1. The Positive Predictive Value of World Health Organization (WHO) Immunologic Criteria for Treatment Failure in a Public Health Antiretroviral Delivery Network in Africa E.H. Geng 1, K. Wools-Kaloustian 2, A. Siika 3, B. Musick 2, D. Lameck 3, R. Kantor 4, J. Hogan 5, S.G., Deeks 1, C. Yiannoutsos 2, J.N. Martin 1, all of the East Africa IeDEA Consortium 1 University of California at San Francisco, Medicine, San Francisco, 2 Indiana University School of Medicine, Medicine, Indianapolis, 3 Moi University School of Medicine, Medicine, Eldoret, Kenya, 4 Brown University, Medicine, Providence, United States,5 Brown University, Biostatistics, Providence, USA Conclusions In the absence of routine HIV RNA determination, this study supports continued use of WHO immunologic failure criteria to guide switch decisions: even though the PPV ’ s are suboptimal, the risk of virologic failure in individuals with immunologic failure is high enough to warrant switch for an individual patient. The differences between each criteria are not sufficiently discriminatory to recommend different clinical responses to each criteria. More than half of these switches, however, using these criteria are unnecessary and increase the cost of global ART delivery. In settings where HIV RNA determination is available only when clinical indicated, patients with immunologic failure should be considered candidates for HIV RNA testing. Point-of-care qualitative HIV RNA testing is an urgent priority in resource-limited settings Background Results Methods e-poster abstract number [A-155-0153-02747] 1950 patients followed for a maximum of 4.6 years had an HIV RNA determination. 927 (48%) experienced an episode of immunologic failure. In 609 (61%) the HIV RNA determination was within the ensuing 12 months and before regimen switch. Millions of HIV-infected patients in Africa are starting life-long regimens of antiretroviral therapy (ART) without the benefit of routine HIV RNA monitoring. The World Health Organization (WHO) has proposed immunologic criteria for switch to second line therapy. The positive predictive value (PPV) of these criteria for detectable HIV RNA levels in routine clinical practice is not well characterized. Patients We examined patients starting ART from Jan. 1 st, 2004 & Sept. 1 st, 2008 in the Academic Model Providing Access to Healthcare network in Kenya who had a clinically indicated HIV RNA determination. Implications Measurements Clinical and demographic characteristics were obtained from the OpenMRS electronic medical records systems at each site. We considered immunologic failure (IF) Type 1 to be a CD4 count of < 100/mm 3 after six months of therapy, Type 2 to be a 50% decline from on-treatment peak and Type 3 to be a fall below the last pre- therapy value. Plasma HIV RNA determinations within 12 months of an immunologic failure event were considered in PPV calculations. Analyses We examined the proportion of patients with an immunologic failure event who had detectable HIV RNA at 1000 and 10,000 c/ml to calculate the PPV of immunologic failure criteria for virologic failure. We fitted a multivariable logistic regression model to identify other factors associated with detectable viremia. PPV ’ s of immunologic failure criteria for virologic failure were suboptimal: most patients with immunologic failure did not have virologic failure. Among the criteria examined, a CD4 value 50% below on- treatment peak yielded the highest PPV for viremia while a failure to rise more than 100 cells after six months of therapy led to the lowest. Combined immunologic failure criteria did not change predictive values substantively. Among patients with immunologic failure, clinical factors such as time on treatment and age further risk stratify for the occurrence of virologic failure. Over a maximum of 4.6 years, the median time of immunologic failure was the shortest for Type 1 alone (9.8 months, IQR 7.2- 11.5) and longest for Type 2 alone (19.7, 13.8-26.6). Results At the time of first immunologic failure, Type 3 was the most common form followed by Type 2 and Type 1. Overlap was greatest between Types 2 and 3. CD4 determinations were made a median of 184 days apart (IQR, 167- 204). The intervals were similar over time. The PPV of immunologic failure Types 1, 2 and 3 for HIV RNA levels > 1000 c/ml were 28.9, 48.7 and 37.0%. At a cut off of 10,000 c/ml the values were 18.5, 32.8 and 22.3% respectively. Combined occurrence of immunologic failure types at the time of first failure yielded PPV’s of 33.3, 47.6 & 37.6% for HIV RNA level > 1000 c/ml and 22.2, 30.2 and 23.3 for 10,000 c/ml. In a model using an outcome of HIV RNA > 10,000 c/ml, each six months on ART was associated with risk of viremia (OR 1.52, 95% CI 1.29-1.78) as was age (OR 0.76, 95% CI 0.60-0.95). Type1Type2Type3T.1&2T.1&3T.2&3Any No with IF event 2844775221948188927 No w/ viral load w/i 1 year 1733143461327126609 No VL> 1000 c/ml 501531284960229 PPV VL>1000 c/ml 28.948.737.030.833.347.637.6 No VL>10,000 c/ml 32103773638143 PPV VL >10,000 c/ml 18.532.822.323.122.230.223.3 In a multivariable model among patients who had an immunologic failure event, each six months on ART (OR 1.19, 95% CI 1.15-1.27) and each 10 years in age (OR 0.87, 95% CI 0.75-0.99) were associated with risk of viremia at 1000 copies/ml.