Upload
tabib
View
28
Download
0
Embed Size (px)
DESCRIPTION
HIV Treatment for Adults and Adolescents. Stefano Vella MD Istituto Superiore di Sanità - Rome - Italy. WHO 2013 Guidelines contribution to fill the treatment g ap. Operational / Programmatic Guidance Improve testing coverage, address late presentation - PowerPoint PPT Presentation
Citation preview
www.ias2013.org Kuala Lumpur, Malaysia , 30 June - 3 July 2013
HIV Treatment for Adults and Adolescents
Stefano Vella MDIstituto Superiore di Sanità - Rome - Italy
WHO 2013 Guidelines contribution to fill the treatment gap
• Operational / Programmatic Guidance – Improve testing coverage, address late presentation
– Optimize care delivery models:
• offer something meaningful in the pre-art period,
• task sharing, decentralization and integration of care, address attrition
• community involvement
• procurement
• Clinical Guidance– Improve the quality of drugs
– Simplify and harmonize 1st line regimens
– Perfect monitoring
– Streamline subsequent treatment lines
– Consider co-infections and co-morbidities
3 000 000
6 000 000
9 000 000
12 000 000
15 000 000
2003 2004 2005 2006 2007 2008 2009 2010
PLHIV in need of ART
Treatment gap
Receiving antiretroviral therapy
WHO’s 2013 Guidelines: the challenge
To find the right balance between:
the “individualized” approach to ART…..
and
the “public health” approach needed to start and maintain on
ART over 20 million persons….…
….considering the different HIV epidemics
….while keeping the same - evidence-based - standard of care!
• Strong evidence of the impact of ART on HIV transmission: o HPTN 052 study
• Emerging data on the impact of ART on HIV incidence at the population level
• Increasing evidence on clinical benefits of early ART initiation: o Observational studies showing impact on HIV mortality and
morbidityo Scientific insights on HIV immunopathogenesis and on the
effects of chronic inflammation associated with HIV infection
• Better regimens: o Better tolerable drugs o Better formulations o New classes
When to start ART: what is new since 2010 ?
When to start ART 2013 WHO consolidated Guidelines
Evaluating Risks & Benefits of earlier ART initiation
Potential benefits
• ↓ risk of HIV transmission (sexual and vertical)
• ↓ risk of TB disease• ↓ risk of serious non-AIDS conditions
(HBV disease, cardiovascular disease, renal disease, liver disease, cancers)
• linkage to care• chance to achieve higher CD4
values (immune recovery)• ↓ long term costs (infections and co
morbidities averted)
Potential risks
• long-term adverse effects / toxicities
• limitation of future treatment options (with drug resistance concerns)
• stigma & discrimination
• ↓ long term adherence ?
• burden on healthcare infrastructure / feasibility
• immediate cost
When to start in adults: what is new in the 2013 Guidelines
Considering both the individual and the Public Health benefit….
• Threshold moved to < 500 CD4 • Priority for reaching all HIV+ symptomatic persons
and those with CD4 ≤ 350 • More CD4-independent situations for ART initiation (in
addition to HIV/TB coinfection and HBV advanced liver disease):– HIV serodiscordant couples, – Pregnancy– Children less than 5 years of age
GL are a “tool” for countries to produce their own guidelines: they will adapt the new threshold(s) with operational / programmatic local context
Guideline AIDS or HIV-Related Symptoms
CD4+ Cell Count < 200/mm3
CD4+ Cell Count 200-350/mm3
CD4+ Cell Count 350-500/mm3
CD4+ Cell Count > 500 cells/mm3
DHHS-USA, 2013 Yes Yes Yes Yes1 Yes2
International AIDS Society-USA, 2012 Yes Yes Yes Yes1 Yes2
British HIV Association, 2012 Yes Yes Yes Consider 3 Defer3
European AIDS Clinical Society, 2012 Yes Yes Yes Consider3 Defer3
World Health Organization, 2013 Yes Yes Yes Yes4 Defer5
(1) Strong strength recommendation based on observational data (A-II)(2) Moderate strength recommendation based on expert opinion (B-III).(3 ) But treat all HIV+ pregnant women, HBV co-infection, HCV co-infection, HIVAN, HIV related neurocognitive disorders, ITP, non-AIDS cancers and serodiscordant couples
(4) Individuals with CD4 < 350 as a priority.(5) But treat all HIV+ pregnant women ,TB co-infection with active disease and HBV co-infection with severe liver disease, and serodiscordant copuls
Major Guidelines for Initiation of Antiretroviral Therapy
2013 WHO consolidated Guidelines
What ARV regimens to be used in adults
One-pill-a-day FDC as preferred 1st line(s)
Reducing the number of preferred regimens
Defining substitution regimens
Harmonizing regimens across different target populations
(TB, Hepatitis B, Pregnant Women)
1st Line ARTAdults and Adolescents
(including pregnant women, TB co-infection and HBV co-infection)
Preferred (FDC) Regimen(s)TDF+3TC (or FTC) + EFV
Alternative RegimensAZT+ 3TC + EFV (or NVP)
TDF+ 3TC (or FTC)+ NVP
Special situationsABC +3TC
+EFV (or NVP)
AZT (or ABC)+ 3TC+ LPV/r or ATV/r
One regimen cannot fit all: alternative, special situations
2013 WHO consolidated Guidelines
Major parameters TDF ABC AZT d4T
Major toxicities Renal and bone toxicity
ABC hypersensitivity
syndrome
Anemia and neutropenia Lipodystrophy
and neuropathy
Major drug Interactions Boosted PIs Not significant IFN RBV
INH ddI
Convenience (once vs twice daily regimen)
once daily once or twice daily twice daily twice daily
Safety in pregnancy Yes Yes Yes yesAvailability as triple FDCs Yes No Yes Yes
GI intolerance Not common Not common Frequent Not common
Consistency with pediatric regimens (all ages)
No (only for 3 years and older) Yes Yes Yes
Cost (generic, annual, per patient) US$ 57 US$ 169 US$ 75 US$ 19
Challenges ahead (i): current NRTIs
Phasing out d4T: trends of d4T, AZT and TDF use in adults first line ART (2006 – 2012 )
2006 2007 2009 2010 2011 20120.0
10.0
20.0
30.0
40.0
50.0
60.0
70.0
80.0
Evolution in the APIs use in adults, 2006 - 2012
d4T in 1st line Linear (d4T in 1st line) AZT in 1st lline TDF in 1st line
% o
f tre
ated
pati
ents
24.9%
< 0.1%
N= 12 countries
44%
27.9%
70%
27.9%
HIV/AIDS Department
Challenges ahead (ii): second-line regimens
Target population Preferred second-line regimen
Adults
If d4T or AZT was used in first -line ART TDF + 3TC (or FTC) + ATV/r or LPV/r
If TDF was used in first-line ART AZT + 3TC + ATV/r or LPV/r
Pregnant women Same regimens recommended for adults and adolescents
HIV and TB coinfection
If rifabutin is available Standard PI-containing regimens as recommended for adults and adolescents
If rifabutin is not available
Same NRTI backbones as recommended for adults and adolescents plus double-dose LPV/r (that is, LPV/r 800 mg/200 mg twice daily) or standard LPV dose with an adjusted dose of RTV (that is, LPV/r 400 mg/400 mg twice daily)
HIV and HBV coinfection AZT + TDF + 3TC (or FTC) + (ATV/r or LPV/r)
Comparative Analysis of ATV/r , LPV/r and DRV/r
Major parameters ATV/r LPV/r DRV/rConsistency with pediatric regimens no yes noNumber of pills per day (standard dose as FDC) 1 4 2-4
Convenience (once vs twice daily regimen)once daily twice daily Once or twice
dailySafety in pregnancy yes yes yesGI intolerance (diarrhea) Not frequent common Not frequentAvailability of heat stable FDCs yes yes noUse with TB treatment regimen that contains rifampin no yes no
Hyperbilirrubinemia + - -Dyslipidemia ± + ±Reduction cost potential low low highAccessibility in countries (registration status) low high lowAvailability of generic formulations yes yes yes
• Additional 1st line options
• Better 2nd / 3rd lines
• New strategies (if proven effective)
Nucleosides Integrase Inhibitors Non-nucleosides Protease Inhibitors
Available agents / combinations
Raltegravir Rilpivirine (FDC) Darunavir (boosted FDC)
Elvitegravir (FDC)
Investigational agents / combinations
TAF (TDF prodrug) Dolutegravir (FDC) MK-1439 TMC 310911
New drugs and new combinations shall be
made available, globally,
at affordable price,when possible as FDCs
Need to move forward: towards the 2015 guidelines…..
17 April 2013
2013 WHO ART Guidelines in Adults: a summary
Topic 2002 2003 2006 2010 2013When 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 LoadTesting
No No (Desirable)
Yes(Tertiary centers)
Yes(Phase in approach)
Yes(VL preferred for monitoring)
Earlier initiation
Simpler treatment
Less toxic, more robust regimens
Better monitoring
HIV/AIDS Department
17 April 2013
2013 WHO ART Guidelines in Adults: a summary
Topic 2002 2003 2006 2010 2013When 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 LoadTesting
No No (Desirable)
Yes(Tertiary centers)
Yes(Phase in approach)
Yes(VL preferred for monitoring)
Earlier initiation
Simpler treatment
Less toxic, more robust regimens
Better monitoring
HIV/AIDS Department Evidence-based, but intentionally aspirational…
MONITORING ART RESPONSE
Targeted viral load monitoring (suspected
clinical or immunological failure)
Routine viral load monitoring (early
detection 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 testing after 3–6
months
Evaluate for adherence concerns
Viral load >1000copies/ml
Test viral load
70% greater resuppression rate after adherence intervention
Viral load as a tool to reinforce adherence and discriminate between treatment failure and non-adherence:
need to expand the availabity of point-of care diagnostics
A “game changer” document, and an important steptowards the global alignment of the HIV standard of care
2013 WHO consolidated Guidelines
Acknowledgements
Guideline Development Group
Co-chairs:
Anthony Harries, Gottfried Hirnschall
Elaine Abrams (International Center for AIDS Care and Treatment Programs, Mailman School of
Public Health, Columbia University, USA)
Tsitsi Apollo (Ministry of Health and Child Welfare, Zimbabwe)
Kevin De Cock (United States Centers for Disease Control and Prevention, USA)
Serge Eholie (ANEPA/Treichville Hospital, Abidjan, Côte d’Ivoire)
Adeeba Kamarulzaman (University of Malaya, Malaysia)
Yogan Pillay (National Department of Health, South Africa)
Denis Tindyebwa (African Network for the Care of Children Affected by AIDS, Uganda)
Stefano Vella (Istituto Superiore di Sanità, Italy)
Special thanks to all members of the Guideline Development Groups, the Peer Review panel and to those who contributed to the GRADE systematic reviews and supporting evidence which informed the
guidelines process.
WHO Department of HIV
Andrew Ball Philippa Easterbrook
Meg Doherty Eyerusalem Kebede Negussie
Nathan Shaffer Lulu Muhe
Nathan FordMarco Vitoria
Joseph Perriëns
Guideline Development Group
Pedro Cahn (Fundación Huesped, Argentina), Alexandra Calmy (University of Geneva, Switzerland), Frank
Chimbwandira (Ministry of Health, Malawi), David Cooper (University of New South Wales and St Vincent’s Hospital, Australia), Judith Currier (UCLA Clinical AIDS Research & Education Center, USA), François Dabis (School of Public
Health (ISPED) of the University Bordeaux Segalen, France), Charles Flexner (Johns Hopkins University, USA), Tendani Gaolathe (Princess Marina Hospital, Botswana), Beatriz Grinsztejn (Fundação Oswaldo Cruz – FIOCRUZ,
Brazil), Diane Havlir (University of California at San Francisco, USA), Charles Holmes (Centre for Infectious
Disease Research in Zambia, Zambia), John Idoko (National Agency for the Control of AIDS, Nigeria), Kebba Jobarteh
(Centers for Disease Control and Prevention, Mozambique), Elly Katabira (Makarere University, Uganda),
Nagalingeswaran Kumarasamy (Y.R. Gaitonde Centre for AIDS Research and Education, India), Volodymyr Kurpita
(All-Ukrainian Network of People Living with HIV, Ukraine), Karine Lacombe (Agence Nationale de Recherche sur le
Sida et les Hépatites Virales (ANRS), France), Albert Mwango (Ministry of Health, Zambia), Leonardo Palombi
(DREAM Program, Community of Sant’Egidio, Rome, Italy), Anton Pozniak (Chelsea and Westminster Hospital, United Kingdom), Luis Adrián Quiroz (Derechohabientes Viviendo
con VIH del IMSS, Mexico), Kiat Ruxrungtham (Chulalongkorn University, Chula Vaccine Research Center, King Chulalongkorn Memorial Hospital, Thailand), Michael Saag (University of Alabama at Birmingham, USA), Gisela
Schneider (German Institute for Medical Mission, Germany), Yanri Subronto (Universitas Gadjah Mada, Indonesia) and Francois Venter (University of the Witwatersrand, South
Africa)