News From The Journal Of Clinical Investigation: May 9, 2011

http://www.medicalnewstoday.com/releases/224726.php

"Article Date: 10 May 2011 - 2:00 PDT

Variable HIV peptide stability in human cytosol is critical to epitope presentation and immune escape

Key to the success of vaccines that provide protection from infection with viruses is their ability to stimulate immune cells known as CD8+ T cells. By analyzing protein fragments (peptides) derived from HIV, a team of researchers, led by Sylvie Le Gall, at Harvard Medical School, Boston, has now generated data that suggest new ways to modify the CD8+ T cell-stimulating components of a vaccine such that they trigger a more effective protective response.

CD8+ T cells are stimulated to respond to an invading virus when they see viral peptides bound to a cell surface protein complex known as MHC-I. The team analyzed the repertoire of HIV-derived peptides inside primary human cells and found that they persisted for different lengths of time before being degraded (i.e., showed different levels of stability). The sequence of the peptide determined its stability and this in turn determined how effectively it stimulated CD8+ T cells. Further analysis identified ways to modulate the stability of a peptide such that it enhanced CD8+ T cell-recognition and activity, providing a potential new approach to designing the CD8+ T cell-stimulating components of a vaccine."

http://www.hiv-reservoir.net/index.php/Latest...o-hit-hiv-reservoirs.html

"Wednesday, 20 April 2011 10:40

Gold-based Drug May Pave the Way to a Cure for AIDS

A new breakthrough in AIDS research is reported by an International group in the journal AIDS, the leading scientific publication in the field.

Rome, April 20, 2011 - For Immediate Release-


Using a compound containing gold and approved for treatment of rheumatoid arthritis, researchers (from the Italian Institute of Health, “La Sapienza” University of Rome, the Vaccine and Gene Therapy Institute, Florida, and Bioqual, Maryland) have been able to hit the hidden stock of HIV which cannot be targeted by current antiretroviral therapies. Similarly to the dark matter in a galaxy, in this stock the virus is of course physically present but in a form that can hardly be measured precisely and cannot be targeted by drugs or the immune system. The larger this “dark stock”, the more difficult it is for the immune system to keep the infection under control. In the new study, conduced in monkeys infected with a virus very close to HIV, the so-far elusive hidden viral stock (which scientists refer to as the reservoir) has for the first time been struck by a drug-based attack in the chronic phase of the infection. HIV lies “stocked” in a dormant form in one particular type of immune cells, i.e. the central and transitional memory CD4+ T-cells. These cells are long-lived, and cannot be eliminated by the immune system because the virus is hidden. If antiretroviral therapies are suspended, sooner or later, the virus will wake up thus re-starting the progression of the disease. In order to rid HIV from the body, the cells harbouring the dormant virus must be eliminated. This goal has been the “Holy Grail” of AIDS research, at least in the last few years..."

http://www.hiv-reservoir.net/index.php/Latest...an-horse-against-hiv.html

"Thursday, 14 April 2011

Trojan Horse Against HIV

an article published this month in PLoSone, a new strategy to activate latent HIV and deplete reservoirs is proposed. Nanoparticles containing Bryostatin, a NFkB activator, have been designed to target latently infected cells more precisely: the Trojan Horse strategy applied to HIV research...

The idea is quite interesting: encapsulate factors able to reactivate HIV from latency in nanoparticles capable to enhance delivery in tissues, brain, or even specific cells. In particular, liposomes offer a biodegradable vehicle which is capable of carrying a variety of substances to target sites either through passive or active targeting. The targeting strategy may help prevent toxicity due to generalized immune activation during efforts to purge latent HIV.


This work is published in the April 2011 issue of PLoSone by the California team of Jerome A. Zack (1).

Bryostatin has been demonstrated to activate latent HIV at nanomolar concentrations in vitro (2). Bryostatin-1 has been tested in clinical trials for anti-cancer properties. Bryostatin-2, which was used in this experiment, can also activate PKC at nanomolar concentration.


Bryostatin-2 was packaged in lipid nanoparticles (LNP-Bry) and tested in cell lines and in the SCID-hu (Thy/Liv) mouse model for HIV latency. LNP-Bry were non-toxic in all cell types including PBMCs.

One major potential of this construct is the possibility to incorporate both a latency activator and a protease inhibitor in the construct. This strategy may be particularly important if particles are developed to enter anatomical sites that are not easily penetrated by some antiretroviral drugs, like the brain. To this end, the authors incorporated nelfinavir in the LNP-Bry and the particle was capable in vitro both to stimulate latent virus and inhibit virus spread.

Finally, some selectivity can be added to this construct to minimize activation of other cells. The main problem is that latently-infected cells do not bear specific cell surface markers to identify them. However, the authors chose the CD4 receptor as the target and demonstrated that these particles were able to preferentially activate CD4+ cells. This was possible by coating the nanoparticles with anti-CD4 antibodies.

This original experiment therefore leads to the construction of a kind of Trojan Horse against HIV, able to target specifically different kind of cells, and both deliver anti-latency agents and antiretrovirals. A genious weapon in the battle against HIV persistence!..."

http://www.aidsbeacon.com/news/2011/05/27/mos...es-with-their-clinicians/

"May 27, 2011

Most Women With HIV Do Not Discuss Fears, Pregnancy Issues With Their Clinicians

Results from a study published this week indicate that many women with HIV never discuss issues specific to HIV-positive women during visits with their clinicians, particularly issues relating to HIV management prior to or during pregnancy.

The researchers speculated that gender-based issues were not discussed during visits with the women’s health care providers because clinicians had a lack of experience, comfort, or knowledge of these issues or expected that patients’ concerns would be attended to by other physicians.

“Clinicians caring for HIV-infected women need to incorporate regular discussions about the reproductive plans of their patients. These plans change over time and clinicians need to modify their recommendations and treatment strategies accordingly,” said Dr. Kathleen Squires, a physician at Jefferson Medical College of Thomas Jefferson University in Philadelphia and lead author of the study.

“The study suggested that there is substantial room for improvement to reach this goal,” she added.

Based on their results, the study authors recommended that practitioners discuss issues such as family and pregnancy planning with HIV-positive patients. They also recommended that clinicians discuss other treatment-related psychological, social, and emotional aspects of HIV and offer routine screening for depression and other problems.

The proportion of women with HIV in the United States has increased over the past two decades. As of 2006, women comprised about one quarter of the HIV-positive population in the U.S.

According to the study authors, HIV-positive women face a unique set of health, social, and psychological problems. HIV and antiretroviral therapy may affect women differently than men. Also, rates of depression tend to be higher among HIV-positive women compared with HIV-positive men.

In addition, the use of highly active antiretroviral therapy during pregnancy, together with use of caesarean sections and avoidance of breast-feeding, have reduced rates of mother-to-child HIV transmission in the U.S. to less than 2 percent. As a result, more women with HIV may consider pregnancy and childbirth.

However, there is little information available on the effectiveness with which medical providers address potential pregnancy in women with HIV, and few studies have examined the gender-specific health needs of women with HIV.

In this study, researchers conducted a survey with 700 HIV-positive women to get feedback about communication barriers with their health care providers. Participants were recruited from 29 AIDS information, counseling, and treatment centers across the U.S.

Participants had a median age of 42.5 years and had been receiving antiretroviral therapy for an average of eight years. Two hundred of the women were Caucasian, 200 were Hispanic, and 300 were African-American.

Concerns About Gender, Racial Differences In HIV Progression And Treatment

More than half of the women (55 percent) had never discussed gender-based differences in treatment response with their practitioners, even though 46 percent of the women thought their disease affected them differently than men. Caucasian and African-American women were least likely to have discussed this issue with their HIV health care providers. Also, women with male health care providers were less likely than women with female health care providers to have discussed this topic (41 percent versus 51 percent, respectively).

However, 96 percent of women who did discuss gender-based differences in treatment response with their practitioners were satisfied with the answers they received.

More than half of the women (59 percent) felt that their culture, ethnicity, or language affected the care they received. Hispanic and African-American women were more likely to report this issue than Caucasian women. Also, women in the South were more likely to report this issue than women in the West or Northeast.

About one third of the women had seen three or more providers since starting HIV treatment, and 43 percent said they had changed providers because of communication issues.

Childbearing And Caregiver Issues

More than a third of the women (39 percent) had children. Of the women who had been pregnant prior to the survey or who were considering pregnancy, nearly half (48 percent) were never asked by their health care providers if they had or were thinking about having children. More than half (57 percent) had not talked about treatment options with their practitioners before becoming pregnant.

Of the women who were pregnant or had been pregnant at the time of the survey, 42 percent were either “not very aware” or “not at all aware” of the treatment options available to pregnant women with HIV.

Overall, 61 percent of women felt they could have children if given appropriate medical care but 59 percent felt society strongly discourages them from doing so.

Women with HIV who lived in the South were more likely to feel society discouraged them from having children than those living in the Northeast or Midwest. Those who received care from a nurse practitioner or physician assistant were also less likely to experience this attitude than those treated by infectious disease specialists or general practitioners.

Fifty-two percent of the women identified themselves as caregivers, and 43 percent said living with HIV has made it harder for them to look after their families. More women in the South compared with the Northeast felt this way (50 percent versus 37 percent, respectively).

The researchers speculated that concerns about stigma may encourage women with HIV, especially those who are caregivers, to keep their HIV status confidential as long as possible and hesitate to seek early care.

Social Support And Depression

Most women in the survey thought factors such as suppressing viral load (amount of HIV in the blood), achieving long-term success with medications, and being able to live normal lives were important aspects of their treatment.

Women who wanted extra support beyond what their practitioners could provide found it through support groups, therapists, family, and friends. Most Caucasian women identified therapists as sources of additional support, while Hispanic and African-American women mostly identified support groups.

Women in the Midwest and Northeast were more likely to get extra support from a support group or therapist, while women in the South were more likely to get support from family and friends.

Seventy-three percent of women said they had struggled “a great deal” or “somewhat” in managing their daily lives, while one third of the women experienced changes in sleep patterns, loss of energy, unexplained aches or pains, feelings of sadness or worry, and anxiety.

In addition, 27 percent had five or more feelings commonly associated with depression, although other studies have reported higher rates of depression among HIV-positive women.

A majority of the women (58 percent) said they were comfortable talking to their providers about their depression-related feelings, but women in the South were less likely to feel comfortable than women in the rest of the country."

June 5, 2011
Doctors claim to have "functional cure" for HIV
Timothy Ray Brown was diagnosed with HIV in 1995, but is now the first to have the virus completely eliminated from his body

http://www.cbsnews.com/stories/2011/06/05/eveningnews/main20069146.shtml