Challenges to replacing CD4 testing with
viroloigical monitoring
Andrew Hill,
Pharmacology Research Laboratories,
University of Liverpool, UK
World AIDS Conference, Washington, USA, July 2012 [MSF Satellite]
HIV RNA and CD4 counts
CD4 counts
- show which asymptomatic patients should be started on antiretroviral
treatment (<350 or <500 cells/µL in different guidelines)
- Guide to prophylaxis for opportunistic infections (<200 cells/uL)
HIV RNA
-
much more sensitive than CD4 count, as a measure of treatment failure.
predicts risk of HIV transmission,
predicts emergence of drug resistance
can be a marker of poor adherence
Questions
1. If a patient has CD4 counts above 350 cells/µL and HIV RNA
<50 copies/mL, what is the use of continued CD4 testing?
2. Can we monitor with HIV RNA alone during long-term
antiretroviral treatment?
CD4 counts over 144 weeks in one patient,
while HIV RNA <50 (MONET trial)
1000
900
800
700
CD4
600
count 500
cells/uL
If the baseline CD4 count is above 350 cells/uL,
will the CD4 counts always stay above 200 cells/uL,
while the HIV RNA is suppressed?
400
300
200
CD4 count below 200 cells/µL: higher risk of AIDS
100
0
0
20
40
60
80
100
120
Weeks on treatment (HIV RNA <50 copies/mL)
140
160
Can we monitor with HIV RNA alone?
Research question – while HIV RNA remained suppressed, did patients
always keep CD4 counts at safe levels (i.e. above 200 cells/µL)?
1. In the MONET trial, 256 patients with HIV RNA <50 copies/mL at
screening were treated with DRV/r + 2NRTI or DRV/r monotherapy, for
144 weeks.
2. CD4 counts were measured at a central laboratory, at screening,
baseline, then every 12-16 weeks up to Week 144.
3. In this analysis, we compared the CD4 counts at baseline with the
lowest CD4 counts seen during 144 weeks of treatment, while the HIV
RNA stayed below 50 copies/mL.
MONET 144 weeks: CD4 count by study visit
Mean CD4 cell count (+/-SD)
1200
DRV/r+2NRTIs
DRV/r
1000
800
600
400
200
0
0
20
40
60
80
100
120
140
N
129 126 125 121 121 120
115
117
116
114
107
106
108
N
127 126 120 121 114
113
109
107
106
105
104
102
111
160
J Arribas et al. HIV Medicine 2012 [published ahead of print]
Over three years, only 2/230 patients showed a fall in
CD4 <200 cells/uL, while HIV RNA was <50 copies/mL
1
Lowest CD4 counts during three-year follow up, for patients with HIV RNA <50 copies/mL at baseline
CD4 counts
at screening/baseline versus lowest CD4 count during treatment
in the MONET
trial
Mean of screening
Lowest CD4 counts over three years:
and baseline CD4 counts
<200
200-350
350-500
>500 cells/µL
<200 cells/µL (n=1)
1 (100%)
0
0
0
200-350 cells/µL (n=22)
1 (4.5%)
17 (77.3%)
4 (18.2%)
0
350-500 cells/µL (n=60)
1 (1.7%)
7 (11.7%)
46 (76.7%)
6 (10.0%)
>500 cells/µL (n=148)
0
2 (1.4%)
20 (13.5%)
126 (85.1%)
______________________________________________________________________________________
Patient #1 with short-term CD4 decline below 200
From baseline to Week 144, HIV RNA was <50 copies/mL
No change in treatment
CD4 percentage remained in the range of 24-30%
700
600
500
CD4
count
cells/uL
400
300
200
100
0
0
20
40
60
80
100
120
Weeks on treatment (HIV RNA <50 copies/mL)
140
160
Patient #2 with short-term CD4 decline below 200
From baseline to Week 144, HIV RNA was <50 copies/mL.
No change in treatment. CD4 percentage was in the range of 2227% throughout the trial, except for a single result of 17% when
the absolute CD4 count was also low.
600
500
400
CD4
count
cells/uL
300
200
100
0
0
20
40
60
80
100
120
Weeks on treatment (HIV RNA <50 copies/mL)
140
160
Royal Free cohort, London
Follow-up of 166 patients on antiretroviral therapy with HIV RNA <50
copies/mL and CD4 counts above 500 cells/µL
Only five of the 166 patients (3%) showed a decline in CD4 count <350
cells/µL during 47 weeks of follow up. All were isolated reductions:
_________________________________________________________________________
Patient Baseline
Low visit
Follow up visit
_________________________________________________________________________
1
532
262
374
2
740
330
705
3
650
331
792
4
560
347
392
5
642
349
404
_________________________________________________________________________
Phillips et al. AIDS 2002, 16: 1073-1075
Conclusions
 For patients with CD4 counts above 350 cells/µL and HIV RNA <50 copies/mL on
antiretroviral treatment, there was no clear benefit for CD4 testing in the MONET
trial and two cohort studies
 In the MONET Trial and the Royal Free cohort, a small number of patients had
short-term reductions in CD4 count, which then rose at the next visit with no
change in treatment.
 Monitoring patients with HIV RNA alone seems feasible – this analysis needs to be
repeated in larger cohorts of patients, preferably in developing countries