1. Hopital Pitié Salpérière
HIV Therapy Failure
Pr Christine Katlama
Hopital Pitié Salpérière
EACS Advanced Course
Sept 2010
SOLTHIS

2. Antiretroviral Therapy Objectives
Stop HIV disease evolution
Restore immunity
Stop HIV immune activation
Control HIV replication in compartments and reservoirs
Reduce risk of resistance emergence
Reduce transmission
This can only be obtained with maximal viral suppression

3. Control of viral replication has to be maximal
Individual level
Health
Stop disease progression
Optimize immune restoration
Prevent resistance
Optimize survival
Daily normal life
- to have children
- Maximal reduction of sexual transmission risk
Population level
Reduced transmission
progressive control and decrease of epidemics
- Decrease in tuberculosis
Longer durability of efficacy of first lines ART
Decrease of global cost of HIV

4. Viral replication has to maximally suppressed
Maximal suppression of HIV required to
Prevent disease progresion
Decrease immune activation
Prevent resistance
Which level of viral suppression ?
1000 cp/ml : clinical benefit
 200 cp/ml : clinical and immunological
 50 cp/ml : resistance
Tomorrow : 1 cp ?
Which benefits
on reservoirs and activation ?

5. Management of treatment failure
Epidemiology of ART failure
Diagnosis of ART failure
Reasons for ART failure
Consequences of ART failure
Management of ART failure

6. Epidemiology of ART failure
Overall ART failure in developping countries has decreased over time !!
Better understanding of reasons for failure
Use of virological monitoring
More effective and better tolerated drugs
Greater number of drug classes
Lack of report of treatment failure in RSL may be only due
to lack of access to viral load or drugs …

7. Second line failure in MSF programmes
Cross-sectional study in 27 ART sites in RLC
Routine CD4 monitoring
VL for second line only in 4 sites
First line: > 95% D4T; < 15% EFV
Second line: > 70% LPV/r; 30% TDF; 28% DDI
Inclusion criteria:
Adults who were ART naive when starting 1st line
Switch from NNRTI-based FL to PI-based SL
At least 6 months on SL
Pujades et al. CROI

8. Diagnosis of 2nd line failure in MSF 2
16.1 % Clinical symptoms : new stage 3 or 4 event after 6 months of ART
4.1% Immunological parameters :
decline of CD4 to or below baseline value, or
decline of ≥50% from on treatment peak value after 6 months of ART; or
CD4 <100 cells/µl after 1 year of ART; with measurement confirmed within 3 months
1.7% Virological failure : HIV RNA >10,000 copies/ml; with confirmed within 3 months
Any criteria of failure: 18.8% after a median of 22 months
Pujades et al. CROI

9. Second line failure in Khayelitsha MSF
25% virological failure at 2 years on 2nd line
Add references to first line!
Time in years to next confirmed failure after switch (2 x >=5000 copies/mL)
Boulle et al. (unpublished) 9

10. Mortality on second line in Khayelitsha
10% on 2nd line had died within 2 years
Boulle et al. (unpublished)

11. Ressource Limited countries : Risk factors for treatment failure
First line failure :
concurrent TB treatment,
self reported poor adherence during the previous week
Second line failure:
Changing 1 NRTI instead of 2
Other PI than LPV/r
attending a public clinic
not having a refrigerator at home
TB treatment
No association with sex, type of clinic, duration of treatment, age, educational level, being unemployed, income level.
El Khatib. AIDS. 2010; Pujades et al. CROI

12. Diagnosis of ART failure
viral load
BQL
50cp/ml
 Consider
absolute viral load :
duration of virologic failure 4 2 1 3
- low < copies/ml
- moderate copies/ml
- high > copies/ml

13. Mechanisms for Virological Failure
 Inadequate ARV potency/resistance
 Poor compliance
 Drug- drug interactions
Low plasma drug concentrations
insufficient to control viral replication
Development of viral resistance

14. Reasons for treatment failure
Resistant Viruses
Inadequate treatment/prescriptions : dosage, drug interactions ,
Patients :
- poor adherence
- toxicity
- self treatment interruptions
- transient lost to follow up
Long life therapy is an individual challenge !!

15. Prevention of adherence problems
Education to long life treatment
Patient should be THE actor of his therapy
- provide their results regularly
Provide long enough prescription
Consider minor intolerance..
Social reasons
Psychological distress

16. Consequences of persistent replicative viremia
Accumulation and archive of resistance
Immune activation induced by HIV replication
Decrease of CD4
HIV disease progression
Increased risk of HIV transmission
Resistant virus transmission

17. Cross-sectional study of patients >12 m. on ART in Soweto.
First Line RX L1
Second line Rx L2
Viraemia
12%
33%
R to NRTI
64%
29%
R to NNRTI
81%
54%
R to PI 2% 6%
El Khatib. AIDS. 2010

18. International recommendations : When to switch:
Consider any viral load above < 50 as to be investigated
Viral load > 400 cp/ml / tretment failure
VL > 50 cp/ml repeatedly
VL>50 cp/ml : Blip ..try to understand why
Current drugs allow full viral suppression .
So always try to understand why a VL is not < 20 cp/ml

19. New WHO 2009 recommendations: When to switch:
Where available, use viral load (VL) to confirm treatment failure.
Where routinely available, use VL every 6 months to detect viral replication.
A persistent VL above copies/ml confirms treatment failure.
When VL is not available, use immunological criteria to confirm clinical failure.

20. Step 1 : To diagnose a situation of virological failure
1 Confirm viral replication
- Blips is defined as VL between 50 and 200 cp/ml
- Isolated blip should not be considered as failure
2 Evaluate adherence :
- the main reason for early failure or rebound after VL< 50cp/ml is discontinuation of therapy
- many situations in life where a » compliant « patients will stop transitorily treatment
- Monitoring plasma drug concentration at time of virological failure may help to understand certain situations

21. Step 2 : To analyse a situation of virological failure 2
Evaluate type and duration of virogical failure :
- rebound after undetectability
- persistant replication /intermittent replication
- level of viral replication ? Higher is VL …more antiviral potency needed
Number of CD4 cells : clinical risk of progression?
Patient:
- commitment to Rx, socio-psychological context ..

22. Step 3: To evaluate what sensitive drugs are left (2 )
PAST : what resistance has been accumulated ?
- Prior History of ARV , CD4 and VL
- Resistance testing : current /past
Longer the virus has replicated ..greater is the risk for resistance
Higher the viral load has been ..higher may be the level of resistance
NOW: What really active drugs left ?

23. Management of treatment failure : to analyse and to understand
Treatment history ? VL and CD4 at baseline ?
Adherence to therapy ? High viral load may indicate defect in adherence..smoothly ask patients
Level of resistance ?
Longer the virus has replicated ..greater is the risk for resistance
Higher the viral load has been ..higher may be the level of resistance
Higher VL is, more viral potency needed to control virus
At least 2 active drugs

24. New WHO recommendations 2009:Second line ART
1. A boosted protease inhibitor (PI/r) plus two nucleoside
analogues (NRTIs) are recommended for second-line ART.
2. ATV/r and LPV/r are the preferred boosted PI’s for secondline
ART.
3. Simplification of second NRTI options is recommended.
• If d4T or AZT has been used in first-line, use TDF + 3TC
or FTC as the NRTI backbone in second-line.
• If TDF has been used in first-line, use AZT + 3TC as the
NRTI backbone in second-line.

25. Combination of active drugs : the only way to success

26. Recently Approved New or Novel Antiretroviral Agents
Mature virus
PIs
Darunavir Tipranavir
Entry inhibitors
CCR5 inhibitorsMaravirocVicriviroc
Reverse transcriptase inhibitors
Etravirine
This is a summary of some of the recently approved new or novel antiretroviral agents, starting with the entry inhibitor maraviroc, a novel CCR5 antagonist; the next-generation NNRTI etravirine, which is active against most NNRTI-resistant viruses; and the integrase inhibitor raltegravir. Some newer PIs include darunavir and tipranavir, which were developed specifically for activity against PI-resistant virus.
Integrase inhibitors
Raltegravir
Elvitegravir 26 26

27. Raltegravir is highly and fastly effective
BENCHMRK - Percent of Patients With HIV RNA <50 copies/mL (95% CI)
STARTMRK – Percent of Patients With HIV RNA <50 copies/mL (95% CI) (Non-Completer = Failure)
100 mL
86%
Weeks
Percent of Patients with
HIV RNA <50 Copies/mL 2 4 8 12 16 24 32 40 48 20 60 80
100
82%
Non-inferiority
p-Value<0.001
62% 80 60
Percent of Patients with
p<0.001
HIV RNA <50 Copies/ 40
33% 20 2 4 8 12 16 24 32 40 48
Weeks
281
279
278
280
282
Raltegravir 400 mg b.i.d.*
Efavirenz 600 mg q.h.s.*
232
231
230
229
118
117
Raltegravir *
Placebo*

28. BENCHMRK-1 & -2: Raltegravir in Treatment-Experienced Patients
Current Analysis:
Week 48
Planned follow-up:
Week 156
Raltegravir 400 mg BID + OBR*
(BENCHMRK-1: n = 232;
BENCHMRK-2: n = 230)
HIV-infected patients with triple-class resistance and HIV-1 RNA > 1000 copies/mL
(BENCHMRK-1: N = 352;
BENCHMRK-2: N = 351)
Placebo + OBR*
(BENCHMRK-1: n = 118;
BENCHMRK-2: n = 119)
*Investigator-selected OBR based on baseline resistance data and history; inclusion of darunavir and tipranavir permitted.
1. Cooper DA, et al. CROI Abstract Steigbigel R, et al. CROI Abstract 789.

29. BENCHMRK-1: HIV-1 RNA < 50 c/mL at Week 48
100 80
65%
62% 60
Patients (%)
P < .001
P < .001 40 20
33%
31% 2 4 8 12 16 24 32 40 48
Weeks
Raltegravir* n =
232
231
231
230
229
232
229
230
231
Placebo* n =
118
118
118
118
117
118
118
118
118
* Each + OBT; P-value was derived from a logistic regression model adjusted for BL HIV-1 RNA level (log10), first ENF use in OBT, first DRV use in OBT, active PI in OBT.
Cooper DA, et al. CROI Abstract 788. Adapted with permission of Merck & Co., Inc., Whitehouse Station, New Jersey, USA, Copyright © 2008 Merck & Co., Inc., All Rights Reserved.

30. BENCHMRK-1 & -2: HIV-1 RNA < 50 c/mL at Week 48, Overall and by GSS
Subgroup
Percent of Patients n
Raltegravir
443 64
Total
228 34
Placebo
GSS:
112 45 65 3
Virologic failures carried forward.
For patients with GSS=1, 4 ART agents represented at least 80% of the active agents in OBT: darunavir (52%, 52% in raltegravir and placebo groups, respectively), enfuvirtide (8%, 16%), tenofovir (12%, 6%), and tipranavir (11%, 11%).
Rates of virologic suppression also greater with RAL vs placebo when analyzed by baseline PSS
Similar results when assessing PSS by number of fully active drugs and by number of fully or partially active drugs
166 67 1 92 37
158
≥ 2 75 68 59 20 40 60 80
100
1. Cooper DA, et al. CROI Abstract Steigbigel R, et al. CROI Abstract 789. 30

31. Raltegravir Resistance
Three pathways defined by primary mutations at 143, 148, and 155
Replicative capacity decreased with 155
Secondary mutations lead to higher resistance
Q148 pathway is preferred
Q ndary mutations
higher levels of resistance
less impact on RC (replication capacity)
Mixed populations generally resolve to Q148
Virus population can switch from N155 to Q148
Low genetic barrier to resistance
Cumulative mutations
Cross resistance with EVG
Hazuda et al ICAAC 2008

32. Raltegravir : summary Disadvantages
High Potency
Fast antiviral effect
Excellent tolerance
Few drug drug interactions
No metabolic effects
Disadvantages
Low genetic barrier to resistance : rapid emergence of R
Need active companion drugs
BID regimen 32

33. Darunavir : a new PI generation
A drug potent at all stages of HIV disease
Virologic robustness
Good tolerability
Potential for QD if no resistance to DRV
Prezista binding within HIV-1 protease
Key point
Prezista fits neatly into and has a very stable position in the catalytic pocket in the HIV-1 protease enzyme (numbers on figure represent the distance in Ångströms between Prezista and the amino acids that make up the protease).
Data on file. Tibotec BVBA, Mechelen, Belgium.
A key drug in the context of RSL countries
mutation frequency 33

34. POWER 1 and 2: CV VL < 50 copies/mL at Week 48 (ITT-TLOVR)
100
DRV/RTV 600/100 mg BID 80
*P < .001 vs comparator PI/RTV.
Control
45*
46* 60
Patients With VL< 50 c/mL (%) 40 12 10 20 1 2 4 8 12 16 20 24 28 32 36 40 44 48
Weeks
Not all patients had reached Week 48 at the time of analysis; patients who had not reached Week 48 were censored at their last available visit.
Lazzarin A, et al. IAC Abstract TUAB0104. 34

35. Darunavir TITAN: Study design
Treatment-experienced, lopinavir (LPV)-naïve, HIV-1-infected patients were randomised (1:1) to DRV/r 600/100mg bid, or LPV/r 400/100mg bid, plus optimised background therapy (2 NRTIs/NNRTIs) for 96 weeks.
Primary endpoint: HIV-1 RNA <400 copies/ml
Treatment phase (96 weeks)
Screening phase (4 weeks)
DRV/r 600/100mg bid + OBR
Rollover or follow-up phase after 1 and 4 weeks
Treatment-experienced, LPV-naïve
VL ≥1,000 copies/mL
Stable HAART (≥12 wks) or STI (≥ 4 wks)
TITAN is an ongoing, randomised, controlled trial. It is an international 96-week study, with primary analysis at Week 48.
Patients were screened for eligibility and had to be:
treatment experienced but naïve to lopinavir
have documented HIV infection
have a viral load of greater than one thousand copies per mL
to have been on stable HAART therapy or off treatment for 12 weeks or more.
A total of 595 patients were randomised to treatment of either, darunavir 600mg with 100mg ritonavir or lopinavir 400mg, again with the same low dose of ritonavir.
Both treatments were administered twice daily, and all patients also received an optimised background regimen. This consisted of at least 2 to 3 antiretrovirals from the NRTI and NNRTI classes.
LPV/r patients were allowed to switch to new formulation upon its approval by the regulatory authorities. At the time of this analysis 18% had switched top the new formulation.
Background
Patients co-infected with chronic hepatitis B or C were allowed to enter the trial if their condition was clinically stable and they were not expected to require hepatitis treatment during the study period.
Randomisation was performed using a centralised system to ensure balance across treatments groups and across two stratification factors (the use of an NNRTI in the OBR and screening plasma viral load of <50,000 or 50,000 copies/mL).
Darunavir was administered as 300-mg tablets, ritonavir as 100-mg capsules and lopinavir-ritonavir as 133.3/33.3-mg capsules. During the study, a new formulation of lopinavir-ritonavir (200/50-mg tablet) became available. The study protocol was amended to allow patients randomised to lopinavir-ritonavir to switch to the new formulation as soon as it was approved by local regulatory authorities; subsequently, all patients on this arm would be switched to the new formulation.
Patients who experienced virological failure (defined as plasma viral load >400 copies by week 16 or beyond) or a treatment-related grade 4 AE or a confirmed grade 4 laboratory abnormality were eligible to participate in the planned rollover phase. Results of the 48-week primary analysis are reported here.
LPV/r* 400/100mg bid + OBR
785 screened, 595 patients randomised and treated

36. Patients with VL <400 copies/mL (% [95%CI])
TITAN: confirmed virological response (<400 copies/mL) up to Wk 48 (PP-TLOVR)
100 90 80 70 60 50 40 30 20 10
77%*
68%
Patients with VL <400 copies/mL (% [95%CI])
DRV/r (n=286) LPV/r (n=293)
*Estimated least square mean difference in response vs LPV/r = 9% (95% CI 2;16); p<0.001
BAS 4 8 12 16 24 36 48
Time (weeks)
PP – per protocol

37. TITAN: Less virological failures with DRV/r than with LPV/r – Week 96
14%
41/298
26%
76/297 10 20 30
DRV/r
LPV/r
VFs (%)
Never suppressed
Rebounders
p0.001*
n=28
Note: VFs included “rebounders” (patients who had VL >400 copies/mL after an initial virologic suppression) and patients who were “never suppressed” (patients who lost or never achieved HIV-1 RNA <400 copies/mL after Week 16)
Week 48 analysis: 31 VFs in the DRV/r arm and 65 VFs in the LPV/r arm
*Exact Chi-Squared Test

38. Effect of Baseline Resistance on Response to DRV*
Number of BL PI Resistance-Associated Mutations 60 50
Correlates to FC > 10< 40 40
% With HIV-1 RNA < 50 copies/mL 30 20 10
CPI
Darunavir
≤ 5 6 7 8 9 10 11
≥ 12
BL mutations associated with diminished response
V11I, V32I, L33F, I47V, I50V, I54L, I54M, G73S, L76V, I84V, and L89V
Presence associated with a higher number of PI mutations
DRV response remained higher than that of CPI
*Analysis excludes ENF-treated patients
De Meyer S, et al. CROI Abstract 157.

39. Darunavir : Virologic efficacy % HIV RNA < 50 copies/ml à S48
100 80
84 %
78 % 60
71 %
60 %
% Patients avec CV <50 copies/mL) 40
45 % 20
11 %
POWER
TITAN
ARTEMIS
DRV
800/100 q.d
DRV
600/100 b.i.d
DeJesus E et al, 47th ICAAC chicago 2007
Valdez-Madruga J, et Al. Lancet 2007; 370: 49-58
Clotet B. et al. The Lancet 2007, 369 : 39

40. Etravirine DUET study : Efficacy
Response (<50 copies/mL) at Week 48 (ITT-TLOVR)
CV < 50 c/ml at W48 according to active molecules in OBT (PSS)
61%
40%
Patients with viral load <50 copies/mL at Week 48 (%) (± 95% CIs)
Time (weeks)
Placebo + BR (n=604)
ETR + BR (n=599) 10 20 30 40 50 60 70 80 90
100 2 4 8 12 16 24 32 48
p<0.0001 40

41. DUET-1 and -2: Predictors of response and resistance at failure17 25 1 2 3
< 50 copies/mL (%) 10 20 30 40 50 60 70 80 90
100
≥ 4
No. of Baseline ETR Mutations 16 8 6 75 58 41
ETR + OBR 44 38
121/161
64/147
73/121
59/157
37/64
17/68
13/32
6/24
7/28
3/18
13 mutations associated with ETR resistance
- V90I
- L100I
- V106I
- Y181C/I/V
≥ 3 ETR mutations impacts ETV sensitivity ; uncommon 14% of patients at baseline
Most common ETR RAM at failure :V179F/I and Y181C/I
Placebo + OBR
- V179D/F
- G190A/S
- A98G
- K101E/P
ETR, etravirine; OBR, optimized background regimen.
As etravirine is a NNRTI, one might predict that a subset of HIV-infected people with existing NNRTI resistance would have virus that is cross-resistant to the next-generation agents. To be eligible for the DUET-1 and DUET-2 trials, subjects had to be NNRTI-experienced and have documented evidence of NNRTI mutations either in the past or at the time of screening. In a subanalysis, the investigators examined the screening genotypes of the enrolled patients and were able to demonstrate a relationship between 13 specific mutations and etravirine response (listed on the slide). The figure on the right-hand portion of the slide shows that among patients who received etravirine plus an OBR, there was a stepwise attenuation in the virologic response when an increasing number of baseline etravirine resistance-associated mutations (RAMs) were present. When there were 3 or more present, the virologic response was no better than the response observed in the overall placebo group. However, only approximately 14% of the patients who were enrolled in the DUET studies actually had 3 or more of the etravirine RAMs, so the overwhelming majority would have been predicted to have a virologic response. It is worth noting that K103N is not one of the etravirine RAMs because this drug was developed to have activity against viruses with K103N.
Patients (%)
Cahn P, et al. ICAAC Abstract H Intelence [package insert]. Raritan, NJ: Tibotec Therapeutics; 2008. 41 41 41 41 41

42. MOTIVATE 1 and 2: MVC in Treatment-Experienced Patients With R5 Virus
Randomized, double-blind, placebo-controlled, phase IIb/III study
2:2:1 randomization;
stratified by ENF use and HIV-1 RNA < or  100,000 c/mL
Week 24
planned endpoint analysis
Week 48
Patients infected with R5;
HIV-1 RNA ≥ 5000 copies/mL;
stable ART or no ART for ≥ 4 weeks; previous ART experience with ≥ 1 agent (≥ 2 for PIs) from 3 of the 4 antiretroviral drug classes for ≥ 6 months or documented resistance to members of 3 of 4 classes
(N = 1049)
MVC* 150 mg or 300 mg BID + OBR
(n = 426)
MVC* 150 mg or 300 mg QD + OBR
(n = 414)
ART, antiretroviral therapy; ARV, antiretrovirals; DLV, delavirdine ; ENF, enfuvirtide; FDA, US Food and Drug Administration; MOTIVATE, Maraviroc plus Optimized Background Therapy in Viremic, ART-Experienced Patients; MVC, maraviroc; OBR, optimized background regimen; R5, CCR5 tropic; TPV, tipranavir; X4, CXCR4 tropic.
Placebo + OBR
(n = 209)
*Patients receiving PI (except TPV) or delavirdine received 150 mg; all others received 300 mg.
Hardy D, et al. CROI Abstract 792. 42 42 42

43. MOTIVATE 1 and 2: Combined Virologic Efficacy at Week 48
100
Placebo + OBT (n = 209) 90
MVC QD + OBT (n = 414) 80
MVC BID + OBT (n = 426) 70 60
Patients With HIV-1 RNA < 50 c/mL (%) 50
45.5%* 40
43.2%* 30 20
16.7% 10
*P < vs placebo 4 8 12 16 20 24 28 32 36 40 44 48
Time (Weeks)
Hardy D, et al. CROI Abstract 792.

44. MOTIVATE 1&2 Change in HIV-1 RNA and CD4
Week
-0.53
-2.30
-2.41 -3
-2.5 -2
-1.5 -1
-0.5 4 8 12 16 20 24 32 40 48
PBO (N=209)
MVC QD (N=414)
MVC BID (N=426)
120
105
100 89 80
Median change from baseline in HIV RNA (log10 copies/ml)
Median change from baseline in CD4+ T-Cell Count (cells/mm3) 59 60 40 20 2 4 8 12 16 20 24 32 40 48
Week
Rapid decrease in HIV RNA > 2 log by W4
Rate of < 50 cp/ml : 45% in MVC vs 17% in OBT
Rapid increase in CD4 > 60 cells by W4

45. Control of viral replication in treatment experienced patients
Lesson 1: Any new drug should
be combined with active drugs…
at least 2 active compounds
Lesson 2 : Earlier is better
a failing strategy should be modified
even in case of low VL and high CD4 -
Lesson 3 : Less access to new drugs you have more potent should be the regimen

46. Which treatment after 1st line treatment failure
AZT or D4T/3TC
ABC/3TC
TDF/FTC
ABC/3TC
TDF/FTC
Adherence
= Principal raison d’échec
Treatment adherence =
main issue
2 NRTI +
PI/r + +
Lopi/r
Ataza/r
PI/r QD
DRV/r
ATV/r
LPV/r
AZTor D4T/3TC
ABC/3TC
TDF/FTC
2 NRTI +
NNRTI
NNRTI
EFV
ETV Ou +
EFV

47. Which treatment after 2nd line treatment failure
AZT or D4T/3TC
ABC/3TC
TENO/FTC
NRTI = A R
V histoire IP
LPV/r – ATV/r =
EFV /NVP
NNRTI =
2 new drugs /classes DRV/ETV
PI/RAL
2 NRTI
+ DRV/r
2 NRTI
+ ETV
Other

48. TRIO: DRV/r + ETR + RAL in highly-experienced viraemic patients (96 week study)
103 patients enrolled 1
100 90 80 70
2.4
log10copies/ml
(-1.9 to -2.9) 60
Patients with HIV RNA <50 copies/mL and 95% CI (%)
HIV RNA delta from week 0 (log 10 copies/mL) median and IQR -1 50 40 30
90%
(95% CI; 85%–96%) -2
This is a Phase II non-comparative multi-center trial
Patients enrolled in this study received raltegravir, etravirine and darunavir and may have also received NRTIs and/or enfuvirtide, based on the physician’s discretion
The primary endpoint of the study was the 24 week viral suppression defined as an HIV RNA below 50 cp/ml
slide
Follow-up until 96 weeks of these patients is ungoing 20 10 -3 2 4 8 12 16 20 24 2 4 8 12 16 20 24
Time (weeks)
Time (weeks)
Intent to treat analysis
Yazdanpanah Y, et al. 17th IAC [Presentation THAB0406]. 48 48

49. How to combine new drugs in patients with resistant viruses ?PI
ETV
If no NRTIs R
Low viral replication
or ? + PI
ETV +
VL and resistance
Target Maximal viral suppression
DRV
RAL + +
ETV
RAL
DRV +

50. Major role for HIV clinical team
Every patient should have access to viral load monitoring
Any detectable viral load means virological failure
Any failure should be investigated
- compliance
- drug interactions or inadequate dosages
- résistance
Any virological failure should lead to intervention
- compliance issues and reinforce education
- change ARV therapy

51. Conclusion Art failure: not a fatality
Access to viral load monitoring: mandatory tool for long term success
Training to management of ART failure
Potent and safe drugs needed to control and prevent ART failure. 51