10
*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)

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Page 1: POSTER PRESENTATIONShivglasgow.org/wp-content/uploads/2016/12/7.-Opportunistic-Infectio… · 07-12-2016  · 2. Marais S, ThwaitesG, SchoemanJF, et al. Tuberculousmeningitis: a uniform

*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)

Page 2: POSTER PRESENTATIONShivglasgow.org/wp-content/uploads/2016/12/7.-Opportunistic-Infectio… · 07-12-2016  · 2. Marais S, ThwaitesG, SchoemanJF, et al. Tuberculousmeningitis: a uniform

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

Page 3: POSTER PRESENTATIONShivglasgow.org/wp-content/uploads/2016/12/7.-Opportunistic-Infectio… · 07-12-2016  · 2. Marais S, ThwaitesG, SchoemanJF, et al. Tuberculousmeningitis: a uniform

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

Page 4: POSTER PRESENTATIONShivglasgow.org/wp-content/uploads/2016/12/7.-Opportunistic-Infectio… · 07-12-2016  · 2. Marais S, ThwaitesG, SchoemanJF, et al. Tuberculousmeningitis: a uniform

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

Page 5: POSTER PRESENTATIONShivglasgow.org/wp-content/uploads/2016/12/7.-Opportunistic-Infectio… · 07-12-2016  · 2. Marais S, ThwaitesG, SchoemanJF, et al. Tuberculousmeningitis: a uniform

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.

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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]

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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

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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

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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.

Page 10: POSTER PRESENTATIONShivglasgow.org/wp-content/uploads/2016/12/7.-Opportunistic-Infectio… · 07-12-2016  · 2. Marais S, ThwaitesG, SchoemanJF, et al. Tuberculousmeningitis: a uniform

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