Consolidated guidelines on the use of antiretroviral drugs for treating

Transcription

1 TB conference, June 2014, Durban, South Africa Consolidated guidelines on the use of antiretroviral drugs for treating and preventing HIV infection Dr Augustin Ntilivamunda Objectives of 2013 WHO consolidated Guidelines (1) 1. To provide updated, evidence based clinical recommendations outlining public health approach to providing ARV drugs for HIV treatment and prevention. 2. To provide guidance on key operational and service delivery issues that need to be addressed to increase access to HIV services. 17/06/

2 Objectives of 2013 WHO consolidated Guidelines (2) 3. To provide programmatic guidance for decision makers and planners at the national level on adapting and setting priorities for implementing the clinical and operational recommendations 17/06/ Concept Behind Consolidation Characteristics of the 2013 guidelines Consolidation across populations and ages Consolidation along the continuum of care Consolidation with existing guidelines 2

3 WHO M Different components of the new guidelines WHAT TO DO? When to start or switch Which regimen to use How to monitor Co infections & co morbidities HOW TO DECIDE? Clinical Guidance for Programme Managers Operational HOW TO DO IT? Service delivery Diagnostics Drug supply Prioritization Equity and ethics Monitoring & Evaluation Clinical recommendations for treating people with HIV Earlier initiation of ART (CD4 500) Immediate ART for all children below 5 years Start ART at any CD4 count for certain populations of PLHIV: - TB disease, - People with hepatitis B virus (HBV) co-infection - Severe or chronic liver disease, - HIV-positive partners in sero-discordant couples - Pregnant and breastfeeding women 17/06/

4 Operational guidance recommendations Use of Fixed Dose Combinations as a preferred approach Strategies to improve retention in HIV care and adherence to ART Task shifting to address human resource gaps 17/06/ Guidance for Programme Managers (1) Design an inclusive and transparent process Discuss key data needed for evidencebased decisions Examine key parameters for decision making Review tools for costing and planning Discuss implementation considerations 4

5 Guidance for program managers (2) Adapting recommendations to the epidemic and health system country context Define potential indicators for monitoring performance programmes across continuum of care 17/06/ HIV COUNSELING AND TESTING 17/06/

6 Main issues HIV Counseling & Testing Despite new urgency to test, poor progress in scale up < 50% of PLHIV aware of their stats (less men than women, in generalized epidemics) Many people test late Many tests are re tests Inequity poor service provision, especially for some groups men, adolescents & key populations People test alone confidentiality emphasized & disclosure often not actively supported Poor linkages to prevention, care, & treatment in most HTC settings Sometimes poor quality services including testing HCT in Health Facilities In generalized epidemics : PITC should ldbe recommended ddto everyone in all health facilities In concentrated and low level epidemics: PICT should be recommended in all health facilities for: adults, adolescents &children (including exposed children) who present in clinical settings with signs & symptoms associated with HIV PITC should be considered in STI, hepatitis and TB services, ANC and services for key populations. 6

7 Community Based HCT Moving testing into the community Home based (door to door) o Community o Index case Campaigns Campaigns plus (+) o HTC + malaria, safe water, non communicable diseases (e.g. IHD, DM, BP, BMI) Outreach (e.g. mobile) o General populations o Key populations Workplaces, schools HIV PREVENTION 17/06/

8 HIV Prevention based on ARV Drugs 1. Oral pre-exposure exposure prophylaxis (PrEP) 2. ART for prevention among sero-discordant couples 3. Post-exposure prophylaxis (PEP) 4. Opportunities for Biomedical Interventions 5. Combination HIV prevention Combination HIV Prevention Biomedical Interventions Structural Interventions HIV prevention HIV testing and linkage to care and ART Multiple disciplines and Approaches Behavioral interventions Community Interventions Adapted from T Coates 8

9 TREATMENT 17/06/ Recommendations: CD4 Independent Conditions Initiate patients with 500!!! INITIATE ART REGARDLESS OF CD4 COUNT OR CLINICAL STAGE ADULTS WITH HIV CHILDREN < 5 YEARS OLD WITH HIV and active TB disease and HBV co infection with severe liver disease RECOMMENDATION Strong, low quality evidence Strong, low quality evidence who are pregnant or breastfeeding Strong, moderatequality of evidence in a HIV sero discordant partnership Infants diagnosed in the first year of life Children infected with HIV between one and below five years of age Strong, high quality evidence Strong, moderatequality of evidence Conditional, very lowquality evidence 9

10 Rationale: One Regimen For All Preferred 1 st line regimen: TDF + 3TC (or FTC) + EFV Simplicity: regimen is very effective, well tolerated and available as a single, once daily FDC and therefore easy to prescribe and easy to take for patients facilitates adherence Harmonizes regimens across range of populations (Adults, Pregnant Women (1 st trimester), Children >3 years, TB and Hepatitis B) Simplifies drug procurement and supply chain by reducing number of preferred regimens (phasing out d4t) Sf Safety in pregnancy Efficacy against HBV EFV is preferred NNRTI for people with HIV and TB (pharmacological compatibility with TB drugs) and HIV and HBV coinfection (less risk of hepatic toxicity) Affordability (cost declined significantly since 2010) One regimen cannot fit all: preferred, alternative, special situations Preferred Regimens Alternative Regimens 1st Line ART Adults and Adolescents (including pregnant women, TB co infection and HBV co infection) TDF+3TC (or FTC) + EFV 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

11 PMTCT 17/06/ Evolution of WHO PMTCT ARV Recommendations PMTCT ART 4 weeks AZT; AZT+ 3TC, or SD NVP No recommendation AZT from 28 wks + SD NVP AZT from 28wks +sdnvp +AZT/3TC 7days Option A (AZT +infant NVP) Option B (triple ARVs) Option B or B+ Moving to ART for all PW/BF CD4 <200 CD4 <200 CD4 <350 CD4 <500 Move towards: more effective ARV drugs, extending coverage throughout MTCT risk period, and ART for the mother s health 11

12 CHILDREN 17/06/ ,000 children received ART in 2012 ART eligible Substantial gap between need and coverage On ART (WHO, Global Report 2013) 12

13 AGE GROUP When to start ART 2010 RECOMMENDATIONS <1 YEARS Treat ALL Strong recommendation, moderate quality evidence Children AGE 2013 RECOMMENDATIONS GROUP < 1 YEAR Treat ALL Strong recommendation, moderate quality evidence 1 2 YEARS Treat ALL Conditional recommendation, very low quality evidence 2 5 YEARS Initiate ART with CD4 count 750 cells/mm3 or <25%, irrespective of WHO clinical stage 1 5 YEARS Treat ALL Conditional recommendation, very lowquality evidence Priority: children <2 years or WHO stage 3 4 or CD4 count 750 cells/mm3 or < 25% 5 YEARS Initiate ART with CD4 count 350 cells/mm3 (As in adults), irrespective of WHO clinical stage AND WHO clinical stage 3 or 4 5 YEARS CD4 500 cells/mm3 Conditional recommendation, very lowquality evidence CD4 350 cells/mm³ as a priority (As in Adults) Strong recommendation, moderate quality evidence OPPORTUNISTIC INFECTIONS 17/06/

14 Reducing the Burden of HIV in TB Patients All TB patients should be offered HIV testing Persons with TB and HIV should be provided cotrimoxazole preventive therapy (CPT) Persons with TB and HIV should be provided ART Scale up implementation of the 3 I s ART in PLHIV and TB Adults, adolescents and children over 3 years Preferred first line ART regimen Efavirenz is preferred NNRTI in patients starting ART (TDF + 3TC (or FTC) + EFV ) while on TB treatment (strong recommendation, high quality evidence) Second line ART regimen Rifampicin reduces effective concentrationsofof PIs If rifabutin available If rifabutin not available use standard PI regimens provide double dose Lopinavir/ritonavir(LPV/r) (800mg/200mg or 400mg/400mg twice daily) 14

15 HIV Hepatitis Hepatitis B Co infection Liver disease emerged as a leading cause of death in PLHIV and HBV higher rates of chronicity / less spontaneous HBV clearance accelerated liver fibrosis progression, cirrhosis and hepatocellular carcinoma higher liver related mortality decreased ARV response Initiate in all individuals with CD4 500 cells/mm 3 AND regardless of CD4 cell count in presence of severe chronic liver disease* (strong recommendation, low quality evidence) Insufficient evidence to support ART initiation in all HBV infected above 500 *Severe chronic liver disease includes cirrhosis and end stage liver disease and is categorized into compensated and decompensated stages. Decompensated cirrhosis is defined by the development of clinically evident complications of portal hypertension (ascites, variceal haemorrhage and hepatic encephalopathy) or liver insufficiency (jaundice). Summary of Adult Guidelines Topic When to start 1 st Line 8 options - AZT preferred 2 nd Line Boosted and non-boosted PIs CD4 200 CD4 200 CD Consider CD4 350 for TB Earlier initiation 4 options - AZT preferred 8 options -AZT or TDFpreferred - d4t dose reduction Simpler treatment CD Irrespective CD4 for TB and HBV 6 options &FDCs - AZT or TDF preferred - d4t phase out Boosted PIs Boosted PI Boosted PI -IDV/r LPV/r, - ATV/r, DRV/r, FPV/r - Heat stable FDC: SQV/r LPV/r, SQV/r ATV/r, LPV/r CD Irrespective CD4 for TB, HBV, PW and SDC - CD4 350 as priority 1 preferred option & 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 Less toxic, more robust regimens No No (Desirable) Yes (Tertiary centers) Better monitoring Yes (Phase in approach) Yes (preferred for monitoring, use of PoC, DBS) 15

16 OPERATIONAL CONSIDERATIONS 17/06/ Considerable operational challenges 32 16

17 Losses along the Continuum of Care 15-30% drop out of care at each step from testing to ART 50% lost to care After 5 years Mugglin et al, Trop Med Int Health, 2013 Western Cape Provincial Dept. of Health, South Africa, 2013 Adherence support WHO 2013 Recommendations: Minimizing out of pocket payments Use of fixed-dose combinations Strengthening drug supply Patient counseling and education Mobile phone text messages Wilkinson, SAJHIV Med, 2013 Lester et 34 al, Lancet

18 Retention in Care: Potential interventions No specific recommendations: multiple interventions necessary to retain patients in care No single or package of interventions support retention in all context Service decentralization Improved patient provider interaction Social and peer support Training of health workers Programme monitoring and focused evaluation of retention Other key Operational Considerations Integration Decentralization of care & treatment HIV Drug Resistance Task shifting Laboratory and diagnostics Drug supply management Pharmacovigilance Kuala Lumpur, Malaysia, 30 June 3 July

19 Service Integration of ART with ANC/MCH Care, TB Care, OST Settings RECOMMENDATION ART initiation and maintenance in pregnant/bf women and their infants in MNCH settings, with link to ongoing HIV care and ART. ART initiation in TB care settings in high TB and HIV burden settings, with linkage to ongoing HIV care and ART. TB treatment and diagnosis in HIV care settings in high burden of HIV and TB. ART initiation and maintenance in inject able drug user settings. STRENGTH &QUALITY OF EVIDENCE Strong recommendation, and Very low quality of evidence Strong recommendation, Very low quality of evidence Strong recommendation and Very Low quality of evidence Strong recommendation and Very Low quality of evidence Implementation considerations o Collaboration across different programmes o Implement TB infection control in all HIV and TB care settings o Ensure continuity of care and linkage to chronic HIV care services Decentralization of HIV Care & Treatment to Primary Care And Community Settings Central/Regional Hospitals Clinical teams led by nurse or clinical officer Option 1: District hospital Option 2: Community-based care Option 3: RECOMMENDATIONS ART initiation at hospital and maintenance at peripheral health facility. ART initiation and maintenance at peripheral health facility. ART initiation at peripheral health facility with maintenance at community level. STRENGTH &QUALITY OF EVIDENCE Strong recommendation, Low quality of evidence Strong recommendation, Low quality of evidence Strong recommendation and Moderate quality of evidence 19

20 WHO HIV Drug Resistance Surveillance and Monitoring Strategy Surveillance of Transmitted HIVDR in Recently Infected Populations Surveillance of HIVDR in Children <18 months of Age Monitoring of HIVDR Early Warning Indicators Surveillance of pretreatment HIVDR in Populations Initiating ART Surveillance of Acquired HIVDR in Populations Receiving First Line ART MONITORING 17/06/

21 Monitoring Along the HIV Care Cascade Diagnosis i (Pre ART) Care Antiretrovir al Treatment Viral Suppression PLHIV Linkage to care Denominator Cohort in Care Retention Adherence Retention Population Common Indicators Along the Cascade PLHIV HIV diagnosis Missed opportunities Linkage and Enrolment in HIV care Antiretroviral treatment Viral suppres sion Population level Impact Not tested nor identified Identified HIV+ not linked to HIV care (pre ART+ART) ART initiation did not happen ART adherence is suboptimal Results Current routinely collected indicators PLHIV # tested t estimate # tested + # on ART ART retention at 12m, 24m. Improve data quality of current indicators and collect other information to improve programmes and maximize impact Current data often only focus on # tested & # ART 21

22 Laboratory Monitoring Move to VL monitoring Viral load is recommended as the preferred monitoring approach to diagnose and confirm ARV treatment t t failure If viral load is not routinely available, CD4 count and clinical monitoring should be used to diagnose treatment failure Lack of access should not be barrier to initiating ART Need to strengthen systems and access Lack of VL or CD4 capacity should not prevent initiation of ART Moving 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 reasonable price and possibly 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

23 Implementation 2013 WHO Guidelines: The way forward (1) Prepare national plan for adoption and implementation of the new guidelines Ensure that the Plans are incorporated into NSPs to facilitate resource mobilization from Government, donors and the Global Fund Organize National Adaptation Workshops Finalize and launch national ARV Guidelines Implementation 2013 WHO Guidelines: The way forward (2) Implement communication plan for the use of National ARV Guidelines Pay attention to PSM issues Prepare and disseminate JOB AIDS Plan and implement training workshops on the new guidelines Facilitate the work of Civil Society Pay attention to children and key populations 23

24 Impact of changing from 2010 to 2013 Guidelines Global Eligibility: Increase from currently 17 million to 26 million. Preventive effect will lead to decrease of number eligible after Mortality: Save three million additional lives globally by 2025 leading to a 39% reduction in AIDS related deaths by Incidence: Reduce new HIV infections by 36% leading to 3.5 million additional new HIV infections averted by 2025 HIV Treatment Saves Lives 24

25 Thank you 49 25