoc, M; Charrière, E; Ronat, V; Lucht, F; Botelho-Nevers, E (Saint-Etienne, France)
P152 Does syphilis impact on HIV infection when both diagnoses are concomitant? Palacios, R*; González-Domenech, C; Antequera, I; Ruiz-Morales, J; Nuño, E; Clavijo, E; Márquez, M; Santos, J (Málaga, Spain)
Backgroundq HIV-infection is a major risk factor for development of active tuberculosis (TB) and has been associated with poor outcome and high relapse rates 1,2,3
q HIV-positive patients co-infected with TB have anti-TB drug concentrations lower than reference ranges4; however the relationship betweenconcentrations of anti-TB drugs and treatment response remains controversial. We sought to evaluate if there is an association between lowconcentrations of first-line anti-TB drugs and delayed sputum conversion in a cohort of HIV-TB co-infected Ugandan adults.
Christine Sekaggya-Wiltshire(1), Bruno Ledergerber (2), Amrei von Braun (1,2), Mohammed Lamorde(1), Allan Buzibye(1), Nadia Eberhard(1,2), Alexandra Scherrer (2), Rita Nakijoba(1), Daniel Muller(2), Ursula Gutteck (2), Natascia Corti(2), Joseph Musaazi(1), Kamya
Moses(3), Barbara Castelnuovo(1), Andrew Kambugu(1), Jan Fehr(2)
1. Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda 2. Division of Infectious Diseases and HospitalEpidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland 3. Department of Medicine, College of Health Sciences, MakerereUniversity, Kampala, Uganda
MethodsWe enrolled HIV-infected Ugandan adults diagnosed with a first episode of pulmonary TB (microbiologically confirmed or clinically diagnosed). TB wasdiagnosed using sputum smear, culture and or GeneXpert. Patients were excluded if they had TB of any organ requiring treatment for more than 6months, previous treatment for mycobacteria other than TB (MOT), pregnancy, decompensated liver and renal disease. Patients with resistance toany first line anti-TB drug were withdrawn from the study. All patients received a fixed dose regimen consisting of isoniazid, rifampicin, ethambutol andpyrazinamide using World Health Organization weight bands.q Pharmacokinetic analysis: patients underwent pharmacokinetic sampling 1, 2, and 4 hours after drug intake to estimate the maximum drug
concentrations (eCmax); at 2, 8, and 24 weeks of TB-treatment using high-performance liquid chromatography (HPLC-UV).q Outcomes and follow up: sputum microscopy and culture were done at baseline, week 2, week 8, and week 24.Analysisq We compared the eCmax of isoniazid, rifampicin, ethambutol and pyrazinamide with the standard reference ranges5. Low concentrations were
defined as an eCmax below the previously described cut-offs: rifampicin <8mg/L and isoniazid <3mg/L, ethambutol <2mg/L and pyrazinamide<20mg/L at any of weeks 2, 8 or 24 5
q Cox regression and Kaplan-Meier curves were used to determine the association between the time to sputum conversion dynamics and anti-TBdrug concentrations.
Conclusions
Figure 1. Figure: Kaplan Meier showing probability of remaining smear or culture positive over time among those with 0/1/2 drugs below the cut-off
Acknowledgements
ResultsFrom April 2013 to May 2015, we included 227 HIV infected patients with positive sputum cultures or smears at baseline; 58% were male (Table 1).Patients with low isoniazid and rifampicin concentrations at any time point were less likely to undergo sputum conversion before the end of follow-upcompared to those with normal concentrations at all time-points (HR:0.51; 95%CI:0.35-0.72; P<0.001 and HR:0.61; 95%CI:0.44-0.84; P=.003respectively) (Table 2) In addition, patients with ≥ 1 drugs below the cut-off had a higher probability of remaining culture/smear positive over timecompared to those with no drug below the cut-off (Figure 1).
1. Holland, D.P., et al., Therapeutic drug monitoring of antimycobacterial drugs in patients with both tuberculosis and advanced humanimmunodeficiency virus infection. Pharmacotherapy, 2009. 29(5): p. 503-10.
2. Perriens, J.H., et al., Increased mortality and tuberculosis treatment failure rate among human immunodeficiency virus (HIV)seropositive compared with HIV seronegative patients with pulmonary tuberculosis treated with "standard" chemotherapy in Kinshasa,Zaire. Am Rev Respir Dis, 1991. 144(4): p. 750-5.
3. Perriens, J.H., et al., Pulmonary tuberculosis in HIV-infected patients in Zaire. A controlled trial of treatment for either 6 or 12 months. NEngl J Med, 1995. 332(12): p. 779-84.
4. . Burhan, E. et al. Isoniazid, Rifampin, and Pyrazinamide Plasma Concentrations in Relation to Treatment Response in IndonesianPulmonaryTuberculosis Patients. AAC ASM. 2013. Vol 57 p. 3614–3619
5. Peloquin, C.A., Therapeutic drug monitoring in the treatment of tuberculosis. Drugs, 2002. 62(15): p. 2169-83
Backgroundq HIV-HIV-HIV infection is a major risk factor for development of active tuberculosis (TB) and has been associated with poor outcome and high relapse rates 1,2,3
q HIV-HIV-HIV positive patients co-infected with TB have anti-TB drug concentrations lower than reference ranges4; however the relationship betweenconcentrations of anti-TB drugs and treatment response remains controversial. We sought to evaluate if there is an association between lowconcentrations of first-line anti-TB drugs and delayed sputum conversion in a cohort of HIV-TB co-infected Ugandan adults.
Christine Sekaggya-Wiltshire(1), Bruno Ledergerber (2), Amrei von Braun (1,2), Mohammed Lamorde(1), Allan Buzibye(1), Nadia Eberhard(1,2), Alexandra Scherrer (2), Rita Nakijoba(1), Daniel Muller(2), Ursula Gutteck (2), Natascia Corti(2), Joseph Musaazi(1), Kamya
Moses(3), Barbara Castelnuovo(1), Andrew Kambugu(1), Jan Fehr(2)
1. Infectious Diseases Institute, College of Health Sciences, Makerere University, Kampala, Uganda 2. Division of Infectious Diseases and HospitalEpidemiology, University Hospital Zurich, University of Zurich, Zurich, Switzerland 3. Department of Medicine, College of Health Sciences, MakerereUniversity, Kampala, Uganda
MethodsWe enrolled HIV-HIV-HIV infected Ugandan adults diagnosed with a first episode of pulmonary TB (microbiologically confirmed or clinically diagnosed). TB wasdiagnosed using sputum smear, culture and or GeneXpert. Patients were excluded if they had TB of any organ requiring treatment for more than 6months, previous treatment for mycobacteria other than TB (MOT), pregnancy, decompensated liver and renal disease. Patients with resistance toany first line anti-TB drug were withdrawn from the study. All patients received a fixed dose regimen consisting of isoniazid, rifampicin, ethambutol andpyrazinamide using World Health Organization weight bands.q Pharmacokinetic analysis: patients underwent pharmacokinetic sampling 1, 2, and 4 hours after drug intake to estimate the maximum drug
concentrations (eCmax); at 2, 8, and 24 weeks of TB-treatment using high-performance liquid chromatography (HPLC-UV).q Outcomes and follow up: sputum microscopy and culture were done at baseline, week 2, week 8, and week 24.Analysisq We compared the eCmax of isoniazid, rifampicin, ethambutol and pyrazinamide with the standard reference ranges5. Low concentrations were
defined as an eCmax below the previously described cut-offs: rifampicin <8mg/L and isoniazid <3mg/L, ethambutol <2mg/L and pyrazinamide<20mg/L at any of weeks 2, 8 or 24 5
q Cox regression and Kaplan-Meier curves were used to determine the association between the time to sputum conversion dynamics and anti-TBdrug concentrations.
Conclusions
Figure 1. Figure: Kaplan Meier showing probability of remaining smear or culture positive over time among those with 0/1/2 drugs below the cut-off
Acknowledgements
ResultsFrom April 2013 to May 2015, we included 227 HIV infected patients with positive sputum cultures or smears at baseline; 58% were male (Table 1).Patients with low isoniazid and rifampicin concentrations at any time point were less likely to undergo sputum conversion before the end of follow-upcompared to those with normal concentrations at all time-points (HR:0.51; 95%CI:0.35-0.72; P<0.001 and HR:0.61; 95%CI:0.44-0.84; P=.003respectively) (Table 2) In addition, patients with ≥ 1 drugs below the cut-off had a higher probability of remaining culture/smear positive over timecompared to those with no drug below the cut-off (Figure 1).
1. Holland, D.P., et al., Therapeutic drug monitoring of antimycobacterial drugs in patients with both tuberculosis and advanced humanimmunodeficiency virus infection. Pharmacotherapy, 2009. 29(5): p. 503-10.
2. Perriens, J.H., et al., Increased mortality and tuberculosis treatment failure rate among human immunodeficiency virus (HIV)seropositive compared with HIV seronegative patients with pulmonary tuberculosis treated with "standard" chemotherapy in Kinshasa,Zaire. Am Rev Respir Dis, 1991. 144(4): p. 750-5.
3. Perriens, J.H., et al., Pulmonary tuberculosis in HIV-HIV-HIV infected patients in Zaire. A controlled trial of treatment for either 6 or 12 months. NEngl J Med, 1995. 332(12): p. 779-84.
4. . Burhan, E. et al. Isoniazid, Rifampin, and Pyrazinamide Plasma Concentrations in Relation to Treatment Response in IndonesianPulmonaryTuberculosis Patients. AAC ASM. 2013. Vol 57 p. 3614–3619
5. Peloquin, C.A., Therapeutic drug monitoring in the treatment of tuberculosis. Drugs, 2002. 62(15): p. 2169-83
P142
Corresponding addresses:*[email protected]
Allsponsorsandpartners:qAbbvieqBristol-MyersSquibbqGileadSciencesqJanssenPharmaceuticalsqMerck&CoqRoche-DiagnosticsqShimadzu
q ViiV-Healthcareq VereinLungeZurichq MEPI-MESAUconsortium
q SOUTHstudyteamq SOUTHstudypatients
Characteristics N= 227
Gender (males) 134 (59%)Age (median, in years) 34 (IQR: 29 - 40)BMI (median, in kg/m2) 19.2 (IQR: 17.7 - 21.5)
BMI <18 74 (32.6%)Time since HIV diagnosis (median, in months)
6.0 (IQR: 0.5, 11.0)
WHO stage III 200 (88.1%)WHO stage IV 18 (7.9%)CD4 count (median, in cells/µL) 190 (IQR: 66 - 340) CD4 count <200 cells/µL 97 (51.6%)CD4 count <50 cells/µL 41 (21.8%)First line ART at baseline 46 (20.2%)Second line ART at baseline 3 (1.3%)
Table 1. Baseline characteristics
Low isoniazid or rifampicin concentrations in HIV-TB co-infected patientsresulted in delayed sputum conversion.This has potential implications on TB transmission.
References
Drug HR(95%CI) P-value
Isoniazid(<3mg/L) 0.51(0.35– 0.74) <0.001
Rifampicin(<8mg/L) 0.61(0.44– 0.85) 0.003
Ethambutol(<2mg/L) 0.81(0.60– 1.09) 0.167
Pyrazinamide(<20mg/L) 0.97(0.40– 2.36) 0.949
Low rifampicin and isoniazid concentrations are associated with delayed sputum conversion in HIV positive patients co-infected with tuberculosis in
Uganda
Table 2: Association between drug concentrations below the reference range and sputum conversion by the end of follow-up
C. S
ekag
gya1
* , A
. Kuz
nik2
, M. L
amor
de1
1. In
fect
ious
Dis
ease
s In
stitu
te, M
aker
ere
Uni
vers
ity, K
ampa
la, U
gand
a2.
Reg
ener
on P
harm
aceu
tical
s, T
arry
tow
n, N
ew Y
ork,
Uni
ted
Stat
es o
f Am
eric
a
Background
Ison
iazi
dpr
even
tive
ther
apy
(IPT
)ha
sbe
enre
com
men
ded
byth
eW
orld
Hea
lthO
rgan
izat
ion
(WH
O)
for
the
trea
tmen
tof
late
nttu
berc
ulos
is(T
B)in
patie
nts
infe
cted
with
HIV
.In
Uga
nda,
the
upta
keof
IPT
isst
illlo
ww
ithse
vera
lpe
riod
sof
scar
city
ofis
onia
zid
ever
yye
ar.
The
aim
ofth
isst
udy
was
tode
term
ine
the
cost
effe
ctiv
enes
sof
IPT
amon
gH
IVin
fect
edpa
tient
sin
anur
ban
out-
patie
ntcl
inic
inK
ampa
la,U
gand
a.
Methods
Usi
ngde
cisi
onan
alys
is,
we
mod
eled
the
impa
ctof
IPT
vers
usno
IPT
onco
sts
and
patie
ntou
tcom
es,
usin
ga
prob
abili
tyof
deve
lopi
ngT
Bof
2.5%
inth
eIP
Tar
man
d7.
5%in
the
no-IP
Tar
m,
base
don
apu
blis
hed
sour
ce1 .
We
estim
ated
the
med
ian
daily
pric
eof
ison
iazi
dat
$0.0
48ov
erth
eco
urse
of6
mon
ths,
base
don
anin
tern
atio
nald
rug
pric
elis
ts2 .
We
also
incl
uded
the
cost
offir
stan
dse
cond
line
TB
trea
tmen
tat
$12.
90an
d$1
10.7
,re
spec
tivel
y,ba
sed
onpu
blis
hed
sour
ces2
.T
heT
Bas
soci
ated
mor
talit
yra
te(1
0.5%
)an
dfa
ilure
/rel
apse
rate
(12.
4%)
asso
ciat
edw
ithT
Btr
eatm
ent
was
obta
ined
from
asy
stem
atic
revi
ewof
first
line
trea
tmen
tof
TB
inH
IVin
fect
edpa
tient
s3.
We
used
alif
eex
pect
ancy
of35
.1ye
ars
estim
ate
from
ast
udy
onpa
tient
son
Com
bine
dA
ntir
etro
vira
lT
hera
pyin
Uga
nda4
.St
udy
resu
ltsw
ere
expr
esse
din
cost
per
disa
bilit
yad
just
edlif
eye
ars
(DA
LY)
aver
ted
and
com
pare
dag
ains
tW
HO
cost
-effe
ctiv
enes
sth
resh
olds
.
ISO
NIA
ZID
PR
EVEN
TIV
E T
HER
AP
Y IS
HIG
HLY
CO
ST E
FFEC
TIV
E A
MO
NG
TB
-HIV
CO
-IN
FEC
TED
PA
TIE
NT
S IN
UG
AN
DA
Conclusion
Use
of I
PT is
hig
hly
cost
effe
ctiv
e in
TB-
HIV
co-
infe
cted
pa
tient
s. H
ealth
pro
vide
rs s
houl
d be
enc
oura
ged
to in
crea
se
com
plia
nce
with
WH
O g
uide
lines
on
trea
tmen
t of
late
nt T
B.
Results
The
full
cour
se o
f IPT
is a
ssoc
iate
d w
ith a
cos
t of
$8.
64, b
ut
appr
oxim
atel
y $1
.33
of w
hich
are
offs
et d
ue t
o re
duce
d ne
ed fo
r fir
st a
nd s
econ
d lin
e T
B th
erap
y, y
ield
ing
a ne
t co
st o
f $7.
31. I
PT
is a
lso
asso
ciat
ed w
ith a
red
uctio
n in
DA
LYs
by 0
.118
, yie
ldin
g a
cost
/DA
LY a
vert
ed o
f $62
, whi
ch is
wel
l bel
ow U
gand
an p
er
capi
ta G
DP.
Table:DecisiontreeanalysisforcosteffectivenessofIPT
References
1.A
kolo
C,e
t al
. Tre
atm
ent
of la
tent
tub
ercu
losi
s in
fect
ion
in H
IV in
fect
ed p
erso
ns. T
he C
ochr
ane
data
base
of s
yste
mat
ic r
evie
ws.
201
0(1)
:Cd0
0017
1.2.
MSH
. Int
erna
tiona
l Dru
g Pr
ice
Indi
cato
r G
uide
. Cam
brid
ge, M
A, U
SA: M
anag
emen
t Sc
ienc
es fo
r H
ealth
. 200
8.3.
Man
abe
YC
, et
al. R
ifam
pici
n fo
r co
ntin
uatio
n ph
ase
tube
rcul
osis
tre
atm
ent
in U
gand
a: a
cos
t-ef
fect
iven
ess
anal
ysis
. Plo
S on
e. 2
012;
7(6)
:e39
187.
4. M
ills
EJ, e
t al
. Life
exp
ecta
ncy
of p
erso
ns r
ecei
ving
com
bina
tion
antir
etro
vira
l the
rapy
in lo
w-in
com
e co
untr
ies:
a c
ohor
t an
alys
is fr
om U
gand
a. A
nnal
s of
inte
rnal
med
icin
e. 2
011;
155(
4):2
09-1
6.
Trea
tmen
tN
o tre
atm
ent
Res
ult
Prob
ility
of T
B (%
)2.
57.
5Pr
obilit
y of
Mor
talit
y/TB
(%)
10.5
10.5
Prob
abilit
y of
Tre
atm
ent F
ailu
re (%
)12
.412
.4Li
fe E
pect
ancy
(Yea
rs)
35.1
35.1
Dis
coun
ted
Life
Exp
ecta
ncy
22.4
822
.48
DAL
Y0.
0590
10.
1770
3C
ost o
f Firs
t Lin
e Th
erap
y ($
)12
.912
.9Se
cond
Lin
e Th
erap
y ($
)11
0.7
110.
7C
ost o
f IN
H fo
r 6 m
onth
s ($
)8.
640
Tota
l Cos
t ($)
9.31
2.00
Red
uctio
n in
DAL
Y0.
1180
2Fi
rst a
nd s
econ
d lin
e TB
ther
apy
($)
1.33
Net
cos
t of I
PT ($
)7.
31C
ost/D
ALY
aver
ted
($)
$62
P143
P144
R. Jipa1, E. Manea², I. Olaru³, S. Merisor², C. Niculae², A. Hristea¹´²
1. Carol Davila University of Medicine and Pharmacy, Bucharest, RO; 2. National Institute for Infectious Diseases “Prof. Dr. Matei Bals”, Bucharest, RO; 3. Division of Clinical Infectious Diseases, German Center for Infection Research Tuberculosis Unit, Research Center Borstel, Borstel, DE
Predictingthein-hospitalmortalityintuberculous meningitis
• Mortality in tuberculous meningitis (TBM) varies from around 20% in HIVnegative patients to more than 50% in HIV positive patients.• A prediction score for unfavorable outcome including altered consciousness,neurological deficit, hydrocephalus,vasculitis, immunosuppression and diabetesmellitus has been recently published (1).Objective:• Assess if this prediction score is better associated with mortality than
neurological staging in HIV-infected versus HIV non-infected patients.
• Retrospective study of patients admitted with TBM between 2005-2015 in atertiary care facility.• Hospital records were reviewed and data on patient history, epidemiologicalcharacteristics, clinical findings including neurological examination, laboratoryand imaging findings were analyzed.• Patients were defined as having TBM according to a consensus definitionpublished by Marais (2) et al. and further divided into three categories of TBM(definite, probable and possible).• Neurological stages were classified according to the Medical ResearchCouncil (MRC) definitions (3).• HAMSI scoring (1) was calculated for all patients for further distribution ofmortality.
.• We identified 115 patients of which 32 (28%) patients were in MRC stage 1,58( 50%) were in stage 2 and 25(22%) in stage 3. Patient characteristics areshown in table 1.
Table 1. Patient characteristics
•Immunosupression, particularly HIV infection, is associated with highermortality in TBM.• Higher Hamsi score and advanced neurological impairment were associatedwith higher mortality.• Hamsi score was similar with clinical staging in predicting in-hospital mortality.•In advanced HIV disease the mortality was not associated with CD4 cell count.
RESULTS
Contact details: [email protected]
METHODS
BACKGROUND
RESULTS
CONCLUSIONS
REFERENCES1. Erdem H, Ozturk-Engin D, Tireli H, et al. Hamsi scoring in the prediction of unfavorable outcomes from tuberculous meningitis: results of Haydarpasa-II study. J Neurol. 2015.
262(4):890-898.2. Marais S, Thwaites G, Schoeman JF, et al. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis. 2010; 10(11):803-12.3. Medical Research Council Streptomycin treatment of tuberculous meningitis. Lancet. 1948; 1(6503):582-96.
Mortality according to neurological staging
Comparison of ROC curves
• Area under ROC curve for Hamsi score versus clinical staging was 0,775versus 0,721, respectively.
Mortality distribution according to HAMSI score
CD 4 levels in HIV deceased vs survivor
patients
Median HAMSI score in HIV infected vs non-infected
patients
Factors associated with in-hospital mortality
MaioMaio A, A, A, CoutinhoCoutinho D, D, NunesNunes S, S, S, Velez JVelez J, Freitas F, Oliveira C MaioMaio A, A, A, CoutinhoCoutinhoCoutinhoInfectious Diseases Ward
D, D, D, Infectious Diseases Ward Infectious Diseases Ward –
NunesNunesNunesNunesD, –– Centro
Velez JVelez JVelez J, Freitas F, Oliveira C , Freitas F, Oliveira C Nunes S, S, S, Centro Centro Hospitalar
, Freitas F, Oliveira C , Freitas F, Oliveira C , Freitas F, Oliveira C HospitalarHospitalarHospitalar do
, Freitas F, Oliveira C , Freitas F, Oliveira C do do Baixo
, Freitas F, Oliveira C , Freitas F, Oliveira C BaixoBaixo Vouga
, Freitas F, Oliveira C VougaVouga –
, Freitas F, Oliveira C , Freitas F, Oliveira C –––– Aveiro
Tuberculosis (TB) and human immunodeficiency virus (HIV) have been closely linked since the emergence of AIDS.Worldwide, TB is the most common opportunistic infection affecting HIV-seropositive individuals and remains the most commoncause of death in patients with acquired immune deficiency syndrome (AIDS). HIV greatly increases the risk of active disease fromTB and leads to more frequent extrapulmonary involvement, atypical manifestations and paucibacillary disease, which can delaydiagnosis and adequate treatment.
Retrospective analysis of files pertaining inpatients with TB and concurrent HIV infection admitted betweenJanuary 2005 and December 2014. Data were analysed using χ2 or Fisher exact test. A p-value < 0.005 was considered as having astatistical significant relation. Odds ratio (OR) was also calculated.
- 222 patients with TB were admitted to theInfectious Diseases Ward.
- 48 patients had concurrent HIV infection (21,6%).
- 3 patients had concomitant PTB and ETB.
- No statistical difference was found between thePTB and ETB group (p=0.052).
Pulmonary tuberculosis(PTB)
Extrapulmonary tuberculosis(ETB)
Total Total
Cases(n)
15 (31.3%)Men - 12 (80.0%)
Women - 3 (20.0%)
36 (75.0%)Men - 29 (80.6%)
Women - 7 (19.4%)Median age
(years) 34 (IQR 31.5-43.0) 43 (IQR 32.0-50.0)
Lengh of stay(days) 17 (IQR 11.0-24.0) 18 (IQR 8.8-27.8)
Diagnosis n (%)
Confirmed (culture or PCR + smear) 17 (35,4%)Probable (PCR or smear or histology) 16 (33,3%)Possible (clinical criteria) 15 (31,3%)
- 70.8% of cases diagnosed at HIV diagnosis (n=34). The remainderoccurred in patients with poor adherence to HIV treatment regimens.
- CD4 count was obtained in 40 patients.
- Median CD4 count was 74.5 cells/µL (13 - 136).
- Median viral load was 211066 copies/mL (1430 - 4430000).
15
1110
8
8
3 1PulmonaryDisseminatedLymphaticMeningealPleuralGastrointestinalOsteoarticular
- HIV infection was associated with presence of disseminated (p-value 0.000, OR 12.64), pleural (p-value 0.000, OR 8.50), meningeal(p-value 0.000, OR 2.96) and lymphatic forms of TB (p-value 0.000, OR 2.38).
- HIV absence was associated with pulmonary (p-value 0.000, OR 4.08) and osteoarticular forms (p-value 0.000, OR 5.42) of TB.
- Six patients died (PTB n=2 vs ETB n=5).
- No particular prevalence of any TB form was observed.
Risk of ETB in HIV positive patients seems to be higher than for PTB. We found an association of HIV infection withdisseminated, pleural, meningeal and ganglionar forms of disease. Definitive diagnosis is typically difficult due to paucibacillarydisease and empirical therapy, based on clinical suspicion, is not unusual. A timely diagnosis and a prompt, and adequate,treatment can favourably alter the prognosis in this population.
11.1. DhedaDheda K,K,K, BarryBarry CECE 333rd,rd, MaartensMaartens GGG.G. TuberculosisTuberculosis.Tuberculosis. LancetLancet 20152015.2015. 222.22. SlootSloot R,R, SchimSchim vanvan derder LoeffLoeff MF,MF, KouwKouw PM,PM, BorgdorffBorgdorff MWMW.MW.MW.MW RiskRisk ofof tuberculosistuberculosis afterafter recentrecent exposureexposure.exposure. AAA 101010-10-yearyear followfollow-follow-upupup studystudy ofof contactscontacts ininin AmsterdamAmsterdam.Amsterdam. AmAm JJ RespirRespir CritCrit CareCare MedMed 20142014;2014; 190190:190:10441044.1044. 3333.HwangHwang JJ etetet alalal.
11. DhedaDhedaDhedaal. Incidence
K,K,K,DhedaDheda K,IncidenceIncidenceIncidence and
BarryBarryBarryandand Risk
CECECE 33rd,BarryBarry CERiskRiskRisk factors
rd,rd,rd,factorsfactorsfactors of
MaartensMaartens GGG.MaartensMaartensofofofofof Tuberculosis
TuberculosisTuberculosisTuberculosisTuberculosisTuberculosisTuberculosis in
TuberculosisTuberculosisTuberculosisTuberculosisinininin Patients
LancetLancetLancetTuberculosisTuberculosis.PatientsPatients with
LancetLancet 20152015Lancetwithwith Human
2222. SlootSlootSlootSloot R,R, SchimSchim201520152015.HumanHumanHuman Immunodeficiency
vanvanvanSchimSchim vanImmunodeficiencyImmunodeficiencyImmunodeficiency Virus
derder LoeffLoeffLoeffderderVirusVirus Infection
LoeffInfectionInfection.
MF,InfectionInfection. J
KouwKouwMF,MF,MF,MF,MF,JJJJ Korean
PM,PM,PM,KouwKouw PM,KoreanKoreanKorean Med
BorgdorffPM, BorgdorffBorgdorffMedMed Sci
BorgdorffBorgdorffSciSci 2013Borgdorff
20132013;MWBorgdorffBorgdorff
20132013;; 28MWMWMW2828282828:
.MWMW.MW.MWMWMW2828::: 374
RiskRisk374374374-
RiskRiskRiskRisk374374374--377
of377377.
ofofof377377377377. 4
tuberculosistuberculosis4444.tuberculosistuberculosistuberculosistuberculosistuberculosis44444. Leedstuberculosis
LeedsLeeds ILtuberculosistuberculosistuberculosis
ILILILIL ettuberculosis aftertuberculosis
etetetet alafterafterafteralalalalal.
after recentafterafterafteralal. Site
recentrecentSiteSiteSite of
recent exposureexposureexposureexposure. AAAArecentrecentrecentofofofof Extrapulmonary
yearyearyearyear followfollowfollow10101010ExtrapulmonaryExtrapulmonaryExtrapulmonaryExtrapulmonary Tuberculosis
followfollowTuberculosisTuberculosisTuberculosis is
studystudystudy ofofofupupupupupisisisis Associated
contactsof contactscontactsAssociatedAssociated with
contactscontactscontactswithwith HIV
AmsterdamAmsterdaminininHIVHIV Infection
AmsterdamInfectionInfection.
AmsterdamAmsterdamAmsterdam. AmAmAmAmsterdamAmsterdamInfectionInfection. Clinical
J RespirRespirRespirAmAm JClinicalClinical Infectious
CritCrit CareCareCareCritCritInfectiousInfectious Diseases
MedMedCare MedMedDiseasesDiseases 2012
Med20122012;
20142014201420122012;; 55
2014201455555555(
20142014555555((1
20142014;(((11);1111)):
190190190190190190190)))))::: 75190190190
7575757575-190:10441044
7575--811044.10441044104410441044104481818181818181.
Use of dolutegravir in combination with rifampicin based TB therapy in HIV/TB co-infected patients
Cevik M1,Vincent R2,McGann H2
1Regional Infectious Diseases Unit, Western General Hospital, Edinburgh, UK, 2Infectious Diseases Department, St James’s University Hospital, Leeds, UK
This small study highlights the use of twice daily DTG in combination with RIF as a safe and efficacious treatment option in HIV/TB co-infected population.
In this cohort all patients tolerated this combination well with no serious adverse events including TB-IRIS.
However more robust clinical data are needed to establish the longer term efficacy, safety and tolerability of twice daily DTG in combination with RIF
Background
Conclusion
Methods
• Tuberculosis remains a significant cause of morbidity and mortality among patients infected with HIV
• Rifampicin (RIF)-based therapy is the first line TB treatment however there are significant drug interactions between TB and HIV therapy as RIF is a potent inducer of cytochrome p450 and UGT
• Dolutegravir(DTG) is substrate of UGT1A1 and CYP3A4 both induced by RIF1 (Fig 1)
• Coadministration of RIF decreases DTG plasma concentrations that can lead to reduced concentrations of DTG with risk of treatment failure or resistance
• A Phase I study showed that DTG at 50 mg twice daily given together with RIF was well-tolerated and resulted in DTG concentrations similar to those of DTG 50 mg given once daily2
• It is recommended to use DTG 50mg BD when given with RIF
• Our HIV MDT at Leeds Teaching Hospitals has approved the use of DTG in TB/HIV co-infected patients who had adverse reactions with efavirenz or where efavirenz was contraindicated
• We aim to present real world experience from Leeds of our HIV/TB coinfected patients who were on RIF based TB therapy in combination with DTG based regimen
References: 1) Reese M, Savina P, Generaux GT et al. In Vitro Investigations into the Roles of Drug Transporters and Metabolizing
Enzymes in the Disposition and Drug Interactions of Dolutegravir, a HIV Integrase Inhibitor. Drug Metabolism and Disposition February 2013, 41 (2) 353-361
2) Dooley K, Sayre P, Borland J et al. Safety, tolerability, and pharmacokinetics of the HIV integrase inhibitor dolutegravir given twice daily with rifampin or once daily with rifabutin: results of a phase 1 study among healthy subjects. J Acquir Immune Defic Syndr. 2013 Jan 1;62(1):21-7
P147
Figure 1: Metabolic profile of DTG
Results
• All HIV/TB co-infected patients who were on DTG-based ART and was receiving RIF-based TB therapy were identified.
• Data were retrospectively collated through electronic patient records and case note review. Descriptive statistics were performed to examine demographics, baseline characteristics, CD4 count and HIV viral load.
• We identified 7 patients (1 male) who were on DTG based regimen in combination with RIF. Patient demographics are displayed in Table 1.
• Median age was 41 years (27-48) and all were black african in origin
• 5 patients were naive to ART whereas 2 were ART experienced. 1 patient had transmitted resistance but there was no other baseline resistance mutations identified.
• DTG was used 50mg BD in all patients. 3 patients were on 3TC/ABC/ DTG and 4 patients were on FTC/TDF/DTG
• At baseline median CD4 count was 90 cells/mL (3-365), 5 patients had CD4 <100 cells/mL. At 6 months after initiation of ART, median CD4 count improved to 230 cells/mL (104-625).
• At baseline 1 of the ART experienced patients had HIV RNA of 240,000 copies/mL. This patient with known transmitted drug resistance (T69 deletion, Y181C, G190A mutations) had well documented poor adherence, had stopped her treatment completely prior to re-starting ART and was prescribed FTC/TDF/DTG 2 weeks after starting TB therapy
Figure 2. % of patients with a VL < 40 copies/ml
%
0
25
50
75
100
Time since starting DTG
Baseline 6 months
ART-naïve ART-experienced
• At 6 months 6/7 patients were virally suppressed. The patient with poor adherence discussed earlier had a HIV RNA of 3,100 c/ml. Repeat HIV RNA a month later was suppressed but resistance testing showed a new M184 view mutation with no integrate mutations and the patients treatment regimen was changed.
• All patients successfully completed TB therapy
• During the treatment there were no Grade 3/4 side effects and no patient developed TB- associated Immune reconstitution inflammatory syndrome (IRIS)
Number (%)
ART-naïve (%)
ART- exp (%)
Total 7 (100) 5 (100) 2 (100)
Gender Female 6 (86) 5 (100) 1 (50)
Age (years) >40 5 (70) 4 (80) 1 (50)
Risk for HIV acquisition MSM 1 (14) 0 (0) 1 (50)
HIV RNA >100,000 c/mL 4 (57) 3 (60) 1 (50)
TB diagnosis
Disseminated 5 (70) 4(80) 1 (50)
CNS involvement 1 (14) 0 (0) 1 (50)
Pulmonary only 1 (14) 1 (20) 0 (0)
Table 1. Patient demographics
HIV Drug Therapy Glasgow, 23-26 Oct 2016 correspondence: [email protected]
How Effective Are The UK Guidelines For Screening For Latent TB Infection In People Living
With HIV? Baggott A1, Cevik M2, McGann H1
1Infectious Diseases Department, St James’s University Hospital, Leeds, UK 2Infectious Diseases Unit, Western General Hospital, Edinburgh, UK
• This cohort of 31 patients identifies 14 cases of active, fully sensitive TB that could have potentially been prevented if they had been screened earlier in their HIV infection. However, this does assume no indeterminate or false negative IGRA results, which is unlikely.
• Clinicians in Leeds have not been screening for latent TB in patients diagnosed with HIV. The lack of clarity and conflicting advice in these national guidelines together with the complexity of the BHIVA guideline may have contributed to this situation.
• Excluding patients on ART for more than two years from high prevalence countries would have lost the opportunity to potentially prevent 3 cases of active TB. • Despite the reduced TB risk for those on ART, as shown in the START (3) study, patients from high prevalence TB countries continue to have a higher risk and
hopefully this will be reviewed in the 2017 guideline. • Updated guidelines with clear recommendations for TB screening in people living with HIV are needed.
Background
• This cohort of 31 patients identifies
Conclusion
Methods
• The 2016 NICE TB guidelines recommend screening for TB in people living with HIV with a CD4 count < 200.
• Otherwise screening should depend on risk as in the general population. • It recommends using an interferon gamma release assay (IGRA) and a
Mantoux test together in HIV infection where the CD4 count is <200, and with an IGRA test alone in less severe immunocompromise. (1)
• The 2011 BHIVA TB guideline recommends the use of IGRA alone for diagnosing latent TB. (2)
• It specifies three categories of patients to whom this testing should be offered:
• A retrospective review was conducted of all patients diagnosed with both TB
and HIV in the Leeds Teaching Hospitals Trust during the past five years. • We examined if patients with risk factors for TB had been screened for latent
TB with an IGRA test at the time of HIV diagnosis and, if so, what the result had been and how this had influenced treatment.
• Demographic data was collected about the patients and their laboratory results, treatment histories and treatment outcomes were analysed.
References: 1.) NICE Guidelines (NG33). Tuberculosis: Prevention, diagnosis, management and service organisation. January 2016. 2.) British HIV Association guidelines for the treatment of TB/HIV coinfection. AL Pozniak, KM Coyne, RF Miller, MCI Lipman, AR Freedman, LP Ormerod, MA Johnson, S Collins and SB Lucas. 2011. 3.) Initiation of Antiretroviral Therapy in Early Asymptomatic HIV Infection. The INSIGHT START Study Group. N Engl J Med 2015; 373:795-807.
HIV Drug Therapy Glasgow, 23-26 Oct 2016
Results and Analysis • The cohort consisted of 31 patients. 25 were Black African in ethnicity (22 born
in Africa and 3 born in the UK), one was South East Asian, four were White Other (born in medium TB incidence countries) and one was White British.
• The median age was 43 with a range from 27 to 59. • 16 were diagnosed with HIV more than six months before they were diagnosed
with TB and 15 were diagnosed with TB at the same time (within six months) as they were diagnosed with HIV.
• Two patients had MDRTB and screening for latent TB infection would not have prevented them from developing active disease. As such, 14 patients were identified who might have benefited from timely TB screening and chemoprophylaxis.
• The five patients who did not meet BHIVA criteria for screening were excluded because of their length of time on treatment. Three of these were from high incidence countries but were excluded as they had been on HAART for 4-9 years with CD4 counts ranging from 365 to 498. The two patients who did not meet the NICE criteria were excluded because their CD4 counts were greater than 200, at 219 and 290, and they had no other defined TB risk factors.
• Of the 31 patients, 29 survived and 2 died. Interestingly, IGRA testing would not have prevented adverse outcomes in either of the two patients who died, in one because he had MDRTB and, in the other, because he presented with advanced HIV and active TB with a falsely negative IGRA result.
1. Those born in a high TB incidence country, who have been on HAART for less than two years, regardless of CD4 count.
2. Those born in a medium TB incidence country, who have been on HAART for less than two years and whose CD4 count is <500.
3. Those born in a low TB incidence country (for Caucasians), not on HAART or who have been on HAART for less than six months and whose CD4 count is <350. (2)
• (It does not give clear guidance on testing those of non-Caucasian ethnicity
born in low TB incidence countries). • There is not a clear consensus between these guidelines on which patients to
screen or how this should be done and also the recommendations in the BHIVA guideline are quite complex.
Image 1. QuantiFERON testing tubes
Only two patients were found to have had IGRA testing at any time: 1. One patient had a positive T-spot test, 15 days before being diagnosed with
active TB. This was seven years after he had first been diagnosed with HIV. His CD4 count at the time was 195.
2. One patient had a negative QuantiFERON test, two months before starting treatment for active TB. This was 17 days after his HIV diagnosis, when his CD4 count was 31.
Of the 16 patients who had been diagnosed with HIV more than six months before they were diagnosed with TB, it seemed that 11 would have fulfilled the criteria for being offered TB screening as per BHIVA guidance (Table 3) and 14 would have fulfilled the criteria as per NICE guidance (Table 4). In the majority of cases this was due to having been born in a high incidence country, to meet the BHIVA guidelines, or due to having a CD4 count <200 or being born in a high incidence country, to meet the NICE guidelines.
Interval between HIV and TB diagnosis
High incidence
birth country, ART <2y
Medium incidence
birth country, ART <2y, CD4
<500
Low incidence birth country, ART <6m, CD4
<350
Does not meet BHIVA criteria for
LTBI screening
Within 6 months 12 1 2 0
More than 6 months 8 1 2 5
Interval between HIV and TB diagnosis CD4 <200
CD4>200 but other risk
factors
Does not meet NICE criteria for testing
Within 6 months 14 1 0
More than 6 months 7 7 2
Table 3. Numbers of Patients Who Met BHIVA Criteria For Testing (n =31) Table 4: Numbers of Patients Who Met NICE Criteria for Testing (n =31)
P148
CD4 Count At TB Diagnosis Number of Patients <200 21
200-350 5
350-500 5
Table 1. CD4 Count At TB Diagnosis Length of Time on HAART Number of Patients
Never been on HAART 20
Fewer than six months on HAART 5
Six months to one year on HAART 2
More than two years on HAART 4
Table 2. Length of Time on HAART at TB Diagnosis
Incidence and survival in HIVIncidence and survival in HIV--infected patients with central nervous systeminfected patients with central nervous systemopportunistic infections in the opportunistic infections in the cARTcART era: a 10era: a 10--year Romanian single center experience year Romanian single center experience
Oprea Cristiana1,2, Ianache Irina2, Popa Ionut2, Ene Luminita2, Radoi Roxana2, Tardei Gratiela2, Ungureanu Eugenia2, Erscoiu Simona1,2, Ceausu Emanoil1,2, Calistru Petre1,2
1Carol Davila University of Medicine and Pharmacy, Bucharest ; 2Victor Babes Clinical Hospital for Infectious and Tropical Diseases Infectious Diseases Bucharest, Romania
Despite the global decline in the cART era, HIV-associated neurological opportunistic infections (CNS-OIs) remain an important cause of morbidity and mortality especially in resource-limited settings. The aim of our study was to evaluate the incidence of CNS-OIs (including brain tumors) and the factors related to survival in HIV infected patients admitted in a tertiary health care facility
5
1713
20
15
29
24
40
35
22
0
5
10
15
20
25
30
35
40
45
2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Num
ber o
f ca
ses
Characteristics of HIV infected patients diagnosed with CNS OIs
Retrospective study on HIV-infected patients diagnosed with CNS-OIs at Victor Babes Hospital Bucharest between January 2006 and December 2015. Diagnosis of CNS OIs was definitive in cases with positive microbiological exams and brain biopsy or presumptive (typical clinical, epidemiological, neuroimaging techniques). We evaluated demographic, immunologic, virologic variables, treatment characteristics and survival in patients with: cerebral toxoplasmosis (TOXO), cryptococcal meningitis (CNM), tuberculous meningitis (TBM), progressive multifocal leukoencephalopathy (PML), CMV encephalitis (CMVE) and primary cerebral lymphoma (PCNSL)Statistical analysis:Comparison between CNS-OIs groups was performed using SPSS v 19.0: unpaired t test or Mann Whitney test for continuous and Fischer's exact or chi square test for nominal variables. Survival rates were compared using Kaplan Meier methods.
Year 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015
Total no of HIV cases
931 1100 1382 1481 1538 1566 1856 2093 2499 2564
CNS OIs nIncidence/Year (%)
5
0.5
17
1.5
13
0.9
20
1.3
15
0.9
29
1.8
24
1.2
40
1.9
35
1.4
22
0.8
Socio-demographic and clinical characteristics TotalGender - male n (%) 121 (56.2)
Age (years) at HIV diagnosis median (IQR) 28 (17, 38)
Age (years) at CNS OI diagnosis median (IQR) 29 (23, 40)
Time (years) between HIV and CNS OI dx. median (IQR) 1 ( 0,10)
CNs OIs and HIV diagnosed simultaneously n (%) 74 (33.6)
Modes of HIV acquisition n (%)heterosexual contact (HSX)parenteral (PI)injecting drug use (IDU)MSMvertical
116 (52.7)85 (38.5)15 (6.8)
2 (0.9)2 (0.9)
ARV failure at CNS OI diagnosis n (%) 90 (40.9)
CD4 cell count/mm3 at CNS OI diagnosis median (IQR) 35 (13, 86)
Nadir CD4 cell count/mm3 median (IQR) 23 (10, 56)
HIV - RNA log 10 in plasma (copies/mL) median (IQR) 5.24 (4.1, 5.7)Overall mortality rate n (%) 94 (42.7)
17,010 person-years (PY): 215 patients diagnosed with 220 CNS-Ois(incidence 12.9/1000 PY)
Distribution of CNS-OIs diagnosed during the 10 years study period (2006-2015) n= 220
64 62
4137
106
34 34
24 23
51
30 28
17 14
5 5
0
10
20
30
40
50
60
70
TOXO PML TBM CNM PCNSL CMVE
total males females
Num
ber
of c
ases
CNS - OIs TOXO PML TBM CNM PCNSL CMVE
n (%) 64 (29) 62 (28.1) 41 (18.6) 37 (16.8) 10 (4.5) 6 ( 2.7)
•The incidence and mortality rate of CNS-OIs inRomanian HIV infected patients were high and did notdecrease significantly during the study period.•CNS OIs and HIV infection were diagnosedsimultaneously in one third of patients.•Sexual and IDU mode of HIV transmission, older ageat CNS OIs diagnosis, low CD4 cell count, low nadirCD4 cell count and high VL (>5 log10 copies/mL) wereassociated with shorter median survival time andhigher mortality in all cases.•Patients with CNS OI with parenteral mode of HIVacquisition had a better survival and a lower mortalityrate.•HIV-related mortality and morbidity in patients withCNS-OIs was increased due to late presentationand/or non-adherence to cART.
Distribution of CNS-OIs by modes of HIV acquisition
0%
20%
40%
60%
80%
100%
PML TBM CM PCNSL CMVE TOXO
2425 20
94
34
37 10 14
12
21
5 3 721 1
HSX PI IDU MSM Vertical
Types of CNS OIs HSXn=116
PIn=85
IDUn=1
P value
PML n (%) 24 (15.3) 37 (23.5) 0 (0.0) <0.0001
TBM n (%) 25 (10.8) 10 (3.3) 5 (5.9) 0.6
CNM n (%) 20 (10.8) 14 (8.9) 3 (0.0) 0.9
PCNSL n (%) 9 (2.7) 1 (5.6) 0 (1.9) 0.06
CMVE n (%) 4 (3.6) 2 (2.2) 0 (1.9) 0.7
TOXO n (%) 34 (0.0) 21 (0.0) 7 (1.9) 0.2
Comparison between age at HIV infection and age at CNS-OI diagnosis by modes of HIV acquisition
HSXn=116
PIn=85
IDUn=15
Pvalue
Age at HIV diagnosis (yrs.)median (IQR)
35(28, 43)
11(8, 18)
31(29, 37)
<0.0001
Age at CNS OI diagnosis (yrs.)median (IQR)
38(31, 43)
22(20, 25)
31(30, 37)
<0.0001
Comparison between age at HIV infection and age at CNS-OI diagnosis for different types of CNS OI
TOXOn=64
PMLn=62
MTBn=41
CMn=37
PCNSLn=10
CMVEn=6
P value
Age at HIV diagnosis (yrs.)median (IQR)
31(23, 41)
21(10, 31)
32(23, 37)
30(21, 38)
37(26, 51)
30(14, 41)
0.02
Age at CNS OIs diagnosis (yrs.)
median (IQR)
29(24, 41)
26(22, 33)
34 (26, 40)
29(25, 38)
43(32, 49)
32(23, 41)
0.02
Comparison between CD4 cell count and HIV viral load for the most frequent types of CNS OIs
PMLn=62
MTBn=41
CNMn=37
PCNSLn=10
CMVEn=6
TOXOn=64
Pvalue
CD4 cell count/mm3
median (IQR) 39
(16, 103)65
(23, 122)21
(11, 56)40
(16, 78)23
(11, 48)29
(11, 63)0.08
Nadir CD4 cell count/mm3
median (IQR)
33(12, 77)
37 (19, 65)
13(8, 28)
32 (11, 41)
13 (8, 21)
23 (11, 54)
0.06
HIV-RNA log10 copies/mLmedian (IQR)
4.76(2.85, 5.39)
5.32 (4.46, 5.84)
5.37(4.61, 5.76)
5.71(5.14, 5.87)
5.89(5.58, 5.92)
5.33 (4.97, 5.80)
0.007
0 10 20 30 40 50 60 70
39
65
21
40
23
29
33
37
13
32
13
23 Median nadir CD4 cell count/mm3
Median CD4 cell count/mm3
Comparison between CD4 cell count and HIV viral load by different modes of HIV acquisition
HSXn=116
PIn=85
IDUn=15
Pvalue
CD4 cell count/mm3
median (IQR) 40
(15, 91)28
(11, 77)24
(14, 42)0.52
Nadir CD4 cell count/mm3
median (IQR) 29
(12, 65)17
(8, 56)20
(11, 36)0.28
HIV - RNA log10 copies/mLmedian (IQR)
5.36(4.69, 5.85)
4.83(3.02, 5.52)
5.59(5.32, 5.84)
0.001
40
28
24
29
17
20
0 5 10 15 20 25 30 35 40 45
HSX
PI
IDUs Median nadir CD4 cell count/mm3
Median CD4 cell count/mm3
Correlation between modes of HIV acquisition, survival and mortality rate in CNS OIs
HSXn=116
PIn=85
IDUn=15
Pvalue
Survival (months)median (IQR)
74 (1.9, 36.8)
35.3(7.9, 71.9)
16.2(2.9, 19.6)
0.001
Mortality n (%) 60 (51.7) 25 (29.4) 7 (46.6) 0.006
Early mortality n (%) 43 (37.0) 12 (14.1) 5 (33.3) 0.001
Comparison between survival and mortality rate for the most frequent types of CNS OIs
PMLn=62
MTBn=41
CMn=37
PCNSLn=10
CMVEn=6
TOXOn=64
P value
Survival (months) median (IQR)
22.1 (3.15, 5.12)
14.9 (4.0, 27.6)
16.2(2.3, 44.3)
2.3 (1.2, 4.1)
38 (11.8, 78.9)
17.8 (2.7, 43.1)
0.08
Mortality n (%) 23 (37.0) 20 (48.7) 18 (48.6) 7 (70.0) 2 (33.3) 24 (37.5) 0.31
Early mortality n (%) 16 (25.8) 8 (19.5) 12 (32.4) 7 (70.0) 1 (16.6) 19 (29.6) 0.05
Results
Kaplan-Meier survival estimates by HIV-modes of acquisition
Patients with parenteral mode of HIV acquisition during early childhood hadsignificantly better survival compared to those with sexual transmission orwith injectable drug users (p =0.001)
Kaplan Meier survival curves according to specific CNS OIs types
Patients with PCNSL had the lowest survival rate
Kaplan-Meier survival estimates by age at CNS-OIs diagnosis
Patients with older age (>30 years) at CNS OI diagnosis showed a significant worse survival compared to those diagnosed at younger age (p = 0.0001)
Kaplan-Meier survival estimates by HIV viral load
Patients with high HIV viral load (> 5 log10 copies/mL) at CNS OI diagnosis showed a significant worse survival. (P= 0.0002)
Conclusions
Kaplan-Meier survival estimates by CD4 cell count
Patients with low CD4 cell count (<100/mm3) at CNS OI diagnosis showed a significant worse survival compared to those with CD4>100/mm3 (P < 0.05)
Background Methods
P 150
MTBCNM
Inspiteofinterna-onalguidelines,vaccinecoverageofHIV-infectedpa-entsremainslow.
AmandineGagneux-Brunon,AnneFrésard,MaëlleDetoc,ElenaCharrière,VéroniqueRonat,FrédéricLucht,ElisabethBotelho-NeversDepartmentofInfec-ousandTropicalDiseases,UniversityHospitalofSaint-E-enne,FranceCentred’Inves-ga-onClinique-1408,Vaccinologie,INSERM
FrenchGuidelines IDSAGuidelines BHIVAGuidelines EACSGuidelines
DTP Boosterevery10years
Boosterevery10years
Boosterevery10years
Asingeneralpopula-on
Pertussis Asingeneralpopula-on(peopleincontactwithyoungchildren,Healhcareworkers)
Asingeneralpopula-on
Asingeneralpopula-on
Asingeneralpopula-on
MMR Innonimmunepa-entswithaCD4count>200/mm3
Innonimmunepa-entswithaCD4count>200/mm3
Innonimmunepa-entswithaCD4count>200/mm3
Innonimmunepa-entswithaCD4count>200/mm3
Pneumococcal Allpa-entswith13-Valentconjugateand23-Valentpolysaccharidicvaccine
Allpa-entswith13-Valentconjugateand23-Valentpolysaccharidicvaccine
Allpa-entswith13-Valentconjugateand23-Valentpolysaccharidicvaccine
13-ValentconjugateVaccine
Hepa--sB Allnon-immunepa-ents
Allnon-immunepa-ents
Allnon-immunepa-ents
Allnon-immunepa-ents
Influenza Everyyear Everyyear
Everyyear
Everyyear
Background: HIV-infected pa-ents are at-risk of vaccinepreventable diseases. There are specific guidelines for theirimmuniza-on., Several studies previously pointed a lowvaccinecoverageinthispopula-on.OuraimwastoevaluatethevaccinecoverageofHIV-infectedpa-entsforspecificandnonspecificvaccinesinourcenterandtoiden-fyriskfactorsforincorrectimmuniza-oninthispopula-on.
Methods:• Inclusion of all consen-ng pa-ents in our center older than 18years
• Collec-onofinforma-onconcerningImmuniza-onfrompersonalcharts,andvaccina-onbythereferentphysicianofeachpa-ents.
• Data collec-on in personal charts for HIV viral load, CD4 cellcount, comorbidi-es: diabetes mellitus, cardiac failure, renalinsufficiency, Chronic obstruc-ve pulmonary disease, viralhepa--s,cancerwerecollected
• Immuniza-on was considered up-dated if data were inaccordancetotheFrenchguidelines(Table1)
Dataavailable CorrectImmunizaBon(up-to-date)
VaccinecoverageinthegeneralpopulaBoninFrance
DTP
425(74.7%) 261(61.6%) 44-62.3%
Pertussis 356(62.6%) 96(27%) NotevaluatedMMR 279(49.0%) 26(9.3%) 65.7%in
Teeanagers8-44%inHealthcareworkers
Hepa--sB 474(83.3%) 282(59.5%) 42.4%Pneumococcal 403(70.8%) 107(26.5%) 8.3%inat-risk
popula-onInfluenza 436(76.6%) 229(52.5%) 49%Hepa--sA(vaccina-onrecommendedin275pa-ents)
vaccina-onrecommendedin275pa-ents
75(27.3%) Notevaluated,notrecommended
N=561(%)Malesex 407(72.5%)Age[range],years 49.3[18-83]
HIVviralload<40copies/mL 527(93.9%)CD4lymphocytescount(cell/mm3) 688±304ComorbiditiesDiabetesmellitusChronicheartfailureChronicPulmonaydiseaseMalignancyChronicRenalfailureModeratetosevereliverdiseaseOthersignificantcomorbidity
213(38%)26(4.6%)10(1.8%)16(2.9%)3(0.5%)10(1.8%)46(8.2%)102(18.1%)
RegularlyattendingGP 408(72.7%)Holderofavaccinationcard 295(52.6%)
Univariate MulBvariateAnalysis
DTP Nofactorassociated Nofactorassociated
Pertussis Repor-ngnocomorbidi-es
MMR Repor-ngnocomorbidi-esYoungerageHigherCD4+count
YoungerageHigherCD4count
Hepa--sB Repor-ngnocomorbidi-es Youngerage
Pneumococcal OlderageLowerCD4+countUndetectableHIVviralloadFemalegenderRepor-ngcomorbidi-es
FemalegenderRepor-ngcomorbidi-esUndetectableHIVviralload
Influenza OlderageComorbidi-es
Olderage
Table 4: Factors associated with correct immunizaBon in HIV-infected paBents (Variablesincluded in the model for logisBc regression: age, gender, CD4 count, detectable orundetectableHIVviralload,presenceofanothercomorbidBes.)
Table3:Vaccine coverage inHIV-infectedpaBents, (percentageof correct immuniza-onwerecalculatedinpa-entsprovidingavaccina-oncard,orwithvaccina-onstatusreportedinmedicalrecord).Vaccinecoverage in thegeneralpopulaBonwasestablishedwithdata from InsBtutNaBonaldeVeilleSanitaire.
Table 1: Overview of principal guidelines for ImmunizaBon in HIV-infected paBents (FrenchGuidelines:Priseenchargemédicaledespa-entsvivantavecleVIH,Recommanda-onsduHautConseil de la Santé Publique: vaccina-ons des sujets immunodéprimés, Infec-ous DiseasesSocietyofAmerica,Bri-shHIVAssocia-on,EuropeanAIDSclinicalSociety)
Results
Table2:ClinicalCharacterisBcsofincludedpaBents(n(%)forcategoricalvariables,MedianandRangeforage,meanandSDforCD4count),GP=generalphysician)
Discussion/Conclusion:• Obtaininginforma-onaboutimmuniza-oninHIV-infected
pa-entsisdifficultinspiteofcomputerizedmedicalrecord,vaccina-onbookletbeingrarelyhandledbypa-ents.
• Vaccinecoverageremainslowinspiteofinterna-onalguidelinesespeciallyforMMR,pertussis,invasivepneumococcaldisease,andviralhepa--sA.
• VaccinecoverageforInfluenzaremainsunderthe75%objec-veinthispar-cularpopula-on.
• Limits:• Noserologicaltes-ngforMMRimmuniza-on• MissingDataforagreatnumberofpa-ents
• Vaccinehesitancywasreportedin50%ofpa-entsandmaycontributetothislowvaccinecoverage.
References:ValourF,ColeL,VoirinN,GodinotM,AderF,FerryT,etal.Vaccina-oncoverageagainsthepa--sAandBviruses,Streptococcuspneumoniae,seasonalflu,andA(H1N1)2009pandemicinfluenzainHIV-infectedpa-ents.Vaccine.2014Jul31;32(35):4558–64.Grabmeier-PfistershammerK,PoepplW,HerknerH,Touzeau-RoemerV,HuschkaE,RiegerA,etal.HighneedforMMRvaccina-oninHIVinfectedadultsinAustria.Vaccine.2014Oct14;32(45):6020–3.Grabmeier-PfistershammerK,HerknerH,Touzeau-RoemerV,RiegerA,BurgmannH,PoepplW.Lowtetanus,diphtheriaandacellularpertussis(Tdap)vaccina-oncoverageamongHIVinfectedindividualsinAustria.Vaccine.2015Jul31;33(32):3929–32.
Does syphilis impact on HIV infec4on when both diagnoses are concomitant?
Palacios, R; González-‐Domenech, CM; Antequera, I; Ruiz-‐Morales, J; Nuño, E; Clavijo, E; Márquez, M; *Santos, J
Hospital Virgen de la Victoria, UGC Infec4ous Diseases and Microbiology/IBIMA Malaga, Spain
P-‐152
Background
• Syphilis causes viral load blips in virologically suppressed pa4ents
on an4retroviral therapy (ART), as well as a reduc4on in the CD4
lymphocyte count [1,2]. The importance of this interac4on is that
co-‐infec4on increases the risk of HIV transmission [3].
• The aim of this study was to examine whether syphilis impacts on
HIV infec4on when both infec4ons are diagnosed at the same 4me
in men who have sex with men (MSM).
Material and Methods
• Patients: all cases of HIV-MSM diagnosed at our centre in 2009-2015
• Exclusion criteria: prior diagnosis of syphilis
• Diagnostic criteria for syphilis:
- Positive treponemal and rapid plasma reagin (RPR), except for patients
with primary syphilis, who only require a positive RPR
• Epidemiological, clinical, immunological and virological variables
• Comparison between patients with and without diagnosis of syphilis and HIV
at the same time
• Statistical analysis performed by SPSS 16.0
Results
Conclusions
1. Syphilis does not impact on the clinical presenta4on nor on the immunovirological parameters when the diagnoses of both syphilis and HIV are coincident.
2. The specific weight that Treponema pallidum infec4on may have in HIV infected pa4ents not on an4retroviral therapy is minimum.
References
1. Palacios R, et al. Impact of syphilis infec4on on HIV viral load and CD4 cell counts in HIV-‐infected pa4ents. J Acquir Immune Defic Syndr 2007; 44:356-‐359.
2. Jarzebowski W, et al. Effect of early syphilis infec4on on plasma viral load and CD4 cell count in human immunodeficiency virus-‐infected men: results from the FHDH-‐ANRS CO4 cohort. Arch Intern Med 2012; 172:1237-‐1243.
3. Dong Z, et al. HIV incidence and risk factors in Chinese young men who have sex with men-‐-‐a prospec4ve cohort study. PLoS One 2014;9:e97527.
n = 409
72 337
with and without syphilis
email: [email protected]
Late diagnosis: lymphocyte CD4 < 350 cells/µl. Advanced HIV disease: AIDS w/wo lymphocyte CD4 <200 cells/µl. Quantitative variables are represented as median (IQR) whereas qualitative variables as n (%).
Table 1. Comparison between pa4ents with and without syphilis