title: Deciphering the Effects of Injectable Pre-exposure Prophylaxis for Combination Human Immunodeficiency Virus Prevention.
abstract: Background.A long-acting injectable formulation of rilpivirine (RPV), under investigation as antiretroviral pre-exposure prophylaxis (PrEP), may facilitate PrEP adherence. In contrast, cross-resistance between RPV and nonnucleoside reverse-transcriptase inhibitors comprising first-line antiretroviral therapy (ART) could promote human immunodeficiency virus (HIV) drug resistance and reduce PrEP's effectiveness.Methods.We use novel mathematical modeling of different RPV PrEP scale-up strategies in KwaZulu-Natal, South Africa, to investigate their effects on HIV prevention and drug resistance, compared with a reference scenario without PrEP.Results.Pre-exposure prophylaxis scale-up modestly increases the proportion of prevalent drug-resistant infections, from 33% to ≤37%. The change in the number of prevalent drug-resistant infections depends on the interplay between PrEP factors (coverage, efficacy, delivery reliability, and scale-up strategy) and the level of cross-resistance between PrEP and ART. An optimistic scenario of 70% effective RPV PrEP (90% efficacious and 80% reliable delivery), among women aged 20-29 years, prevents 17% of cumulative infections over 10 years while decreasing prevalent resistance; however, prevention decreases and resistance increases with more conservative assumptions. Uncertainty analysis assuming 40%-70% cross-resistance prevalence predicts an increase in prevalent resistance unless PrEP's effectiveness exceeds 90%.Conclusions.Prioritized scale-up of injectable PrEP among women in KwaZulu-Natal could reduce HIV infections, but suboptimal effectiveness could promote the spread of drug resistance.
authors.affiliation: Departments of Infectious Disease and Quantitative Health Sciences , Cleveland Clinic , Ohio.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Glaubius
authors.affiliation: Division of Infectious Diseases , School of Medicine, University of Pittsburgh.
authors.forename: Urvi M
authors.initials: UM
authors.lastname: Parikh
authors.affiliation: Pittsburgh Supercomputing Center , Carnegie Mellon University , Pennsylvania.
authors.forename: Greg
authors.initials: G
authors.lastname: Hood
authors.affiliation: Division of Infectious Diseases , School of Medicine, University of Pittsburgh.
authors.forename: Kerri J
authors.initials: KJ
authors.lastname: Penrose
authors.affiliation: Division of Infectious Diseases, Department of Medicine , Stanford University , California.
authors.forename: Eran
authors.initials: E
authors.lastname: Bendavid
authors.affiliation: Division of Infectious Diseases , School of Medicine, University of Pittsburgh.
authors.forename: John W
authors.initials: JW
authors.lastname: Mellors
authors.affiliation: Departments of Infectious Disease and Quantitative Health Sciences, Cleveland Clinic, Ohio; Section of Infectious Diseases, Department of Medicine, and Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas.
authors.forename: Ume L
authors.initials: UL
authors.lastname: Abbas
keywords: HIV prevention; South Africa; drug resistance; mathematical model; pre-exposure prophylaxis