856. HIV Prevention and Drug Resistance from Antiretroviral Therapy and Pre-exposure Prophylaxis: A Mathematical Modeling Analysis
Session: Poster Abstract Session: HIV Detection, Screening, and Prevention
Friday, October 4, 2013
Room: The Moscone Center: Poster Hall C
  • glaubius2013idsa-upload.pdf (177.8 kB)
  • Background: Long-acting injectable pre-exposure prophylaxis (PrEP) agents such as the non-nucleoside reverse transcriptase inhibitor (NNRTI) rilpivirine (RPV) could be pivotal for optimizing PrEP effectiveness for HIV prevention. However, cross-resistance between RPV PrEP and first-generation NNRTIs in first-line ART raises concerns about the spread of HIV drug resistance.

    Methods: We developed a mathematical model that incorporates heterogeneity in sexual behavior, HIV transmission and disease progression, and HIV drug resistance to represent the South African HIV epidemic with ART and PrEP rollout. We simulated a baseline scenario of ART rollout covering 80% of infected persons having CD4 ≤ 350 cells/μL by 2017 with 96% effectiveness of ART against HIV transmission. We compared this to scenarios of ART combined with RPV PrEP rollout starting in 2015 and reaching 10% coverage of all susceptible persons (“unprioritized PrEP”) or 90% coverage of high risk susceptible persons (“prioritized PrEP”). We assumed 0%–100% PrEP efficacy against wild-type virus, with 10% relative efficacy against virus with RPV cross-resistance, which emerged in 0%–100% of donors having NNRTI resistance.

    Results: A scenario of combined ART plus unprioritized PrEP with 90% efficacious PrEP, in which 20% of NNRTI-resistant donors have RPV cross-resistance, prevents 6% of new infections over ten years while maintaining drug resistance prevalence near 17%, compared to ART alone. ART plus prioritized PrEP uses far fewer person-years of PrEP (2.1 million versus 17.7 million for unprioritized PrEP) yet prevents 14% of new infections, while drug resistance prevalence increases to 19%. Prevalent cases of resistance decrease by 1.6% with ART plus unprioritzed PrEP but increase by 2.4% with ART plus prioritized PrEP. In sensitivity analyses (Figure), ART plus unprioritzed PrEP decreases cases of drug resistance when PrEP efficacy is high (>70%) or RPV cross-resistance is limited (≤40%).

    Conclusion: ART rollout combined with PrEP prioritized to high risk persons prevents more HIV infections than ART alone or in combination with unprioritized PrEP. Implementation of unprioritized PrEP may reduce cases of HIV drug resistance, while prioritized PrEP may increase drug resistance.


    Robert Glaubius1, Greg Hood2 and Ume Abbas1, (1)Infectious Disease and Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH, (2)Pittsburgh Supercomputing Center, Pittsburgh, PA


    R. Glaubius, None

    G. Hood, None

    U. Abbas, None

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