Collection |

HIV

Since the initial isolation of HIV more than 30 years ago, research has elucidated the viral life cycle, how HIV interacts with its host and the mechanisms of pathogenesis. Alongside these seminal discoveries, anti-retroviral drugs and additional treatment options have been developed that aim to prevent and cure HIV infection. Despite this progress, the AIDS pandemic is still ongoing; approximately 37 million people are infected with HIV worldwide, and infection remains incurable. With this collection, we hope to bring renewed attention to the latest developments in HIV research and how they are affecting efforts towards prevention, treatment and cure. 

The collection combines Reviews and Research articles recently published across several Nature journals. It also includes links to additional content, such as recent News articles and previous Special Focuses on HIV. Finally, you can find information on the Nature webinar that marks the 2015 World AIDS Day: “Eliminating HIV: bringing together prevention, treatment and cure”, featuring Steven Deeks (UCSF), Susan Buchbinder (UCSF) and Robert Siliciano (Johns Hopkins).

The content of this collection has been chosen by the editors of Nature Reviews Microbiology.

Reviews

Millions of people are infected with human immunodeficiency virus (HIV) globally. Antiretroviral therapy offers substantial benefit to those infected or at risk of infection — controlling viraemia and delaying the onset of acquired immune deficiency syndrome (AIDS). Here, the authors describe the basic and clinical research advances in this important global health issue.

Primer | | Nature Reviews Disease Primers

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.

Timeline | | Nature Reviews Microbiology

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.

Review Article | | Nature Reviews Microbiology

Combination antiretroviral therapy (cART) has revolutionized the treatment of HIV-1 infection, but the mechanistic basis of successful treatment is poorly understood. In this Opinion article, Siliciano and Laskey present a model to assess the efficacy of antiretroviral drugs and argue that this is a more accurate metric to predict the success of cART than current metrics.

Opinion | | Nature Reviews Microbiology

Recent efforts have focused on the development of therapies that could eradicate HIV-1 infection or achieve a durable remission of viraemia in the absence of antiretroviral therapy; however, targeting viral quiescence within specific cellular reservoirs so that residual infection can be cleared remains a challenge. In this Review, Margolis and colleagues explore new approaches to eradicate established HIV-1 infection.

Review Article | | Nature Reviews Microbiology

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.

Viewpoint | | Nature Reviews Microbiology

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.

Opinion | | Nature Reviews Microbiology

Although studies in 2D cell culture systems have provided great insights into the biology and pathogenesis of HIV-1 infection, such studies cannot account for many aspects of host physiology that affect HIV-1in vivo. Fackler et al. discuss the development and application of more integrative studies, including organotypic 3D culture systems, small-animal models and advanced live-cell imaging, and the impact of such studies on our understanding of the mechanisms of HIV-1 spread.

Review Article | | Nature Reviews Microbiology

Erectile dysfunction (ED) is often overlooked in men with HIV, despite its high prevalence in affected men of all ages. In this Review, Santi and colleagues discuss the aetiology and social issues associated with ED in men with HIV, and provide useful advice for the clinician treating such patients.

Review Article | | Nature Reviews Urology

HCV and HIV co-infection is associated with accelerated hepatic fibrosis progression and higher rates of liver decompensation and death compared to HCV monoinfection. However, with multiple direct acting antiviral agents in development to treat HCV, a unique opportunity exists to redefine the treatment paradigm for co-infected patients. In this Review, the authors address the epidemiology, natural history, pathogenesis and management of HIV and HCV co-infection.

Review Article | | Nature Reviews Gastroenterology & Hepatology

HIV infection is associated with renal diseases including HIV-associated nephropathy, HIV-immune-complex kidney disease, thrombotic microangiopathy and disorders associated with nephrotoxic HIV therapies. Here, the authors review the epidemiology, histopathology, mechanisms, genetic susceptibility, diagnosis and treatment of HIV-associated nephropathies and highlight remaining questions for future research.

Review Article | | Nature Reviews Nephrology

Combination antiretroviral therapy (cART) has substantially prolonged the lives of patients with HIV infection, but these individuals have an increased risk of coronary heart disease and myocardial infarction compared with uninfected individuals. In this Review, Reiss and colleagues discuss the control of both traditional and immune risk factors, and the appropriate selection of cART regimens, to reduce the risk of cardiovascular complications in patients with HIV.

Review Article | | Nature Reviews Cardiology

In this Review, Heyns et al. provide an update on the urological complications associated with HIV and AIDS in men treated during the ART era, focusing on papers published within the past decade.

Review Article | | Nature Reviews Urology

Research

In two separate papers, Massimo Pizzato and colleagues and Heinrich Göttlinger and colleagues identify previously unrecognized restriction factors for HIV-1. In the absence of the HIV-1 Nef protein, the multipass transmembrane proteins SERINC3 and SERINC5 become incorporated into assembling virions and profoundly block HIV-1 infection. The Nef protein, which is normally expressed by HIV-1, counteracts this activity by down-regulating SERINC3 and SERINC5 from the cell surface, thereby preventing their incorporation into virions. These findings identify SERINC5, and to a lesser extent SERINC3, as the agents responsible for the long-sought anti-HIV-1 activity that is overcome by Nef. This raises the possibility that SERINC5 might have potential as a basis for anti-HIV-1 therapeutics.

Article | | Nature

In two separate papers, Massimo Pizzato and colleagues and Heinrich Göttlinger and colleagues identify previously unrecognized restriction factors for HIV-1. In the absence of the HIV-1 Nef protein, the multipass transmembrane proteins SERINC3 and SERINC5 become incorporated into assembling virions and profoundly block HIV-1 infection. The Nef protein, which is normally expressed by HIV-1, counteracts this activity by down-regulating SERINC3 and SERINC5 from the cell surface, thereby preventing their incorporation into virions. These findings identify SERINC5, and to a lesser extent SERINC3, as the agents responsible for the long-sought anti-HIV-1 activity that is overcome by Nef. This raises the possibility that SERINC5 might have potential as a basis for anti-HIV-1 therapeutics.

Article | | Nature

Infection by human immunodeficiency virus type 1 (HIV-1) requires the integration of the viral genome into host DNA, and the virus is known to integrate preferentially into a subset of transcriptionally active genes. Mauro Giacca and colleagues report here that nuclear location influences target gene selection. They show that hotspots preferentially targeted by the virus are more commonly found in the outer shell of the nucleus proximal to the nuclear pore rather than centrally, implying that perhaps because of the short half-life of HIV-1 integrase, the virus interacts with the first open chromatin regions it encounters on its route into the nucleus.

Letter | | Nature

The passive administration of broadly neutralizing antibodies (bNAbs) to HIV has been effective against HIV-1 infection in humanized mice and macaque models of HIV-1 infection. It has been suggested that bNAbs, administered passively or by viral vectors, may be effective for prevention and immunotherapy in humans. The safety and efficacy of the approach had not been tested in humans previously but here Michel Nussenzweig and colleagues report the results of a phase I study of passive immunization with neutralizing antibodies directed at CD4 binding sites, and show that the treatment transiently reduces HIV viral loads in humans.

Letter | | Nature

Antiretroviral therapy does not cure HIV-1 infection: despite drug treatment, most patients still have latent reservoirs of the virus. This study of immune cells isolated from 30 HIV-1-infected patients who had been on antiretroviral therapy for at least two years and had maintained undetectable plasma HIV-1 RNA levels, shows that these viral reservoirs are dominated by viruses with cytotoxic T lymphocyte escape mutations. This finding implies that future directions in therapeutic vaccine design may need to focus on boosting broad cytotoxic T lymphocyte responses.

Letter | | Nature

Reservoirs of virus infection, impervious to antiviral drugs, are a serious obstacle to attempts to eradicate human immunodeficiency virus type 1 (HIV-1). Dan Barouch and colleagues explore the timing of the formation of these reservoirs in a monkey model. They find that antiviral treatment as early as three days after infection of macaques with simian immunodeficiency virus — prior to the onset of viraemia — fails to prevent the seeding of viral reservoirs, and the virus eventually rebounds when drug treatment is discontinued.

Letter | | Nature

This study describes a novel class of highly potent HIV-1 entry inhibitors that can be delivered with a gene-therapy vector to provide an effective alternative to conventional vaccines for HIV-1. To enter cells, HIV-1 first binds its cellular receptor CD4, then the co-receptor CCR5 or CXCR4 The new entry inhibitor consists of the immunoadhesin CD4-Ig fused to a sulfopeptide mimicking CCR5. This fusion, called eCD4-Ig, avidly binds the Env protein of HIV-1 and irreversibly inactivates it. Michael Farzan and colleagues show that this inhibitor has exceptional potency and breadth and can neutralize 100% of a diverse panel of neutralization-resistant HIV-1. When delivered to macaques using an adeno-associated virus, it can protect them from multiple challenges with virus.

Letter | | Nature

Our understanding of immature HIV — the form of the virus leaves the cell — is based on purified components assembled in vitro in a manner thought to mimic the true state. Here John Briggs and colleagues resolve the structure of the protein shell within intact heterogeneous immature HIV-1 particles. Using cryo-electron tomography and sub-tomogram averaging (averaging thousands of aligned sub-volumes containing the same structural unit), the authors determine the structure of the capsid lattice at at 8.8 Å. The structure shows that the arrangement of capsid in immature HIV-1 is very different from that seen in the mature HIV-1 capsid core, and reveals the tertiary and quaternary interactions that mediate HIV-1 assembly.

Letter | | Nature

The human protein APOBEC3G (A3G) inhibits HIV-1 replication, but the viral protein Vif counteracts by inducing A3G degradation. Here Miyakawa et al. show that the antiretroviral drug AZT restores A3G function in vitroby stimulating expression of a host protein, ASK1, which interferes with the action of Vif.

Article | Open Access | | Nature Communications

The elimination of latently infected cells is a sought after goal in the treatment of HIV-1 infections. Here the authors develop an approach to eliminate latently HIV-1 infected cells by using an immunomodulatory protein, which can activate viral gene expression in these cells and direct T lymphocytes to lyse them in vitro.

Article | Open Access | | Nature Communications