Presented by Viviane Dias Lima, PhD

1. Cumulative plasma HIV-1 level as a novel tool to evaluate antiretroviral therapy efficacy at the individual and public health levels Abstract MOAC0303 Presented by Viviane Dias Lima, PhD Co-authors: Juan Sierra-Madero, Zunyou Wu, Joel Singer, David Milan, Evan Wood, Mark W. Hull, P. Richard Harrigan, Julio S.G. Montaner No conflict to declare

2. HAART’s Individual and Public Health Benefits

3. The relative efficacy of “candidate” HAART regimens has been typically evaluated in clinical trials based on the rate of suppression of plasma viral load at a pre-specified time point during follow up (e.g. 48 weeks). However, plasma viral load can vary during a patient’s treatment history due to a number of factors: incomplete adherence, co-morbidities, immunizations, or even technical issues related to the assay used.

4. From a public health point of view, there has been a growing interest regarding the secondary benefit of HAART on the prevention of HIV transmission. • It is, therefore, imperative that validated endpoints are explored to simultaneously capture the individual and public health benefit of HAART. Here, we evaluate a measure of cumulative viremia as a novel candidate tool to potentially assess HAART’s efficacy, at the individual and at the public health levels.

5. Methods

6. Randomized Clinical Trial (NCT00162643) • A prospective open label RCT conducted in 10 clinical sites from 5 different states in Mexico. • Eligible participants were ≥18 years old, naïve to HAART and with a CD4<200 cells/mm3 and a plasma viral load ≥1000 copies/mL and recruited from 01/01/2005 to 31/01/2007. • Initial HAART: 2 nRTIs + either efavirenz ( NNRTI), or lopinavir\r (PI\r).

7. Cohort Study • Data were extracted from the HOMER Cohort from the BCCfE. • Treatment naïve individuals (≥18 years old) enrolled between 01/01/2000 to 28/02/2009 and followed until the last available plasma viral load before 28/02/2010. • Initial HAART: 2 nRTIs + either efavirenz or nevirapine ( NNRTI), or lopinavir\r or atazanavir\r (PI\r).

8. HAART’s Efficacy • Endpoints: plasma viral load <50 and <400 copies/mL at week 48 and a measure of cumulative viremia. • Number of plasma viral load measurements: • RCT: At baseline, weeks 8, 24, 32 and 48. • All measurements from baseline until the 48th week of follow-up.

9. Cumulative Viremia as the plasma viral load AUC over 48 weeks Note: pVL = plasma viral load

10. Results

13. Conclusions

14. Based on these results, cumulative viremia represents an adequate endpoint for evaluating HAART’s efficacy in clinical trials and observational studies. The measure of cumulative viremia captures the full viral load trajectory over time and, therefore, it may be ideally suited to evaluate the impact of HAART on HIV transmission. Cumulative viremia should be explored further as a tool to, simultaneously, evaluate the individual and public health efficacy of HAART.

15. Thanks! We thank the staff from the BCCfE for their assistance and commitment to maintain a state of the art database and, our patients for participating in our study. We also thank the patients and staff involved in the Mexican Randomized Clinical Trial (NCT00162643).