Bringing Gene Therapies for HIV Disease to Resource-Limited Parts of the World

McCune, Joseph M.; Turner, Emily H.; Jiang, Adam; Doehle, Brian P.

doi:10.1089/hum.2020.252

Cited by 8 publications

(7 citation statements)

References 59 publications

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“…While ART has made HIV disease manageable for many, this is not the case for most – especially for those in resource-limited parts of the world where the prevalence of disease is high, adherence is difficult, and the availability of ART is increasingly uncertain. For these individuals, it is important to find a way to maintain durable viral suppression absent guaranteed provision of and/or long-term adherence to ART [ 195 ].…”

Section: Comments By Leadersmentioning

confidence: 99%

Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?

Harper,

Betts,

Lichterfeld

et al. 2024

PAI

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Once a death sentence, HIV is now considered a manageable chronic disease due to the development of antiretroviral therapy (ART) regimens with minimal toxicity and a high barrier for genetic resistance. While highly effective in arresting AIDS progression and rendering the virus untransmissible in people living with HIV (PLWH) with undetectable viremia (U=U) [1, 2]), ART alone is incapable of eradicating the “reservoir” of resting, latently infected CD4+ T cells from which virus recrudesces upon treatment cessation. As of 2022 estimates, there are 39 million PLWH, of whom 86% are aware of their status and 76% are receiving ART [3]. As of 2017, ART-treated PLWH exhibit near normalized life expectancies without adjustment for socioeconomic differences [4]. Furthermore, there is a global deceleration in the rate of new infections [3] driven by expanded access to pre-exposure prophylaxis (PrEP), HIV testing in vulnerable populations, and by ART treatment [5]. Therefore, despite outstanding issues pertaining to cost and access in developing countries, there is strong enthusiasm that aggressive testing, treatment, and effective viral suppression may be able to halt the ongoing HIV epidemic (ie, UNAIDS’ 95-95-95 targets) [6–8]; especially as evidenced by recent encouraging observations in Sydney [9]. Despite these promising efforts to limit further viral transmission, for PLWH, a “cure” remains elusive; whether it be to completely eradicate the viral reservoir (ie, cure) or to induce long-term viral remission in the absence of ART (ie, control; Figure 1). In a previous salon hosted by Pathogens and Immunity in 2016 [10], some researchers were optimistic that a cure was a feasible, scalable goal, albeit with no clear consensus on the best route. So, how are these cure strategies panning out? In this commentary, 8 years later, we will provide a brief overview on recent advances and failures towards identifying determinants of viral persistence and developing a scalable cure for HIV. Based on these observations, and as in the earlier salon, we have asked several prominent HIV cure researchers for their perspectives.

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Section: Comments By Leadersmentioning

confidence: 99%

Progress Note 2024: Curing HIV; Not in My Lifetime or Just Around the Corner?

Harper,

Betts,

Lichterfeld

et al. 2024

PAI

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“…CGT approaches may confer scientific comparative advantages compared with other HIV cure research strategies under investigation. For example, CGT HIV cure strategies address the underlying biology of HIV infection [ 59 ] and have the potential to become one-time regimens that could eventually be scaled-up globally [ 1 , 60 ], although it is unclear whether they will be able to protect against HIV reinfection risk and transmissibility [ 61 ]. As indicated by informants in our study, scientific advancements in the field of CGT HIV cure research may also benefit other molecular genetic diseases.…”

Section: Discussionmentioning

confidence: 99%

Ethical and practical considerations for cell and gene therapy toward an HIV cure: findings from a qualitative in-depth interview study in the United States

et al. 2022

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Background HIV cure research involving cell and gene therapy has intensified in recent years. There is a growing need to identify ethical standards and safeguards to ensure cell and gene therapy (CGT) HIV cure research remains valued and acceptable to as many stakeholders as possible as it advances on a global scale. Methods To elicit preliminary ethical and practical considerations to guide CGT HIV cure research, we implemented a qualitative, in-depth interview study with three key stakeholder groups in the United States: (1) biomedical HIV cure researchers, (2) bioethicists, and (3) community stakeholders. Interviews permitted evaluation of informants’ perspectives on how CGT HIV cure research should ethically occur, and were transcribed verbatim. We applied conventional content analysis focused on inductive reasoning to analyze the rich qualitative data and derive key ethical and practical considerations related to CGT towards an HIV cure. Results We interviewed 13 biomedical researchers, 5 community members, and 1 bioethicist. Informants generated considerations related to: perceived benefits of CGT towards an HIV cure, perceived risks, considerations necessary to ensure an acceptable benefit/risk balance, CGT strategies considered unacceptable, additional ethical considerations, and considerations for first-in-human CGT HIV cure trials. Informants also proposed important safeguards to developing CGT approaches towards an HIV cure, such as the importance of mitigating off-target effects, mitigating risks associated with long-term duration of CGT interventions, and mitigating risks of immune overreactions. Conclusion Our study identified preliminary considerations for CGT-based HIV cure across three key stakeholder groups. Respondents identified an ideal cure strategy as one which would durably control HIV infection, protect the individual from re-acquisition, and eliminate transmission to others. Known and unknown risks should be anticipated and perceived as learning opportunities to preserve and honor the altruism of participants. Preclinical studies should support these considerations and be transparently reviewed by regulatory experts and peers prior to first-in-human studies. To protect the public trust in CGT HIV cure research, ethical and practical considerations should be periodically revisited and updated as the science continues to evolve. Additional ethics studies are required to expand stakeholder participation to include traditionally marginalized groups and clinical care providers.

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“…Given the philanthropic mission of the Bill & Melinda Gates Foundation to "help all people lead healthy and productive lives," the Gates Foundation's HIV Frontiers Program was initiated in early 2019 to bring disparate and necessary strengths to the fore, encouraging the sharing of expertise and resources required to tackle the otherwise risky, aspirational, and long-term goal of discovering gene therapies accessible to all. 5 Conspicuous disease areas for initial focus include HIV and sickle cell disease (SCD), life-threatening disorders afflicting millions in sub-Saharan Africa and other regions, for which standard-of-care therapy is inadequate and genetic cures are now in sight. 6,7 Particularly in the case of SCD, it is increasingly evident that ex vivo manipulation of HSCs is likely to provide clinical benefits that, for cost and complexity reasons alone, will be challenging to distribute at scale to most of those in need.…”

mentioning

confidence: 99%