HIV Treatment for Adults and Adolescents. Stefano Vella MD Istituto Superiore di Sanità - Rome - Italy

Transcription

1 HIV Treatment for Adults and Adolescents Stefano Vella MD Istituto Superiore di Sanità - Rome - Italy Kuala Lumpur, Malaysia, 30 June - 3 July 2013

2 PLHIV in need of ART WHO 2013 Guidelines contribution to fill the treatment gap Treatment gap Receiving antiretroviral therapy 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 1 st line regimens Perfect monitoring Streamline subsequent treatment lines Consider co-infections and co-morbidities

3 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!

4 When to start ART: what is new since 2010? 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 morbidity o 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

5 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

6 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

7 Major Guidelines for Initiation of Antiretroviral Therapy Guideline AIDS or HIV-Related Symptoms CD4+ Cell Count < 200/mm 3 CD4+ Cell Count /mm 3 CD4+ Cell Count /mm 3 CD4+ Cell Count > 500 cells/mm 3 DHHS-USA, 2013 Yes Yes Yes Yes 1 Yes 2 International AIDS Society-USA, 2012 British HIV Association, 2012 European AIDS Clinical Society, 2012 World Health Organization, 2013 Yes Yes Yes Yes 1 Yes 2 Yes Yes Yes Consider 3 Defer 3 Yes Yes Yes Consider 3 Defer 3 Yes Yes Yes Yes 4 Defer 5 (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

8 2013 WHO consolidated Guidelines What ARV regimens to be used in adults One-pill-a-day FDC as preferred 1 st line(s) Reducing the number of preferred regimens Defining substitution regimens Harmonizing regimens across different target populations (TB, Hepatitis B, Pregnant Women)

9 2013 WHO consolidated Guidelines One regimen cannot fit all: alternative, special situations 1st Line ART Preferred (FDC) Regimen(s) Adults and Adolescents (including pregnant women, TB coinfection and HBV co-infection) TDF+3TC (or FTC) + EFV Alternative Regimens AZT+ 3TC + EFV (or NVP) TDF+ 3TC (or FTC)+ NVP Special situations ABC +3TC +EFV (or NVP) AZT (or ABC)+ 3TC + LPV/r or ATV/r

10 Challenges ahead (i): current NRTIs Major parameters TDF ABC AZT d4t Major toxicities Renal and bone toxicity ABC hypersensitivity syndrome Major drug Interactions Boosted PIs Not significant Convenience (once vs twice daily regimen) once daily once or twice daily Anemia and neutropenia IFN RBV twice daily Lipodystrophy and neuropathy INH ddi twice daily Safety in pregnancy Yes Yes Yes yes Availability 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

11 % of treated patients Phasing out d4t: trends of d4t, AZT and TDF use in adults first line ART ( ) Evolution in the APIs use in adults, % d4t in 1st line AZT in 1st lline TDF in 1st line % 44% 27.9% % < 0.1% N= 12 countries HIV/AIDS Department

12 Challenges ahead (ii): second-line regimens Target population Adults Pregnant women If d4t or AZT was used in first -line ART If TDF was used in first-line ART Preferred second-line regimen TDF + 3TC (or FTC) + ATV/r or LPV/r AZT + 3TC + ATV/r or LPV/r Same regimens recommended for adults and adolescents If rifabutin is available Standard PI-containing regimens as recommended for adults and adolescents HIV and TB coinfection 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)

13 Comparative Analysis of ATV/r, LPV/r and DRV/r Major parameters ATV/r LPV/r DRV/r Consistency with pediatric regimens no yes no Number of pills per day (standard dose as FDC) Convenience (once vs twice daily regimen) once daily twice daily Once or twice daily Safety in pregnancy yes yes yes GI intolerance (diarrhea) Not frequent common Not frequent Availability of heat stable FDCs yes yes no Use with TB treatment regimen that contains rifampin no yes no Hyperbilirrubinemia Dyslipidemia ± + ± Reduction cost potential low low high Accessibility in countries (registration status) low high low Availability of generic formulations yes yes yes

14 Need to move forward: towards the 2015 guidelines.. Additional 1 st line options Better 2 nd / 3 rd lines New strategies (if proven effective) New drugs and new combinations shall be made available, globally, at affordable price, when possible as FDCs 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

15 2013 WHO ART Guidelines in Adults: a summary Topic When to start CD4 200 CD4 200 CD Consider CD4 350 for TB Earlier initiation CD Irrespective CD4 for TB and HBV CD Irrespective CD4 for TB, HBV, PW and SDC - CD4 350 as priority 1 st Line 8 options - AZT preferred 2 nd Line Boosted and non-boosted PIs 4 options - AZT preferred Boosted PIs -IDV/r LPV/r, SQV/r 8 options - AZT or TDFpreferred - d4t dose reduction Boosted PI - ATV/r, DRV/r, FPV/r LPV/r, SQV/r 6 options &FDCs - AZT or TDF preferred - d4t phase out Boosted PI - Heat stable FDC: ATV/r, LPV/r 2 options & FDCs - TDF and EFV preferred across all populations Boosted PIs - Heat stable FDC: ATV/r, LPV/r 3 rd Line None None None DRV/r, RAL, ETV DRV/r, RAL, ETV Viral Load Testing No Simpler treatment Less toxic, more robust regimens No (Desirable) Yes (Tertiary centers) Better monitoring Yes (Phase in approach) Yes (VL preferred for monitoring) 17 April 2013 HIV/AIDS Department

16 2013 WHO ART Guidelines in Adults: a summary Topic When to start CD4 200 CD4 200 CD Consider CD4 350 for TB Earlier initiation CD Irrespective CD4 for TB and HBV CD Irrespective CD4 for TB, HBV, PW and SDC - CD4 350 as priority 1 st Line 8 options - AZT preferred 2 nd Line Boosted and non-boosted PIs 4 options - AZT preferred Boosted PIs -IDV/r LPV/r, SQV/r 8 options - AZT or TDFpreferred - d4t dose reduction Boosted PI - ATV/r, DRV/r, FPV/r LPV/r, SQV/r 6 options &FDCs - AZT or TDF preferred - d4t phase out Boosted PI - Heat stable FDC: ATV/r, LPV/r 2 options & FDCs - TDF and EFV preferred across all populations Boosted PIs - Heat stable FDC: ATV/r, LPV/r 3 rd Line None None None DRV/r, RAL, ETV DRV/r, RAL, ETV Viral Load Testing No Simpler treatment Less toxic, more robust regimens No (Desirable) Yes (Tertiary centers) Better monitoring Yes (Phase in approach) Yes (VL preferred for monitoring) 17 April 2013 HIV/AIDS Department Evidence-based, but intentionally aspirational

17 MONITORING ART RESPONSE Targeted viral load monitoring (suspected clinical or immunological failure) Test viral load Routine viral load monitoring (early detection of virological failure) 70% greater resuppression rate after adherence intervention Viral load >1000 copies/ml Evaluate for adherence concerns Repeat viral load testing after 3 6 months Viral load 1000 copies/ml Viral load >1000 copies/ml Maintain first-line therapy Switch to second-line therapy 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

18 2013 WHO consolidated Guidelines A game changer document, and an important step towards the global alignment of the HIV standard of care

19 Acknowledgements 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. 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) WHO Department of HIV Andrew Ball Philippa Easterbrook Meg Doherty Eyerusalem Kebede Negussie Nathan Shaffer Lulu Muhe Nathan Ford Marco 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)