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Advances in PrEP
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Bob Grant: Pre-exposure Chemprophylaxis for Prevention of HIV among Trans-women and MSM: iPREx Study
Albert Liu: BMD Loss in HIV- Men Participating in a TDF PrEP Clinical Trial in San Francisco
Kathy Mulligan: Effects of FTC/TDF on Bone Mineral Density in Seronegative Men from 4 Continents: DEXA Results of the Global iPrEx Study
Rivet Amico: Adherence Indicators and PrEP Drug Levels in the iPrEx Study
Peter Anderson: Interpreting Detection Rates of Intracellular FTC-TP and TFV-DP: The iPrEx Trial
Teri Leigler: Drug Resistance and Minor Drug Resistant Variants in iPrEx
Uma Abbas: Predicting the Impact of ART and PrEP with Overlapping Regimens on HIV Transmission and Drug Resistance in South Africa
Timothy Hallett: ART or PrEP for HIV Prevention in HIV Serodiscordant Partnerships: A Mathematical Modeling Comparison
http://app2.capitalreach.com/esp1204/servlet/tc?c=10164&cn=retro&s=20445&&dp=player.jsp&e=13726&mediaType=podiumVideo
Predicting the Impact of ART and PrEP with Overlapping Regimens on HIV Transmission and Drug Resistance in South Africa
Ume Abbas*1, R Glaubius1, A Mubayi1, G Hood2, and J Mellors3
1Cleveland Clin Fndn, OH, US; 2Pittsburgh Supercomputing Ctr, PA, US; and 3Univ of Pittsburgh, PA, US
Background: Access to ART is increasing in South Africa with tenofovir (TDF)+lamivudine (3TC)/emtricitabine (FTC)+efavirenz (EFV)/nevirapine (NVP) as the first-line regimen. TDF and TDF+FTC are promising pre-exposure prophylaxis (PrEP) agents, but they overlap with first-line ART raising concerns about drug resistance. Here we predict the combined impact of ART and PrEP rollout on the spread of HIV and drug resistance using mathematical modeling.
Methods: We developed and analyzed deterministic and stochastic models that incorporate heterogeneity in sexual behavior, HIV transmission, HIV disease progression, and emergence of drug resistance to represent the heterosexual HIV epidemic in South Africa with ART and PrEP rollout. Model output includes: cumulative new infections prevented, and prevalence of transmitted and acquired resistance from ART and PrEP. Uncertainty and sensitivity analyses were performed to determine prediction uncertainty and sensitivity to parameter variability. Scenario analyses were used to examine the effect on outcomes of specific inputs as well as inadvertent PrEP use.
Results: ART alone initiated at CD4 counts ²200 cell/µL with 80% coverage decreases cumulative new infections over 10 years by 21% but increases prevalence of drug resistance to 8.5% (3% transmitted and 5.5% acquired resistance). In an optimistic scenario of ART combined with PrEP that assumes 70% PrEP efficacy, 80% adherence and 50% coverage, new infections decrease by 38% and resistance prevalence increases to 11.4% (4.1% transmitted and 6.3% acquired resistance from ART; 0.4% transmitted and 0.7% acquired resistance from PrEP). Including inadvertent PrEP use among acutely infected persons in the antibody-negative phase has minimal effect on outcomes. By contrast, inadvertent PrEP use among 5% of infected persons increases resistance prevalence to 14.6%. A realistic scenario of ART plus PrEP assuming 50% PrEP efficacy, adherence and coverage with PrEP dropout rate of 20%/year, decreases infections by 25% and increases resistance prevalence to 9.5%. Uncertainty analysis of 50,000 simulations predicts a median 28% (IQR 25 to 31%) decline in infections and 9% (IQR 8 to 11%) prevalence of drug resistance after 10 years of ART and PrEP rollout.
Conclusions: ART combined with PrEP is likely to have a bigger HIV prevention impact than either strategy alone, but overlapping drugs will increase drug resistance prevalence. ART is predicted to contribute more to resistance than is PrEP. However, inadvertent PrEP use by persons with established HIV could increase resistance from PrEP.
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ART or PrEP for HIV Prevention in HIV Serodiscordant Partnerships: A Mathematical Modeling Comparison
Timothy Hallett*1, J Baeten2, R Heffron2, G De Bruyn3, S Delany-Moretlwe3, G Gray3, L Johnson4, J McIntyre3, H Rees3, and C Celum2
1Imperial Coll London, UK; 2Univ of Washington, Seattle, US; 3Univ of the Witwatersrand, Johannesburg, South Africa; and 4Univ of Cape Town, South Africa
Background: ARV medications hold tremendous promise for HIV prevention, when used as ART to reduce the infectiousness of HIV+ persons and as pre-exposure prophylaxis (PrEP) by HIV- persons to reduce HIV acquisition. Heterosexual HIV serodiscordant couples (i.e., in which 1 member is HIV+ and the other HIV-) are a priority for prevention interventions. For couples in which the HIV+ partner is asymptomatic and has CD4 counts higher than national guidelines for ART, either earlier ART initiation for the HIV+ partner or PrEP could be considered for HIV-1 prevention. The relative effectiveness and costs of PrEP versus earlier ART initiation in HIV-1 serodiscordant couples have not been evaluated.
Methods: We constructed a mathematical model to examine the impact and cost-effectiveness of different strategies for the implementation of PrEP relative to earlier initiation of ART within HIV serodiscordant couples. The model included sexual behaviors of the couple, outside partners, disease progression, pregnancy, and treatment outcomes and was parameterized with data from South African HIV serodiscordant couples in the Partners in Prevention HSV/HIV Transmission Study.
Results: Although the up-front cost of PrEP is high, the overall cost per infection averted can be substantially offset by future savings in ARV medicines, due to infections averted. The impact of PrEP strongly interacts with couples' sexual behavior and targeting to those couples at most risk can increase efficiency. If each year of PrEP costs less than one third of a year of ART and the effectiveness of PrEP in trials exceeds 65%, then it would be more cost-effective to provide the HIV- partner with PrEP than to initiate ART earlier in the HIV+ partner (at a CD4 cell count of 350 instead of 200, which is still common in many settings). Lower levels of PrEP effectiveness would be tolerated if PrEP costs can be lowered or can be targeted to higher risk couples (e.g., higher sexual frequency, lower condom use, or outside partners).
Conclusions: PrEP among HIV serodiscordant couples could have substantial prevention impact and be cost-effective if targeted to couples based on risk behaviors and prior to ART for the HIV+ partner, and if the costs of PrEP delivery can be reduced below current forecasts.
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