Dataset Information

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.

SUBMITTER: Glaubius RL

PROVIDER: S-EPMC5047428 | biostudies-literature | 2016 Sep

REPOSITORIES: biostudies-literature

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Deciphering the Effects of Injectable Pre-exposure Prophylaxis for Combination Human Immunodeficiency Virus Prevention.

Glaubius Robert L RL Parikh Urvi M UM Hood Greg G Penrose Kerri J KJ Bendavid Eran E Mellors John W JW Abbas Ume L UL

Open forum infectious diseases 20160616 3

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 differen ...[more]

PMID: 27703992

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Project description:ObjectivesAn effective clinical decision support system (CDSS) may address the current provider training barrier to offering preexposure prophylaxis (PrEP) to youth at risk for human immunodeficiency virus (HIV) infection. This study evaluated change in provider knowledge and the likelihood to initiate PrEP after exposure to a PrEP CDSS. A secondary objective explored perceived provider utility of the CDSS and suggestions for improving CDSS effectiveness.MethodsThis was a prospective study using survey responses from a convenience sample of pediatric providers who launched the interruptive PrEP CDSS when ordering an HIV test. McNemar's test evaluated change in provider PrEP knowledge and likelihood to initiate PrEP. Qualitative responses on CDSS utility and suggested improvements were analyzed using framework analysis and were connected to quantitative analysis elements using the merge approach.ResultsOf the 73 invited providers, 43 had available outcome data and were included in the analysis. Prior to using the CDSS, 86% of participants had never been prescribed PrEP. Compared to before CDSS exposure, there were significant increases in the proportion of providers who were knowledgeable about PrEP (p = 0.0001), likely to prescribe PrEP (p < 0.0001) and likely to refer their patient for PrEP (p < 0.0001). Suggestions for improving the CDSS included alternative "triggers" for the CDSS earlier in visit workflows, having a noninterruptive CDSS, additional provider educational materials, access to patient-facing PrEP materials, and additional CDSS support for adolescent confidentiality and navigating financial implications of PrEP.ConclusionOur findings suggest that an interruptive PrEP CDSS attached to HIV test orders can be an effective tool to increase knowledge and likelihood to initiate PrEP among pediatric providers. Continual improvement of the PrEP CDSS based on provider feedback is required to optimize usability, effectiveness, and adoption. A highly usable PrEP CDSS may be a powerful tool to close the gap in youth PrEP access and uptake.

Project description:BackgroundOral pre-exposure prophylaxis (PrEP) prevents HIV infection in men who have sex with men (MSM); however, adherence is an ongoing concern. Long-acting injectable PrEP is being tested in phase 3 trials and could address challenges associated with adherence. We examined the potential effectiveness of long-acting injectable PrEP compared with oral PrEP in MSM.MethodsWe used an agent-based model to simulate HIV transmission in a dynamic network of 11 245 MSM in Atlanta, GA, USA. We used raw data from studies in macaque models and pharmacokinetic data from safety trials to estimate the time-varying efficacy of long-acting injectable PrEP. The effect of long-acting injectable PrEP on the cumulative number of new HIV infections over 10 years (2015-24) was compared with no PrEP and daily oral PrEP across a range of coverage levels. Sensitivity analyses were done with varying maximum efficacy and drug half-life values.FindingsIn the absence of PrEP, the model predicted 2374 new HIV infections (95% simulation interval [SI] 2345-2412) between 2015 and 2024. The cumulative number of new HIV infections was reduced in all scenarios in which MSM received long-acting injectable PrEP compared with oral PrEP. At a coverage level of 35%, compared with no PrEP, long-acting injectable PrEP led to a 44% reduction in new HIV infections (1044 new infections averted [95% SI 1018-1077]) versus 33% (792 infections averted [763-821]) for oral PrEP. The relative benefit of long-acting injectable PrEP was sensitive to the assumed efficacy of injections received every 8 weeks, discontinuation rates, and terminal drug half-life.InterpretationLong-acting injectable PrEP has the potential to produce larger reductions in HIV transmission in MSM than oral PrEP. However, the real-world, population-level impact of this approach will depend on uptake of this prevention method and its effectiveness, as well as retention of patients in clinical care.FundingNational Institute on Drug Abuse and National Institute of Mental Health.

Project description:IntroductionAlthough pre-exposure prophylaxis (PrEP.) is an efficacious HIV prevention strategy, its preventive benefit has not been shown among young women in sub-Saharan Africa, likely due to non-adherence. Adherence may be improved with the use of injectable long-acting PrEP methods currently being developed. We hypothesize that providing long-acting PrEP to women using injectable contraceptives, the most frequently used contraceptive method in South Africa, could improve adherence to PrEP, result in a reduction of new HIV infections, and be a relatively easy-to-reach target population. In this modelling study, we assessed the epidemiological impact and cost-effectiveness of providing long-acting PrEP to injectable contraceptive users in Limpopo, South Africa.MethodsWe developed a deterministic mathematical model calibrated to the HIV epidemic in Limpopo. Long-acting PrEP was provided to 50% of HIV negative injectable contraceptive users in 2018 and scaled-up over two years. We estimated the number of HIV infections that could be averted by 2030 and the drug price of long-acting PrEP for which this intervention would be cost-effective over a time horizon of 40 years, from a healthcare payer perspective. In the base-case scenario we assumed long-acting PrEP is 75% effective in preventing HIV infections and 85% of infected individuals are on antiretroviral drug therapy (ART) by 2030. In sensitivity analyses we adjusted PrEP effectiveness and ART coverage. Costs between $519 and $1119 per disability-adjusted life-year (DALY) averted were considered potentially cost-effective, and <$519 as cost-effective.ResultsWithout long-acting injectable PrEP, 224,000 (interquartile range 176,000 to 271,000) new infections will occur by 2030; use of long-acting injectable PrEP could prevent 21,000 (17,000 to 26,000) or 9.8% (8.9% to 10.6%) new HIV infections by 2030 (including 6000 (4000 to 7000) in men). Long-acting PrEP would prevent 34,000 (29,000 to 39,000) or 12,000 (8000 to 15,000) at 75% and 95% ART coverage by 2030 respectively. To be considered potentially cost-effective the annual long-acting PrEP drug price should be <$16, and/or ART coverage remains at <85% in 2030.ConclusionsProviding long-acting PrEP to injectable contraceptive users in Limpopo is only potentially cost-effective when long-acting PrEP drug prices are low. If low prices are not feasible, providing long-acting PrEP only to women at high risk of HIV infection will become important.

Dataset Information

Deciphering the Effects of Injectable Pre-exposure Prophylaxis for Combination Human Immunodeficiency Virus Prevention.

Publications

Deciphering the Effects of Injectable Pre-exposure Prophylaxis for Combination Human Immunodeficiency Virus Prevention.

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