Challenges to replacing CD4 testing with viroloigical monitoring

1. 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]

2. 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. • predictsrisk of HIV transmission, • predicts emergence of drug resistance • can be a marker of poor adherence

3. Questions • If a patient has CD4 counts above 350 cells/µL and HIV RNA <50 copies/mL, what is the use of continued CD4 testing? • Can we monitor with HIV RNA alone during long-term antiretroviral treatment?

4. CD4 counts over 144 weeks in one patient, while HIV RNA <50 (MONET trial) CD4 count cells/uL If the baseline CD4 count is above 350 cells/uL, will the CD4 counts always stay above 200cells/uL, while the HIV RNA is suppressed? CD4 count below 200 cells/µL: higher risk of AIDS Weeks on treatment (HIV RNA <50 copies/mL)

5. 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)? • 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. • CD4 counts were measured at a central laboratory, at screening, baseline, then every 12-16 weeks up to Week 144. • 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.

6. MONET 144 weeks:CD4 count by study visit Mean CD4 cell count (+/-SD) J Arribas et al. HIV Medicine 2012 [published ahead of print]

7. Over three years, only 2/230 patients showed a fall in CD4 <200 cells/uL, while HIV RNA was <50 copies/mL CD4 counts at screening/baseline versus lowest CD4 count during treatment

8. 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% CD4 count cells/uL Weeks on treatment (HIV RNA <50 copies/mL)

9. 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 22-27% throughout the trial, except for a single result of 17% when the absolute CD4 count was also low. CD4 count cells/uL Weeks on treatment (HIV RNA <50 copies/mL)

10. 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

11. 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