A Curative Regimen Would Decrease HIV Prevalence But Not HIV Incidence Unless Targeted to an ART-Naïve Population

HIV curative strategies currently under development aim to eradicate latent provirus, or prevent viral replication, progression to AIDS, and transmission. The impact of implementing curative programs on HIV epidemics has not been considered. 

We developed a mathematical model of heterosexual HIV transmission to evaluate the independent and synergistic impact of ART, HIV prevention interventions and cure on HIV prevalence and incidence. The basic reproduction number was calculated to study the potential for the epidemic to be eliminated. We explored scenarios with and without the assumption that patients enrolled into HIV cure programs need to be on antiretroviral treatment (ART). 

In our simulations, curative regimes had limited impact on HIV incidence if only ART patients were eligible for cure. Cure implementation had a significant impact on HIV incidence if ART-untreated patients were enrolled directly into cure programs. Concurrent HIV prevention programs moderately decreased the percent of ART treated or cured patients needed to achieve elimination. 

We project that widespread implementation of HIV cure would decrease HIV prevalence under all scenarios but would only lower rate of new infections if ART-untreated patients were targeted. Current efforts to identify untreated HIV patients will gain even further relevance upon availability of an HIV cure.

Below:   ART and HIV prevention coverage drive decreases in epidemic potential if only ART treated patients are eligible for cure interventions

Full article at:  http://goo.gl/HF1tZo

By:  Dimitrov DT1,2, Kiem HP3,4, Jerome KR1,5, Johnston C4, Schiffer JT1,4.

• 1Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
• 2Department of Applied Mathematics, University of Washington, Seattle, Washington, USA.
• 3Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.
• 4Department of Medicine, University of Washington, Seattle, Washington, USA.
• 5Department of Laboratory Medicine, University of Washington, Seattle, Washington, USA.
• Sci Rep. 2016 Feb 24;6:22183. doi: 10.1038/srep22183. 

More at:  https://twitter.com/hiv insight

And: http://twitter.com/Prison Health

Town Hall: HIV Cure Research Panel Discussion

Via: http://goo.gl/ZrlNsO  By: https://twitter.com/uctelevision

Town Hall: HIV Cure Research

Via: http://goo.gl/ZrlNsO  By: https://twitter.com/uctelevision

HIV-1 Functional Cure: Will the Dream Come True?

The reservoir of human immunodeficiency virus type 1 (HIV-1), a long-lived pool of latently infected cells harboring replication-competent viruses, is the major obstacle to curing acquired immune deficiency syndrome (AIDS). Although the combination antiretroviral therapy (cART) can successfully suppress HIV-1 viremia and significantly delay the progression of the disease, it cannot eliminate the viral reservoir and the patient must continue to take anti-viral medicines for life. 

Currently, the appearance of the ‘Berlin patient’, the ‘Boston patients’, and the ‘Mississippi baby’ have inspired many therapeutic strategies for HIV-1 aimed at curing efforts. However, the specific eradication of viral latency and the recovery and optimization of the HIV-1-specific immune surveillance are major challenges to achieving such a cure. Here, we summarize recent studies addressing the mechanisms underlying the viral latency and define two categories of viral reservoir: ‘shallow’ and ‘deep’. We also present the current strategies and recent advances in the development of a functional cure for HIV-1, focusing on full/partial replacement of the immune system, ‘shock and kill’, and ‘permanent silencing’ approaches.

Below:  A feasible strategy for the functional cure of HIV-1. Firstly, ‘shock and kill’ strategies could be quite useful in kicking out the ‘shallow’ latent viruses and eliminating them. Then, ‘silencing’ strategies, which permanently inactivate the ‘deeply’ silenced viruses, accompanied by potent anti-HIV-1 immune surveillance, could subsequently be utilized to achieve the functional cure of HIV-1

Below:  Strategies for recovery and optimization of anti-HIV-1 immune surveillance. The combination of bNAbs with autologous adoptive transfer of HIV-1-specific CD8 + T cells and/or HIV-1-resistant CD4 + T cells could be an effective therapeutic modality for the functional cure of HIV-1

Full article at:  http://goo.gl/eRNiKQ

By: Chao Liu¹², Xiancai Ma¹², Bingfeng Liu¹², Cancan Chen¹² and Hui Zhang^12*

¹Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China

²Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China

 

More at:  https://twitter.com/hiv_insight

And: http://twitter.com/Prison_Health

Hawaii HIV Cure Initiative

Learn more at:  http://ht.ly/UDhBF

HIV Persistence in the Setting of Antiretroviral Therapy: When, Where and How Does HIV Hide?

Advances in the treatment of HIV infection have dramatically reduced the death rate from AIDS and improved the quality of life of many HIV-infected individuals. However, the possible long-term toxicity associated with antiretroviral therapy (ART), stigma and cost, all contribute to the necessity of finding a cure for HIV infection. In infected individuals taking ART, HIV persists in a small number of cells that can survive for the lifetime of the infected person. These persistently infected cells, usually referred as the ‘reservoirs for HIV infection’, are the main barriers to a cure. The diversity of the tissues and cellular types in which HIV persists, as well as the multiplicity of the molecular mechanisms contributing to HIV persistence, complicate the efforts to develop a safe, effective, and globally accessible cure for HIV. In this review, we summarise recent data that contribute to our understanding of HIV persistence during ART by addressing three questions pertaining to the HIV reservoir: (1) when is the reservoir established; (2) where is the reservoir maintained; and (3) how does the reservoir persist?

Below:  Clinical definition of the HIV reservoir. Untreated HIV infection is characterised by high levels of viral replication that can be measured in the plasma of HIV-infected individuals. ART reduces viral replication to undetectable levels by standard viral load measurements. When ART is interrupted, HIV replication resumes, revealing that HIV persisted in cellular and anatomical ‘reservoirs’ during ART and that these reservoirs can re-ignite infection.

Full article at: http://goo.gl/RgZMc6

By: Deanna A. Kulpa1 and Nicolas Chomont2,*

1Vaccine and Gene Therapy Institute Florida, Port St Lucie, Florida, USA

2Department of Microbiology, Infectiology and Immunology, Université de Montréal, Faculty of Medicine, and Centre de Recherche du CHUM, Montréal, Quebec, Canada

More at:  https://twitter.com/hiv_insight

HIV Cure Science Terminology

Read at [PDF]:   http://ht.ly/QHTtF MT @ProjectInform