title: Antiretroviral therapy and pre-exposure prophylaxis: combined impact on HIV transmission and drug resistance in South Africa.
abstract: BACKGROUND
  The potential impact of antiretroviral therapy (ART) and pre-exposure prophylaxis (PrEP) with overlapping and nonoverlapping antiretrovirals (ARVs) on human immunodeficiency virus (HIV) 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 a CD4 lymphocyte cell count <200 cells/µL (80% coverage and 96% effectiveness) prevents 20% of HIV 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 nonoverlapping ARVs prevents slightly more infections (37%) and reduces resistance prevalence to 7.2%.
  
  
  CONCLUSIONS
  Combined ART + PrEP is likely to prevent more HIV 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 transmission and drug resistance.
authors.affiliation: Departments of Infectious Diseases and Quantitative Health Sciences, Cleveland Clinic, Ohio 44195, USA.
authors.forename: Ume L
authors.initials: UL
authors.lastname: Abbas
authors.forename: Robert
authors.initials: R
authors.lastname: Glaubius
authors.forename: Anuj
authors.initials: A
authors.lastname: Mubayi
authors.forename: Gregory
authors.initials: G
authors.lastname: Hood
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
mesh_terms: D000293:Adolescent; D000328:Adult; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active / Q000379:methods; D018791:CD4 Lymphocyte Count / Q000379:methods; D024882:Drug Resistance, Viral; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control* / Q000635:transmission; D015497:HIV-1; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D013019:South Africa; D055815:Young Adult
chemical_list: D019380:Anti-HIV Agents
keywords: ART; HIV drug resistance; HIV epidemic; HIV transmission; PrEP; South Africa; antiretroviral therapy; chemoprophylaxis; mathematical model; pre-exposure prophylaxis