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

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?

Questions

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CD4 counts over 144 weeks in one patient, while HIV RNA <50 (MONET trial)

Weeks on treatment (HIV RNA <50 copies/mL)

CD4

countcells/uL

CD4 count below 200 cells/µL: higher risk of AIDS

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?

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

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DRV/r+2NRTIs DRV/r

Mea

n C

D4

cell

coun

t (+

/-S

D)

N 129 126 125 121 121 120 115 117 116 114 107 106 108

N 127 126 120 121 114 111 113 109 107 106 105 104 102

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

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%)

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CD4 counts at screening/baseline versus lowest CD4 count during treatment

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Patient #1 with short-term CD4 decline below 200

Weeks on treatment (HIV RNA <50 copies/mL)

CD4

countcells/uL

From baseline to Week 144, HIV RNA was <50 copies/mLNo change in treatmentCD4 percentage remained in the range of 24-30%

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Patient #2 with short-term CD4 decline below 200

Weeks on treatment (HIV RNA <50 copies/mL)

CD4

countcells/uL

From baseline to Week 144, HIV RNA was <50 copies/mL. No change in treatment. CD4 percentage was in the range of 22-27% throughout the trial, except for a single result of 17% when the absolute CD4 count was also low.

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