Alarming rates of virological failure and drug resistance in patients on long-term antiretroviral treatment in routine HIV clinics in Togo. Abla A. KONOU, Anoumou Y. DAGNRA, Nicole VIDAL, Mounerou SALOU, Zakillatou ADAM, Assétina SINGO-TOKOFAI, Eric DELAPORTE, Mireille PRINCE-DAVID, Martine PEETERS

Introduction Scaling up of ART (AIDS. 2015 Nov 28;29(18):2527-30) Universal access to ART: goal almost achived Scaling up of ART Monitoring treatment efficiency (WHO june 2013) Epidemiological surveillance of resistance: virological monitoring +++: monitoring the effectivness of treatment Early detection of resistance Adequate therapeutic switch (AIDS. 2015 Nov 28;29(18):2527-30) Increase in patients on ART

Introduction Togo HIV prevalence : 2,5% Scaling up ARV in 2008 rapid increase of patients on ART 10579 (2008) to 37511 (2014) : with ≈30% duration ART≥ 6 ans (CNLS, 2014) Limitations: Insufficient human resources in the management Almost absence of virological monitoring

Introduction Epidemiological surveillance of resistance in limited-ressource settings today? Constatation Absence of virological monitoring in limited-ressource countries Reasons - limited resources - lack of qualified staff (Rowley C, CID 2014; Sigaloff K et al, Lancet 2015) Consequences emergence of drug resistance + ART ineffective

Introduction Epidemiological surveillance program: less data - => high rate of virological failure: M12 et M24: 17,7%- 26% - => drug resistance mutation No data on virological responses on patients on ART in long-term long-term treatment efficiency? Study: virological response on patients on ART at M ≥ 48 months Dagnra, et al, JIAS 2011 Aghokeng et al, CID 2014 Konou et al, Aids Res& Ther 2015

Objectives Specific objectives Evaluate long-term ART efficacity without virological monitoring Specific objectives Estimate virological failure rate Determine drug resistance mutation frequency Describe drug resistance mutations

Methods Cross-sectional study on 2012 sample collection: 5regions inclusion criteria HIV-1 infected patients years ≥ 18 ans TOGO citizens ART duration M ≥ 48 months Informed consent sample collection: 5regions BIOLIM/FSS-UL- Togo Viral load ABBOTT m2000 IRD Montpellier – France Genotypic drug resistance tests: ANRS in-house protocol - Gène pol - ANRS algorithm Lomé

Virological failure: 39.6% Results 867 patients 767 patients on 1st line 100 patients With IP regimen Virological failure: 39.6% 42.2% (324) 19% (19) Samples sequenced: 173 164 9

Virological failure and ART duration

1st line and IP regimen patients viral load

Drug resistance mutation frequency(DRM) INTI INNTI IP ART regimen 1st line: 2 INTI + 1 INNTI (n=164) Switch to 2nd line (n=8) IP regimen as 1st line (n=1) MDR (n) 99,4% (163) 75% (6) 100 % (1) NRTI+NNRTI 98,8% (161) 100% (6) NRTI only 0,6% (1) 100% (1) NNRTI only NRTI+NNRTI+IP 50% (3) Frequent drug mutations

Thymidin Analog Mutations (TAMs) Patients with TAMs: 71% (115/163) TAM accumulation: 50%-66.6% Years on ART and DRM TAM accumulation and viral load

Resistance to ART regimen at sampling 98.5% No efficient treatment!!!

Crossed resistance Molecules INTI + INNTI IP regimen TDF 2.1% (3/144) 28.6% (2/7) ABC 30.5% (50/164) 42.9% (3/7) DDI 11% 518/164) ETR 21.3% (35/164) RPV 64% (105/164) 57.1% (4/7) SQV LPV 50% (1/2) ATV 100% (2/2) FPV This study rate > Mali’s study rates (Fofana et al, JAC 2014)

Conclusion High rate of virological failure: 39,6% Drug resistance mutation: almost all patients Emergency: include virological monitoring Risk: resistant virus epidemic if nothing is done Promote stronger molecules on first line regimen Increasing access to ARVs has clearly improved in the country but in the long-term this can be dramatic in the absence of virological monitoring

UNIVERSITE DE LOME - FSS /UL FACULTE DES SCIENCES DE LA SANTE DEPARTEMENT DES SCIENCES FONDAMENTALESET BIOLOGIQUES