WHO 2013 Consolidated ARV Guidelines What is new for PMTCT and Paediatric HIV Care and Treatment? Nathan Shaffer PMTCT Technical Lead, WHO 8 th Interest Workshop Lusaka, Zambia 5 May 2014 Excellent healthcare locally delivered
Objectives of Presentation o Context of new consolidated guidelines o Adult recommendations o Pregnant and breastfeeding women o Children o Emerging issues and future directions o Summary
Why new WHO guidelines in 2013? Advances in science/technology and in vision Technologies (incl. PoC CD4 and VL, new drug formulations) ART for individual and population benefits HIV as a chronic health condition Increasing focus on treatment adherence and retention in care Chronic care models decentralization, integration Despite scale-up, continuing challenges Low ART coverage among children, adolescents and key populations Major gaps in quality and in retention along the continuum of care
WHO 2013 Consolidated ARV 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
Concept Behind Consolidation Consolidation across populations and ages Consolidation along the continuum of care Consolidation of new with existing guidance
Simpler, less toxic drugs Point of care diagnostics Delivery models
TARGET POPULATION (ARV-NAIVE) HIV+ ASYMPTOMATIC CD4 350 cells/mm 3 HIV+ SYMPTOMATIC Summary of Changes in Recommendations When to Start in Adults 2010 ART GUIDELINES 2013 ART GUIDELINES WHO clinical stage 3 or 4 regardless of CD4 cell count CD4 500 cells/mm 3 (CD4 350 cells/mm 3 as a priority) No change STRENGTH OF RECOMMENDATION & QUALITY OF EVIDENCE Strong, moderatequality evidence Strong, moderatequality evidence PREGNANT AND BREASTFEEDING WOMEN WITH HIV HIV/TB CO- INFECTION HIV/HBV CO- INFECTION HIV+ PARTNERS IN SD COUPLE CD4 350 cells/mm 3 or WHO clinical stage 3 or 4 Presence of active TB disease, regardless of CD4 cell count Evidence of chronic active HBV disease, regardless of CD4 cell count No recommendation established Regardless of CD4 cell count or WHO clinical stage No change Evidence of severe chronic HBV liver disease, regardless of CD4 cell count Regardless of CD4 cell count or WHO clinical stage Strong, moderatequality evidence Strong, low-quality evidence Strong, low-quality evidence Strong, high-quality evidence
Summary of Changes in Recommendations: What to Start in Adults FIRST-LINE REGIMENS (PREFERRED ARV REGIMENS) TARGET POPULATION HIV+ ADULTS 2010 ART GUIDELINES 2013 ART GUIDELINES AZT or TDF + 3TC (or FTC) + EFV or NVP STRENGTH & QUALITY OF EVIDENCE HIV+ PREGNANT WOMEN HIV/TB CO-INFECTION AZT + 3TC + NVP or EFV AZT or TDF + 3TC (or FTC) + EFV TDF + 3TC (or FTC) + EFV (as fixed dose combination) Strong, moderatequality evidence HIV/HBV CO-INFECTION TDF + 3TC (or FTC) + EFV
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) 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)
Recommendations: VL Monitoring for ART Response RECOMMENDATION Viral load is recommended as the preferred monitoring approach to diagnose and confirm ARV treatment failure If viral load is not routinely available, CD4 count and clinical monitoring should be used to diagnose treatment failure STRENGTH Strong recommendation, low-quality evidence Strong recommendation, moderate-quality evidence
2013 ARV Consolidated Guidelines Pregnant and Breastfeeding Women
Evolution of WHO PMTCT ARV Recommendations PMTCT ART 2001 2004 2006 2010 Launch June 2013 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
Changes in earlier guidelines PMTCT guidelines have changed every 3-4 years, based on new clinical trials results Covering more of the MTCT risk period More complex, more effective Increasing emphasis on treatment of the mother Major implementation issues and challenges Routine HIV testing (PITC) ART and ARV initiation in MNCH settings CD4 testing to determine ART eligibility Breastfeeding and weaning strategies Postpartum follow up
New 2013 PMTCT Recommendations All pregnant and breastfeeding women infected with HIV should initiate triple ARVs (ART), which should be maintained at least for the duration of mother-tochild transmission risk. Women meeting treatment eligibility criteria should continue lifelong ART. (strong recommendation, moderate-quality evidence) Option B+ For programmatic and operational reasons, particularly in generalized epidemics, all pregnant and breastfeeding women infected with HIV should initiate ART as lifelong treatment. (conditional recommendation, low-quality evidence) Option B In some countries, for women who are not eligible for ART for their own health, consideration can be given to stopping the ARV regimen after the period of mother-to-child transmission risk has ceased. (conditional recommendation, low-quality evidence) TDF + 3TC Pregnancy/Breast (or FTC) + EFV as a fixed-dose Feeding combination warrants (FDC) ART is recommended initiation as the preferred option to initiate ART Major issue now is not when to start but whether to stop (strong recommendation, moderate-quality evidence)
Rationale: Shift from Option A to B+ or B BENEFITS FOR MOTHER AND CHILD Ensures all ART eligible women initiate treatment Prevents MTCT in future pregnancies Potential health benefits of early ART for non-eligible women Reduces potential risks from treatment interruption Improves adherence with once daily, single pill regimen Reduces sexual transmission of HIV BENEFITS FOR PROGRAM DELIVERY & PUBLIC HEALTH Reduction in number of steps along PMTCT cascade Same regimen for all adults (including pregnant women) Simplification of services for all adults Simplification of messaging Protects against transmission in discordant couples Cost effective
Programmatic considerations for B+ Initiate all HIV+ pregnant and breastfeeding women on ART Operational and programmatic advantages to lifelong ART for pregnant and breastfeeding women ( B+ ), particularly in settings with: Generalized epidemics High fertility (though need to strengthen FP) Long duration of breastfeeding Limited access to CD4 to determine ART eligibility High partner serodiscordance rates National programmes need to decide B or B+ Support for initiation, adherence throughout MTCT risk period and linkage to chronic ART care critical for both B and B+
Rapid transition from short-course prophylaxis to Option B+, Malawi Option B+ begins
Rapid Change Towards B/B+ Transition in PMTCT Regimens in the 22 Global Plan Priority Countries 2013 Option A Option B Option B+ Planned/piloting Option B+ Implementing Not a priority country After 2010 WHO PMTCT ARV guidelines As of June 2013
PMTCT Implementation Issues Adequate planning for changes in guidelines Expansion and integration of ART into PMTCT sites Supply chain for ARVs (avoidance of stock-outs) Task-shifting for ART initiation Adherence, retention, follow up, linkages with chronic ART All MNCH sites become ART sites Access to ART monitoring Major challenge for PMTCT and MNCH settings: How to expand access to VL monitoring? How to utilize CD4 data, especially for women with high baseline CD4?
Key research gaps: Pregnant Women The GDG recommended more research to support the new recommendations, inform programmatic decisions, and promote optimal implementation. (P. 104, 2013 CGL) ARV toxicity surveillance: Safety of early, lifelong ART for pregnant and breastfeeding women? Maternal toxicity, pregnancy toxicity (stillbirth, low birth weight, prematurity, birth defects) and infant toxicity? Mother-to-child transmission and mother and child health impact: Impact on overall HIV-free survival and and overall MTCT rate (at the end of breastfeeding as well as at 6-weeks)? Impact on maternal morbidity and mortality, sexual transmission, and the longterm success of first-line ART? Adherence and retention: Acceptability of ART to women, especially those who initiate lifelong ART before they meet «adult eligibility» criteria» Adherence and retention rates for women with both low and high CD4? Health systems and community interventions needed to achieve high levels of adherence and retention in setting of universal ART?
WHO 2013 Clinical Guidance for Antiretroviral Therapy in Children
80 70 60 50 40 30 20 10 0 30% The gap between adult and child ART coverage is widening 29% [25-31] 59% [56-66] 34% 34% [29-36] 2011 2012 68 % [65-75] Children Adult Source: Global AIDS Response Progress Reporting (WHO/UNICEF/UNAIDS) and 2013 UNAIDS estimates. Identify HIV-infected children in a timely manner Ensure that ART is promptly initiated with the most effective drugs in the appropriate formulation
Programmatic Challenges Key issues for Paeds Treatment and Care Case-finding and early ART initiation EID coverage remains poor PITC not well implemented Limited availability of pediatric formulations and difficulties in harmonizing regimens with adults Poor retention of children on ART and in care Technical Challenges Provide the most effective regimen to deal with high VL and rapid disease progression Optimization of ART treatment sequencing
New Paeds Recommendations, 2013 ART should be initiated in all children below five years of age, regardless of CD4 count or WHO clinical stage. Infants diagnosed in the first year of life (strong recommendation, moderate-quality evidence). Children infected with HIV between one and below five years of age (conditional recommendation, very low-quality evidence). ART should be initiated in all children five years of age and older with CD4 cell count 500 cells/mm 3, regardless of WHO clinical stage. CD4 count 350 cells/mm 3 (strong recommendation, moderate-quality evidence). CD4 count between 350 and 500 cells/mm 3 (conditional recommendation, very-lowquality evidence). LPV/r-based regimen for children <3 years, regardless of NNRTI exposure with ABC + 3TC or AZT + 3TC EFV-based regimens for children > 3 years For 3 years to < 10 years (or <35 kg), the NRTI backbone ABC + 3TC AZT or TDF + 3TC or FTC For children 10 years and 35 kg, TDF + 3TC or FTC ; AZT + 3TC;ABC + 3TC
Expanding treatment and improving outcomes for children Earlier initiation of ART in children Reduce barriers to ART initiation Improve retention in care Reduce morbidity and improve immunological and response and long term outcomes For children > 5years, harmonize with adults guidelines ARV recommendations balance efficacy, toxicities, resistance, sequencing, feasibility and simplification while acknowledging the particular limitations of drugs for children
Key Operational Considerations Adherence Retention across the continuum of care Integration & linkage Decentralization of care & treatment Task shifting (NIMART) Laboratory and diagnostics Drug supply management Kuala Lumpur, Malaysia, 30 June - 3 July 2013
WHO ARV Consolidated Guidelines Summary and Future Directions
ART Possible policy scenarios for future ART eligibility Estimated millions of people eligible for ART in LMIC in 2012 28.6m 30.4m 33m 1 2 3 CD4 500 + Serodiscordant couples & Pregnant women & Children <5yrs Recommended in 2013 CD4 500 + SDC, PW, & Children<5yrs Children <15yrs Key populations (MSM, PWID, SW, TG) HCV, ESRD & >50yrs All HIV+ Test and treat
Adult Clinical and Implementation Science Research Priorities/ Gaps Clinical Baseline screening and time of initiation in presence of co-infections and comorbidities Role of new drugs in optimization of ART regimens Frequency and strategic use of CD4 and VL to monitor treatment response Implementation Science Pre-ART retention ART retention Linkage to care Adherence and viral load suppression
PMTCT Clinical and Implementation Science Research Priorities/ Gaps Clinical ART initiation (B vs. B+) Late presenters and incident infection during pregnancy and breastfeeding What to start in PW (optimizing safe, effective regimen) EID and final diagnosis What to start in exposed infants: move from 1 to 3 drug neonatal prophylaxis? Implementation Science How to find those not in ANC How to retain mothers starting in B+/B programmes Retesting late in pregnancy and BF Demand creation and links with the community Special management for high risk mothers/infants (late presenters, serconverters) VL access and use for PW
WHEN to test? EID and Infant Dx Diagnosis? Should current EID recommendations (6 wks) be revised? Testing Performance? Late enough to optimize sensitivity and detection of infections Early enough to intervene for high risk infants, reduce mortality Mortality Retention Programmatic feasibility Minimize costs Utilize new technologies (eg. PoC, SMS printers) Birth? 6 weeks? Final Diagnosis? Key example of IS to inform new guidelines
Paediatric/ Adolescent Clinical and IS Research Priorities/ Gaps Clinical How to identify exposed and infected children outside of PMTCT? Finding infants who are lost PITC in paeds OPD/hospital settings Consider expanded treatment threshold (<15yrs) Simplification strategies for drug access & adherence, esp for infants and adolescents Implementation Science Strategies to target chldren/ adolescents to link to care, promote demand, adherence Tracing LTFU Reduction of social/structural barriers for youth testing/ care PITC outside PMTCT settings Optimal models of service delivery/ paediatric and youth friendly services
Overview New Recommendations 2013 guidelines Clinically relevant o Earlier initiation of ART (CD4 500) o Immediate ART for children below 5 years o ART for all pregnant and breastfeeding women with HIV (Option B/B+) and lifelong ART (Option B+) o Harmonization of ART across populations (e.g., adults and pregnant women, B/B+) and age groups o Simplified, fewer, and less toxic 1 st line regimens (TDF/XTC/EFV) Operationally relevant o Use of Fixed Dose Combinations as a preferred approach o Improved patient monitoring to support better adherence and detect earlier treatment failure (increased use of VL) o Recommend task shifting, decentralization, and integration o Community based testing to complement broader HTC
WHO ARV Consolidated Guidelines Thank you!