CROI 2015 Program and Abstracts

Abstract Listing

Poster Abstracts

1120 A Predictive Risk Model for First-Line Treatment Failure in South Africa Julia K. Rohr 1 ; Prudence Ive 2 ; Rebecca H. Berhanu 2 ; Kate Shearer 2 ; Mhairi Maskew 2 ; Lawrence Long 2 ; Ian Sanne 2 ; Matthew P. Fox 1 1 Boston University School of Public Health, Boston, MA, US; 2 University of Witwatersrand, Johannesburg, South Africa; 3 Right to Care, Johannesburg, South Africa

Background: Although individual predictors of first line antiretroviral therapy (ART) failure have been identified, few studies in resource-limited settings have been large enough for predictive modeling. Understanding the absolute risk of first line failure is useful for patient monitoring and for effectively targeting limited resources for second line ART. The aims of this study are to estimate absolute risk of failure of first line ART over 5 years on treatment as a function of key demographic, clinical, and immunologic factors at the start of ART, and to develop a predictive model that can be applied to other South African clinic populations. Methods: This is an observational cohort study using medical records from 9 clinics across South Africa, including patients initiated on first line ART after 2004 with at least 6 months of follow-up time. The predictive model for virologic failure on first line (2 consecutive viral load levels >1000 copies/mL) was developed using accelerated failure time models (Weibull distribution), with stepwise selection of potential predictor variables at the start of ART. Multiple imputation was used to impute missing variables. The final predictive model was selected using an internal-external cross validation procedure using Harrell’s C statistic to measure discrimination and difference between 5-year actual and predicted survival to measure calibration. Results: 71,154 patients were included in the analysis, with an average of 21.5 months (IQR: 8.8-41.5) of follow-up time on first line ART. The final predictive model included age, sex, NNRTI on first line, baseline CD4 count, mean corpuscular volume, hemoglobin, history of tuberculosis, missed visits in the first 6 months on treatment, and an interaction between age and sex. Quintiles of the population were used to create 5 risk groups, where the highest risk group had 24.4% risk of failure over 5 years, and the lowest risk group had 9.4% risk of failure over 5 years. A simplified prognostic score to identify an individual’s risk group was calculated directly from the model parameters (Table).

Poster Abstracts

Conclusions: The predictive model was able to discriminate between patients at higher risk of first line virologic failure. Identification of patients at highest risk of failure is useful for patient monitoring and referral for adherence counseling to improve patient outcomes and avoid the high cost of second line ART. 1121 U.S. Population Benefits of HIV Preexposure Prophylaxis for Injection Drug Users Cora Bernard 1 ; Margaret L. Brandeau 1 ; Douglas K. Owens 2 ; Keith Humphreys 2 ; Eran Bendavid 1 ; Mark Holodniy 2 ; ChristopherWeyant 1 ; Jeremy D. Goldhaber-Fiebert 1 1 Stanford University, Stanford, CA, US; 2 VA Palo Alto Health Care System, Palo Alto, CA, US Background: A Centers for Disease Control and Prevention (CDC)-sponsored randomized trial of daily oral preexposure chemoprophylaxis (PrEP) with Truvada demonstrated efficacy in preventing HIV infection among injection drug users (IDUs) in Thailand. CDC recommends PrEP for men who have sex with men (MSM) based on its effectiveness and cost-effectiveness. CDC also recommends considering PrEP for IDUs, though there are currently no estimates of PrEP’s potential population health benefits for IDUs in the US. Methods: We developed a dynamic model of HIV in the US for IDU, MSM, and lower risk groups that captured both sexual and injection transmission routes as well as preferential mixing between groups. The model used transition rates from the published literature and reflected current HIV prevalence and incidence, use of condoms and methadone maintenance therapy, HIV screening and awareness, and antiretroviral treatment (ART) rates consistent with CDC estimates for each risk group. For the period 2014-2034, we compared projections for two PrEP scenarios – PrEP efficacy as observed in the Thailand trial, PrEP half as efficacious as the trial – to projections for the status quo. We calculated projected HIV incidence and prevalence reductions in 2034 relative to the status quo for IDUs, as well as for MSM and lower risk groups not targeted by the intervention. Results: Providing PrEP to all IDUs reduces HIV incidence and prevalence in IDUs by approximately 75% and 65%, respectively, an upper bound on population benefit. If efficacy is 50% of trial-reported levels, PrEP for all IDUs reduces HIV incidence and prevalence in IDUs by 50% and 43%. Because PrEP use includes frequent HIV screening, it substantially increases detection of new infections and the proportion of IDUs on ART. Through its effects on transmission, PrEP use in IDUs also reduces HIV incidence and prevalence in MSM

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CROI 2015