This document discusses the challenges of diagnosing HIV, AIDS, and co-infections. It notes that distinguishing between HIV infection, AIDS, and co-infections can be difficult. Point-of-care rapid tests have helped increase HIV testing, though they cannot identify acute HIV infections. The document emphasizes the importance of confirming positive rapid HIV tests with supplemental tests due to the potential for false positives in low prevalence populations.

1. Dall’HIV
all’AIDS
fino
alla
co-­‐infezione:
una
diagnosi
difficile
?
Francesco
Castelli
Clinica
Mala)e
Infe)ve
e
Tropicali
Università
di
Brescia
e
Spedali
Civili
di
Brescia
Centro
collaboratore
OMS
per
la
co-­‐infezione
TB-­‐HIV
1°
Convegno
Interdisciplinare
Milano,
21-­‐22
Marzo
2014

2. Global
Burden
of
Disease
2010
h"p://ghdx.healthmetricsandevalua6on.org/global-­‐burden-­‐disease-­‐study-­‐2010-­‐gbd-­‐2010-­‐data-­‐downloads

3. Global
Burden
of
Disease
2010
h"p://ghdx.healthmetricsandevalua6on.org/global-­‐burden-­‐disease-­‐study-­‐2010-­‐gbd-­‐2010-­‐data-­‐downloads

4. Abbreviated
HIV
treatment
cascade
for
sub-­‐Saharan
Africa,
2012
Source: UNAIDS global report 2013

5. GTB:
policy
on
collaboraLve
TB/HIV
acLviLes
WHO
recommends
providing
HIV
tesLng
and
counselling
to
paLents
with
presumpLve
and
diagnosed
TB
HIV:
ART
consolidated
guidelines

6. Percentage
of
TB
paLents
with
known
HIV
status
by
country,
2012
(Global
TB
repot
2013)
GLOBAL TB
PROGRAMME
Ref:
Global
TB
Control
Report
2013

8. Number
of
TB
paLents
with
known
HIV
status
2004-­‐2012
(WHO
Global
report
2013)

9. Percent
of
TB
paLents
with
known
HIV
status
2004-­‐2012
(WHO
Global
report
2013)
2.8 million of notified TB patients had a documented
HIV test result in 2012 (46%) - an increase from
2.5 million and 40% respectively in 2011, and 15
times the level of 3.1% reported in 2004.

10. Estimated number
of cases
Estimated number
of deaths
HIV-associated TB 1.1 million (13%)
(range: 1.0–1.2 million)
320,000
(range: 400,000–460,000)
0–24
25–49
50–99
100–299
300 and higher
No estimate available
The Global Burden of TB, 2012
TB is responsible for one in five AIDS deaths
TB
Global
report
2013

11. La co-infezione TB/HIV in Italia
• Assenza
di
un
registro
per
la
co-­‐infezione
• S6ma
di
≈
4,000
casi
di
TB
/
anno
• S6ma
di
10%
di
prevalenza
infezione
HIV
in
nuovi
casi
TB
E’
possibile
fare
una
pianificazione
degli
interven6
di
prevenzione
e
cura
in
assenza
di
un
sistema
di
informazione
?

12. Treatment outcomes for HIV-positive and
HIV-negative TB patients, 2011.
WHO Global report 2013
GLOBAL TB
PROGRAMME

13. 1. Reduce
sexual
transmission
of
HIV
by
50%
by
2015
2. Halve
the
transmission
of
HIV
among
people
who
inject
drugs
by
2015
3. Eliminate
HIV
infec6ons
among
children
and
reduce
maternal
deaths
4. Reach
15
million
people
living
with
HIV
with
lifesaving
an6retroviral
treatment
by
2015
5. Halve
tuberculosis
deaths
among
people
living
with
HIV
by
2015
6. Close
the
global
AIDS
resource
gap
7. Eliminate
gender
inequali6es
and
gender-­‐based
abuse
and
violence
and
increase
the
capacity
of
women
and
girls
to
protect
themselves
from
HIV
8. Eliminate
HIV-­‐related
s6gma,
discrimina6on,
puni6ve
laws
and
prac6ces
9. Eliminate
HIV-­‐related
restric6ons
on
entry,
stay
and
residence
10. Strengthen
HIV
integra6on
2011 UN Political Declaration on HIV and AIDS
key targets

14. EsLmated
number
of
tuberculosis-­‐related
deaths
among
people
living
with
HIV,
globally
and
for
Africa,
2004–2012
GLOBAL TB
PROGRAMME
Ref:
UNAIDS
Global
Report
2013

15. GLOBAL TB
PROGRAMME
Ref:
Global
TB
Control
Report
2013
TB/HIV
intervenLons:
further
progress
ART
and
CPT
enrolment
among
TB
paLents

16. Inequity
of
ART
provision
to
TB
paLents

17. Lab
methods
for
HIV
tesLng
The
diagnosis
of
HIV
infecLon
can
reliably
be
established
by
very
sensiLve
ELISA
tests
(detecLng
concomitantly
Abs
and
Ags)
and
confirmed
by
very
specific
immunoblot
tests.
Point
of
Care
(POC)
test
to
detect
HIV
infecLon
are
available
and
are
recommended
by
WHO
since
1997
World
Health
OrganizaQon.
Revised
RecommendaQons
for
the
SelecQon
and
Use
of
HIV
AnQbody
Tests
hUp://www.who.int/docstore/wer/pdf/1997/wer7212.pdf

18. POC rapid tests for the diagnosis of
HIV infection
Point-­‐of-­‐care
rapid
tests
for
HIV
anLbody
detecLon
have
facilitated
the
scale-­‐up
of
HIV
counseling
and
tesLng
throughout
resource
constraint
se_ngs
[1].
The
sensiLvity
of
these
tests
approaches
100%
and
is
equivalent
to
that
of
EIA
[2].
These
tests
cannot
idenLfy
persons
with
acute
HIV
infecLon
who
have
not
yet
developed
specific
anLbodies
[3].
1. Parekh
Clin
Pathol
2010;134:
537
2. Van
den
Berk
J
Clin
Microbiol
2003;
41:
3868
3. Stekler
JD
Clin
Infect
Dis
2009;
49:
444

19. Why
Provide
Rapid
HIV
TesLng?
1.
A
laboratory
and
lab
equipment
are
not
requested.
2.
Can
be
performed
by
trained
clinical
personnel
The
negaLve
predicLve
value
of
a
screening
test
is
high
è
A
client
with
a
negaLve
rapid
HIV
test
result
can
be
told
he/she
is
not
infected.
As
with
any
screening
test,
the
posiLve
predicLve
value
of
a
reacLve
rapid
HIV
test
is
low
in
populaLons
with
low
prevalence
è
Every
reacLve
rapid
test
must
be
confirmed
by
a
supplemental
test
3.
Many
persons
do
not
return
for
the
results
of
convenLonal
tests.
Almost
all
clients
receive
their
rapid
HIV
test
results
because
results
can
be
provided
immediately
during
the
tesLng
visit.

20. Timing
of
tesLng
is
important
because
Lming
of
ART
makes
the
difference
• Offer
the
HIV
test
as
soon
as
TB
is
diagnosed
(if
not
done
before)
• Ensure
rapid
turn-­‐around
6me
for
a
posi6ve
test
(including
confirmatory
test)

21. Effect
of
AnLretroviral
Drugs
during
Tuberculosis
Therapy:
the
SAPiT
trial
Abdool
Karim
SS,
N
Engl
J
Med
2010;
362:697-­‐706
• HR for mortality in arm A = 0.45 (0.26 –
0.79) p=0.005 for any CD4
• HR = 0.54 for CD<200
• HR = 0.08 for CD4>200
Trial stopped by the ethical committee

22. WHO recommendation
• Start ART in all HIV infected individuals with active
tuberculosis irrespective of CD4 cell count
(strong recommendation – Low quality of evidence)
TB/HIV guidelines 2012 and
ART consolidated guidelines 2013
Ensure
ART
treatment
during
TB
treatment
• Anti-TB treatment should be initiated first, followed by ART as soon as
possible within the first 8 weeks of treatment.
• Those TB/HIV patients with profound immunosuppression (e.g. CD4
counts <50 cells cells/mm3) should receive ART immediately within the
first 2 weeks of initiating TB treatment.

24. Point-of-care CD4 testing can increase retention
in care prior to starting treatment and can also
reduce time to eligibility assessment, which may
result in more eligible patients being initiated on
ART.

25. 2013 WHO ART Guidelines in Adults: Summary
Topic 2002 2003 2006 2010 2013
When to start CD4 ≤200 CD4 ≤ 200 CD4 ≤ 200
- Consider 350
- CD4 ≤ 350 for TB
CD4 ≤ 350
-Irrespective CD4 for TB and
HBV
CD4 ≤ 500
-Irrespective CD4 for TB, HBV,
PW and SDC
- CD4 ≤ 350 as priority
1st Line 8 options
- AZT preferred
4 options
- AZT preferred
8 options
- AZT or TDFpreferred
- d4T dose reduction
6 options &FDCs
- AZT or TDF preferred
- d4T phase out
2 options & FDCs
- TDF and EFV preferred
across all populations
2nd Line Boosted and
non-boosted PIs
Boosted PIs
-IDV/r LPV/r, SQV/r
Boosted PI
- ATV/r, DRV/r, FPV/r LPV/r,
SQV/r
Boosted PI
- Heat stable FDC: ATV/r,
LPV/r
Boosted PIs
- Heat stable FDC:
ATV/r, LPV/r
3rd Line None None None DRV/r, RAL, ETV DRV/r, RAL, ETV
Viral Load
Testing
No No
(Desirable)
Yes
(Tertiary centers)
Yes
(Phase in approach)
Yes
(preferred for monitoring,
use of PoC, DBS)
Earlier
ini6a6on
Simpler
treatment
Less
toxic,
more
robust
regimens
Be"er
monitoring
HIV/AIDS DepartmentEvidence-based, but intentionally aspirational…

27. MONITORING ART RESPONSE
Targeted
viral
load
monitoring
(suspected
clinical
or
immunological
failure)
Rou6ne
viral
load
monitoring
(early
detec6on
of
virological
failure)
Switch
to
second-­‐line
therapy
Maintain
first-­‐line
therapy
Viral
load
≤1000
copies/ml
Viral
load
>1000
copies/ml
Repeat
viral
load
tes6ng
aeer
3–6
months
Evaluate
for
adherence
concerns
Viral
load
>1000
copies/ml
Test
viral
load
70%
greater
resuppression
rate
afer
adherence
intervenLon

28. • L’importanza dell’integrazione dei servizi

29. Results: One stop service model in Rwanda
Decentralisation of services and task shifting to nurses
Percent shows out of all identified HIV positive TB patients nationally
TB nurse
§ Provides HIV testing
§ Draws blood for CD4
§ Provides ART and CPT
0
20
40
60
80
100
120
2005 2006 2007 2008 2009 2010 2011 2012
ART for TB patients CPT for TB patients

30. Health officers and nurses
(Health center)
Physicians
( Hospitals)
Mortality (%) 11 8
Lost to follow up (%) 13 25
Retention rate (%) 76 67
Median CD4 count (IQR) 322 (242, 414) 301 (217,411)
Nurses and health officers can initiate ART with
better results (Assefa Y et al, 2011)
Outcome of patients initiated ART by nurses and physicians
after 24 months of follow up, Ethiopia.

31. Use the decentralized TB services to provide ART
ART services are still too centralized and too few
Number of facilities providing TB and ART, 2011

32. Early
TB
diagnosis
in
PLHIV

33. The cascade of care
With signs/symptoms
Other diagnostic tests
Treat
for
TB
if
sugges6ve
Initial test
Treat
for
TB
if
posi6ve
Clinical decision

34. 34 |
WHO
guidance
documents
GLOBAL TB
PROGRAMME

35. Xpert
MTB/RIF
as
the
iniLal
diagnosLc
test

36. Global scale-up of Xpert MTB/RIF
CumulaLve
number
of
GeneXpert
instrument
modules
and
Xpert
MTB/RIF
cartridges
procured
under
concessional
pricing
Data
provided
by
FIND
2012
2013
2011
2010
42
524
681
1,441
2,401
2,979
3,602
4,660
5,017
6,181
7,553
9,625
10,561
40.790
86.320
191.900
329.350
591.450
863.790
1.107.330
1.482.550
1.891.970
2.315.380
3.196.920
4.214.990
5.219.960
0
2.000
4.000
6.000
8.000
10.000
12.000
0
1.000.000
2.000.000
3.000.000
4.000.000
5.000.000
Q4
Q1
Q2
Q3
Q4
Q1
Q2
Q3
Q4
Q1
Q2
Q3
Q4
August
2012:
“Buy-­‐down”
with
the
manufacturer
by
PEPFAR,
USAID,
UNITAID
and
Bill
&
Melinda
Gates
Founda6on
-­‐―
the
price
of
the
cartridge
dropped
to
9.98
USD
in
145
eligible
countries
Q4
2012-­‐Q2
2013:
Global
shortage
in
Xpert
MTB/RIF
cartridges

37. Impact
of
Xpert
MTB/RIF
in
clinical
pracLce
The
TB-­‐NEAT
study
is
a
randomized
parallel-­‐group
mul6centre
trial
evalua6ng
the
impact
of
Xpert
MTB/RIF
in
five
primary-­‐care
health
facili6es
in
four
African
countries
(South
Africa,
Zimbabwe,
Zambia
and
Tanzania).
Eligible
pa6ents
were
randomly
assigned
to
nurse-­‐performed
Xpert
MTB/RIF
or
microscopy.
The
XTEND
study
is
a
cluster-­‐randomized
trial
evalua6ng
the
impact
of
Xpert
MTB/RIF
in
South
Africa,
involving
20
laboratories
and
2
primary
care
clinics
per
laboratory;
one
clinic
used
Xpert
MTB/RIF
as
the
ini6al
diagnos6c
test
while
the
other
con6nued
using
microscopy.
The
two
studies
confirm
that
to
show
significant
impact
on
clinically
important
outcomes
for
drug-­‐sensiLve
TB
paLents,
adopLon
of
Xpert
MTB/
RIF
needs
to
be
complemented
with
strengthened
health
systems
that
allow
for
the
Lmely
iniLaLon
of
appropriate
treatment
and
a
reducLon
in
the
use
of
empirical
treatment
without
bacteriological
confirmaLon.
Churchyard
G
et
al.
CROI,
Boston
USA,
3-­‐6
March
2014
Theron
G
et
al.
Lancet
Infect
Dis
2014

38. The end