PPT Castelli "Dall'HIV all'AIDS fino alla coinfezione: una diagnosi difficile?"

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

Global Burden of Disease 2010

h"p://ghdx.healthmetricsandevalua6on.org/global-‐burden-‐disease-‐study-‐2010-‐gbd-‐2010-‐data-‐downloads

Abbreviated HIV treatment cascade for sub-‐Saharan Africa, 2012

Source: UNAIDS global report 2013

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

Percentage of TB paLents with known HIV status by country, 2012 (Global TB repot 2013)

GLOBAL TB

PROGRAMME

Ref: Global TB Control Report 2013

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

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.

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

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 ?

Treatment outcomes for HIV-positive and HIV-negative TB patients, 2011.

WHO Global report 2013

GLOBAL TB

PROGRAMME

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

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

GLOBAL TB

PROGRAMME

Ref: Global TB Control Report 2013

TB/HIV intervenLons: further progress ART and CPT enrolment among TB paLents

Inequity of ART provision to TB paLents

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

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

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.

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)

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

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.

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.

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 Department

Evidence-based, but intentionally aspirational…

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

•  L’importanza dell’integrazione dei servizi

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

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.

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

Early TB diagnosis in PLHIV

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 |

WHO guidance documents

GLOBAL TB

PROGRAMME

Xpert MTB/RIF as the iniLal diagnosLc test

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

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

The end

PPT Castelli "Dall'HIV all'AIDS fino alla coinfezione: una diagnosi difficile?"

Health & Medicine

Transcript of PPT Castelli "Dall'HIV all'AIDS fino alla coinfezione: una diagnosi difficile?"