How Researchers Are Now Trying to Cure More HIV+ People

We are constantly reading headlines about the latest HIV cure. After years of being exposed to these inflamed news reports, we may get desensitized to the fact that there is actually progress being made in that field. Ever since Timothy Brown was proven to be cured, the search for a cure for HIV that is accessible worldwide has intensified. There is more funding now as different research groups compete to get there first. But we have had set backs that have taught us important lessons.

I decided to interview two leading HIV Cure research advocates on a Google hangout (webcast) to pick their brains about what has happened to people who have entered HIV cure studies. In particular, I wanted to get an update on the outcome with people who have been exposed to stem cell transfers, stem cell/CD4 cell manipulation, and those who seemed to control the virus after stopping antiretrovirals. I hope you will find this webcast as enlightening as I did!


Richard Jefferys began working in the HIV/AIDS field in 1993 at the nonprofit AIDS Treatment Data Network in New York City. Since that time he has written for the International AIDS Vaccine Initiative’s IAVI Report and, in late 2001, he joined the Treatment Action Group (TAG) where he now directs the Michael Palm Basic Science, Vaccines and Cure Project. The project covers the pathogenesis and immunology of HIV infection and advocates for the development of immune-based therapies, effective vaccines, and a cure.

Robert Reinhard serves as the Community Liaison and a Steering Committee member of the CanCURE research consortium, a Canadian national team grant to understand the role of myeloid/macrophage cells in HIV persistence and cure strategies. He is also a research associate and community team member in the University of Toronto laboratory of Mario Ostrowski developing a therapeutic HIV vaccine. Robert is a member of the International AIDS Society Towards an HIV Cure Industry Collaboration working group.


What Can We Look Forward to in HIV Cure Research? Conversation With Research Advocate Richard Jefferys

This past March, the 20th Conference on Retroviruses and Opportunistic Infections (CROI) brought an unprecedented flurry of mainstream interest in potential HIV cure strategies.’s Nelson Vergel sat down with leading HIV cure research activist Richard Jefferys for an update on current important aspects, and controversies, in HIV cure research. Jefferys, who coordinates the Basic Science Vaccines and Prevention Project at Treatment Action Group in New York City, is at the forefront not only of gathering data and information from different studies, but also of educating other activists on the new language of immune-based therapies. Read Part One of this conversation.

Part Two Here

Two More Patients Are Cured of HIV- And This Time With A Less Complex Regimen

“Both the surviving patients had been receiving prolonged antiretroviral therapy and received stem cell transplants with a reduced-intensity conditioning regimen of chemotherapy designed to eradicate the cancer and eliminate the existing bone marrow. In the case of the two patients under investigation, the conditioning regimen did not include radiotherapy and it did not eliminate the residual lymphocyte population. In contrast, the ‘Berlin patient’ received a much more aggressive regimen which eliminated existing bone marrow cells.
The transplants also differed from the ‘Berlin patient’ because they did not come from donors with genetic resistance to HIV infection (a CCR5 delta 32 mutation), so the cells were susceptible to HIV infection.”
“To date, Patient A has been off treatment for seven weeks and Patient B for 15 weeks. Neither patient has yet shown any evidence of viral replication by RNA testing or any evidence of HIV DNA in PBMCs. Week-six testing of larger blood samples from Patient B has similarly failed to detect HIV.
Neither transplant recipient showed any evidence of HIV-specific immune responses.”

New HIV Eradication Study: The Use of a Personalized ImmuneTherapy (AGS-004) with a Reservoir Activating Agent

Argos Therapeutics Announces Plans for HIV Eradication Study 

“To create AGS-004, ribonucleic acid (RNA) is isolated from HIV particles obtained from patients, and dendritic cells are generated from a single leukapheresis procedure. Selected RNAs are then used to “program” the dendritic cells with the patient-specific payload to trigger an immune response against the patient’s HIV infected cells. These patient-specific, antigen-loaded dendritic cells are formulated into a ready-to-use, intradermal injection.
In Argos Therapeutics’ proposed study, AGS-004 will be combined with one or more agents that are capable of activating the latent HIV reservoir thereby making infected cells ‘visible’ to the immune system. Once the latent HIV has been activated, AGS-004 will be able to identify and kill HIV infected cells, with no added toxicity. The proposed Phase 2 study will aim to treat HIV patients who are currently taking antiretroviral therapy (ART), to evaluate the impact on decreasing or potentially eradicating the infected cells.”

ResearchMatch Connects HIV Study Volunteers with Researchers

I highly encourage everyone to join our important attempt to accelerate the cure of HIV.  Research Match also helps connect patients with other diseases with private investigators. Please forward to your friends and families.  Anyone can participate.
Thank you in advance for supporting this platform!

Contact: Kathy Edson
ResearchMatch Connects HIV Study Volunteers with Researchers
Nashville, TN – June 1, 2013 — ResearchMatch (RM), the country’s first nationwide, non-profit research volunteer recruitment platform for all health conditions is launching an HIV sub-registry in collaboration with Program for Wellness Restoration (PoWeR), a national grassroots HIV advocacy andeducation organization.
RM has a simple goal – to bring together two groups of people who are searching for each other: people who are trying to find research studies, and researchers who are looking for people to participate in their studies. It is a free, secure online registry that has been developed by major academicinstitutions across the country that want to engage others in the mission of today’s ethical, expedited research that will hopefully make a real difference for people with HIV/AIDS in the future.
The Centers for Disease Control (CDC) estimates that 1,148,200 persons are living with HIV infection in the United States, including 207,600 (18.1%) who are unaware of their HIV status. Although great strides have been made in developing medications that treat HIV, research volunteers are needed foremerging HIV cure research studies that may lead to a functional HIV cure in the future. Presently, is the only non-profit clinical trials registry that proactively connects potential volunteers and researchers.
“ will make a dramatic difference in accelerating HIV cure research by connecting researchers with volunteers who want to help but don’t know how to get involved or where to turn. The hope is that many people will register to volunteer and that academic and research institutions will takeadvantage of this free service that promotes faster study enrollment,” said Nelson Vergel, HIV activist/educator and director of PoWeR.

All volunteers who register with RM indicating HIV as one of their conditions will be informed of enrolling studies in their area and also be connected with investigators who register studies at sites in their area. New RM registered members will also be prompted to consider answering optional questionsabout their condition to enhance the precision and prescreening process for matching volunteers and research teams.
To register as a volunteer or a researcher, please visit

is a national partnership created as a centralized, web-based recruitment
registry, connecting individuals who are interested in participating in
research with researchers nationwide. The site is a funded in part by the
National Institutes of Health (NIH) and Clinical and Translational ScienceAward
(CTSA) program grants. The CTSA program is led by the NIH’s National Center for
Advancing Translational Science (NCATS). The content of this website is solely
the responsibility of ResearchMatch and Vanderbilt University and does not
necessarily represent the official views of the NIH.
Program for Wellness Restoration

Program for
Wellness Restoration (PoWeR) is a national non-profit all-volunteer
organization that provides patient-friendly educational information to
HIV-positive people and their healthcare providers about ways to improve HIV
treatment response, side effects and quality of life. More information can be
found at



Unprecedented Immune Reconstitution Drives HIV Viral Reservoir Depletion
Encouraging Preliminary Anti-Viral HIV Data during Treatment Interruption in Ongoing SB-728-T Phase 2 Trials

Richmond, California, May 15, 2013 – Sangamo BioSciences, Inc. (Nasdaq: SGMO) announced today the presentation of new clinical data from its program to develop a ZFP Therapeutic® for HIV/AIDS. The data, which demonstrate that SB-728-T treatment results in a reduction in the HIV reservoir in HIV-infected subjects, are being presented at the 16th Annual Meeting of the American Society of Gene and Cell Therapy (ASGCT). The meeting is being held in Salt Lake City from May 15-18, 2013.

HIV-infected subjects enrolled in Sangamo’s ongoing SB-728-902 clinical trial (Cohorts 1-3) received a single infusion of SB-728-T which resulted in a durable increase in total CD4 T-cells driven by increased ZFN-modified CD4 central memory T-cells. The extent of exposure of subjects to circulating zinc finger nuclease (ZFN) CCR5 protected CD4 T cells correlated with a long-term decrease in the peripheral blood mononuclear cell (PBMC) HIV reservoir as measured by proviral DNA. In addition, two of four evaluable subjects in Cohort 5 of this study showed a decrease of greater than one log in their viral load during a sixteen week treatment interruption (TI) with one of the subjects achieving a transiently undetectable viral load during the TI period. In subjects in which viral load decreased, a measureable anti-HIV response was observed, specifically a multi-functional response of CD8 T-cells to elements of HIV core proteins.

“These data are quite remarkable,” commented Dale Ando, M.D., Sangamo’s vice president therapeutic development and chief medical officer. “In previous clinical studies, a decline in the HIV reservoir has never been observed in subjects on long-term anti-retroviral therapy (ART) and any increase in the levels of CD4 cells in HIV-infected subjects is often associated with a concomitant increase in the size of the reservoir. In contrast, a single SB-728-T treatment of subjects on long-term ART produced a significant and durable improvement in CD4 count and, in the majority of subjects, a notable decrease in the HIV reservoir over time. An observed correlation with circulating ZFN CCR5 protected CD4 cells is extremely promising.”

Summary of Clinical Data

SB-728-0902 Cohorts 1-3 in Immunologic Non-Responders (INR)

Treatment of HIV subjects with a single infusion of SB-728-T leads to long-term increases in CD4 counts (up to 3 years in some subjects).

Long-term increases in CD4 counts correlate with increased CD4 central memory and increased

ZFN CCR5 protected central memory T-cells.

The extent of long-term exposure to circulating ZFN-CCR5 protected CD4 cells correlates with long- term decreases in the PBMC HIV reservoir.

SB-728-0902 Cohort 5 (CCR5 delta-32 Heterozygotes)

Post SB-728-T infusion, a 16-week ART TI can lead to viral load reduction from initial peak.

o Two out of four subjects showed reduction in viral load during TI

o One subject achieved transient undetectable viral load during TI

The best viral load reduction responses are seen in subjects with CD8 T-cell HIV gag immune responses that are polyfunctional (expression of multiple cytokines) and the highest levels of bi-allelic modification of the CCR5 gene.

SB-728-1101 Immunologic Responders with Cytoxan Conditioning

Accrual and treatment in progress with ten subjects infused to date.

Analysis of numbers of modified SB-728-T cells and viral load during TI is in progress.

Viral load decreases correlate with highest levels of estimated biallelic CCR5 modification

Decreases in viral load from peak to the end of TI correlated with mean circulating bi-allelic

ZFN CCR5 protected CD4 cells during the TI for all patients to date who fully completed TI per protocol in SB-728-Penn, 902 Cohort 5 (CCR5 delta-32 Heterozygotes) and 1101 studies.

“These data continue to demonstrate the important link between SB-728-T-driven immune reconstitution and HIV viral load depletion,” said Rafick-Pierre Sékaly, Ph.D., Co-Director & Chief Scientific Officer, The Vaccine & Gene Therapy Institute of Florida (VGTI Florida), whose laboratory carried out the immunologic analyses. “Specifically, SB-728-T treatment protects long-term central memory CD4 T-cells from HIV-infection which is key for the successful development of an immunologic approach to HIV. ZFN-protected central memory cells are driving positive effects on total CD4 T-cell counts in treated subjects and appear to also play a role in breaking the cycle of HIV reservoir maintenance.”

“We are very encouraged by our data to date and by our continued progress in understanding the factors required to maximize the potential of this novel immunologic approach to a functional cure for HIV,” stated Geoff Nichol, M.B., Ch.B., Sangamo’s executive vice president of research and development. “Sangamo has demonstrated that we have the necessary factors for success: SB-728-T is well-tolerated; the modified cells engraft and traffic throughout the body, appear to be immunologically active, and importantly, persist.

We observe an unprecedented increase in total CD T-cell levels which correlates with the levels of ZFN-protected CD4 central memory T-cells, and a related long-term decrease in the viral reservoir. We have also observed reduction in viral loads during TI, to undetectable levels transiently in one of four subjects, providing a second example of this observation. Viral load changes during TI continue to correlate with circulating bi-allelic ZFN CCR protected CD4 cells. In addition, we have identified key immunologic markers of inflammation that correlate with the degree of engraftment and can potentially aid in the selection of subjects for which SB-728-T may be most effective.”

Dr. Nichol continued, “In our ongoing studies, we will continue to investigate these parameters including the threshold engraftment levels of biallelically modified T-cells and the types of HIV- reactive cells necessary to mount an immune response to the virus. We look forward to presenting the results of these completed studies at the end of 2013.”

The data were presented today by Dale Ando, M.D., Sangamo’s vice president of therapeutic development and chief medical officer in a Scientific Symposium entitled “Challenges and Success of Gene Therapy Product Approval.” Dr. Ando also chaired the symposium.

Data will also be presented from Sangamo’s Phase 1 clinical trial SB-728-902 Cohorts 1-3 in a second presentation at 2:15 pm MT, on Thursday, May 16, 2013, Abst.#: 58 “Long-term CD4 Reconstitution in HIV Subjects Receiving ZFN CCR5 Modified CD4 T-Cells (SB-728-T) May Be Attributed to the Sustained Durability of the Central Memory T-Cell Subset.”

Summary of Clinical Trial Design

About SB-728-902 Cohorts 1-3

The study is an open-label Phase 1 clinical trial to evaluate the safety and tolerability of single infusions of an escalating dose of an autologous (a patient’s own) CD4+ T-cell product genetically modified at the CCR5 gene by CCR5-specific ZFNs (SB-728-T). The trial enrolled nine HIV-infected subjects (three cohorts of three subjects each) who have sub-optimal T-cell levels and no detectable viral load on long-term ART. Subjects remained on their existing antiviral therapy while receiving treatment with SB-728-T.

About SB-728-902 Cohort 5

Up to 20 HIV-infected subjects heterozygous for the CCR5 delta-32 mutation (i.e. with one CCR5 gene that is naturally modified) who are currently on ART are being enrolled and will receive a single intravenous infusion of SB-728-T (5 to 30 billion modified cells). Two months after SB-728-T treatment, subjects undergo a 16 week TI during which time their anti-retroviral therapy is discontinued. ART will be reinstituted in subjects whose CD4 T-cell counts drop to cells/ mm3 and/or whose HIV-RNA increases to 100,000 /mL for three consecutive weekly measurements. At the end of the TI, subjects with a sustained detectable HIV viral load are reinstituted on ART. Subjects with an undetectable viral load can remain off ART until HIV RNA levels are detectable or their CD4 T-cell count drops below 350 cell/mm3 for three consecutive weekly measurements.

About SB-728-1101
SB-728-1101 is an open-label, dose escalation, multi-center study designed primarily to evaluate the safety and tolerability of escalating doses of cyclophosphamide (Cytoxan®) administered one day prior to SB-728-T infusion. Cytoxan is a drug that is used to transiently reduce the numbers of T-cells in the body which then rapidly repopulate once the drug is discontinued. Such lymphodepletive treatment has been used to enhance engraftment of adoptively transferred T-cells in the treatment of cancer and as therapy for numerous autoimmune diseases. The drug has been previously used in HIV-infected individuals and studies demonstrate that, while the drug was transiently lymphodepleting, it did not significantly reduce total CD4 T-cell counts over the long-term and was adequately tolerated.

In addition to safety, the study is evaluating the effect of escalating doses of Cytoxan on SB-728-T engraftment, the effect of SB-728-T treatment on viral load following ART interruption, the change in CD4+ T-cell counts in peripheral blood and the long-term persistence of SB-728-T.

At least 9 HIV-infected subjects on ART are being enrolled into 3 dose-escalating cohorts (3 subjects/cohort), and will receive intravenous Cytoxan (200 mg, 500 mg/m2 or 1000 mg/m2). Within each cohort, treatment is staggered so that each subsequent subject cannot be infused with Cytoxan until at least 2 weeks after the preceding subject. One day after receiving Cytoxan, subjects are infused with SB-728-T (5 to 30 billion cells). Six weeks after SB-728-T infusion, subjects with CD4 cell counts ≥500 cells/ mm3 undergo a 16 week TI during which time their anti-retroviral therapy is discontinued. ART will be reinstituted in subjects whose CD4 T-cell counts drop to  t500 cells/mm3and/or whose HIV-RNA increases to >100,000 copies/ mL for three consecutive weekly measurements. At the end of the TI, subjects with a sustained detectable viral load or CD4 T-cell count cells/ mm3 are reinstituted on ART. Subjects with an undetectable viral load can remain off ART until HIV RNA levels are detectable or their CD4 T-cell count drops below 500 cells/mm3 for three consecutive weekly measurements.

Additional Presentations at ASGCT

Twelve additional presentations from Sangamo and its collaborators will be featured later in the week and include data from preclinical and research-stage human therapeutic programs.  Therapeutic areas
include additional presentations
 ZFP-based approaches for monogenic diseases such
as hemophilia, including applications of Sangamo’s proprietary In Vivo Protein Replacement Platform,
hemoglobinopathies, and oncology.  Developments in gene-editing
technology applications will also be
in presentations at the
All abstracts for the meeting are
online at  2013 ASGCT Meeting Abstracts.
About Sangamo
Sangamo BioSciences, Inc. is focused on research and development of novel DNA-binding proteins for
therapeutic gene regulation and genome editing. It has ongoing Phase 2 and Phase 1/2 clinical trials to
 novel  ZFP
 Therapeutic®  for  the  treatment  of  HIV/AIDS.

Sangamo’s other therapeutic programs are focused on monogenic diseases, including hemophilia and
as  sickle cell anemia and beta-thalassemia,  and  a program in  Parkinson’s disease. Sangamo’s core competencies enable the engineering of a class of DNA-binding proteins known as
zinc finger DNA-binding proteins (ZFPs).   Engineering of ZFPs that recognize a specific DNA sequence enables the creation of
sequence-specific ZFP
Nucleases (ZFNs) for gene modification and
ZFP transcription  factors  (ZFP 
TFs)  that  can
 control  gene
 expression  and,  consequently,
 cell  function.
Sangamo has entered into
a strategic collaboration with Shire to develop therapeutics for hemophilia,
Huntington’s disease and other monogenic diseases and has established strategic partnerships with
companies in non-therapeutic
applications of its technology including Dow AgroSciences and Sigma- Aldrich Corporation. For more information about Sangamo, visit the company’s website at

Therapeutic® is a
registered trademark
Sangamo BioSciences, Inc.
This press release may contain
forward-looking statements based on Sangamo’s current expectations. These
forward-looking statements
include, without limitation, the research and development of novel ZFP
 TFs  and
 ZFNs  as 
ZFP  Therapeutics
 and  therapeutic  applications  and
 scope  of
 such applications of Sangamo’s
technology platform to specific human diseases and unmet medical
needs, including a potential functional cure of HIV/AIDS, the
expansion of clinical studies of SB-728-T in HIV-infected individuals, expected timing for the presentation of clinical trial data, the development
of ZFP Therapeutics for monogenic diseases and stem cell applications. Actual results may differ materially from
these forward-looking statements due to a number of factors, including uncertainties relating to whether clinical trials will validate and support tolerability and efficacy of ZFP Therapeutic approaches, technological challenges, Sangamo’s ability to develop commercially viable products and technological developments by our competitors. See Sangamo’s SEC filings, and in particular, the risk
factors described in the Company’s Annual Report on Form 10-K and most recent Quarterly Report on Form
10-Q. Sangamo assumes no obligation to update the forward-looking information contained in this press release.
Sangamo BioSciences, Inc.
Wolffe, Ph.D.

“Functional Cure” of HIV Claimed for Baby Treated 30 Hours After Birth


“Functional Cure” of HIV Claimed for Baby Treated 30 Hours After Birth

20th Conference on Retroviruses and Opportunistic Infections, March 3-6, 2013, Atlanta

Mark Mascolini

An HIV-infected US infant treated from 30 hour after birth had no detectable viral load, no detectable HIV DNA in blood cells, and no HIV-specific antibodies at 26 months of age on standard tests, even though antiretroviral therapy (ART) stopped at age 18 months [1]. Deborah Persaud (Johns Hopkins University) and colleagues believe their findings confirm “a state of functional HIV cure.”

Speedy treatment after birth appeared to work like postexposure prophylaxis (PEP), stopping HIV from getting a foothold in this baby’s body and establishing a latent viral reservoir. Evidence that the baby was infected persisted, however, in vanishingly small levels of HIV RNA and HIV DNA detectable in blood and cells. But the researchers do not believe these viral traces can reestablish active infection.

US HIV experts including Daniel Kuritzkes (Harvard) and Steven Deeks (University of California, San Francisco) are reserving judgment on whether the child had established HIV infection, the New York Times reports [2]. “The one uncertainty is really definitive evidence that the child was indeed infected,” Kuritzkes told the Times.

Persaud and colleagues believe their findings show the infant did have HIV infection–though perhaps not an established latent reservoir. “For pediatrics, this is our Timothy Brown,” Persaud told the Times, referring to the “Berlin patient” cured of HIV after bone marrow transplantation from a donor with cells resistant to HIV.

The researchers confirmed exposure to HIV by checking maternal HIV antibody and plasma HIV RNA tests, including HIV resistance testing. The baby appeared to be infected with wild-type (nonmutant) HIV-1 subtype B. Persaud and coworkers believe they documented HIV infection in the infant through standard HIV DNA polymerase chain reaction and plasma HIV RNA testing. Positive HIV DNA and HIV RNA testing on separate infant blood samples collected on the second day of life showed that the child carried HIV that was genetically matched to the mother’s virus. Plasma viral load at that point was around 20,000 copies [2], relatively low for an infant.

Three-drug treatment of the Mississippi infant began within 30 hours of birth and continued to the age of 18 months. Plasma HIV RNA tests remained positive on days 7, 12, and 20, then became undetectable at age 29 days. From 1 through 26 months, plasma HIV RNA remained below the detection limit of a 20-copy assay repeated 16 times.

Clinicians stopped antiretroviral therapy at age 18 months. Ultrasensitive assays detected a single copy of HIV RNA at age 24 months and 37 copies of HIV DNA per million peripheral blood mononuclear cells (PBMCs) enriched for monocytes. Samples yielded no evidence of replication-competent HIV after coculture of 22 million purified resting CD4 cells.

When the infant was 26 months old, an ultrasensitive assay spotted 4 HIV DNA copies per million PBMCs but no 2-LTR circles (which indicate that HIV genetic material is being imported into the nucleus of an infected cell). Standard clinical assays remain negative for HIV RNA, PBMC HIV DNA, and HIV-specific antibodies.

“This is the first well-documented case of functional cure in an HIV-positive child,” Persaud and colleagues maintain. The case, they believe, “suggests that very early ART may prevent establishment of a latent reservoir and achieve cure in children.”

The child is now 2.5 years old and has not taken antiretrovirals for a year.

1. Persaud D, Gay H, Ziemniak C, et al. Functional HIV cure after very early ART of an infected infant. 20th Conference on Retroviruses and Opportunistic Infections. March 3-6, 2013. Atlanta. Abstract 48LB.
2. Pollack A, McNeil DG Jr. In medical first, a baby with H.I.V. is deemed cured. New York Times. March 4, 2013.

Is the End of AIDS in Sight?

Reality Check: Is the End of AIDS in Sight?
Dr Francois Dabis from the Bordeaux School of Public  Health at the University of  Bordeaux (Segalen, France) gave an excellent talk today at CROI-2013 that is easily understood by any lay person who wants to know how far we have come in HIV and the challenges ahead