Preexposure prophylaxis will have a limited impact on HIV-1 drug resistance in sub-Saharan Africa: a comparison of mathematical models.
BACKGROUND
Preexposure prophylaxis (PrEP) with tenofovir and emtricitabine can prevent new HIV-1 infections, but there is a concern that use of PrEP could increase HIV drug resistance resulting in loss of treatment options. We compared standardized outcomes from three independent mathematical models simulating the impact of PrEP on HIV transmission and drug resistance in sub-Saharan African countries.


METHODS
All models assume that people using PrEP receive an HIV test every 3-6 months. The models vary in structure and parameter choices for PrEP coverage, effectiveness of PrEP (at different adherence levels) and the rate with which HIV drug resistance emerges and is transmitted.


RESULTS
The models predict that the use of PrEP in conjunction with antiretroviral therapy will result in a lower prevalence of HIV than when only antiretroviral therapy is used. With or without PrEP, all models suggest that HIV drug resistance will increase over the next 20 years due to antiretroviral therapy. PrEP will increase the absolute prevalence of drug resistance in the total population by less than 0.5% and amongst infected individuals by at most 7%. Twenty years after the introduction of PrEP, the majority of drug-resistant infections is due to antiretroviral therapy (50-63% across models), whereas 40-50% will be due to transmission of drug resistance, and less than 4% to the use of PrEP.


CONCLUSIONS
HIV drug resistance resulting from antiretroviral therapy is predicted to far exceed that resulting from PrEP. Concern over drug resistance should not be a reason to limit the use of PrEP.
aDepartment of Virology, Erasmus Medical Centre, Erasmus University, Rotterdam, the Netherlands bDepartments of Infectious Diseases and Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA cDepartment of Infection and Population Health, University College London dDepartment of Infectious Disease Epidemiology, Imperial College London, London, UK eDivision of Infectious Diseases, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA fPharmAccess Foundation and Department of Global Health, Academic Medical Center of the University of Amsterdam, Amsterdam Institute for Global Health and Development, Amsterdam, The Netherlands.
David A M C
DA
van de Vijver
Brooke E
BE
Nichols
Ume L
UL
Abbas
Charles A B
CA
Boucher
Valentina
V
Cambiano
Jeffrey W
JW
Eaton
Robert
R
Glaubius
Katrina
K
Lythgoe
John
J
Mellors
Andrew
A
Phillips
Kim C
KC
Sigaloff
Timothy B
TB
Hallett
D000225:Adenine / Q000031:analogs & derivatives / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D017954:Africa South of the Sahara; D000368:Aged; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000627:therapeutic use; D024882:Drug Resistance, Viral; D000068679:Emtricitabine; D005260:Female; D015658:HIV Infections / Q000453:epidemiology / Q000517:prevention & control* / Q000821:virology*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008962:Models, Theoretical; D063065:Organophosphonates / Q000627:therapeutic use; D065129:Pre-Exposure Prophylaxis / Q000379:methods / Q000706:statistics & numerical data*; D000068698:Tenofovir; D055815:Young Adult
D019380:Anti-HIV Agents; D063065:Organophosphonates; D003841:Deoxycytidine; D000068698:Tenofovir; D000068679:Emtricitabine; D000225:Adenine