Human Immunodeficiency Virus Research Research Articles

Recent Advances in Humanized Mice: Accelerating the Development of an HIV Vaccine

Recent advances in the development of humanized mice hold great promise to advance our understanding of protective immunity to human immunodeficiency virus (HIV) infection and to aid in the design of an effective HIV vaccine. This supplement of the Journal of Infectious Diseases summarizes work in the humanized mouse model presented at an HIV Humanized Mouse workshop in Boston, Massachusetts, in November 2012, including recent advances in the development of humanized mice, the trafficking of human immune cells following mucosal HIV transmission, the role of immune activation and Toll-like receptor agonists in the control of HIV, the induction and efficacy of HIV-specific cellular and humoral immune responses, and the preclinical modeling of novel anti-HIV therapeutics. Many gaps remain in our understanding of how to design an effective HIV vaccine and novel therapeutics to eliminate the viral reservoir. Promising early results from studies in humanized mice suggest great potential and enthusiasm for this model to accelerate these critical areas of HIV research.

A multinational study of self‐compassion and human immunodeficiency virus‐related anxiety

This study represents an initial effort at examining the association between the construct of self-compassion and human immunodeficiency virus (HIV)-related anxiety in a multinational population with HIV disease. Previous studies have found that self-compassion is a powerful predictor of mental health, demonstrating positive and consistent linkages with various measures of affect, psychopathology and well-being, including anxiety. Cross-sectional data from a multinational study conducted by the members of the International Nursing Network for HIV Research (n = 1986) were used. The diverse sample included participants from Canada, China, Namibia, the United States of America and the territory of Puerto Rico. Study measures included the anxiety subscale of the Symptom Checklist-90 instrument, the Brief Version Self-Compassion Inventory and a single item on anxiety from the Revised Sign and Symptom Checklist. Study findings show that anxiety was significantly and inversely related to self-compassion across participants in all countries. We examined gender differences in self-compassion and anxiety, controlling for country. Levels of anxiety remained significantly and inversely related to self-compassion for both males (P = 0.000) and females (P = 0.000). Levels of self-compassion and anxiety varied across countries. Self-compassion is a robust construct with cross-cultural relevance. A culturally based brief treatment approach aimed at increasing self-compassion may lend itself to the development of a cost effective adjunct treatment in HIV disease, including the management of anxiety symptoms.

Restrictions to HIV-1 replication in resting CD4+ T lymphocytes

CD4+ T lymphocytes represent the main target cell population of human immunodeficiency virus (HIV). In an activated state, CD4+ T cells residing in lymphoid organs are a major reservoir of ongoing HIV-1 replication in infected individuals. In contrast, resting CD4+ T cells are highly resistant to productive HIV-1 infection, yet are massively depleted during disease progression and pose a substantial latent reservoir for the virus in vivo. Barriers preventing replication HIV-1 in resting CD4+ T cells include a rigid layer of cortical actin and, early after HIV-1 entry, a block that limits reverse transcription of incoming viral RNA genomes. Defining the molecular bases of these restrictions has remained one of the central open questions in HIV research. Recent advances unraveled mechanisms by which HIV-1 bypasses the entry block and established the host cell restriction factor SAMHD1 as a central determinant of the cellular restriction to HIV-1 reverse transcription in resting CD4+ T cells. Our current molecular and pathophysiological understanding of the multi-faceted interactions of HIV-1 with resting CD4+ T lymphocytes will be discussed.

Multilabel classification for exploiting cross-resistance information in HIV-1 drug resistance prediction

Antiretroviral treatment regimens can sufficiently suppress viral replication in human immunodeficiency virus (HIV)-infected patients and prevent the progression of the disease. However, one of the factors contributing to the progression of the disease despite ongoing antiretroviral treatment is the emergence of drug resistance. The high mutation rate of HIV can lead to a fast adaptation of the virus under drug pressure, thus to failure of antiretroviral treatment due to the evolution of drug-resistant variants. Moreover, cross-resistance phenomena have been frequently found in HIV-1, leading to resistance not only against a drug from the current treatment, but also to other not yet applied drugs. Automatic classification and prediction of drug resistance is increasingly important in HIV research as well as in clinical settings, and to this end, machine learning techniques have been widely applied. Nevertheless, cross-resistance information was not taken explicitly into account, yet. In our study, we demonstrated the use of cross-resistance information to predict drug resistance in HIV-1. We tested a set of more than 600 reverse transcriptase sequences and corresponding resistance information for six nucleoside analogues. Based on multilabel classification models and cross-resistance information, we were able to significantly improve overall prediction accuracy for all drugs, compared with single binary classifiers without any additional information. Moreover, we identified drug-specific patterns within the reverse transcriptase sequences that can be used to determine an optimal order of the classifiers within the classifier chains. These patterns are in good agreement with known resistance mutations and support the use of cross-resistance information in such prediction models. dominik.heider@uni-due.de Supplementary data are available at Bioinformatics online.

Immune restoration after antiretroviral therapy: the pitfalls of hasty or incomplete repairs.

Antiretroviral therapy (ART) is a life-saving intervention in human immunodeficiency virus (HIV) infection. Immune restoration after ART dramatically reduces the incidence and severity of opportunistic diseases and death. On some occasions, immune restoration may be erratic, leading to acute inflammatory responses (known as immune reconstitution inflammatory syndrome) shortly after ART initiation, or incomplete, with residual inflammation despite chronic treatment, leading to non-infectious morbidity and mortality. We propose that ART may not always restore the perfect balance of innate and adaptive immunity in strategic milieus, predisposing HIV-infected persons to complications of acute or chronic inflammation. The best current strategy for fully successful immune restoration is early antiretroviral therapy, which can prevent acquired immunodeficiency syndrome (AIDS)-associated events, restrict cell subset imbalances and dysfunction, while preserving structural integrity of lymphoid tissues. Future HIV research should capitalize on innovative techniques and move beyond the static study of T-cell subsets in peripheral blood or isolated tissues. Improved targeted therapeutic strategies could stem from a better understanding of how HIV perturbs the environmental niches and the mobility and trafficking of cells that affect the dynamic cell-to-cell interactions and determine the outcome of innate and adaptive immune responses.

Restrictions to HIV-1 replication in resting CD4+ T lymphocytes

CD4+ T lymphocytes represent the main target cell population of human immunodeficiency virus (HIV). In an activated state, CD4+ T cells residing in lymphoid organs are a major reservoir of ongoing HIV-1 replication in infected individuals. In contrast, resting CD4+ T cells are highly resistant to productive HIV-1 infection, yet are massively depleted during disease progression and represent a substantial latent reservoir for the virus in vivo. Barriers preventing replication of HIV-1 in resting CD4+ T cells include a rigid layer of cortical actin and, early after HIV-1 entry, a block that limits reverse transcription of incoming viral RNA genomes. Defining the molecular bases of these restrictions has remained one of the central open questions in HIV research. Recent advances unraveled mechanisms by which HIV-1 bypasses the entry block and established the host cell restriction factor SAMHD1, a deoxynucleoside triphosphate triphosphohydrolase, as a central determinant of the cellular restriction to HIV-1 reverse transcription in resting CD4+ T cells. This review summarizes our current molecular and pathophysiological understanding of the multi-faceted interactions of HIV-1 with resting CD4+ T lymphocytes.

Retention in Care and Health Outcomes of Transgender Persons Living With HIV

To the Editor—Little is known about the health outcomes of transgender persons living with human immunodeficiency virus (HIV), or PLWH [1]. Discrimination and social isolation may decrease engagement in care, while concerns about adverse interactions between antiretroviral therapy (ART) and hormone therapy may reduce ART receipt and medication adherence in this population [2–4]. We examined whether retention in care, use of ART, and HIV suppression differed between transgender and nontransgender PLWH. We performed a retrospective cohort study of HIV-infected adults (≥18 years) initiating care at 13 HIV clinics in the HIV Research Network (HIVRN) between 2001 and 2011. Clinics are located in the Northeastern (n = 6), Midwestern (n = 1), Southern (n = 3), and Western (n = 3) regions of the United States. Data from patients’ medical records were abstracted, quality assured, and assembled into a uniform database [5]. All clinics had institutional review board approval. Gender was self-identified and categorized as nontransgender men, nontransgender women, and transgender. Dichotomous outcomes were retention in care (≥2 primary HIV visits ≥90 days apart), use of ART, and HIV suppression (median HIV RNA <400 copies/mL) in each calendar year. Multivariate logistic regression, adjusted for age, race/ethnicity, HIV risk, insurance, CD4 count, calendar year, and site of care, examined associations between gender and each outcome. Because patients contributed data in multiple years, we used generalized estimating equations, clustered on patient, with exchangeable working correlation and robust standard errors to deal with the correlation across years for individual patients. Two-sided testing was used, with a P value of <.05 considered significant. A total of 36 845 PLWH, of whom 285 self-identified as transgender, received care at HIVRN clinics between 2001 and 2011 (Table ​(Table1).1). Transgender patients were more likely to be young and Hispanic, and to be men who have sex with men as their HIV risk behavior compared to nontransgender PLWH. Transgender persons were retained in care, received ART, and achieved HIV suppression in 80%, 76%, and 68% of patient-years, respectively. Corresponding results were 81%, 77%, and 69% for nontransgender men, and 81%, 73%, and 63% for nontransgender women. Table 1. Demographics and Outcomes of Study Sample by Gender Identity In multivariate analyses, retention in care was similar for nontransgender men compared with transgender PLWH (adjusted odds ratio [AOR], 1.15; 95% confidence interval [CI], .94–1.42), but was higher for nontransgender women (AOR, 1.32; 95% CI, 1.08–1.64). Use of ART was similar for nontransgender men (AOR, 0.98; 95% CI, .78–1.23) and nontransgender women (AOR, 0.81; 95% CI, .64–1.02) compared to transgender PLWH. Likewise, nontransgender men (AOR, 1.11; 95% CI, .89–1.39) and nontransgender women (AOR, 1.13; 95% CI, .90–1.42) had similar rates of HIV suppression as transgender PLWH. Compared to prior studies, which document low ART coverage and suboptimal adherence to HIV treatment in transgender PLWH, these results reflect improvements in health equity for HIV-infected transgender individuals [3, 6]. Advances in HIV therapy, including new antiretroviral drugs with simplified dosing and greater tolerability, and treatment guidelines may explain these findings [7, 8]. This study is limited by its retrospective nature, small sample of transgender individuals, and focus on patients engaged in care. While our findings may not generalize to all transgender PLWH, they suggest that when engaged in care transgender PLWH have similar outcomes as nontransgender men and women.

Challenges of cross-cultural research: Lessons from a U.S.-Asia HIV collaboration

Many Asian countries have scaled up their research to combat human immunodeficiency virus (HIV). HIV experts from the West have teamed up with these countries to assist in designing research protocols and providing necessary training. In this paper, we document the formation and maintenance of international and interdisciplinary HIV research collaboration among cross-disciplinary researchers working in the United States, Taiwan, and China. We conducted international social-behavioral HIV studies in several major metropolitan areas in Asia. Culturally sensitive issues that could be attributed to social and disciplinary differences have emerged throughout the collaboration process, including questions of who should be the research leader, where should resources be allocated, how should tasks be shared, which topics are valuable for investigation, and what survey questions are allowable. There is now a window of opportunity for greater international and interdisciplinary collaboration; however, for such collaboration to flourish, team dynamics in international research collaboration should be carefully identified and managed before studies are begun.

Inguinal Lymph Node and Rectal Mucosal Biopsies for HIV Research Protocols in a Developing Nation: Patient Outcomes and Lessons Learned

Human immunodeficiency virus (HIV) can be controlled but not cured with current antiretroviral drugs due to persistence of virus in cellular and anatomic reservoir sites, including lymph nodes and gut associated lymphoid tissues. An understanding of these sites is an important step in developing a cure for HIV. Given evidence that the architecture and function of lymphatic tissues varies geographically and may impact HIV reservoir size and disease progression, collection and analysis of lymphatic tissues from geographically distinct populations is important.

Preexposure prophylaxis for adolescents and young adults at risk for HIV infection: is an ounce of prevention worth a pound of cure?

An alarming proportion of incident human immunodeficiency virus (HIV) infections worldwide occur in youth. In the United States, 69% of all new infections among youth occurred in young men who have sex with men (YMSM). Recent studies show the promise of preexposure prophylaxis (PrEP) for preventing HIV infection, but research efforts suffer from disproportionately low representation of the youth who are most at risk. Youth-focused research is critical and should include behavioral, community, and biomedical interventions to create a comprehensive HIV prevention package. The many ethical, legal, and regulatory considerations in conducting HIV research among, and in providing care services to, youth must be addressed so that those at high risk and most likely to benefit can have unfettered access to safe and effective health-promoting interventions. YMSM and minority youth are at substantial HIV risk and urgently need effective HIV prevention tools for which the short and long-term benefits and risks have been carefully considered.

Reactivation of Latent HIV-1 by Inhibition of BRD4

HIV-1 depends on many host factors for propagation. Other host factors, however, antagonize HIV-1 and may have profound effects on viral activation. Curing HIV-1 requires the reduction of latent viral reservoirs that remain in the face of antiretroviral therapy. Using orthologous genetic screens, we identified bromodomain containing 4 (BRD4) as a negative regulator of HIV-1 replication. Antagonism of BRD4, via RNA interference or with a small molecule inhibitor, JQ1, both increased proviral transcriptional elongation and alleviated HIV-1 latency in cell-line models. In multiple instances, JQ1, when used in combination with the NF-κB activators Prostratin or PHA, enhanced the invitro reactivation of latent HIV-1 in primary Tcells. These data are consistent with a model wherein BRD4 competes with the virus for HIV-1 dependency factors (HDFs) and suggests that combinatorial therapies that activate HDFs and antagonize HIV-1 competitive factors may be useful for curing HIV-1 infection.

Modeling HIV infection and therapies in humanized mice

The human immunodeficiency virus (HIV) type-1 is a human-specific virus. The lack of a widely available small-animal model has seriously hampered HIV research. In 2004, a new humanised mouse model was reported. It was based on the intrahepatic injection of human CD34+ cord blood cells into newborn, highly immunodeficient mice. These mice develop a lymphoid system of human origin and are highly susceptible to HIV infection and showed disseminated infection, persistent viraemia and characteristic helper CD4+ T-cell loss. Here, we will briefly review the various existing humanised mouse models and highlight their value to the study of HIV infection.

Changing patterns in HIV/AIDS stigma and uptake of voluntary counselling and testing services: The results of two consecutive community surveys conducted in the Western Cape, South Africa

Voluntary counselling and HIV testing (VCT) has been associated with decreased human immunodeficiency virus (HIV) risk behaviour, but in South Africa, which has the largest HIV/acquired immune deficiency syndrome (AIDS) epidemic in the world, uptake of VCT remains low. HIV/AIDS-associated stigma has been identified as a barrier to HIV testing. This study explored changes in stigma, and VCT access in a peri-urban South African community with high HIV prevalence, following education and research interventions, as well as the introduction of a wide-scale antiretroviral therapy (ART) programme. Two cross-sectional community surveys assessing HIV knowledge, attitudes and uptake of VCT services were conducted. The first survey was performed in 2004 prior to the implementation of a community-based HIV awareness and education campaign, HIV prevention research studies and the introduction of an ART programme. The second survey was performed in 2008 after a three-year education programme, the implementation of HIV-related research studies and following the scale-up of the ART programme. The same study design was used in both the 2004 and 2008 surveys: 10% of households were randomly selected and all residents aged ≥ 14 years were invited to complete a self-administered questionnaire. Overall basic knowledge of HIV/AIDS increased from 2004 to 2008 (p=0.04) and stigmatisation towards HIV-positive individuals decreased over the same time period (p<0.001). Increasing knowledge score was significantly associated with a lower stigma score (p<0.001). Decreasing stigma score was associated with knowing someone who was HIV infected (p<0.001), or who had died from HIV/AIDS (p=0.04). The proportion of participants who had undergone HIV testing increased from 2004 to 2008 (40 vs. 70%, respectively) and, in particular, VCT increased from 26 to 43%. In adjusted analysis, participants who had undergone HIV testing were more likely to have a higher HIV knowledge score (p=0.02) and a lower stigma score (p=0.09). A reduction in levels of HIV/AIDS-associated stigma was noted in a community burdened with high HIV prevalence, as was an increase in reported VCT. These findings may be the result of a number of interventions including a wide-spread and targeted education campaign, and the “normalisation” of HIV through the availability of ART. Given the role of HIV/AIDS-associated stigma in influencing choices to access HIV testing, and the benefits associated with HIV testing, interventions to reduce stigma in communities affected by this disease should be encouraged.

Immunity to Human Immunodeficiency Virus (HIV) Infection

Immunity to Human Immunodeficiency Virus (HIV) Infection

True story about HIV: theory of viral sequestration and reserve infection

Radical cure of infectious disease lies in the principle that the contagion is eliminated and its propagation within the body is stopped. By understanding the true mechanisms of human immunodeficiency virus (HIV) infection, effective cure is possible. Vertical research in HIV/acquired immunodeficiency syndrome (AIDS) has produced much advanced data about its nature without discovering a true cure, implying that the infective concept may have been missed. Overall, current interventions have had a significant impact on the pandemic, but they definitely have not achieved a cure. Given that modern research has already provided almost all significant data on HIV/AIDS, this inevitably means that understanding of the HIV and AIDS mechanism in the human body and population is less than sufficient. This paper advances a new concept using the available scientific data in an attempt to open a new frontier in HIV research.

De novo assembly of Euphorbia fischeriana root transcriptome identifies prostratin pathway related genes

BackgroundEuphorbia fischeriana is an important medicinal plant found in Northeast China. The plant roots contain many medicinal compounds including 12-deoxyphorbol-13-acetate, commonly known as prostratin that is a phorbol ester from the tigliane diterpene series. Prostratin is a protein kinase C activator and is effective in the treatment of Human Immunodeficiency Virus (HIV) by acting as a latent HIV activator. Latent HIV is currently the biggest limitation for viral eradication. The aim of this study was to sequence, assemble and annotate the E. fischeriana transcriptome to better understand the potential biochemical pathways leading to the synthesis of prostratin and other related diterpene compounds.ResultsIn this study we conducted a high throughput RNA-seq approach to sequence the root transcriptome of E. fischeriana. We assembled 18,180 transcripts, of these the majority encoded protein-coding genes and only 17 transcripts corresponded to known RNA genes. Interestingly, we identified 5,956 protein-coding transcripts with high similarity (> = 75%) to Ricinus communis, a close relative to E. fischeriana. We also evaluated the conservation of E. fischeriana genes against EST datasets from the Euphorbeacea family, which included R. communis, Hevea brasiliensis and Euphorbia esula. We identified a core set of 1,145 gene clusters conserved in all four species and 1,487 E. fischeriana paralogous genes. Furthermore, we screened E. fischeriana transcripts against an in-house reference database for genes implicated in the biosynthesis of upstream precursors to prostratin. This identified 24 and 9 candidate transcripts involved in the terpenoid and diterpenoid biosyntehsis pathways, respectively. The majority of the candidate genes in these pathways presented relatively low expression levels except for 1-hydroxy-2-methyl-2-(E)-butenyl 4-diphosphate synthase (HDS) and isopentenyl diphosphate/dimethylallyl diphosphate synthase (IDS), which are required for multiple downstream pathways including synthesis of casbene, a proposed precursor to prostratin.ConclusionThe resources generated in this study provide new insights into the upstream pathways to the synthesis of prostratin and will likely facilitate functional studies aiming to produce larger quantities of this compound for HIV research and/or treatment of patients.

Determination of Molecular Structures of HIV Envelope Glycoproteins using Cryo-Electron Tomography and Automated Sub-tomogram Averaging

Since its discovery nearly 30 years ago, more than 60 million people have been infected with the human immunodeficiency virus (HIV) (www.usaid.gov). The virus infects and destroys CD4+ T-cells thereby crippling the immune system, and causing an acquired immunodeficiency syndrome (AIDS) 2. Infection begins when the HIV Envelope glycoprotein "spike" makes contact with the CD4 receptor on the surface of the CD4+ T-cell. This interaction induces a conformational change in the spike, which promotes interaction with a second cell surface co-receptor 5,9. The significance of these protein interactions in the HIV infection pathway makes them of profound importance in fundamental HIV research, and in the pursuit of an HIV vaccine.The need to better understand the molecular-scale interactions of HIV cell contact and neutralization motivated the development of a technique to determine the structures of the HIV spike interacting with cell surface receptor proteins and molecules that block infection. Using cryo-electron tomography and 3D image processing, we recently demonstrated the ability to determine such structures on the surface of native virus, at ˜20 Å resolution 9,14. This approach is not limited to resolving HIV Envelope structures, and can be extended to other viral membrane proteins and proteins reconstituted on a liposome. In this protocol, we describe how to obtain structures of HIV envelope glycoproteins starting from purified HIV virions and proceeding stepwise through preparing vitrified samples, collecting, cryo-electron microscopy data, reconstituting and processing 3D data volumes, averaging and classifying 3D protein subvolumes, and interpreting results to produce a protein model. The computational aspects of our approach were adapted into modules that can be accessed and executed remotely using the Biowulf GNU/Linux parallel processing cluster at the NIH (http://biowulf.nih.gov). This remote access, combined with low-cost computer hardware and high-speed network access, has made possible the involvement of researchers and students working from school or home.

Determination of Molecular Structures of HIV Envelope Glycoproteins using Cryo-Electron Tomography and Automated Sub-tomogram Averaging

Since its discovery nearly 30 years ago, more than 60 million people have been infected with the human immunodeficiency virus (HIV) (www.usaid.gov). The virus infects and destroys CD4+ T-cells thereby crippling the immune system, and causing an acquired immunodeficiency syndrome (AIDS) 2. Infection begins when the HIV Envelope glycoprotein "spike" makes contact with the CD4 receptor on the surface of the CD4+ T-cell. This interaction induces a conformational change in the spike, which promotes interaction with a second cell surface co-receptor 5,9. The significance of these protein interactions in the HIV infection pathway makes them of profound importance in fundamental HIV research, and in the pursuit of an HIV vaccine. The need to better understand the molecular-scale interactions of HIV cell contact and neutralization motivated the development of a technique to determine the structures of the HIV spike interacting with cell surface receptor proteins and molecules that block infection. Using cryo-electron tomography and 3D image processing, we recently demonstrated the ability to determine such structures on the surface of native virus, at ˜20 Å resolution 9,14. This approach is not limited to resolving HIV Envelope structures, and can be extended to other viral membrane proteins and proteins reconstituted on a liposome. In this protocol, we describe how to obtain structures of HIV envelope glycoproteins starting from purified HIV virions and proceeding stepwise through preparing vitrified samples, collecting, cryo-electron microscopy data, reconstituting and processing 3D data volumes, averaging and classifying 3D protein subvolumes, and interpreting results to produce a protein model. The computational aspects of our approach were adapted into modules that can be accessed and executed remotely using the Biowulf GNU/Linux parallel processing cluster at the NIH (http://biowulf.nih.gov). This remote access, combined with low-cost computer hardware and high-speed network access, has made possible the involvement of researchers and students working from school or home.

The impact of HIV research on health outcome and healthcare policy

Human immunodeficiency virus (HIV) infection and the acquired immunodeficiency syndrome (AIDS) have shown an almost unique linkage between biomedical research and improved healthcare outcomes. A transformation has been seen between 1981 when AIDS was a rapidly fatal condition, to the present dramatic survival prolongation. HIV infection is a chronic illness requiring ongoing modern therapy. Parallels and interactions between HIV research and cancer research are close. The ability of novel therapies to suppress HIV replication and restore host immunity has decreased the incidence and progression of cancers in HIV patients. The rapid application of new knowledge to patient care and health policy in HIV has key lessons for other disease areas. Patient and Public Involvement has been influential in research activity and funding. The availability of laboratory markers of disease has been central to the successful application of novel HIV therapies. Active development and management of cooperative large-scale clinical trials supported by advocacy groups was influential. HIV investigators have been at the forefront of identifying cost-effective treatments that can be widely applied. The science, clinical research and political response to the HIV epidemic offer a model generalizable to other serious diseases. Opportunities to share the experiences and lessons learned from HIV should be sought, particularly in the cancer research community.

Towards a world free from HIV and AIDS?

Approximately 30 years ago, in June 1981, it was reported from theCenter forDiseaseControl andPrevention (CDC) that five, otherwise healthy, homosexual men in California had presented with pneumonia caused by Pneumocystis jiroveci pneumonia, a rare disease seen exclusively in individualswith a severely suppressed immune system. Several reports confirmed the initial observation and lent support to the possibility that a new sexually transmitted, infectious agent was circulating within the gay community in the United States. The clinical condition was named acquired immunodeficiency syndrome (AIDS). Two years later, a research team at the Institut Pasteur under the guidance of Francoise Barre-Sinoussi and Luc Montagnier isolated human immunodeficiency virus (HIV), the causative agent of AIDS, from a lymph node biopsy of a French patient. The isolation and characterization of HIV paved the way for the design of diagnosticmethods to identify the virus in blood andbloodproducts and towards the development of novel antiretroviral treatment (ART) to control HIV replication in infected patients. For their discoveries, Barre-Sinoussi and Montagnier were awarded the Nobel Prize in Physiology and Medicine in 2008.