2. 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

3. 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 Nov 28;29(18): )
Increase in patients on ART

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

5. 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

6. 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

7. 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

8. 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

9. 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

10. Virological failure and ART duration

11. 1st line and IP regimen patients viral load

12. 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

13. 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

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

15. 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)

16. 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

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