Ultra-long-acting removable drug delivery system for HIV treatment and prevention

Kovářová, Martina; Benhabbour, S. Rahima; Massud, Ivana; Spagnuolo, Rae Ann; Skinner, Brianna; Baker, Caroline; Sykes, Craig; Mollan, Katie R.; Kashuba, Angela D. M.; Garcı́a-Lerma, J. Gerardo; Mumper, Russell J.; García, J. Víctor

doi:10.1038/s41467-018-06490-w

Cited by 74 publications

(49 citation statements)

References 39 publications

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“…This would increase the proportion of currently non-adherent AYA that switch to LA-ART and allow a higher maximum incremental cost. In addition to injectables, other long-acting formulations such as implants or microarray patch are possible that may have different durations and acceptability to patients [ 41 , 42 ]. A once-weekly formulation of oral ART may be a cost-effective alternative to injectable ART, but there is a lack of clinical data on adherence and programmatic costs.…”

Section: Discussionmentioning

confidence: 99%

Modeling the health impact and cost threshold of long-acting ART for adolescents and young adults in Kenya

et al. 2020

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Background Despite high efficacy of oral antiretroviral therapy (ART), viral suppression among adolescents and young adults (AYA) living with HIV in sub-Saharan Africa (SSA) remains low. Compared to daily oral ART, bimonthly long-acting injectable ART (LA-ART) may simplify adherence, improve clinical outcomes, and decrease HIV transmission in this priority population. However, LA-ART will likely cost more than oral ART and the cost threshold at which LA-ART will be cost effective in SSA has not been evaluated. Methods We adapted a mathematical model of HIV transmission and progression in Kenya to include HIV acquisition and viral suppression among AYA (age 10–24). We projected the population-level health and economic impact of providing LA-ART to AYA over a 10-year time horizon assuming oral ART costs of US$233 annually and a two-month duration of viral suppression per LA-ART injection. We calculated the maximum cost at which switching from oral to LA-ART would be considered cost-effective, using thresholds of $500 and $1,508 per disability-adjusted life year averted (WHO's threshold of HIV treatment interventions and Kenya's gross domestic product per capita). Findings Assuming 85% of AYA switch from oral to injectable formulations, LA-ART is estimated to prevent 40,540 infections and 20,480 deaths over 10 years. The maximum increase in the annual per-person cost of receiving LA-ART is estimated to be $89 and $236 for LA-ART to be cost-effective under the thresholds of $500 and $1,508 per DALY averted, respectively. The cost threshold was lower when non-adherent oral ART AYA users were assumed to be less likely to switch to LA-ART. Interpretation Providing LA-ART to AYA can be cost-effective in Kenya if it is less than twice the cost of oral ART. Long-acting injectable ART for priority populations with low viral suppression has the potential to cost-effectively avert disability and death. Funding National Institutes of Health (R01 HD085807; PI: Kohler)

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Section: Discussionmentioning

confidence: 99%

Modeling the health impact and cost threshold of long-acting ART for adolescents and young adults in Kenya

et al. 2020

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“…Antiviral therapy dCA [45,56] EFdA [57] RAL [45] PD-1 mAb [58] PG16 bNAb [59] PGT121 bNAb [60] 3TC, TDF [61] AZT, ddI, IDV [52] FTC, RPV, DTG [46,57] FTC, TAF, EVG [62] FTC, TDF, DTG [37,46,51,53,63] FTC, TDF, RAL [37,46,51,63] FTC, TDF, RAL, 3B3(Fv)-PE38 immunotoxin [64] FTC, TDF, RAL, IFNα14 [61,65] Pre-exposure prophylaxis (PrEP) C5A peptide [66] Cc-griffithsin [67] CD4 AsiCs [68] CD4-expressing Lactobacillus acidophilus [69] CD4mc P-III-48 [70] DTG-ultra LA [71] EFdA [72] G2-S16 PCD [73] IgA [74] MVC [75] RAL-LA [76] RPV-LA [39,77] siCCR5 LFA-1 I-tsNP [78] TNV gel [79][80][81] VRC01 bNAb [82] FTC, TAF [83] FTC, TDF [36,43,84,85] TAF, EVG…”

Section: Strategy Therapeutic Agent(s) Reference(s)mentioning

confidence: 99%

Moving beyond the mousetrap: current and emerging humanized mouse and rat models for investigating prevention and cure strategies against HIV infection and associated pathologies

et al. 2020

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The development of safe and effective combination antiretroviral therapies for human immunodeficiency virus (HIV) infection over the past several decades has significantly reduced HIV-associated morbidity and mortality. Additionally, antiretroviral drugs have provided an effective means of protection against HIV transmission. Despite these advances, significant limitations exist; namely, the inability to eliminate HIV reservoirs, the inability to reverse lymphoid tissues damage, and the lack of an effective vaccine for preventing HIV transmission. Evaluation of the safety and efficacy of therapeutics and vaccines for eliminating HIV reservoirs and preventing HIV transmission requires robust in vivo models. Since HIV is a human-specific pathogen, that targets hematopoietic lineage cells and lymphoid tissues, in vivo animal models for HIV-host interactions require incorporation of human hematopoietic lineage cells and lymphoid tissues. In this review, we will discuss the construction of mouse models with human lymphoid tissues and/or hematopoietic lineage cells, termed, human immune system (HIS)-humanized mice. These HIS-humanized mouse models can support the development of functional human innate and adaptive immune cells, along with primary (thymus) and secondary (spleen) lymphoid tissues. We will discuss applications of HIS-humanized mouse models in evaluating the safety and efficacy of therapeutics against HIV reservoirs and associated immunopathology, and delineate the human immune response elicited by candidate HIV vaccines. In addition to focusing on how these HIS-humanized mouse models have already furthered our understanding of HIV and contributed to HIV therapeutics development, we discuss how emerging HIS-humanized rat models could address the limitations of HIS-mouse models.

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“…Moreover, a preclinical evaluation of long‐acting RPV was conducted on humanised mice that were vaginally challenged by HIV‐1 transmitted founder virus. The results demonstrated that long‐acting RPV is a potential HIV prevention because it significantly protected vaginal HIV acquisition against the transmitted founder virus . Since RPV can also be combined with other ART as PrEP, many studies have focused on the effect of the combined ART containing RPV.…”

Section: Non‐nucleoside Reverse Transcriptase Inhibitormentioning

confidence: 99%

Antiretroviral agents in pre-exposure prophylaxis: emerging and advanced trends in HIV prevention

Yap

Xin

Tan

et al. 2019

Journal of Pharmacy and Pharmacology

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Objectives Antiretroviral agents (ARVs) have been the most promising line of therapy in the management of human immunodeficiency virus (HIV) infections. Some of these ARVs are used in the pre-exposure prophylaxis (PrEP) to suppress the transmission of HIV. Prophylaxis is primarily used in uninfected people, before exposure, to effectively prevent HIV infection. Several studies have shown that ART PrEP prevents HIV acquisition from sexual, blood and mother-to-child transmissions. However, there are also several challenges and limitations to PrEP. This review focuses on the current antiretroviral therapies used in PrEP. Key findings Among ARVs, the most common drugs employed from the class of entry inhibitors are maraviroc (MVC), which is a CCR5 receptor antagonist. Other entry inhibitors like emtricitabine (FTC) and tenofovir (TFV) are also used. Rilpivirine (RPV) and dapivirine (DPV) are the most common drugs employed from the Non-nucleoside reverse transcriptase inhibitor (NNRTIs) class, whereas, tenofovir disoproxil fumarate (TDF) is primarily used in the Nucleoside Reverse Transcriptase Inhibitor (NRTIs) class. Cabotegravir (CAB) is an analog of dolutegravir, and it is an integrase inhibitor. Some of these drugs are also used in combination with other drugs from the same class. Summary Some of the most common pre-exposure prophylactic strategies employed currently are the use of inhibitors, namely entry inhibitors, non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, integrase and protease inhibitors. In addition, we have also discussed on the adverse effects caused by ART in PrEP, pharmacoeconomics factors and the use of antiretroviral prophylaxis in serodiscordant couples.HIV and pre-exposure prophylaxis Pui Khee Yap et al.

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Ultra-long-acting removable drug delivery system for HIV treatment and prevention

Cited by 74 publications

References 39 publications

Modeling the health impact and cost threshold of long-acting ART for adolescents and young adults in Kenya

Modeling the health impact and cost threshold of long-acting ART for adolescents and young adults in Kenya

Moving beyond the mousetrap: current and emerging humanized mouse and rat models for investigating prevention and cure strategies against HIV infection and associated pathologies

Antiretroviral agents in pre-exposure prophylaxis: emerging and advanced trends in HIV prevention

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