On the efficiency of HIV transmission: Insights through discrete time HIV models

Showa, Sarudzai Portia; Nyabadza, Farai; Hove-Musekwa, Senelani D.

doi:10.1371/journal.pone.0222574

Cited by 4 publications

(8 citation statements)

References 48 publications

(77 reference statements)

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“…For instance, it is common practice to infect the animals with cell-free virus particles to evaluate one treatment, although it is now established that infected body fluids at the origin of mucosal transmissions, such as semen, vaginal fluid, and breast milk, contain both cell-free and cell-associated HIV. As discussed above, the protective abilities of HIV-neutralizing agents (bnAbs and other molecules) are not limited to the neutralization of cell-free virus particles but also includes cell-associated HIV [ 287 ]. Efforts in evaluating mucosal protection against both cell-free virus particles and cell-associated virus in preclinical studies should be encouraged to better model natural infections [ 288 ].…”

Section: Discussionmentioning

confidence: 99%

HIV-1 Entry and Prospects for Protecting against Infection

et al. 2021

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Human Immunodeficiency Virus type-1 (HIV-1) establishes a latent viral reservoir soon after infection, which poses a major challenge for drug treatment and curative strategies. Many efforts are therefore focused on blocking infection. To this end, both viral and host factors relevant to the onset of infection need to be considered. Given that HIV-1 is most often transmitted mucosally, strategies designed to protect against infection need to be effective at mucosal portals of entry. These strategies need to contend also with cell-free and cell-associated transmitted/founder (T/F) virus forms; both can initiate and establish infection. This review will discuss how insight from the current model of HIV-1 mucosal transmission and cell entry has highlighted challenges in developing effective strategies to prevent infection. First, we examine key viral and host factors that play a role in transmission and infection. We then discuss preventive strategies based on antibody-mediated protection, with emphasis on targeting T/F viruses and mucosal immunity. Lastly, we review treatment strategies targeting viral entry, with focus on the most clinically advanced entry inhibitors.

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Section: Discussionmentioning

confidence: 99%

HIV-1 Entry and Prospects for Protecting against Infection

et al. 2021

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“…The transmission of HIV occurs when there is exposure to blood or body fluids containing HIV or HIV-infected cells. The three major routes of transmission are sexual contact, mother-to-baby transmission, and intravenous drug use (IVDU) (Shaw & Hunter, 2012;Showa, Nyadadza, & Hove-Musekwa, 2019). The most common ways of HIV infection in the U.S. are vaginal or anal sex with an HIV-infected partner or sharing of injection drug needles with someone who is HIV positive.…”

Section: Hiv Transmissionmentioning

confidence: 99%

“…The most common ways of HIV infection in the U.S. are vaginal or anal sex with an HIV-infected partner or sharing of injection drug needles with someone who is HIV positive. Male-to-female transmission of HIV is the most common route of transmission (Showa et al, 2019). Less common means of transmission include mother-to-child, being stuck by HIV-contaminated needles, oral sex, blood and blood product transfusions, being bitten by someone infected with HIV, and kissing.…”

Section: Hiv Transmissionmentioning

confidence: 99%

“…Less common means of transmission include mother-to-child, being stuck by HIV-contaminated needles, oral sex, blood and blood product transfusions, being bitten by someone infected with HIV, and kissing. HIV viruses that are CCR5 tropic, that is, strains of HIV that infect T cells displaying the CCR5 receptor, are preferentially transmitted via all three primary routes for reasons that are not entirely understood (Ronen, Sharma, & Overbaugh, 2015;Shaw & Hunter, 2012;Showa et al, 2019). Once transmission occurs, viral and host markers of infection appear in the blood and plasma (Showa et al, 2019).…”

Section: Hiv Transmissionmentioning

confidence: 99%

“…HIV viruses that are CCR5 tropic, that is, strains of HIV that infect T cells displaying the CCR5 receptor, are preferentially transmitted via all three primary routes for reasons that are not entirely understood (Ronen, Sharma, & Overbaugh, 2015;Shaw & Hunter, 2012;Showa et al, 2019). Once transmission occurs, viral and host markers of infection appear in the blood and plasma (Showa et al, 2019).…”

Section: Hiv Transmissionmentioning

confidence: 99%

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Primary care provider prep prescribing practices : southern United States

Traylor¹

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The Southern United States (U.S.) accounts for more than half of new HIV cases annually and African Americans make up the majority of new HIV diagnoses in this region. Pre-Exposure Prophylaxis (PrEP) is an effective biomedical HIV prevention strategy that is underutilized. Few studies have examined the PrEP prescribing practices of primary care providers (PCPs), particularly in the Southern U.S. This cross-sectional survey, driven by the Transtheoretical Model (TTM), examined the prescribing practices of Southern U.S. PCPs. Relationships between PCPs personal and practice variables were examined, together with TTM decisional balance variables. Participants (n=223) who had more African American patients in their practice were more likely to be in a higher TTM stage of change (p = .002) and were more likely to have written a PrEP prescription (p = .001). Access to PrEP resources (OR = 1.85, p = .001), streamlined insurance prior authorization processes (OR = 1.52, p = .010), working with staff who have PrEP knowledge (OR = 1.51, p = .033), having PrEP training (OR = 40.26, p < .001) and having patients who are motivated to take PrEP (OR = 2.19, p = .007) were significant facilitators to PrEP prescribing. Significant barriers to PrEP prescribing included a lack of provider PrEP training (OR = 0.43, p = .003), lack of clinical leadership regarding PrEP (OR = 0.65, p = .018), lack of insurance (OR = 2.74, p = .002), and likelihood of low patient adherence to PrEP (OR = 0.53, p = .001). Findings indicate that this sample of PCPs were more likely to be at a higher TTM stage of change and have written a PrEP prescription if they saw more African American patients in their practice. Further, significant facilitators of PrEP prescribing included access to PrEP resources, streamlined insurance prior authorization processes, working with staff who have PrEP knowledge, having PrEP training, and having patients who are motivated to take PrEP. Significant barriers to PrEP prescribing included a lack of PrEP training, a lack of clinical leadership regarding PrEP, patient lack of insurance, and likelihood of low patient adherence. This study contributes to the body of knowledge regarding PCP PrEP prescribing practices. Findings from this study may inform future interventions that aim to enhance PrEP prescribing among primary care providers who serve Southern African American individuals at risk for acquisition of HIV disease.

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Single-Chain Variable Fragments of Broadly Neutralizing Antibodies Prevent HIV Cell-Cell Transmission

Dorsten

Reh

Trkola

et al. 2022

J Virol

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Broadly neutralizing antibodies (bNAbs) are able to prevent HIV infection following passive administration. Single-chain variable fragments (scFv) may have advantages over IgG as their smaller size permits improved diffusion into mucosal tissues. We have previously shown that scFv of bNAbs retain significant breadth and potency against cell-free viral transmission in a TZM-bl assay. However, scFv have not been tested for their ability to block cell-cell transmission, a model in which full-sized bNAbs lose potency. We tested 4 scFv (CAP256.25, PGT121, 3BNC117 and 10E8v4) compared to IgG, in free-virus and cell-cell neutralization assays in A3.01 cells, against a panel of seven heterologous viruses. We show that free-virus neutralization titers in the TZM-bl and A3.01 assays were not significantly different, and confirm that scFv show a 1 to 32-fold reduction in activity in the cell-free model, compared to IgG. However, whereas IgG show 3.4 to 19-fold geometric mean potency loss in cell-cell neutralization compared to free-virus transmission, scFv had more comparable activity in the two assays, with only a 1.3 to 2.3-fold reduction. Geometric mean IC 50 of scFv for cell-cell transmission ranged from 0.65 μg/ml (10E8v4) to 2.3 μg/ml (3BNC117) with IgG and scFv neutralization showing similar potency against cell-associated transmission. Therefore, despite the reduced activity of scFv in cell-free assays, their retention of activity in the cell-cell format may make scFv useful for the prevention of both modes of transmission in HIV prevention studies. Importance Broadly neutralizing antibodies (bNAbs) are a major focus for passive immunization against HIV, with the recently concluded HVTN AMP (Antibody Mediated Protection) trial providing proof of concept. Most studies focus on cell-free HIV, however cell-associated virus may play a significant role in HIV infection, pathogenesis and latency. Single-chain variable fragments (scFv) of antibodies may have increased tissue penetration, and reduced immunogenicity. We previously demonstrated that scFv of four HIV-directed bNAbs (CAP256-VRC26.25, PGT121, 3BNC117 and 10E8v4) retain significant potency and breadth against cell-free HIV. As some bNAbs have been shown to lose potency against cell-associated virus, we investigated the ability of bNAb scFv to neutralize this mode of transmission. We demonstrate that unlike IgG, scFv of bNAbs are able to neutralize cell-free and cell-associated virus with similar potency. These scFv, which show functional activity in the therapeutic range, may therefore be suitable for further development as passive immunity for HIV prevention.

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On the efficiency of HIV transmission: Insights through discrete time HIV models

Cited by 4 publications

References 48 publications

HIV-1 Entry and Prospects for Protecting against Infection

HIV-1 Entry and Prospects for Protecting against Infection

Primary care provider prep prescribing practices : southern United States

Single-Chain Variable Fragments of Broadly Neutralizing Antibodies Prevent HIV Cell-Cell Transmission

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