Clinical rationale for
viral load testing
Francois Venter
Caveats
• I’m a believer in VLs
Why do we need a rationale???
Why should we do it?
• Best possible way to determine adherence
• Early prevention of resistance – may even re-suppress
• Prevention of unnecessary switch to second
line – See R Hamers
• Objective quality measure of the programme -
% suppression
• Objective quantity measure of the programme
Clinical Failure is Just the Tip of the
Iceberg
VIROLOGIC FAILURE can lead to
IMMUNOLOGIC FAILURE which can lead to
CLINICAL FAILURE
Murri R, et al. JAIDS. 2006;41:23-30. Losina E et al, 15th CROI 2008, #823
Clinical Failure Immunologic Failure Virologic Failure 5
Evolution of WHO ART Guidelines in Adults Topic 2002 2003 2006 2010 2013 When to start CD4 ≤200 CD4 ≤ 200 CD4 ≤ 200 - Consider 350 - CD4 ≤ 350 for TB CD4 ≤ 350 -Irrespective CD4 for TB and HBV CD4 ≤ 500 -Irrespective CD4 for TB, HBV, PW and SDC - CD4 ≤ 350 as priority 1st Line 8 options - AZT preferred 4 options - AZT preferred 8 options - AZT or TDFpreferred - d4T dose reduction 6 options &FDCs - AZT or TDF preferred - d4T phase out 2 options & FDCs - TDF and EFV preferred across all populations
2nd Line Boosted and
non-boosted PIs Boosted PIs -IDV/r LPV/r, SQV/r Boosted PI - ATV/r, DRV/r, FPV/r LPV/r, SQV/r Boosted PI
- Heat stable FDC: ATV/r, LPV/r
Boosted PI
- Heat stable FDC: ATV/r, LPV/r
3rd Line None None None DRV/r, RAL, ETV DRV/r, RAL, ETV
Viral Load Testing No No (Desirable) Yes (Tertiary centers) Yes (Phase in approach) Yes
(preferred for monitoring, use of PoC, DBS)
Earlier initiation Simpler treatment
Less toxic, more robust regimens Better monitoring
Emergence of Mutations During Persistent Viremia on a NRTI/NNRTI Regimen
• 3727 patients in South Africa, CD4 and VL monitoring every 6
months
• 1007 (27%) patients developed viremia (VL >1000c/ml)
• Of 815 subjects with subsequent VL measured, 331 (41%)
resuppressed on their own
Time from detection of viremia (months)
Fr act ion w ith M ut at ion NNRTI M184V/I TAM Hoffmann CJ, et al. CROI 2009, Montreal, Canada. #656
Reflections…
A widening menu of ARV use for treatment and prevention 5,000,000 10,000,000 15,000,000 20,000,000 25,000,000 30,000,000 HIV+ IDU >500 HIV+ MSM >500 HIV+ FSW >500
Sero Discordant Couples >500 Pregnant women >500
Children HIV+ (aged 2-4) Adults 350-500
HIV+/HBV+ >350 TB+/HIV+ >350 <350 not on ART
Children in need (aged <2) On ART (adults and children) 34,000,000
2013
2010
Despite immediate increase from currently 17 million to 26 million people eligible for ART , the preventive effect will lead to
A widening menu of ARV use for treatment and prevention 5,000,000 10,000,000 15,000,000 20,000,000 25,000,000 30,000,000 HIV+ IDU >500 HIV+ MSM >500 HIV+ FSW >500
Sero Discordant Couples >500 Pregnant women >500
Children HIV+ (aged 2-4) Adults 350-500
HIV+/HBV+ >350 TB+/HIV+ >350 <350 not on ART
Children in need (aged <2) On ART (adults and children) 34,000,000
2013
2010
Despite immediate increase from currently 17 million to 26 million people eligible for ART , the preventive effect will lead to
decrease of number eligible after 2020
And we know the result in >90% in
well performing clinics…
• Will be undetectable.
Clinics do not respond timeously
• PoC not available – so “call-backs” the only
way to go
• Health care systems notoriously bad at
contacting patients
• Anecdote: almost no large scale programmes
showing consistent success
• ?make detectable viral loads ‘notifiable’ –
Impact of Community Groups on ART Delivery and Retention in Mozambique
Approximately 4-fold reduction in medical consultations among patients receiving CAG-based care.
Median Follow up time 12.9 months
# Patients remained on care 1269 (97.5%)
# Patients transferred out 83 (6%)
# Deaths 30 (2%)
# LFU 2 (0.2%)
N= 1384
And as for ‘accumulation of resistance
mutations’…
Virologic Response to Second-Line
Therapy with LPV/r in South Africa
• 3365 patients initiating ART since 2004 in Durban, 192 (6%)
have required LPV/r-based 2nd-line ART, majority (72%) due to virologic failure of 1st line
• Median CD4 count at switch = 143/mm3
• NRTI backbone: AZT/DDI (47%), AZT/3TC (29%), d4T/3tC (15%)
• After 6 months, 82% achieved virologic suppression (<50
copies/ml):
– No significant difference by:
• NRTI backbone used
• Indication for 2nd-line ART
• Number of prior 1st-line regimens
• Concurrent TB therapy
– Significant differences were found by gender:
• Women (89%) vs. men (71%); p = 0.01 19
Finally…
• This is NOT a minor addition to laboratory
HIV VL in KZN : 2006-2011 PRAVI MOODLEY DEPT OF VIROLOGY 96,000 162,414 206,000 192,000 218,466 80,000 100,000 120,000 140,000 160,000 180,000 200,000 220,000 2006 2007 2008 2009 2010 N o. of HI V V L Year HIV VL per Year
Conclusions
• Viral load testing adds to programmes, but at
considerable expense, and benefits are small –
other interventions may be less sexy, but more effective
• Far more attention needed to chasing
detectable results and improving systems
• Affordable PoC VL has ability to be
