HIV Drug Resistance and Early Warning Indicators Iyanthi Abeyewickreme
Goal of antiretroviral therapy • To achieve and sustain viral suppression among all those who receive antiretroviral therapy.
Increasing antiretroviral therapy coverage % ART coverage 100
Number of people receiving ART increased from ~2 million in 2005 to ~13 million in 2013
80
60
40
20
0
% of people eligible who are receiving ART (based on 2010 WHO guidelines) Source: UNAIDS Global report 2013
Why does HIV develop drug resistance? • HIV drug resistance refers to the ability of the virus to replicate in the presence of drugs that usually suppress its replication • HIV DR is caused by changes (mutations) in the virus’s genetic structure • Mutations are very common in HIV – as the virus replicates very rapidly – does not contain proteins needed to correct the mistakes it makes – need for lifelong treatment
Three categories of HIVDR relevant to public health 1. Acquired HIVDR (ADR): occurs when mutations are selected for by ARV drugs in populations receiving ART • Suboptimal drug combinations or adherence, treatment interruptions 2. Transmitted HIVDR (TDR): occurs when previously uninfected populations are infected with drug-resistant virus (appropriately measured in recently infected populations) 3. Pre-Treatment HIVDR (PDR): detected in individuals starting ART in which DR can be either transmitted or acquired (previous ARVs: treatment, PMTCT, PrEP/PEP)
Why should countries monitor HIV DR? Surveillance of HIV DR and of conditions favouring the emergence of resistance is • key to preserving the effectiveness of ART and • and protecting the efficacy of the limited therapeutic options • Is essential for the sustainability of HIV programmes
HIV DR Systematic review 2000-2011: SEAR Survey type
Number of studies
Overall HIV prevalence
TDR
10
8 showed low HIVDR levels (<5%)
PDR
23
3 reported moderate levels (5-15%) 20 reported low levels (<5%)
ADR
17
NRTI resistance: ranged from 52-92% NNRTI resistance: ranged from 43-100%
• Suggest current 1st and 2nd line regimens are appropriate for the cohorts studied • Limitations: – – – – –
Studies conducted in Thailand and India only Urban settings, small sample sizes, mixed populations Not representative of the national programmes in the country Unlikely to be generalisable to the region Lack standardised methods: cannot compare data
Trotter et al. Systematic Review of HIV Drug Resistance in the World Health Organization Southeast Asia Region, AIDS Rev, 2014.
WHO 2012 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 Acquired HIVDR in Populations Receiving FirstLine ART
Surveillance of pre-treatment HIVDR in Populations Initiating ART
Early Warning Indicators of HIV Drug Resistance • WHAT? Quality of care indicators --- assess factors associated with virological failure and emergence of HIVDR WHEN? Annual monitoring
WHERE? All ART clinics
HOW? Standardized definitions, targets and extraction tools -- as part of routine M&E
WHY? Results provide clinic specific information offering an opportunity for corrective action
WHO HIV Drug Resistance EWIs 2010
HIVDR Early Warning Indicators (EWI) Proportion of Clinics Achieving WHO-Recommended Targets 2107 clinics (2004-2009), >131,000 people, >50 countries Prescribing practices 100%
75%
Loss to follow-up ≤20%
69%
Retention on first-line ART ≥70%
67%
On time drug pick-up ≥90%
17%
On time appointment keeping ≥80%
58%
Drug supply continuity 100%
65%
Viral load suppression 12 months ≥70%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
85%
WHO Updated HIV Drug Resistance EWIs and Targets - 2012
Example of an EWI target scored card
National EWI surveys, 2005-2014 Countries
EWI surveys
India
2014: Pilot ongoing, ~19 sites
Indonesia 2007: Pilot in 5 sites in Jakarta 2011: 17 hospitals (12 with complete data) 2012: 51 hospitals (26 with complete data) Myanmar 2011: Pilot in 2 sites (1 NGO, 1 govt) 2013: 13 sites nation-wide, plan expansion to 51 sites (govt and NGO) Nepal
2013: Pilot in 3 sites 2014: Expanded to 15 out of 44 treatment sites, covering all regions
Thailand
2006-2007: Scale up 2006-2007 nationally From 2009: Integrated into national programmes 2011: Implemented in >700 hospitals across 76 provinces, Paediatric HIVQUAL-T in 200 hospitals in 30 provinces 2014: 1027 (under universal health coverage scheme) which is > 98% of all government hospitals
Outcome of EWI monitoring in Nepal July 2011 â&#x20AC;&#x201C; July 2012 100%
2(14%) 90% 80%
2(17%) 5(33%)
3 (21%)
70%
10(83%)
60% 50%
15 (100%)
3(20%)
Moderate
9(64%)
Poor
40% 30%
7(47%)
20% 10% 0%
EWI-1 adults
Good
EWI-1 children
EWI-2 Retention in ART care EWI-3 Drug stock out EWI-4 prescribing practices
Sri Lanka
Sri Lanka – Patients on ART by end 2013 ART regimen
Number of patients
First line
406
Substituted 1st line
87
Second line
37
Total
519
Number of ART clinics– 12 Source – 2013 Annual Report of NSACP
Source – 2013 Annual Report of NSACP
EWIs in Sri Lanka • Should consider monitoring EWIs • HIV DR suspected in more than 12 patients? • 2 samples sent to India for HIVDR testing, costing SLR 75,000 per sample • 27 patients currently on second line • Limited therapeutic options available • Need to preserve long-term efficacy and durability of available 1st line and 2nd line drugs • EWIs do not require laboratory testing
WHO-designated national HIVDR laboratories: SEAR 2014
Nepal
Thailand: 1. Siriraj Hospital, Bangkok 2. National Institute of Health, Department of Medical Sciences, Bangkok
Myanmar
India: 1. NARI Pune 2. TRC Chennai Indonesia
WHO-designated Regional HIVDR Laboratories: (i) DRVI, Beijing, China (ii) Burnet Institute, Melbourne, Australia (iii) NSW State Reference Laboratory, Sydney, Australia
HIV DR Surveillance 1. HIVDR surveillance is NOT a special research activity but must be integrated within national HIV strategic plan 2. Routine implementation of HIVDR surveillance is required as: – CRITICAL TO INFORM PROGRAMME PERFORMANCE AND POLICY – EASIER TO IMPLEMENT – GOOD VALUE FOR MONEY !
Will HIVDR increase? • Expansion of ART access (more people on ARV) • Expanded role of ART for both treatment and prevention: – PMTCT Option B + : ART for life to asymptomatic woman – Introduction of PreP
• Change in ART eligibility criteria : ART to asymptomatic people 23
Thank you