Toward a cure for HIV—Seeking effective therapeutic vaccine strategies

Autran, Brigitte

doi:10.1002/eji.201545513

Cited by 13 publications

(8 citation statements)

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“…Our study may imply that the genetic background of the exposed person, the genetic background of the source, and the viral strain could interact with each other to obtain an elite controller. This case which might belong to the extremely rare subset of extreme HIV controllers with undetectable virus loads, might be taken as a model and as a creative step, in a positive direction, for future control of HIV disease ( Autran et al, 2011 , Autran, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

What Is the most Important for Elite Control: Genetic Background of Patient, Genetic Background of Partner, both or neither? Description of Complete Natural History within a Couple of MSM

et al. 2018

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BackgroundWe describe a homosexual man who strongly controlled HIV-1 for ten years despite lack of protective genetic background.MethodsHIV-1 DNA was measured in blood and other tissues. Cell susceptibility was evaluated with various strains. HIV-1-specific (CD4 and CD8 activation markers and immune check points) and NK cells responses were assessed; KIRs haplotypes and HLA alleles were determined.FindingsTwo HIV-1 RNA copies/mL of plasma were detected in 2009, using an ultra-sensitive assay. HIV-DNA was detected at 1.1 and 2 copies/106 PBMCs in 2009 and 2015 respectively, at 1.2 copies/106 cells in rectal cells in 2011. WBs showed weak reactivity with antibodies to gp160, p55 and p25 from 2007 to 2014, remaining incomplete in 2017. CD4 T cells were susceptible to various strains including HIVKON, a primary isolate of his own CRF02_AG variant. CD8 T cells showed a strong poly-functional response against HIV-Gag, producing mainly IFN-γ; a robust capacity of antibody-dependant cell cytotoxicity (ADCC) was observed in NK cells. Case patient was group B KIR haplotype. Neutralizing antibodies were not detected. CD4 and CD8 blood T cells showed normal proportions without increased activation markers. Phylogenetic analyses identified the same CRF02_AG variant in his partner. The patient and his partner were heterozygous for the CCR5ΔD32 deletion and shared HLA-B*07, C*07 non-protective alleles.InterpretationThis thorough description of the natural history of an individual controlling HIV-1 in various compartments for ten years despite lack of protective alleles, and of his partner, may have implications for strategies to cure HIV-1 infection.

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Section: Discussionmentioning

confidence: 99%

What Is the most Important for Elite Control: Genetic Background of Patient, Genetic Background of Partner, both or neither? Description of Complete Natural History within a Couple of MSM

et al. 2018

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“…Further attention is needed to anticipate the challenges related to the ethical implementation of combinatorial HIV cure strategies. Examples include combination gene-editing approaches [ 51 ], latency-reversing agents in synergy with immune-modifying agents [ 43 , 48 , 49 , 52 , 53 ], or different permutations of broadly-neutralizing antibodies paired with different HIV cure approaches [ 54 , 55 ]. There are now over 20 active HIV cure clinical studies using combination products with intersecting mechanisms underway in the United States alone [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

Ethics of HIV cure research: an unfinished agenda

et al. 2021

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Background The pursuit of a cure for HIV is a high priority for researchers, funding agencies, governments and people living with HIV (PLWH). To date, over 250 biomedical studies worldwide are or have been related to discovering a safe, effective, and scalable HIV cure, most of which are early translational research and experimental medicine. As HIV cure research increases, it is critical to identify and address the ethical challenges posed by this research. Methods We conducted a scoping review of the growing HIV cure research ethics literature, focusing on articles published in English peer-reviewed journals from 2013 to 2021. We extracted and summarized key developments in the ethics of HIV cure research. Twelve community advocates actively engaged in HIV cure research provided input on this summary and suggested areas warranting further ethical inquiry and foresight via email exchange and video conferencing. Discussion Despite substantial scholarship related to the ethics of HIV cure research, additional attention should focus on emerging issues in six categories of ethical issues: (1) social value (ongoing and emerging biomedical research and scalability considerations); (2) scientific validity (study design issues, such as the use of analytical treatment interruptions and placebos); (3) fair selection of participants (equity and justice considerations); (4) favorable benefit/risk balance (early phase research, benefit-risk balance, risk perception, psychological risks, and pediatric research); (5) informed consent (attention to language, decision-making, informed consent processes and scientific uncertainty); and (6) respect for enrolled participants and community (perspectives of people living with HIV and affected communities and representation). Conclusion HIV cure research ethics has an unfinished agenda. Scientific research and bioethics should work in tandem to advance ethical HIV cure research. Because the science of HIV cure research will continue to rapidly advance, ethical considerations of the major themes we identified will need to be revisited and refined over time.

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“…Therapeutic vaccination has been also explored in order to boost HIV-specific T-cell responses with the goal of achieving a functional cure after the administration of LRAs 197 . Vaccination with the ALVAC-HIV vaccine (modified recombinant canarypox virus expressing the HIV-1 Env and Gag proteins and a synthetic polypeptide that encompasses the CTL epitopes from Nef and Pol proteins) with or without Remune (inactivated gp120-depleted HIV-1) has been associated with a minor loss of CD4+ T-cell counts and delay of viral rebound after cART withdrawal.…”

Section: Therapeutic Strategies For Hiv Eradicationmentioning

confidence: 99%

Peering into the HIV reservoir

García

Buzón

Benito

et al. 2018

Reviews in Medical Virology

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The main obstacle to HIV eradication is the establishment of a long-term persistent HIV reservoir. Although several therapeutic approaches have been developed to reduce and eventually eliminate the HIV reservoir, only a few have achieved promising results. A better knowledge of the mechanisms involved in the establishment and maintenance of HIV reservoir is of utmost relevance for the design of new therapeutic strategies aimed at purging it with the ultimate goal of achieving HIV eradication or alternatively a functional cure. In this regard, it is also important to take a close look into the cellular HIV reservoirs other than resting memory CD4 T-cells with key roles in reservoir maintenance that have been recently described. Unraveling the special characteristics of these HIV cellular compartments could aid us in designing new therapeutic strategies to deplete the latent HIV reservoir.

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Toward a cure for HIV—Seeking effective therapeutic vaccine strategies

Cited by 13 publications

References 60 publications

What Is the most Important for Elite Control: Genetic Background of Patient, Genetic Background of Partner, both or neither? Description of Complete Natural History within a Couple of MSM

What Is the most Important for Elite Control: Genetic Background of Patient, Genetic Background of Partner, both or neither? Description of Complete Natural History within a Couple of MSM

Ethics of HIV cure research: an unfinished agenda

Peering into the HIV reservoir

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