World Health Organization Strategy for HIV Drug Resistance Surveillance in Low- and Middle- Income Countries

Transcription

1 World Health Organization Strategy for HIV Drug Resistance Surveillance in Low- and Middle- Income Countries Silvia Bertagnolio, MD World Health Organization, Geneva Lusaka, 6 May 2014

2 Key characteristics of the early phase of ART scale-up Key characteristics of original HIVDR surveillance methods Limited access to ART ART availability mostly in urban centers Area-specific Focus on clinic functioning Convenient sampling of clinics (where enrolment would be feasible) t/hiv/pub/ drugresist ance/repor t2012

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4 2004 STRATEGY 2014 STRATEGY Detect an ALERT QUANTIFY the MAGNITUDE of HIVDR Results AREA/CLINIC specific Focus on CLINIC functioning at sentinel sites Suitable for GENERALIZED EPIDEMICS Results non readily available (Prospective methods) Results are NATIONALLY REPRESENTATIVE Focus on ART PROGRAMME functioning Suitable for ALL EPI SETTINGS: lowlevel, concentrated, generalized, and mixed epidemics Results more readily available (cross sectional methods)

5 Surveillance cannot answer all questions about science, programme and drug effectiveness BUT it should address public health HIVDR-related questions: Are 1st-line and 2nd-line regimens, PrEP, PEP effective given population-level HIVDR prevalence?

6 1. Nationally representative sample: results relevant for national decision making 2. Cross-sectional methods: short duration of surveys (max 6 months) 3. Standardized methods: leading to comparable results across countries; trends analysis over time

7 Programatic assessment (ART clinic level) 1. Early Warning Indicators 2. Pre-treatment HIVDR Population Adults and children on ART Adults initiating 1st-line ART Public Health Relevance Identifies clinic level weaknesses allowing corrective action 1st-line, Prep, PEP, regimen selection HIVDR Survey (National Level) 3. Acquired HIVDR 4. HIVDR in infants <18 months Adults on ART for 12(±3) and 48 months Infants <18 months, ART naive & recently diagnosed with HIV 2nd-line (and beyond) regimen selection 1st-line paediatric regimen selection 5. Transmitted HIVDR ARV-naïve recently infected adults Monitor level of transmission of HIVDR; Inform on programme quality (indirect indicator) and future first-line

8 Survey Population Public Health Relevance Early Warning Indicators Pre-treatment HIVDR Acquired HIVDR HIVDR in infants <18 months Transmitted HIVDR Adults and children on ART ARV-naïve and exposed individuals initiating first-line ART Adults receiving ART for and 36 + months; Children on ART for 12months Children <18 months of age recently diagnosed with HIV ARV-naïve populations Identify clinics specific weaknesses allowing corrective action First-line regimen selection Second-line regimen selection First-line paediatric regimen selection PrEP and PEP regimen selection; Help to assess programme quality (indirect indicator) and future first-line 1. Drug stock out 2. Retention in care 3. VL suppression 4. Adherence (drug pick-up) 5. Dispensing of triple drug regimens

9 Survey Early Warning Indicators NEW Pre-treatment HIVDR Acquired HIVDR Population Adults and children on ART Individuals initiating 1 st -line ART Adults receiving ART for and 36 + months; Children on ART for 12months Public Health Relevance Identifies site and programme level weaknesses allowing corrective action Are currently recommended 1st-line regimens still effective for the majority of population initiating ART? Second-line regimen selection HIVDR in infants <18 months Children <18 months of age recently diagnosed with HIV First-line paediatric regimen selection Transmitted HIVDR ARV-naïve populations PrEP and PEP regimen selection; Help to assess programme quality (indirect indicator) and future first-line

10 Main outcomes: HIVDR prevalence o among all ART initiators o among ART initiators without prior ARV exposure Cross section survey Duration: 6 months ART clinics randomly sampled from a list of all clinics initiating ART in the country Clinics are selected proportionally to their size

11 # of clinics # of ART initiators Pts per clinic Total Sample Size * Assuming genotyping failure of 20%, HIVDR among all ART initiators: 10%, confidence interval = 5%, proportion of individuals initiating ART with NNRTI-based regimens: 100%.

12 Survey Population Public Health Relevance Early Warning Indicators Adults and children on ART Identifies site and programme level weaknesses allowing corrective action Pre-treatment HIVDR Acquired HIVDR HIVDR in infants <18 months ARV-naïve and exposed individuals initiating first-line ART Individuals receiving ART (any regimen/line) Children <18 months of age recently diagnosed with HIV First-line regimen selection Is VL suppression rate adequate? Is current second line (and beyond) still effective at population level? First-line paediatric regimen selection Transmitted HIVDR ARV-naïve populations PrEP and PEP regimen selection; Help to assess programme quality (indirect indicator) and future first-line

13 Viral load suppression Resistance Patients on ART Patients on 1st line ART Early (12±3 months) Late ( 48 months) Two main outcomes: Two target populations Two time points:

14 # of clinics Survey of patients on ART for 12 (±3) months* Survey of patients on ART for 48 months** Pts per clinic Sample Size Pts per clinic Sample size * assumed prevalence of VL suppression among individuals sampled = 85%, confidence interval half-length = ±5%, laboratory failure rate of 15%,proportion of individuals sampled receiving first-line ART= 95%; proportion of individuals on first-line ART receiving NNRTI-based regimens=100%.; ** assumed prevalence of VL suppression among individuals sampled =70%, confidence interval width = ±6%, laboratory failure rate of 15%, proportion of individuals sampled still on first-line ART = 95%; proportion of individuals on first-line ART receiving NNRTI-based regimens=100%

15 INPUTS OUTPUTS

16 Survey Population Public Health Relevance Early Warning Indicators Pre-treatment HIVDR Acquired HIVDR Adults and children on ART ARV-naïve and exposed individuals initiating first-line ART Adults receiving ART for and 36 + months; Children on ART for 12months Identifies site and programme level weaknesses allowing corrective action First-line regimen selection Second-line regimen selection HIVDR in infants <18 months Infants<18 months recently diagnosed with HIV Inform first-line paediatric regimen selection Transmitted HIVDR ARV-naïve populations PrEP and PEP regimen selection; Help to assess programme quality (indirect indicator) and future first-line

17 NRTI or NNRTI NNRTI 35,3% 31,8% NRTI Sample size = 201 3,5% 0% 20% 40% 60% 80% 100% Resistance No Resistance NRTI or NNRTI NNRTI NRTI 12,5% 62,9% 62,5% 0% 20% 40% 60% 80% 100% Sample size = 232 Resistance No Resistance

18 Survey Early Warning Indicators Pre-treatment HIVDR Acquired HIVDR HIVDR in infants <18 months Population Adults and children on ART ARV-naïve and exposed individuals initiating first-line ART Adults receiving ART for and 36 + months; Children on ART for 12months Children <18 months of age recently diagnosed with HIV Public Health Relevance Identifies site and programme level weaknesses allowing corrective action First-line regimen selection Second-line regimen selection First-line paediatric regimen selection Transmitted HIVDR ARV-naïve recently infected populations Inform on programme quality (indirect indicator)

19 Survey Sample (n) (eligible Size) 2.5% 5% 7.5% 10% 12.5% 15% n=20 (0.53%,18.8%) (1.24%,22.1%) (2.1%,25.2%) (3.1%,28.2%) (4.2%,31.1%) (5.5%,33.8%) n=30 (0.6%,14.7%) (1.4%,18.1%) (2.5%,21.4%) (3.7%,24.5%) (5.0%,27.4%) (6.4%,30.3%) n=40 (0.6%,14.7%) (1.6%,15.9%) (2.8%,19.1%) (4.1%,22.3%) (5.5%,25.3%) (7.1%,28.2%) n=50 (0.68%,10.9%) (1.7%,14.4%) (3.0%,17.6%) (4.4%,20.8%) (6.0%,23.8%) (7.6%,26.7%) n=100 (0.87%,7.6%) (2.2%,11.0%) (3.8%,14.2%) (5.5%,17.2%) (7.4%,20.1%) (9.3%,23.0%) n=150 (1.0%,6.3%) (2.5%,9.6%) (4.3%,12.7%) (6.2%,15.7%) (8.1%,18.6%) (10.1%,21.4%) n=200 (1.1%,5.6%) (2.8%,8.9%) (4.6%,11.9%) (6.6%,14.8%) (8.6%,17.7%) (10.7%,20.5%) n=250 (1.2%,5.2%) (2.9%,8.4%) (4.8%,11.4%) (6.9%,14.3%) (8.9%,17.1%) (11.1%,19.9%) n=300 (1.3%,4.9%) (3.1%,8.0%) (5.0%,11.0%) (7.1%,13.9%) (9.2%,16.7%) (11.4%,19.4%) n=350 (1.3%,4.7%) (3.2%,7.8%) (5.2%,10.7%) (7.3%,13.5%) (9.4%,16.3%) (11.6%,19.1%) n=400 (1.4%,4.5%) (3.3%,7.6%) (5.3%,10.5%) (7.4%,13.3%) (9.6%,16.1%) (11.8%,18.8%) n=450 (1.4%,4.4%) (3.3%,7.4%) (5.4%10.3%) (7.5%,13.1%) (9.7%,15.8%) (12.0%,18.5%) n=500 (1.5%,4.3%) (3.4%,7.3%) (5.5%,10.1%) (7.7%,12.9%) (9.9%,15.7%) (12.1%,18.4%) n=550 (1.5%,4.2%) (3.5%,7.1%) (5.6%,10.0%) (7.8%,12.8%) (10.0%,15.5%) (12.2%,18.2%) n=600 (1.5%,4.1%) (3.5%,7.0%) (5.6%,10.0%) (7.8%,12.6%) (10.1%,15.4%) (12.3%,18.0%) Recommended Consider Caution

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21 1. Ad hoc HIVDR surveys 2. Use of existing programmatic data VL and HIVDR data, where available as part of routine clinical care, can be an alternative of surveillance data if they are representative of the populations of interest and there are not major biases

22 Individuals who have been on ART for 12 months in January-June 2013 (n=10,000) Individuals who receive a VL test (n=8,000) Individuals with a successful VL test (n=7,200) Individuals with VL > 1000 copies/ml (n=720) Individuals with specimen genotyped (n=550) Individuals with specimen successfully genotyped (n=270) 30% Loss 50% Loss Biased results can lead to inappropriate public health decision making

23 1. If you do it, do it properly! National estimate based on representative sampling 2. Stick to the same method! Methods standardization allows time trends analysis and comparability 3. If you do it, then use it! Globally (to inform ART guidelines) and nationally (to adapt ART guidelines) using country-specific cost-effectiveness models 4. If you have done it once, then repeat it! Regularly, as part of the ART programme evaluation, not just as research 5. Take advantage of it! To identify research questions ; catalyze expansion of capacity for VL monitoring.

24 ❶ ❷ Global Fund PEPFAR National funding Bilateral agreements British Columbia - Center for excellence lab

25 Improved feasibility Improved relevance for national programmes Cost contained Funding opportunities A lot of valuable information for the treatment programmes!