Personalizing prevention: Advances in pharmacotherapy for <scp>HIV</scp> prevention

Brizzi, Marisa; Sherman, Elizabeth M; Green, Sarah B.; Nowicki, Diana N; Drwiega, Emily N; Nicol, Melanie R.; Chastain, Daniel B; Sahloff, Eric G.; Truong, William R; Cluck, David; Badowski, Melissa E; Michienzi, Sarah M; Durham, Spencer H.

doi:10.1002/phar.2796

Cited by 3 publications

(2 citation statements)

References 77 publications

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“…By contrast, extensive modifications of PF74 led to the development of lenacapavir ( LEN ) by Gilead Sciences, which demonstrated subnanomolar antiviral activity against numerous common HIV‐1 subtypes 17 . LEN has earned US Food and Drug Administration approval as a long‐acting anti‐AIDS drug 18,19 . However, due to the genetic heterogeneity of HIV, several drug‐resistant strains have been observed during LEN usage 20–22 .…”

Section: Introductionmentioning

confidence: 99%

Discovery of low‐molecular‐weight phenylalanine derivatives as novel HIV capsid modulators with improved antiretroviral activity and metabolic stability

Jiang,

Gao,

Sharma

et al. 2024

Journal of Medical Virology

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The HIV capsid (CA) protein is a promising target for anti‐AIDS treatment due to its critical involvement in viral replication. Herein, we utilized the well‐documented CA inhibitor PF74 as our lead compound and designed a series of low‐molecular‐weight phenylalanine derivatives. Among them, compound 7t exhibited remarkable antiviral activity with a high selection index (EC50 = 0.040 µM, SI = 2815), surpassing that of PF74 (EC50 = 0.50 µM, SI = 258). Furthermore, when evaluated against the HIV‐2 strain, 7t (EC50 = 0.13 µM) demonstrated approximately 14‐fold higher potency than that of PF74 (EC50 = 1.76 µM). Insights obtained from surface plasmon resonance (SPR) revealed that 7t exhibited stronger target affinity to the CA hexamer and monomer in comparison to PF74. The potential interactions between 7t and the HIV‐1 CA were further elucidated using molecular docking and molecular dynamics simulations, providing a plausible explanation for the enhanced target affinity with 7t over PF74. Moreover, the metabolic stability assay demonstrated that 7t (T1/2 = 77.0 min) significantly outperforms PF74 (T1/2 = 0.7 min) in human liver microsome, exhibiting an improvement factor of 110‐fold. In conclusion, 7t emerges as a promising drug candidate warranting further investigation.

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Section: Introductionmentioning

confidence: 99%

Discovery of low‐molecular‐weight phenylalanine derivatives as novel HIV capsid modulators with improved antiretroviral activity and metabolic stability

Jiang,

Gao,

Sharma

et al. 2024

Journal of Medical Virology

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“…Pharmacists play a crucial role in expanding access to and uptake of PrEP (Brizzi et al, 2023). This field is rapidly growing, and international studies conducted in the USA, Canada, Kenya, and South Africa (Cernasev et al, 2023;Greenwell et al, 2023;MacDonald et al, 2023;Mugo et al, 2017) have demonstrated the valuable contribution of pharmacists to PrEP scale-up.…”

Section: Introductionmentioning

confidence: 99%

Pharmaceutical care effectiveness in brazilian healthcare setting: PrEP knowledge and adherence

Siqueira,

Dewulf,

Siqueira

et al. 2023

CLIUM

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PrEP is a globally effective and safe healthcare technology that substantially reduces HIV incidence. Pharmacists have played a crucial role in promoting PrEP scale-up, however, there is a lack of studies in the Brazilian context. This intervention study, conducted in Central Brazil from 2021 to 2022, assessed pharmaceutical care's effectiveness in enhancing PrEP knowledge and adherence among high-risk individuals for HIV acquisition. Over 80% of 150 participants, were predominantly male, homosexual, averaging 31.4 years old, single, and highly educated, and showed normal liver and kidney function with no HIV seroconversions. The Intervention Group (IG) displayed significant statistical differences in PrEP knowledge (p<0.001) and adherence (p<0.008) compared to the control group. The clinical pharmacist effectively resolved 27 drug-related problems with no adverse effects on participants. This study is pioneering within the Brazilian context, making a significant contribution to the advancement of scientific understanding regarding the role of pharmaceutical services in fostering PrEP utilization in Brazil.

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Primary Care Providers' Information Needs for Prescribing Adolescents HIV Pre-Exposure Prophylaxis

Owens,

Stukenberg,

Grant

et al. 2023

AIDS Education and Prevention

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Although knowledge is a salient determinant in primary care providers (PCPs) prescribing HIV pre-exposure prophylaxis (PrEP) to adolescents, we know little about what information PCPs want about PrEP. We conducted an online mixed-method study to explore the PrEP information needs of a national sample of 351 PCPs. We analyzed data with deductive content analysis and compared themes between respondents who were aware and not aware of PrEP, knowledgeable and not knowledgeable of the prescribing guidelines, and prescribed and never prescribed PrEP to an adolescent. PCPs who were unknowledgeable about PrEP and never prescribed PrEP to an adolescent mentioned manufacturing information, indications and dosing, and contraindications and adverse reactions more so than PCPs who were aware of and prescribed PrEP. A better understanding of the information needs of PCPs could inform provider education interventions. Future research must examine the facilitators and barriers to integrating PrEP information into medical education and clinical settings.

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Personalizing prevention: Advances in pharmacotherapy for HIV prevention

Cited by 3 publications

References 77 publications

Discovery of low‐molecular‐weight phenylalanine derivatives as novel HIV capsid modulators with improved antiretroviral activity and metabolic stability

Discovery of low‐molecular‐weight phenylalanine derivatives as novel HIV capsid modulators with improved antiretroviral activity and metabolic stability

Pharmaceutical care effectiveness in brazilian healthcare setting: PrEP knowledge and adherence

Primary Care Providers' Information Needs for Prescribing Adolescents HIV Pre-Exposure Prophylaxis

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