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Antiretroviral Therapy and Pre-exposure Prophylaxis: Combined Impact on HIV-1 Transmission and Drug Resistance in South Africa/Editorial
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Journal of Infectious Diseases Advance Access published April 9, 2013
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Ume L. Abbas1,4, Robert Glaubius1, Anuj Mubayi1, Gregory Hood2, John W. Mellors3
"The important insights derived from our study are several. First, an ART strategy of treatment initiation at CD4 < 200 cells/mm3 combined with PrEP prevents more infections than either ART-alone or PrEP-alone; however, the incremental benefit of PrEP critically depends on PrEP efficacy, adherence and coverage. Second, the prevalence of HIV-1 drug resistance is largely driven by ART in both ART-alone and ART+PrEP strategies. Third, PrEP-alone results in low prevalence of drug resistance; high PrEP adherence leads to fewer infections and less opportunity for acquired resistance, while low adherence leads to predominantly wild-type breakthrough infections because of low drug pressure for emergence of acquired resistance. Fourth, use of overlapping ARVs for both ART and PrEP could increase drug resistance prevalence compared to ART-alone due to more frequent transmitted resistance. By contrast, resistance prevalence falls with non-overlapping ART+PrEP; however, this decrease is modest because the principal driver of resistance is ART, not PrEP. Fifth, inappropriate PrEP initiation among individuals with undetectable HIV-1 infection produces only a minor increase in the overall resistance prevalence; however, inappropriate PrEP use among persons with established HIV-1 infection could significantly increase drug resistance from PrEP. Lastly, PrEP prevents many more infections per case of resistance than ART does."
. The potential impact of antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) with overlapping and non-overlapping antiretrovirals (ARVs) on HIV-1 transmission and drug resistance is unknown. Methods. A detailed mathematical model was used to simulate the epidemiological impact of ART-alone, PrEP-alone, and combined ART+PrEP in South Africa.
Results. ART-alone initiated at CD4<200 cells/mm3 (80% coverage and 96% effectiveness) prevents 20% of HIV-1 infections over 10 years but increases drug resistance prevalence to 6.6%. PrEP-alone (30% coverage and 75% effectiveness) also prevents 21% of infections but with lower resistance prevalence of 0.5%. The ratio of cumulative infections prevented to prevalent drug-resistant cases after 10 years is 7-fold higher for PrEP than for ART. Combined ART+PrEP with overlapping ARVs prevents 35% of infections but increases resistance prevalence to 8.2%, whereas ART+PrEP with non-overlapping ARVs prevents slightly more infections (37%) and reduces resistance prevalence to 7.2%.
Conclusions. Combined ART+PrEP is likely to prevent more HIV-1 infections than either strategy alone, but with higher prevalence of drug resistance. ART is predicted to contribute more to resistance than is PrEP. Optimizing both ART and PrEP effectiveness and delivery are the keys to preventing HIV-1 transmission and drug resistance.
· Connie Celum,
· Timothy B. Hallett,
· and Jared Baeten
HIV-1 prevention with ART and PrEP: mathematical modeling insights into resistance, effectiveness and public health impact
J Infect Dis. first published online April 9, 2013

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