HIV/AIDS Vaccine Strategy: Kick-Start Immune Response

 

A team of researchers led by scientists at The Scripps  Research Institute in La Jolla,   CA has developed a strategy for  inducing a key part of an effective immune response to HIV. Designing an  effective HIV/AIDS vaccine requires that it would be “safe and look enough like  HIV to kick-start the immune system into neutralizing the virus,” reported ScienceDaily on July 18. The problem is  that the human immune system has trouble with that even when it’s exposed to  real HIV.

By tracing the evolution of HIV antibodies taken from the  blood of rare individuals whose immune systems are naturally able to target and  neutralize the virus (called elite controllers), the researchers may have found  a way to replicate this for everybody.

At the American Crystallographic Association meeting in Hawaii July 20-24, the  team presented multiple crystal structures which show how the virus interacts  with components of the immune system. Examining these structures has allowed them  to reverse-engineer molecules that specifically activate the precursors of  effective, neutralizing antibodies against the virus—molecules that may be  components of a future vaccine against HIV.

“What we tried to do was to learn how those antibodies developed  over the course of natural infection and attempt to guide the immune response  in the direction of what we know works in certain HIV-infected individuals,”  said structural biologist Jean-Philippe Julien, who presented the work in  Hawaii.

He added that their candidate molecule was able to achieve  the desired immune reactions in the test tube, and they are currently testing  it in animals to see if it is able to initiate the desired immune response. If  those experiments go well, he said, further studies will examine whether it can  protect animals against infection, and human trials for safety and vaccine  efficacy would be next, though it may be years before those results are known.

Julien cautioned that the work might not, by itself,  be the final answer that shows how to make an effective HIV/AIDS vaccine, but  it is a step in the right direction. Most likely, Julien said, any future  HIV/AIDS vaccine would combine multiple biological components in order to give  the broadest possible protection against the virus.

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Lymphoma mortality rates remain elevated among HIV-positive people in the United States

Michael Carter
  Published: 26 July 2013

HIV-positive people in the United States diagnosed with certain types of lymphoma continue to have poorer outcomes compared to HIV-negative lymphoma patients, according to research published in the Journal of the National Cancer Institute.

The study involved 23,000 people who received HIV care in the antiretroviral therapy era – 1996 to 2010. Overall, the age at which individuals were diagnosed with lymphoma increased, reflecting the general ageing of the HIV-infected population. There were also shifts in the type of lymphoma diagnosed, with an increasing proportion of non-Hodgkin lymphoma involving a diagnosis of Burkitt lymphoma. Despite improvements in HIV treatment and care, a low CD4 cell count continued to be a characteristic of people diagnosed with lymphoma.

“Patients continue to have severe antecedent immune suppression evidenced by static nadir CD4 counts over time,” the authors comment.

Between a quarter and a third of all deaths in HIV-positive individuals are due to cancer, with many of these deaths due to lymphomas.

Thanks to antiretroviral therapy, the prognosis of most people with HIV is now excellent. European research has shown that HIV-positive people diagnosed with Hodgkin and non-Hodgkin lymphoma now have survival rates similar to those observed in HIV-negative individuals. In contrast, research from the United States suggests that outcomes continue to be poorer for HIV-positive people with non-Hodgkin lymphoma.

Given this discrepancy, a team of investigators looked at lymphoma diagnosis trends among 23,000 people who received HIV care in the United States between 1996 and 2010. Mortality rates and predictors of outcome were also examined.

A total of 476 participants (2%) were diagnosed with a lymphoma, with 79 cases (17%) involving a diagnosis of Hodgkin lymphoma (HL). There were 201 cases (42%) of diffuse large B-cell lymphoma (DLBCL); 56 cases (12%) of Burkitt lymphoma (BL); 54 (11%) lymphomas of the central nervous system and 86 (18%) diagnoses involving another form of non-Hodgkin lymphoma.

A total of 223 (47%) of lymphomas involved people who were already taking antiretroviral therapy. The overall median CD4 cell count at the time of lymphoma diagnosis was 119 cells/mm3 and the participants had a median nadir CD4 cell count of just 52 cells/mm3.

Individuals diagnosed with Hodgkin lymphoma were more likely than individuals with non-Hodgkin lymphoma to be black (p = 0.01), to be taking antiretroviral therapy (p< 0.001), to have a higher CD4 cell count (p = 0.01) and to have an undetectable viral load (p < 0.001).

There were also differences in the characteristics of people diagnosed with the different forms of non-Hodgkin lymphoma.

Individuals with lymphoma of the central nervous system were more likely to be male (p < 0.001), black (p = 0.003), and have a lower nadir CD4 cell count (p < 0.001) and a lower CD4 cell count at the time of cancer diagnosis (p = 0.006) than other non-Hodgkin lymphoma patients. In addition, people with Burkitt lymphoma had higher nadir CD4 cell counts (p = 0.006) and stronger immune systems at the time of lymphoma diagnosis (p < 0.001) compared to individuals without this cancer.

The proportion of non-Hodgkin lymphoma involving a diagnosis of Burkitt lymphoma increased steadily and significantly over the period of the study (p = 0.02). The proportion of lymphoma diagnoses involving a diagnosis of Hodgkin lymphoma fell from 44% between 1996 and 2002 to 36% between 2006 and 2010.

Age at the time of cancer diagnosis increased from a mean of 40 years in the period before 2000 to a mean of 45 years in the period 2006 to 2010 (p < 0.001). There was also a significant increase in the proportion of diagnoses involving gay men (40 to 53%, p = 0.03).

Median CD4 cell count at the time of lymphoma diagnosis increased from 85 cells/mm3 at the start of the study period to 166 cells/mm3 in the period 1996 to 2010 (p = 0.004). The proportion of participants with an undetectable viral load also increased (p = 0.006). However, nadir CD4 cell count remained stubbornly unchanged throughout the 14 years of analysis.

There were 225 deaths during 1525 years of follow-up, providing an overall mortality rate of 15 deaths per 100 person-years.

There was a 62% five-year survival rate for people with Hodgkin lymphoma. Half the participants with Burkitt lymphoma were alive five years after diagnosis as were 44% of those with diffuse large B-cell lymphoma, 43% of people with other forms of non-Hodgkin lymphoma and 22% of individuals diagnosed with primary lymphoma of the central nervous system.

“By comparison,” write the investigators, “5-year survival rates for all United States adults aged less than 65 with HL, BL, DLBCL diagnosed between 2001 and 2007 were 88.4%, 50.5% and 68.7%. Our data therefore suggest that [HIV] patients…with HL and DLBCL fare worse than HIV-uninfected patients.”

There were significant improvements in HIV therapy over the course of the study. However, these were not reflected in mortality trends, which remained largely unchanged.

Independent risk factors for mortality included older age (AHR per additional decade = 1.28; 95% CI, 1.06-1.54); diagnosis of lymphoma while taking HIV therapy (AHR = 2.21; 95% CI, 1.53-3.20), lower CD4 cell count (AHR = 0.81 per 100 cell/mm3 increase; 95% CI, 0.72-0.90) and higher viral load (AHR = 1.13 per log10 copies/ml; 95% CI, 1.00-1.27).

“HIV-associated lymphoma is highly heterogeneous in the current era, and important demographic, immunologic, virologic, and histologic shifts are occurring,” conclude the investigators. “Outcomes remain inferior to registry data for the general population. These results highlight an ongoing need to elucidate lymphoma biology and optimize treatment for this challenging population to reduce deaths from one of the leading causes of mortality in the modern ART era.”

New Exhibit Celebrates 25 Years of San Francisco’s Real Bad Party

 

 

 

photo: Daniel Nicoletta

 

A new multimedia exhibit opening August 8 at The GLBT  History Museum highlights “the history of Real Bad, a queer dance party held in  conjunction with the Folsom Street Fair in San Francisco. ‘Be Bad…Do Good:  Activism with a Beat’ marks the 25th anniversary of the annual event; entirely  produced and funded by volunteers, which has raised nearly $1.7 million for  local GLBT nonprofits,” the Museum announced in a press release.

“‘Be Bad…Do Good’ celebrates a quarter century  of Real Bad, a party with a purpose and with a global following,” says  Suzan Revah, co-curator of the show along with Gina Gatta. “Real Bad  showcases San Francisco’s  distinct generosity of spirit and support for community through  dance-floor tradition, ritual, and activism.”

Revelry and charity have long energized San Francisco’s gay, lesbian, bisexual and  transgender community. Do-it-yourself GLBT fundraising,  fueled activism, and built care organizations at the height of the  AIDS crisis in the 1980s and 1990s. Rejecting the negativity about sex that the  epidemic amplified, the community found joy in street fairs, the collective spirit  of the AIDS Dance-a-Thon, and the ecstasy of dance clubs such as  the Trocadero Transfer.

“Be Bad…Do Good” will feature 1980s party ephemera; Real  Bad posters, invitations, and photos; a video documentary custom-made for the  show; and a wall-size infographic tracing the fundraising impact of the party  over 25 years.

“Be Bad…Do Good” runs August 8 through Oct. 27,  2013. An opening reception is set for Thursday, August 8, 7:00 – 9:00 p.m.  Admission to the museum is $5.00 (general); $3.00 (California students); free for members of  the GLBT Historical Society. For more information, visit the museum’s website.

World Hepatitis Day – Sunday, July 28th

Sunday,  July 28th is World  Hepatitis Day (WHD). With more than 3 million people living with viral  hepatitis in the United    States, WHD offers a critical opportunity  to raise awareness of this deadly, but treatable disease and encourage  everyone to get tested. In particular, viral hepatitis impact minorities   – especially those living with HIV – at an alarming rate.
African Americans are twice as likely to be infected with HCV compared to the  general U.S.  population. Latinos over 40 are 30 percent more likely to be newly infected  with HBV than their non-Hispanic white counterparts, due to lower vaccination  rates. Asian Americans and Pacific Islanders (APIs) represent half of the  estimated 1.4 million HBV-infected persons in the U.S., despite the fact that they  only make up 5 percent of the overall population.
What’s more, approximately one-third of people living with HIV are  co-infected with either HBV or HCV, which can cause long-term illness and  death. Viral hepatitis progresses faster and causes more liver-related health  problems among PLWH than among those who do not have HIV. Although drug  therapy has extended the life expectancy of PLWH, liver disease—much of  which is related to HCV and HBV—has become the leading cause of  non-AIDS-related deaths among PLWH.
Of those living with viral hepatitis in the United States, approximately  three-quarters are “baby boomers” — those born between 1945 and  1965. The Centers for Disease Control and Prevention (CDC) and the United  States Prevention Services Task Force have both updated their testing  recommendations, suggesting that all baby boomers living in the U.S. should  be screened at least once for the disease.
The National Minority AIDS Council (NMAC) is pleased by these new  recommendations, and hopes that physicians and those who meet this testing  criterion will take them to heart. With new and accurate rapid oral testing  now available, screening is easier than ever. Viral Hepatitis is a serious  condition and one that rarely shows symptoms. On this World Hepatitis Day,  NMAC stands with the Viral Hepatitis and HIV/AIDS communities, and urges  action to address these twin epidemics.

2 Men Cured Of HIV? No Trace Of Virus After They Underwent Stem Cell Transplants

 

2 men cured of hiv

 

 

 

 

 

After undergoing stem cell transplants as treatment for cancer, two patients with HIV now have no trace of the virus in their systems and haven’t required their HIV medication for several weeks, doctors reported today.

However, doctors cautioned that it’s still too soon to say that the patients have been definitively cured, as they have only been off their treatments for 15 weeks and seven weeks, respectively.

The research, led by Dr. Timothy Henrich of Harvard Medical School and Brigham and Women’s Hospital in Boston, reported the findings today at the International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

“They are doing very well,” Henrich said at the conference, as reported by the Associated Press. “While these results are exciting, they do not yet indicate that the men have been cured. Only time will tell.”

The two patients had been HIV positive and had been taking antiretroviral medication for their condition. However, they each developed Hodgkin’s lymphoma (one patient reportedly had other blood cancers as well) and so underwent chemotherapy as well as stem cell transplants while still receiving their antiretroviral medications. The Los Angeles Times reported that the men received their transplants at different times; one four-and-a-half years ago, and the other nearly three years ago. After undergoing the stem cell transplants, the virus is now undetectable.

However, the Associated Press reported that more time is needed to determine if the HIV virus isn’t just hiding undetected elsewhere in the body. Dr. Robert Siciliano of Johns Hopkins University explained in a statement that it may take more than a year to make sure viral rebound does not occur, and that doctors will have to continue monitoring the patients.

The first news of these two men came last year at the 2012 International AIDS Conference; back then, they had undetectable HIV levels in their blood plasma, but had not yet been taken off antiretroviral medications.

The approach Henrich and his team have taken is similar to that of Timothy Brown, also known as the “Berlin Patient,” who underwent stem cell transplantation as part of his treatment protocol for leukemia, before being the first person deemed “cured” of HIV. However, in Brown’s case, the stem cells transplanted into him were HIV-resistant stem cells, while in the cases of these two men, the stem cells did not have that genetic mutation for HIV resistance. Brown also received a more intensive chemotherapy regimen.

The Los Angeles Times reported that this method — stem cell transplantation — is likely to be unfeasible for most HIV-positive people. NBC News pointed out last year that the reason why the approach seemed to work for these men is because they had certain gene mutations that made their immune system cells resistant to HIV infection, and that in general, bone marrow transplants are expensive procedures with a 15 percent fatality rate.

This is just one of the latest HIV treatment breakthroughs that have been reported as of late. Earlier this year, a baby born with HIV was considered “functionally cured,” the Associated Press reported. That baby was born to a mother with HIV. The baby was given faster, stronger-than-usual treatment immediately upon birth, even before doctors were able to test that the baby actually was infected with HIV. At the time of the reporting of this news, the child was 2.5 years old and hadn’t needed to take antiretroviral medication for a year.

And just after the news of this baby was reported, researchers from France reported the “functional cure” of 14 adults with HIV, who were treated extremely early with combiantion antiretroviral therapy (cART). Now, their HIV levels are barely detectable, and they have been able to stop taking their treatment