1. MOSY07
HIV Drug Resistance and Antimicrobial Resistance: Science and Action
Results from the Mexico HIVDR survey leading to country and regional responses
Santiago Ávila-Ríos
Centre for Research in Infectious Diseases
National Institute of Respiratory Diseases

2. Conflict of Interest
No conflicts of interest to declare.

3. The threat of HIVDR
Pre-ART HIVDR (PDR) is increasing in countries widely using NNRTI-based regimens.
WHO HIVDR Report 2017

4. Coordinating a public health response to HIVDR
The WHO Global Action Plan on HIVDR provides a fiver-year framework for a global response to HIVDR.

5. WHO PDR Surveys
Since 2014, WHO has developed a standardized methodology to conduct nationally representative PDR (and ADR) surveys.
Nationally representative HIVDR prevalence estimates for 3 groups:
ALL ART initiators (ARV-naïves and re-initiators with prior exposure to ARVs)
ART initiators with prior exposure to ARVs (self report, based on entry questionnaire)
PMTCT-exposed women
Defaulters restarting first line ART after a period of treatment interruption
ARV-naïves initiating ART (self report, based on entry questionnaire)

6. Countries implementing WHO PDR surveys
WHO HIVDR Report 2017

7. EFV/NVP DR ~10% in several countries with results available* * * *
* Surveys excluding persons with prior exposure to ARV
WHO HIVDR Report 2017

8. NNRTI DR in ART starters with prior exposure to ARVs >2-fold higher than in ARV-naïves
Cameroon
Namibia
Uganda
Argentina
Guatemala
Nicaragua
Myanmar
ART-naïve
80.6%
81.7%
88.9%
81.0%
93.9%
85.4%
90.0%
Prior exposed
7.8%
18.0%
1.2%
18.6%
2.8%
12.3%
8.4%
Unknown
11.6%
0.3%
9.9%
0.4%
3.3%
2.3%
1.6%
WHO HIVDR Report 2017

9. Women more affected by NNRTI PDR in some countries
WHO HIVDR Report 2017

10. Where do we go from here? Need to strengthen health system
VL monitoring to identify and promptly manage viral failure
Prevention programmes (to avoid further transmission of HIVDR)
Education on ARV prescription
Need to assess PDR levels in countries lacking information
Data currently being generated useful to convince national programs
Successful surveys to guide implementation of new surveys
International collaborations to provide support in survey design, logistics, HIV genotyping, sample transportation
When levels of NNRTI DR are high, need to identify what response/action is needed
Change to DTG-based regimens in all ART initiators?
Prioritize DTG-based regimens in individuals at high risk of PDR (i.e. people starting first line with previous exposure to ARVs)?
Perform baseline HIVDR tests in all ART initiators and start DTG-based regimens in those with HIVDR?

11. Avila-Ríos, et al., Lancet HIV 2016
PDR survey in Mexico
Drug Class
All
% PDR (95% CI)
Women
Men
Any ARV
13.5 ( )
20.7 ( )
12.1 ( )
NNRTI
9.2 ( )
14.8 ( )
8.1 ( )
NRTI
5.5 ( )
10.3 ( )
4.6 ( ) PI
2.6 ( )
4.2 ( )
2.2 ( )
NNRTI + NRTI
1.4 ( )
5.9 ( )
0.6 ( )
% starting active ART
91.7 ( )
86.6 ( )
92.6 ( )
Avila-Ríos, et al., Lancet HIV 2016

12. Considerations of the Ministry of Health: the case of Mexico
Preferred option: Introduce baseline DR testing to all persons starting ART, because
Cheaper than DTG;
Lab capacity exists (although limited to only 2 labs);
Doctors trained on DR interpretation as DR testing is standard of care in patients failing ART
Alternative option: Switch to DTG-based regiments in all persons starting ART
DTG is currently unaffordable (USD 2200/person/year);
Price negotiations/licensing discussions are urgent;
Considering other INI: elvitegravir (similar price to Atripla) and move to DTG if price negotiations allow it

13. Considerations of the Ministry of Health: the case of Mexico
In a large and complex country such as Mexico, another possible strategy is to diversify the response based on regional DR prevalence
Repeat PDR survey powered to detect intra-national differences in DR prevalence.
Use results to tailor specific regional treatment strategies, e.g.
Implement baseline DR testing in regions with higher PDR, strengthen laboratory capacity.
Prioritise the use of DTG-based regimens in regions with higher PDR.
Re-inforce VL monitoring in regions with higher PDR.
In Mexico, patients starting ART with prior ARV-exposure are systematically started with PI/r
Sub-national PDR survey in 8 regions of Mexico
2017

14. Follow-up studies on the national PDR survey
García-Morales, et al., J Antimicrob Chemother 2017; accepted

15. Potential challenges to action
Change to DTG-based regimens
High drug costs (DTG: USD 2200/person/year) combined with increasing number of persons needing ART and limited growth of available resources
Bureaucracy and administrative barriers that restrict drug availability in countries
Price negotiations hindered by national laws and international treaties
Interests of pharmaceutical companies

16. Potential challenges to action
Baseline HIV genotyping
Laboratory capacity and human resources
Training for doctors in interpreting HIVDR testing results and acting upon them
Shorten time to deliver results
Reduce the cost of DR testing: NGS?
Using modeling for decision making
Preferable, but very specialized area and few people able/available
Long times to develop models

17. Conclusions
NNRTI PDR around 10% is currently being observed in many LMICs.
Countries need to act upon high levels of HIVDR in order to achieve national and global goals to control the HIV epidemic.
Need to implement HIVDR surveillance in countries where information is still lacking
Importance of previous experiences in other countries
Responding to HIVDR might be highly dependent on national resources and scenarios
Use of DTG in all ART starters dependent on drug cost negotiations and licensing
Baseline HIV genotyping in all starters might be an alternative for countries with laboratory capacity in which the use of DTG is unaffordable
Alternative solutions such as prioritising responses based on sub-national PDR surveillance should be considered for large/complex countries

18. Acknowledgements Gustavo Reyes-Terán Claudia García Daniela Tapia
Marissa Pérez
Margarita Matías
Amalia Girón
Ricardo Mendizabal
Felipe Torres
René Gutiérrez
Aleyda Solórzano
Luz María Romero
Carlos Vargas
Edgar Sajquim
Sanny Northbrook
Sandra Juarez
Carlos Magis
Marisol Valenzuela
Eddie León
Silvia Bertagnolio
Neil Parkin
Michael Jordan
Hiwot Haile-Selassie
Giovanni Ravasi