Human immunodeficiency virus (HIV) – the etiologic agent of AIDS – is one of the most intensively studied disease organisms in history. Since its first identification in the early 1980s, HIV has transformed into a pandemic, globally infecting more 36 million people and annually contributing to the deaths of hundreds of thousands of patients – particularly in low income countries. This Milestone charts the history of HIV research on an interactive Timeline, from its origins to the latest developments in HIV treatment, vaccines and insights from the study of HIV/AIDS pathogenesis.
Combination therapy with the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 maintains long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.
In monkeys infected with an AIDS-like virus, a combination of a broadly neutralizing antibody and an immune stimulator during antiretroviral therapy suppressed viral rebound after antiretroviral drug discontinuation.
Genital inflammation undermines the effectiveness of tenofovir gel in preventing HIV acquisition in women
In the absence of genital inflammation, tenofovir gel provides superior prevention against HIV acquisition in women.
Following some high-profile clinical trial failures in recent years, the emphasis in HIV/AIDS vaccine research has shifted away from T-cell-based vaccines that control viral replication towards vaccines that block acquisition of infection. Hansen et al. take a novel route to T-cell-based immunity, using cytomegalovirus (CMV) vectors. They find that vaccination with a rhesus-CMV-based vaccine against simian immunodeficiency virus (SIV) provides long-term protection from SIV challenge in rhesus macaques. Protection seems to be mediated by tissue-resident T-effector memory responses, suggesting that persistent vectors such as CMV may be effective in HIV/AIDS vaccines.
HIV devotes a large portion of its coding capacity to counteracting the function of mammalian antiviral proteins. Landau and colleagues discuss the biology of mammalian restriction factors and the viral accessory proteins that counteract them.
This article describes recent progress in delineating the factors that contribute to spontaneous HIV-1 immune control, with the ultimate aim of translating these studies into clinical strategies to induce a 'functional cure' of HIV-1 infection.
Advances in care over the last 30 years have helped transform HIV from a fatal disease into a chronic, manageable condition for many people. Innovations in treatment and access are at the core of this progress.
The International AIDS Society Towards a Cure Working Group lays out its scientific strategy to achieve a cure for HIV.
Sok and Burton highlight recent developments in the discovery and application of antibodies able to neutralize diverse isolates of HIV, known as ‘broadly neutralizing antibodies’.
Significant strides have been made in the global fight against HIV and AIDS. And yet, HIV remains one of the greatest global health challenges of our time.
In this Opinion article, the authors provide an overview of the recent work that has been carried out investigating broadly neutralizing HIV-1 antibodies and their thoughts on the future prospects of the antibody-based prevention of HIV-1 infection.
Innate effector mechanisms contribute to the control of viremia and modulate the quality of the adaptive immune response to HIV-1. Altfeld and Gale discuss the concerted actions of PRR signaling, innate immune cells and innate-adaptive crosstalk that direct the outcome of HIV-1 infection.
Understanding the success and failure of the HIV-specific cellular immune response has implications for immunotherapies and vaccines for HIV-1. Migueles and Connors discuss the mechanisms that are most likely responsible for durable and potent immunologic control of HIV-1 by the cellular immune response.
Antibody responses to the HIV-1 envelope glycoproteins can be classified into three groups. Burton and Mascola discuss how recent insight into the structure and immunology of non-neutralizing, strain-specific and broadly neutralizing antibodies guide HIV-1 vaccine design and therapeutic strategies.
An effect of host genetic variation on susceptibility to HIV-1 was identified early in the pandemic. McLaren and Carrington discuss the extent to which additional polymorphisms influence HIV-1 disease progression and how analysis of data sets may discover novel gene variants that affect the outcome of HIV-1.
The isolation of HIV-1 was a fundamental step for understanding HIV and the disease it causes. Here, Françoise Barré-Sinoussi, Anna Laura Ross and Jean-François Delfraissy look back on three decades of research that have changed the lives of people infected with HIV and have inspired hope for a cure.
Viral reservoirs pose a major challenge in the efforts towards curing HIV. Here, Churchill, Deeks, Margolis, Siliciano and Swanstrom discuss the cells and tissues that constitute the viral reservoir, how best to measure it and how to target this source of persistent infection.
Entry into the nucleus and integration into the host cell are key steps during HIV-1 infection. In this Review, Lusic and Siliciano discuss viral and host factors that influence HIV-1 integration and how it can be targeted therapeutically.
In this Review, Campbell and Hope describe the interactions between the HIV-1 capsid core and several cellular factors that enable efficient HIV-1 genome replication, timely core disassembly, nuclear import and viral integration into the genome of the target cell.
In this article, Eric Freed reviews recent progress in elucidating the steps involved in HIV-1 assembly, release and maturation, highlighting how these events are orchestrated by the viral Gag precursor protein and how this information is being used to develop novel anti-HIV-1 therapeutics.
HIV-1 infection typically results from the transmission of a single viral variant, the transmitted/founder (T/F) virus. In this Review, Joseph and colleagues discuss how studying these T/F viruses contributes to a better understanding of HIV-1 transmission and affects prevention strategies.
In this Opinion article, Dan Barouch and Louis Picker discuss recent data regarding the clinical development of novel serotype adenovirus and cytomegalovirus vaccine vectors for use in HIV-1 vaccines.