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BASIC SCIENCE PROJECT PUBLICATIONS

Michael Palm HIV Basic Science, Vaccines, and Cure Project Blog
This blog is written by Richard Jefferys, Coordinator of the Michael Palm Basic Science, Vaccines, and Cure Project at Treatment Action Group. The aim of the blog is to provide an opinionated—but hopefully informative—take on research in these areas, with a particular focus on the scientific literature and relevant conference presentations.

2015 Pipeline Report
July 17, 2015 – HIV, HCV, and TB Drugs, Diagnostics, Vaccines, Preventive Technologies, Research Toward a Cure, and Immune-Based and Gene Therapies in Development

HIV Cure Research Fact Sheet
December 2014 – Combination antiretroviral therapy (ART) is a highly effective treatment for HIV infection, preventing progression of the disease in the vast majority of recipients. When ART is accessible and started early in the course of infection, the lifespan of HIV-positive people is typically very close to that of comparable HIV-negative people. But ART can have toxicities, is often costly, and requires strict daily pill taking that can lessen quality of life. Because of the limitations of ART, a cure for HIV infection remains a vital goal for research.

2014 Pipeline Report
July 20, 2014 – HIV, HCV, and TB Drugs, Diagnostics, Vaccines, Preventive Technologies, Research Toward a Cure, and Immune-Based and Gene Therapies in Development.
Read the Basic Science chapters online:


Clinical Trials for People with Suboptimal Immune Reconstitution Despite HIV Suppression
Updated February 10, 2014 – Some individuals who initiate antiretroviral therapy (ART) experience limited recovery of CD4 T-cell numbers despite suppression of HIV viral load to undetectable levels. The most common risk factors for this type of discordant response to ART are low CD4 T-cell count at the time of starting and older age. Individuals in this situation still experience a benefit from ART in terms of a greatly reduced risk of opportunistic infections, illness and death, but their risk of these outcomes is higher than among people with greater CD4 T-cell gains. For this reason, a number of clinical trials are investigating approaches that might boost CD4 T-cell recovery in individuals whose CD4 T-cell counts remain relatively low despite viral load suppression. The purpose of this page is to provide a resource listing of these clinical trials, which will be updated on an ongoing basis.

TAGline 2013 Fall – Over the past several years, there has been a welcome invigoration of the research effort to cure HIV infection. The mainstream media has picked up on this development, and stories about putative or possible cures are appearing more frequently than in the past. Contrary to the impression conveyed by some of these stories, a cure is not likely to announce itself by leaping from a scientist’s test tube waving a flag of victory. To prove their worth, potential curative strategies—whether based on a single approach or a combination—will need to be evaluated in human trials.
 

2013 Pipeline Report
HIV, HCV, and TB
Drugs, Diagnostics, Vaccines, Preventive Technologies, Research Toward a Cure, and Immune-Based and Gene Therapies in Development
June 30, 2013 – Visit www.PipelineReport.org to:

  • Read the report online
  • Download individual chapters as PDFs
  • Browse for specific information by agent
June 3, 2013 – Little more than a decade ago, it was almost inconceivable that the issue of aging with HIV infection would emerge as an important concern. But it has now become clear that combination antiretroviral therapy (ART) can suppress virus replication for many years—likely for life—in most people who can access the drugs, and the opportunistic infections that were once the primary causes of illness have largely evanesced everywhere treatment is available. Morbidity and mortality from HIV infection has plummeted, and the survival of HIV-positive individuals is edging ever closer to that of comparable HIV-negative people. With the specter of AIDS having finally been chased from the near horizon, attention has turned to health problems that may lie further down the road.
 
TAGline 2013 Spring - A subset of people on antiretroviral therapy (ART) experience limited or no recovery of CD4 T-cell counts despite achieving and maintaining undetectable viral loads. Various terms have been used to describe this phenomenon, with the most common being “immunological nonresponders” (INRs). Many studies have documented that INRs face an increased risk of illness and death compared with people with more robust CD4 T-cell gains. Yet there are no approved therapies to improve immune reconstitution, and clinical trials of potential candidates remain few and far between.
 
TAGline 2012 Fall – At the recent International AIDS Conference in Washington, D.C. (AIDS 2012), the research effort to develop a cure for HIV infection attained a higher profile than it ever has in the past. At a press conference on July 19, the International AIDS Society (IAS) officially launched its Global Strategy “Towards an HIV Cure,” in conjunction with a two-day symposium that immediately preceded the main conference. The IAS strategy is chaired by Françoise Barré-Sinoussi and Steven Deeks and involves a multiplicity of stakeholders, including TAG. Details are available free online in a document titled “Full Recommendations, 1st Edition, July 2012.” A shorter summary and commentary have been published in the journals Nature Reviews Immunology and Nature, respectively. In essence, the strategy is a scientific review of the obstacles to curing HIV (as they are currently perceived) and possible approaches to overcoming them. Among the goals is to enhance collaboration among stakeholders and attract new sources of funding to support cure research.
 
HIV, Hepatitis C Virus (HCV), and Tuberculosis (TB) Drugs, Diagnostics, Vaccines, and Preventive Technologies in Development
July 22, 2012 – Visit our new website www.PipelineReport.org to:
  • Read the report online
  • Download individual chapters as PDFs
  • Browse for specific information by agent

TAGline 2012 Spring – In the earliest days after the discovery of HIV in the mid-1980s, uncertainty reigned regarding how the immune system responded to the virus. Initially, it was thought that the time between HIV infection and the development of severe immuno- deficiency and disease represented a period of viral inactivity or latency. In this context, it seemed logical to propose that perhaps vaccination could be used to bolster immune response to HIV and thus delay or even prevent the development of illness. But the first efforts toward this goal quickly mired therapeutic vaccine research in controversy, casting an initial pall across the field that was compounded by the failure of any candidate to show significant efficacy. Additionally, the scientific rationale for the approach evolved as more was learned about the pathogenesis of HIV infection and the types of immune responses that may be effective—and ineffective—at controlling the virus. After a period in which enthusiasm regarding the prospects for therapeutic vaccines waned, the recent resurgence in interest in research aiming to cure HIV infection has offered new reasons to pursue their development.

Report and Commentary from the Fifth International Workshop on HIV Persistence During Therapy
February 2012 – Inaugurated in 2003, the biannual International Workshop on HIV Persistence during Therapy (aka “the persistence workshop”) is the brainchild of researcher Alain Lafeuillade. The meeting presaged the recent explosion of interest in pursuing a cure for HIV infection, a pursuit many had considered quixotic until the case of Timothy Brown came to light in 2008. As has been extensively documented, Brown’s apparent cure resulted from a debilitating odyssey of treatments required for the grim diagnosis of acute myelogenous leukemia, enhanced with a mix of insight and good fortune on the part of his doctor Gero Hütter, who was able to provide a stem cell transplant from a donor lacking the major HIV co-receptor CCR5. The sea change wrought by this fortuitous “proof of concept” was much in evidence at the 2011 persistence workshop this past December; the tentative forays into basic science that were once emblematic of the field are now mixed together with more ambitious plans for advancing ideas into the clinic. Perhaps most strikingly, two large pharmaceutical companies—Gilead and Janssen/Tibotec—described their use of industrial scale screening to search for compounds that are active against latent HIV. This represents an unprecedented expansion of efforts once confined to under-resourced academic labs.

HIV Cure-Related Research Workshop Report
October 2011 – The meeting, sponsored by the AIDS Policy Project, amfAR, Project Inform, and TAG, featured an overview of HIV latency, persistence, and eradication research; lessons from past clinical trials; a review of current or impending trials; and a full discussion of issues including trial design, appropriate markers and endpoints, and development of better assays. Participants heard a presentation on the ethics of clinical trials and discussed the federal regulatory process and how best to engage the several branches of the U.S. Food and Drug Administration (FDA) in a coordinated and collaborative way to work together to ensure that cure-related clinical trials proceed expeditiously, ethically, and safely.

Cure Research Momentum Accelerates
TAGline 2011 Fall – The research effort to discover a cure for HIV infection continues to gain momentum, with several important developments having occurred since the last issue of TAGline.

2011 Pipeline Report - Second Edition
September 2011 – HIV, Hepatitis C Virus (HCV), and Tuberculosis Drugs, Diagnostics, Vaccines, and Preventive Technologies in Development

Tallying the TB vaccines in Clinical Trials
July 2011 – The relatively small community of researchers, policymakers and advocates involved in the search for an effective TB vaccine met in Tallinn, Estonia in September, 2010 to assess the state of the field and discuss the path forward. The sense of urgency driving this research has recently been underscored in the new Global Plan to Stop TB 2011-2015, which explicitly states that without a new vaccine effective against all forms of TB, the goal of eliminating TB as a public health threat by 2050 will not be met. As described by Claire Wingfield in TAG’s annual pipeline report, TB vaccine development has long languished despite the desperate global need, but there are now encouraging signs of progress. On the second day of the Global TB Vaccines Forum, researchers offered summaries of where their candidates stand on the developmental pathway.

Vaccine Breakthrough Comes with Caveats
TAGline 2011 Summer - One of the main sources of pessimism about prospects for an effective HIV vaccine has been the generally poor results obtained in animal models. To date, only a live attenuated SIV (simian immunodefiency virus) vaccine has demonstrated significant efficacy against these challenge viruses, and this approach is too dangerous to be adapted for use in humans.

Clinical Trials Will Play a Vital Role in Charting the Path to an HIV Cure
TAGline 2011 Summer –To build the knowledge necessary to develop a safe and broadly accessible curative therapy, clinical trials of approaches that may be able to deplete HIV from the body or contribute to drug-free control of the virus are being launched.

Microbicide Field Wrestles with the Implications of Success—An Update
TAGline 2011 Winter – On October 25, 2010, the nonprofit microbicide research organization CONRAD announced that the U.S. Food and Drug Administration (FDA) would consider the Vaginal and Oral Interventions to Control the Epidemic (VOICE) trial as a confirmatory trial to the CAPRISA 004 results.

Reinvigorating the Search for a Cure
TAGline 2010 Fall – The International AIDS Society (IAS) held a workshop titled “Towards a Cure: HIV Reservoirs and Strategies to Control Them.” The workshop was a high-profile illustration of the reinvigoration of the research effort toward curing HIV infection.

Microbicide Field Wrestles With the Implications of Success
TAGline 2010 Fall – In July of this year, the stubborn persistence and commitment of microbicide researchers, advocates, and trial participants was finally rewarded with positive results from a South African trial of the gel form of the antretroviral drug tenofovir (trade name Viread).

2010 Pipeline Report – Second Edition
HIV, Tuberculosis, and Viral Hepatitis: Drugs, Diagnostics, Vaccines, Immune-Based Therapies, and Preventive Technologies in Development
September 2010 – This year TAG collaborated with HIV i-Base UK. Simon Collins contributed an in-depth analysis of the Antiretroviral Pipeline and Polly Clayden wrote new chapters for the report on Pediatric Antiretrovirals and HIV diagnostics. The second edition includes information from the XVIII International IAS Conference in Vienna, Austria, July 2010.

Letter to Dr. Fauci to Support HIV and Aging Research
September 20, 2010 – The many complications and comorbidities faced by the aging population of HIV positive people in the United States constitute a rapidly growing medical crisis that has been woefully neglected by U.S. research efforts. According to the Centers for Disease Control, more than half of all HIV-positive Americans will be over the age of 50 by or before the year 2015. Although increasing evidence points to an earlier onset of age related conditions in people living with HIV little is known about pathogenesis, or proper methods to screen for, prevent and manage these conditions, or anticipate the infrastructure needed to deliver care and treatment for people suffering from these conditions.

Inflammatory Debate Over When to Start
TAGline 2010 Summer – Ever since the first anti-HIV drug was approved for prescription, there has been debate and controversy regarding when an HIV-positive person should start antiretroviral therapy (ART). For hundreds of thousands of HIV-positive people diagnosed at higher CD4 counts, this life-altering treatment decision has been fraught with uncertainty due to lack of the most reliable, rigorous evidence -- that derived from well-designed, controlled, randomized clinical trials.

NIAID Workshop: Elimination of HIV Reservoirs
TAGline 2010 Winter – On Friday, January 15, the National Institutes of Allergy & Infectious Diseases (NIAID) sponsored a scientific workshop entitled “The Next Challenge: Elimination of HIV Reservoirs.” The event took place during the Keystone conference on HIV pathogenesis in Santa Fe, New Mexico. The focus of the agenda was on curing HIV infection, a goal once thought far-fetched but recently made to seem more attainable by a case of apparent HIV eradication, described at the workshop by Jeffrey Laurence in a talk entitled: “Proving the Concept: The First Well-Documented Functional, and Probably Complete, Case of HIV Eradication.”

2009 Pipeline Report
HIV, Tuberculosis, and Viral Hepatitis: Drugs, Diagnostics, Vaccines, and Microbicides in Development

July 2009 – TAG’s annual Pipeline Report surveys the developments in medicines and diagnostics most likely to improve the lives of people living with HIV, viral hepatitis, and tuberculosis within the next few years. But in spotlighting what is in the pipeline, the report also identifies critical gaps where research is falling short of the need for better tools to manage these diseases.

Workshop Report: Studying the Impact of Genetic Variation on the Host Response to HIV
July 10, 2009 – On January 8, the Office of AIDS Research convened a two-day workshop to discuss genome-wide association scan (GWAS) studies in HIV infection. GWAS involve studying known variations in the human genetic code (called single nucleotide polymorphisms or SNPs) to find out if these variants impact an outcome of interest, such as the rate of disease progression in HIV-infected individuals. The overall goal of the workshop was to prioritize which facets of HIV infection should be investigated using the GWAS approach, as in addition to evaluating outcomes involving disease progression there are many other possibilities, such as looking for associations with resistance to HIV infection among individuals who remain seronegative despite repeated exposures to the virus. The workshop also discussed key issues related to the conduct of GWAS studies, such as the availability of appropriate cohorts and control groups, and the question of whether potential cohorts have appropriate samples and informed consent.

HIV Vaccine Trial Results: Efficacy and Uncertainty
TAGline 2009 Novermber – First Signal of Vaccine-Mediated Protection Against HIV Infection is Both Celebrated and Questioned.

Letter to NIAID Director Anthony Fauci Opposing the HVTN 505 Vaccine Trial
April 7, 2009 - TAG has previously expressed opposition to the PAVE100A vaccine trial involving the Vaccine Research Center’s DNA and Ad5 candidate(i). With the recent presentation by Dan Barouch of new macaque challenge data involving a DNA/adenovirus prime-boost regimen at the 2009 Keystone meeting(ii), we now must vociferously oppose the proposed descendant of PAVE100A, the HVTN 505 trial.

TAG to NIAID: Recommendations to Stimulate Research on HIV Persistence
TAGline 2009 February - Treatment Action Group’s response to the National Institute of Immunology and Infectious Diseases (NIAID) request for comments on the development of a research funding opportunity on HIV latency and persistence.

The Shrinking of PAVE100: Large-Scale Vaccine Trial Nixed
TAGline 2008 Summer – NIAID's announcement that it would not support the 2,400-person PAVE100 trial left open the possibility of an even smaller trial, solely evaluating the impact on postinfection viral load set point.

2008 Pipeline Report
HIV, Tuberculosis, Hepatitis B, and Hepatitis C: Drugs, Diagnostics, Vaccines, and Microbicides in Development
July 2008 – Treatment Action Group’s annual pipeline report is a review of medical technologies that stand a good chance of benefiting people with HIV within the next few years. It also covers those that may take longer to develop but represent innovation within the field.

TAG's Response to NIAID "Request for Information" on Priorities in Basic HIV Vaccine Research
June 4, 2008 – It is of great concern to TAG that many of our recommendations echo many of those made by TAG eight years ago, which in turn echoed those of the Levine Report almost four years prior to that. Given this observation, we hope that NIAID can understand why we greet this undoubtedly well-intentioned RFI with a certain amount of skepticism and cynicism.

PAVE Gives Pause: Position Statement on the Proposed PAVE100A Vaccine Trial
May 30, 2008 – The failure of Merck's adenovirus serotype 5 (Ad5)-based HIV vaccine to protect against infection or reduce post-infection viral load, combined with the evidence of potentially enhanced susceptibility to HIV acquisition among a subset of trial participants, has inevitably cast a cloud across the Ad5 candidate slated for use in the proposed PAVE100A Phase IIb efficacy trial. TAG recognizes and appreciates the work and commitment of researchers at NIH's Vaccine Research Center (VRC) who have developed the DNA and Ad5 HIV vaccine constructs, and their colleagues involved in PAVE100 who have collaborated in an effort to redesign the trial to ensure safety in the light of the data that emerged from the Merck vaccine trial (STEP/HVTN 502, hereafter referred to as STEP).

STEP Vaccine Trial Halted
New York, NY, September 24, 2007 – The Treatment Action Group (TAG) today issued the following statement about the discontinuation of the STEP study, an HIV vaccine efficacy trial conducted by Merck Research Laboratories and the HIV Vaccine Trials Network (HVTN)

2007 Pipeline Report: Experimental Treatments and Preventive Therapies for HIV, Hepatitis C, and Tuberculosis
July 2007 – The Pipeline Report is the Treatment Action Group’s annual review of experimental technologies that have the potential to solve critical unmet medical needs surrounding HIV infection and AIDS.

Notes from NIAID Workshop on Immune Activation
May 2007 – From November 27-29, 2006, the National Institutes for Allergy and Infectious Diseases (NIAID) held their second workshop on immune activation and HIV pathogenesis, attracting an impressive roster of investigators to the backwaters of Bethesda. The meeting was chaired by Cliff Lane from NIAID and Yves Levy from the ANRS in France, and organized by a committee including Zvi Grossman and Irini Sereti from NIAID, Mike Lederman from Case Western Reserve University and Guido Silvestri from Emory University.

Can Exhausted T Cells Be Revived? The PD-1 Palaver
May 2007 – Anyone who follows HIV research is familiar with how a new potential therapeutic target can suddenly appear in the scientific literature, generating much excitement and hype, only to subsequently shuffle quietly from the scene having failed to deliver on its supposed promise. At first blush, the ominously named receptor called “program death-1” (PD-1) seems like it might fit the profile of such targets-de-jour. The role of PD-1 in shutting down virus-specific T cell responses was first described in a Nature paper in January of 2006, by researchers using a mouse model of chronic viral infection. Over the summer, three separate papers (with a commentary accompanying each) trumpeted data describing the high levels of expression of PD-1 on HIV-specific T cells, suggesting that targeting this receptor might be a way of boosting antiretroviral immunity in people with HIV. It’s legitimate to wonder if the PD-1 palaver is justified, or if the hype has leapt ahead of the science.

Palm Project Interview Series: Steven Deeks
February 8, 2007 - Steven G. Deeks, MD is a highly respected clinician and scientist whose work encompasses both clinical care and research into the pathogenesis of HIV infection. Deeks became widely known among treatment activists for his work on individuals with multi-drug resistant HIV who remain clinically and immunologically healthy despite the fact that their antiretroviral therapies fail to fully control HIV replication. Deeks is now involved in many different projects and collaborations but maintains a particular focus on translational research, which aims to translate advances in basic science into clinically relevant therapies and treatment strategies.

Palm Project Interview Series: Douglas Nixon
February 8, 2007 – Douglas Nixon, M.D., Ph.D. is a renowned cellular immunologist who has been working in the HIV/AIDS field since the late 1980s. Nixon's first published HIV research paper, which came out in Nature in 1988, involved identifying CD8 T cell responses against the virus. At that time, Nixon was working with Andrew McMichael's immunology group at Oxford in the UK but he subsequently moved to the US, first working at the Aaron Diamond AIDS Research Center before establishing his laboratory at the Gladstone Institute, University of California at San Francisco (UCSF).

Palm Project Interview Series: Barbara Shacklett
February 8, 2007 – Barbara Shacklett began studying HIV in the late 1980s and has become a highly respected expert in the under-studied area of mucosal immunity. Shacklett’s laboratory at UC Davis has recently published novel findings regarding the role of mucosal immune responses in individuals who control HIV replication in the absence of therapy. Barbara Shacklett generously took time out to discuss her research with TAG’s BSVP coordinator, Richard Jefferys.

For older publications, please go to the publications page.