World’s First Engineered T Cell Receptor Trial Opens with New Cellular Therapy for HIV

"Researchers at Adaptimmune Limited and the University of Pennsylvania School of Medicine, today announced the approval of an Investigational New Drug (IND) application from the US Food and Drug Administration (FDA) and opening for enrollment of the first ever study using patients’ cells carrying an engineered T cell receptor to treat HIV (SL9  HA-GAG-TCR). The trial may have important implications in the development of new treatments for HIV potentially slowing – or even preventing – the onset of AIDS.

Related Images

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  “Bionic assassins” A new version of killer T cell receptors is added to natural T cell receptors, isolated from a patient, to produce enhanced killer T cells.  These “bionic assassins” have been proven to destroy HIV-infected cells in the laboratory. (Click for larger version.)
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  The T Cell Processing Laboratory for the Generation of Engineered T cells Designed to Fight HIV Infection – Cell sorting. Patient cells are separated out to focus on the population best suited for targeting the HIV-infected cells.  They are then carefully expanded and prepared using the modified T cell receptor. (Click to download high-resolution version.)
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  The T Cell Processing Laboratory for the Generation of Engineered T cells Designed to Fight HIV Infection – Final harvesting. After a period in culture, the patient’s cells are harvested, extensively tested and then re-administered to the patient. (Click to download high-resolution version.)

Related Links

• 2008 News Release: Engineered Killer T-Cell Recognizes HIV-1’s Lethal Molecular Disguises
• University of Pennsylvania School of Medicine
• University of Pennsylvania Health System

Information for Patients

• HIV-infected patients interested in learning more about the trial should contact Larisa Zifchak at: +1 215-349-8091 (larisa.zifchak@uphs.upenn.edu)

The trial makes use of the body’s natural ability to recognize infected cells by enhancing the power of the T cell receptor (TCR) on killer T cells. ...

Last year, with colleagues at the University of Pennsylvania, theyengineered and tested a killer T-cell receptor that can recognize all the different disguises HIV is known to have used to evade detection. The researchers transferred this receptor to the killer T-cells to create genetically engineered "bionic assassins" able to destroy HIV-infected cells in culture. Now, less than a year later, they are taking their unique technology into the clinic. ..."

Read more in Penn Medicine News, October 7, 2009.

Second Analysis of Vaccine Trial Casts Doubts on Result

"Now Cohen reports that a second analysis showed a trend toward benefit in those who were vaccinated, but failed to demonstrate a statistically significant difference. This means the difference was small enough that it could have occurred by chance."

Read more in POZ, October 6, 2009.

Comment: This finding weakens the positive vaccine result. But remember that the line between statistically significant, or not significant but only a trend, is an arbitrary one, depending on history and custom in medical research. Crossing this line does not cross any line in nature.

Food insecurity increases risk of death for patients taking HIV treatment in Canada

"When the researchers took into account possible confounding factors, they still found that food insecure patients had a 50% increase in their risk of death (adjusted hazard ratio [AHR] = 1.51, 95% CI, 1.03-2.23)."

Read more in Aidsmap, October 6, 2009.

Retroviruses Conference (CROI): Deadlines tomorrow (researchers), and October 16 (young investigator awards)

"As a reminder, the deadline for abstract submission for CROI is tomorrow, Tuesday, October 6 at 5:30 pm EDT. Please visit the conference web site, www.retroconference.org, for the submission instructions and subject categories.

"The Scientific Program Committee will provide a large number of young investigator awards for fellows, graduate students and undergraduate students who are presenting their work at the conference. The deadline for young investigator award recommendations is Friday, October 16 at 5:30 pm EDT. Information on this program is available on line (see Awards and Scholarships)."

Read more in CROI dates and deadlines, October 5, 2009.

Avexa Closes Phase III Trial of HIV Drug Apricitabine

"Avexa announced that it is closing a planned 48-week Phase III study of its antiretroviral drug apricitabine (ATC) early in order to analyze the data and make decisions about the drug’s fate, according to a press release the company issued October 2.

"Apricitabine is a second-generation nucleoside reverse transcriptase inhibitor (NRTI) in the same family as Epivir (lamivudine) and Emtriva (emtricitabine) and was designed to work against HIV resistant to those two drugs. A Phase IIb study indicated that ATC does, in fact, work against Epivir- and Emtriva-resistant virus. ...

"'The rationale for closing the trial…was based on two key factors. First, the results may offer key insight into ATC’s role in the overall HIV treatment landscape, and discussions with regulatory authorities may clarify the ATC approval path. Secondly, this will allow for a mature enough data point to enable potential partners the ability to make a definitive decision on licensing of ATC,' stated Julian Chick, PhD, Avexa’s chief executive officer."

Read more in POZ, October 5, 2009.

Topical treatment for pre-cancerous anal cell changes safe and moderately effective

"A course of treatment with topical trichloroacetic acid appears to provide a safe and effective treatment for pre-cancerous cell changes in the anus, US investigators report in a study published in the online edition of the Journal of Acquired Immune Deficiency Syndromes. The treatment was equally effective in HIV-positive and HIV-negative men.

"'Given its ease of use, low cost, and good safety profile, trichloroacetic acid represents a reasonable first-line therapy with carefully selected patients', comment the investigators.

"Higher rates of anal cancer are seen in gay men, especially those with HIV, than in the general population. Anal intraepithelial neoplasia (AIN) is the name given to pre-cancerous changes in the anus. AIN is graded AIN I, AIN II, and AIN III according to its severity."

Read more in Aidsmap, October 5, 2009.

Long-Term Combination Antiretroviral Therapy Is Associated with the Risk of Coronary Plaques in African Americans with HIV Infection

"This study suggests that long-term exposure to ART may be associated with coronary plaques. Because long-term use of ART and HIV replication may be associated with the presence of noncalcified plaques, some of which may be more vulnerable to rupture, an intensive lifestyle intervention to reduce traditional risk factors for coronary artery disease (CAD) is ultimately vital to those who are on ART."

Read more in AIDS Patient Care and STDs, October 5, 2009.

Comment: This trial studied only African Americans. Therefore the same finding may apply to other patients as well -- which seems likely.

Three-quarters of HIV-positive US prisoners stop anti-HIV drugs after release from jail

"Few HIV-positive prisoners in the US continue to take HIV treatment once they are released from jail, Canadian and US investigators report in the online journal PLoS One.

"'We are concerned about the deleterious effects of intermittent therapy in light of the SMART data and the possibility of the development of resistance', comment the investigators.

"They continue, 'our study…highlights the need to support continuous antiretroviral therapy and the importance of continuity of care services for HIV infected persons who enter the cycle of incarceration.'

"HIV is a significant health problem in US prisons especially as it has been estimated that up to a quarter of HIV-positive individuals in the US will be imprisoned at some point."

Read more in Aidsmap, October 2, 2009.

HIV-Infected Adults from Minority Ethnic Groups are Willing to Participate in Research if Asked

"The strongest predictor of participation was being asked (RR 3.0; p<0.001). The majority of patients would agree (65%) or consider (30%) participating in a study if recommended by their PCP [primary care provider]. Being treated like a “guinea pig” was the most common (40%) concern of patients." Read more in AIDS Patient Care and STDs, October 2, 2009.

Immune surveillance below the radar: study offers explanation for acyclovir’s failure to reduce HIV risk

"The background to the work is that HSV-2 infection has been consistently associated with a 2 to 3-fold increased risk of acquiring HIV; a meta-analysis published in 2006 reported a relative risk of 3.1, 2.7 and 1.7 for women, heterosexual men and men who have sex with men, respectively. [3]

"Recently analysed data from the Merck vaccine trial are consistent with these findings in that HSV-2-infected participants were found to have approximately double the risk of acquiring HIV infection during the study.

"The mechanism by which HSV-2 infection increases HIV acquisition risk is not so clear, however, and has been the subject of debate.

...

"The researchers acknowledge in the conclusion to the paper that the number of participants was small, but nevertheless state: “we feel that our central finding – that HSV reactivation leaves a residual inflammatory response not appreciated clinically – is typical of HSV-2 genital lesions.” They also note that “the wide anatomical distribution of HSV-2 in the male and female genital tract underscores the importance that these localized reservoirs of inflammatory cells are likely to have in HIV acquisition.”"

Read more in i-base, September/October 2009.

Many Prisoners Revert to Intermittent Treatment After Incarceration

"Less than 17 percent of HIV-positive inmates on antiretroviral (ARV) therapy continue taking their treatment consistently once they are released from prison, according to a study published September 22 in the online journal PLoS One.

Though there are often still many barriers to effective HIV therapy in prison, researchers have known that some incarcerated people are better able to access and adhere to ARV treatment while in prison than after they are released. Potential reasons for this include lack of housing, employment, access to care and social support. "

Read more in POZ, October 1, 2009.

CD4 responses after viral suppression for more than 7 years on HAART

"Most patients responded well to treatment: the median CD4 cell count after four years of HAART was 560 cells/mm3 (IQR, 390-776).

"However, 151 patients (41%) had a CD4 cell count that was less than 500 cells/mm3 at year 4, of whom 61 eventually had a confirmed increase to >500 cells/mm3. Many of the remaining patients remained below this threshold through 10 years of observation.

"Results strongly correlated with baseline CD4 count: 95%, 75% and 56% of patients who started treatment at >300, 100–200 and <100 cells/mm3 respectively, were able to achieve a CD4 cell count >500 cells/mm3. Baseline CD4 count also correlated with time to reaching CD4 >500 and inversely with magnitude of the changes in CD4 count.

"In multivariate analysis, age was the only factor consistently associated with CD4 cell count increases, with younger patients having greater increases than older patients. HCV coinfection, sex, and pre-HAART nucleoside use were not statistically significant predictors of CD4 cell count increases."

Read more in i-base, September/October 2009.