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. 2011 Apr 15;6(4):e18165.
doi: 10.1371/journal.pone.0018165.

Factors influencing the emergence and spread of HIV drug resistance arising from rollout of antiretroviral pre-exposure prophylaxis (PrEP)

Ume L Abbas  1 , Gregory Hood, Arthur W Wetzel, John W Mellors
Affiliations

Factors influencing the emergence and spread of HIV drug resistance arising from rollout of antiretroviral pre-exposure prophylaxis (PrEP)

Ume L Abbas et al. PLoS One. .

Abstract

Background: The potential for emergence and spread of HIV drug resistance from rollout of antiretroviral (ARV) pre-exposure prophylaxis (PrEP) is an important public health concern. We investigated determinants of HIV drug resistance prevalence after PrEP implementation through mathematical modeling.

Methodology: A model incorporating heterogeneity in age, gender, sexual activity, HIV infection status, stage of disease, PrEP coverage/discontinuation, and HIV drug susceptibility, was designed to simulate the impact of PrEP on HIV prevention and drug resistance in a sub-Saharan epidemic.

Principal findings: Analyses suggest that the prevalence of HIV drug resistance is influenced most by the extent and duration of inadvertent PrEP use in individuals already infected with HIV. Other key factors affecting drug resistance prevalence include the persistence time of transmitted resistance and the duration of inadvertent PrEP use in individuals who become infected on PrEP. From uncertainty analysis, the median overall prevalence of drug resistance at 10 years was predicted to be 9.2% (interquartile range 6.9%-12.2%). An optimistic scenario of 75% PrEP efficacy, 60% coverage of the susceptible population, and 5% inadvertent PrEP use predicts a rise in HIV drug resistance prevalence to only 2.5% after 10 years. By contrast, in a pessimistic scenario of 25% PrEP efficacy, 15% population coverage, and 25% inadvertent PrEP use, resistance prevalence increased to over 40%.

Conclusions: Inadvertent PrEP use in previously-infected individuals is the major determinant of HIV drug resistance prevalence arising from PrEP. Both the rate and duration of inadvertent PrEP use are key factors. PrEP rollout programs should include routine monitoring of HIV infection status to limit the spread of drug resistance.

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Conflict of interest statement

Competing Interests: John W. Mellors reports that he is a consultant to Gilead Sciences, Merck, and RFS Pharmaceuticals, has received grant support from Merck, and owns share options in RFS Pharmaceuticals. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials.

Figures

Figure 1
Figure 1. Simplified Model Flow Diagram.
A. Resistant = acquired resistance and T. Resistance = transmitted resistance.
Figure 2
Figure 2. Outcomes after10 years of PrEP rollout in optimistic, realistic and pessimistic scenarios with four different strategies.
Panel A shows overall prevalence of HIV drug resistance and Panel B shows cumulative new HIV infections prevented.
Figure 3
Figure 3. Overall prevalence of HIV drug resistance after 5, 10, 15 and 20 years of PrEP rollout predicted by uncertainty analysis.
For each time point, results of 10,000 simulations are shown as a box-and-whisker plot; representing the median, upper and lower quartiles, and maximum and minimum values.
Figure 4
Figure 4. Outcomes after10 years of PrEP rollout assuming no inadvertent PrEP uptake in previously infected individuals for optimistic, realistic and pessimistic scenarios, with four different strategies.
Panel A shows overall prevalence of HIV drug resistance and Panel B shows cumulative new HIV infections prevented.
Figure 5
Figure 5. Changes in the prevalence of HIV drug resistance (overall, transmitted, acquired) for10 years after PrEP introduction.
See this image and copyright information in PMC

References

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