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

Conflict of Interest No conflicts of interest to declare.

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

Coordinating a public health response to HIVDR The WHO Global Action Plan on HIVDR 2017-2021 provides a fiver-year framework for a global response to HIVDR.

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)

Countries implementing WHO PDR surveys WHO HIVDR Report 2017

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

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

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

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?

Avila-Ríos, et al., Lancet HIV 2016 PDR survey in Mexico Drug Class All % PDR (95% CI) Women Men Any ARV 13.5 (9.4-19.1) 20.7 (8.4-42.5) 12.1 (8.3-17.4) NNRTI 9.2 (5.6-14.7) 14.8 (4.7-38.0) 8.1 (5.1-12.6) NRTI 5.5 (3.0-9.9) 10.3 (3.5-26.5) 4.6 (2.2-9.5) PI 2.6 (1.1-5.4) 4.2 (0.9-17.0) 2.2 (0.9-5.4) NNRTI + NRTI 1.4 (0.5-4-4) 5.9 (1.5-20.4) 0.6 (0.1-4.3) % starting active ART 91.7 (85.6-95.3) 86.6 (66.0-95.6) 92.6 (87.3-95.8) Avila-Ríos, et al., Lancet HIV 2016

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

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

Follow-up studies on the national PDR survey 2012-2016 García-Morales, et al., J Antimicrob Chemother 2017; accepted

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

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

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

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