Deciphering the Effects of Injectable Pre-exposure Prophylaxis for Combination Human Immunodeficiency Virus Prevention. (16th June 2016)

• Record Type: Journal Article
• Authors: Glaubius, Robert L.; Parikh, Urvi M.; Hood, Greg; Penrose, Kerri J.; Bendavid, Eran; Mellors, John W.; Abbas, Ume L.
• Is Part Of: Open forum infectious diseases. Volume 3:Number 3(2016)
• Publication Date: 2016-06-16
• Subjects: drug resistance -- HIV prevention -- mathematical model -- pre-exposure prophylaxis -- South Africa; Communicable diseases -- Periodicals; Medical microbiology -- Periodicals; Infection -- Periodicals; 616.9
• DOI: 10.1093/ofid/ofw125
• Languages: English
• ISSNs: 2328-8957

Abstract

Abstract : Injectable antiretrovirals including non-nucleoside reverse transcriptase inhibitors are being evaluated for pre-exposure prophylaxis for HIV prevention. Mathematical modeling suggests that injectable pre-exposure prophylaxis among KwaZulu-Natal's at-risk populations could have substantial preventive impact but may increase drug resistance unless highly effective. 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.