CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

WEDNESDAY, FEBRUARY 25, 2015 Session P-K3 Poster Session

Poster Hall

2:30 pm– 4:00 pm ART: Immunologic Response—The Good and The Bad 569 Reference Curves for CD4 Response to Antiretroviral Treatment in HIV-1–Infected Naïve Patients Rodolphe Thiebaut On behalf of the Standard Reference Distribution of CD4Working Group in COHERE in EuroCoord Bordeaux University, Bordeaux, France Background: There is no consensus on how CD4+ T cell should increase in early response to combination antiretroviral treatment (cART). We provide references for CD4+ T cell increases following cART initiation in HIV-1 infected naïve patients with a good virological response at 6 months. Methods: All individuals from the 33 cohorts participating in the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE), aged ≥ 18 years, who started cART for the first time between 1/1/2005 – 1/1/2010, with at least one available measure of CD4 count (in cells/ m L) and HIV-1 RNA ≤ 50 copies/mL at 6 months (+-/ 3 months) after cART initiation were included. Unadjusted and adjusted reference curves and predictions were obtained through quantile regression. Results: Observations from 28,992 patients were included in this analysis. Median (interquartile range IQR) CD4+ T cell count at treatment initiation was 249 (150; 336) cells/ m L. The median observed CD4+ T cell counts at 6 months were 382 (256; 515). The figure shows the 5th, 10th, 25th, 50th, 75th, 90th, 95 th percentiles of the overall population and the CD4 change of a specific individual (dots). A CD4+ T cell count increase of at least 100 cells/mL at 6 months is generally required in order that patients stay ‘on track’ (ie. on the same percentile as when they start), with slightly higher gains required to stay on track for those starting with CD4+ T cell counts in the higher percentiles. Hence, the median line demonstrates that patients who started cART at the median level of 251 cells/ m L needed to have a CD4+ T cell count of 367 cells/ m L at 6 months after cART initiation to remain on the median line. The two most influencing factors explaining the variation of CD4+ T cell count at 6 months were the AIDS stage at cART initiation and the baseline CD4+ T cell count. Predictions adjusted for factors influencing CD4+ T cell levels gave more precise individual predictions. For instance, a 25 years-old woman starting a PI-containing regimen before AIDS stage at 500 cells/ m L with an increase to 600 cells/ m L at 6 months is switching from the 51 percentile to the 46 percentile at 6 months after adjustment for her characteristics.

Poster Abstracts

5 th , 10 th , 25 th , 50 th , 75 th , 90 th , 95 th percentiles of the overall population CD4+ T cell change over months and trajectory for one individual (dots). COHERE. Conclusions: Reference curves and predictions will help clinicians evaluate the immune response early after cART initiation leading to viral control, and may be useful to identify patients with poor CD4 count responses where greater monitoring or further interventions is needed. 570 Comparing Immunological Failure Definitions, Using Tanzanian National HIV Data Fiona Vanobberghen 1 ; Bonita K. Kilama 2 ; AlisonWringe 1 ; Angela Ramadhani 2 ; Basia Zaba 1 ; Donan Mmbando 3 ; JimTodd 1 1 London School of Hygiene and Tropical Medicine, London, United Kingdom; 2 National AIDS Control Program, Dar es Salaam, United Republic of Tanzania; 3 Ministry of Health & Social Welfare, Dar es Salaam, United Republic of Tanzania Background: Rates of first-line treatment failure and switches to second-line therapy are key indicators of national antiretroviral therapy (ART) programmes, but there is little consensus on the immunological failure (IF) criteria to be used in the absence of virological monitoring, which remains too expensive for most African national programmes. Methods: Using routinely-collected data from the Tanzanian HIV programme, we compared IF rates using the criteria of WHO 2010, 2013 and Tanzania 2005, 2009 guidelines (with confirmatory CD4 counts). We included adults initiating ART in 2004-2011 with a pre-treatment CD4 count and ≥ 6 months of follow-up. For the WHO-2010 definition, we assessed sub- hazard ratios (SHRs) for IF and subsequent switch to second-line therapy, using competing risks methods to account for deaths. Results: Among 121,308 adults, 6,108 (5.0%) to 19,380 (16.0%) persons experienced IF depending on the definition (Table). The cumulative probability of IF by 6 years ranged from 13.0% (12.5,13.4) under the WHO-2013 definition to 40.6% (39.8,41.5) under the WHO-2010-unconfirmed definition. Lower IF rates mean persons spending longer on first- line therapy and therefore higher death rates on first-line treatment, with a cumulative probability of death by 6 years of 5.3% (4.9,5.6) under the WHO-2013 definition versus 3.7% (3.4,3.9) under the WHO-2010-unconfirmed definition. IF predictors included ART initiation in dispensaries versus hospitals, being male, lower current weight and lower current CD4 count. Of 7,382 participants in the time-to-switch analysis, 416 (6%) switched, while 355 (5%) died before switching. Four years after IF, the cumulative probability of switching was 7.3% (6.6,8.0) and of death 6.8% (6.0,7.6). Those who immunologically-failed in dispensaries, health centres and government facilities were least likely to switch.

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CROI 2015