intellectual vanities… about close to everything

On Wednesday, Jan. 16 2008, I read, that a man who pleaded guilty Tuesday to ripping the head off a duck in the lobby of a St. Paul, Minn., hotel is not a horrible person. His attorney said: “He’s really a nice young man, he’s humble, he’s hard-working, he was a good student and worked hard to get the job he did,” said attorney Michael Colich. “Nobody’s been willing to look at what good things he’s done in his life and what good things he’ll do in his life.”

Ramsey County District Judge Margaret Marrina said it appeared Clark, 26, had “a substantial amount to drink” before the incident. He will be sentenced next month, the newspaper reported. Although attorney and the prosecution agreed on a sentence — no more than 45 days in jail, two years of probation, 40 hours of community service, a $500 fine, restitution and no pet ownership for two years [sic] — the judge will decide.

On Sunday, Jan. 13, 2008, I read, that “violence is a leading cause of death for Iraqi adults and was the main cause of death in men between the ages of 15 and 59 years during the first 3 years after the 2003 invasion.Although the estimated range is substantially lower than a recent survey-based estimate, it nonetheless points to a massive death toll, only one of the many health and human consequences of an ongoing humanitarian crisis.”

A large national household survey conducted by the Iraqi government and WHO estimates that 151 000 Iraqis died from violence between March 2003 and June 2006.

The study found that on average 128 Iraqis per day died of violent causes in the first year following the invasion and that the average daily violent death toll was 115 in the second year and 126 in the third year. More than half of the violent deaths occurred in Baghdad.

nota bene: “Some homes could not be visited because of high levels of insecurity and more people move residence in times of conflict. These factors were taken into account in the analysis as they may affect the accuracy of the survey work,” said Salih Mahdi Motlab Al-Hasanawi, Minister of Health of Iraq. “Nonetheless, the survey results indicate a massive death toll since the beginning of the conflict.”

That makes a cruel arithmetical average of  123,33 Iraqui lives per day for the first three years of what U.S. President George Bush called a job for US troops to render Iraq democratic and stable.

What I don’t read is,  that any judge were to decide, how many days in jail, how many years of probation, how many hours of community service, how big a fine, restitution a human life in Iraq is worth. And who of the Bush administration is going to be sentenced…

see also:

what i read, and what i don’t… wed, 14 march 2007:U.S. President George Bush said at the Pentagon U.S. troops will stay in Iraq until “the job is done”

HIV patients with declining platelet counts appear to be at increased risk for HIV–associated dementia.

“Human immunodeficiency virus–associated dementia (HIV-D) is a syndrome encompassing a spectrum of cognitive, behavioral and motor deficits that usually has an insidious onset and a chronic progressive course,” the authors write as background information in the article. Therapies leading to longer life for HIV patients have paradoxically increased the prevalence of this condition. Identifying biological markers for the development of HIV–associated dementia is critical both for diagnosing the disorder and for understanding its underlying mechanisms.

Lynn M. Wachtman, D.V.M., M.P.H., of Bloomberg School of Public Health, The Johns Hopkins University School of Medicine, Baltimore, and colleagues studied 396 patients with advanced HIV who were recruited for this prospective study between 1998 and 2003. Participants were examined every six months and completed mental and physical evaluations.

Blood samples were also collected and assessed for platelet count (the number of clotting cells in the blood), hemoglobin levels, CD4 lymphocyte count (a measure of certain types of white blood cells, which reflects the state of the immune system) and plasma HIV RNA levels (which indicate the amount of “viral load,” and predict HIV progression).

After a median (midpoint) follow-up of 31.1 months, 40 participants developed HIV–associated dementia. A decline in platelet count from baseline was associated with the development of dementia within six to 12 months. “Those HIV-infected individuals with a decline in platelets from baseline values at this lagged time point had a two-fold increased risk of dementia” in several different analyses, the authors write. The specific timing of the association indicates that the levels of circulating platelets fluctuate as HIV–associated dementia develops, they note.

“Further analyses indicated that decline from baseline platelet levels was associated with a five- to six-fold increased risk of dementia during the first two years of follow-up, but it was not associated with an increased risk of dementia after two years,” the authors continue. “It is possible that individuals who do not progress rapidly to neurologic compromise differ in respect to immune activation, treatment adherence or virologic control relative to those who develop dementia more rapidly.”

“Because CD4 cell counts and HIV RNA levels have proven not to be predictive of HIV–associated dementia, it is important to investigate alternative serum and hematologic markers,” the authors conclude. “Should these markers be routinely measured in a clinical setting, such as platelet counts, they may prove useful for patient management. This study identifies a significant association between platelet decline and incident HIV–associated dementia.” Further study of platelet levels during HIV–associated dementia may lead both to a specific marker for the development of HIV–associated dementia and a better understanding of how the disease develops.

Arch Neurol. 2007 Sep;64(9):1264-72.

Platelet decline: an avenue for investigation into the pathogenesis of human immunodeficiency virus associated dementia.

Wachtman LM, Skolasky RL, Tarwater PM, Esposito D, Schifitto G, Marder K, McDermott MP, Cohen BA, Nath A, Sacktor N, Epstein LG, Mankowski JL, McArthur JC.

On Monday, July 30 2007, I read that the NYT criticizes Republican congressional leaders who have attacked the proposed expansion of the State Children’s Health Insurance Program (SCHIP), a bipartisan initiative that would increase the number of insured children from low-income families. Republican “leaders may be on message at the White House, where President Bush is foolishly threatening a veto,” but they they “seem way off message for the American public and even their own party caucuses,” the editors write …

What I don’t read is, that there are some 462.430 children were born with no medical insurance since the actual 110th Congress commenced work. The number is increasing by one child in less than one minute’s time 24/7.  Watch the clock at http://www.childrensdefense.org/site/PageServer. I don’t read either, that actually in 2006 overall 6,9 million minors did benefit from this biggest public health initiative since the Medicaid-Programme in the sixties.

On the same day I read, that the WaPo also criticizes Republicans for blocking efforts to boost the number of low-income children who receive health insurance. The editors note that while Republicans say they “want to concentrate on enrolling poor children” in health insurance programs, they “fail to provide enough money to do so effectively.” Do “House Republicans really want to be arguing for taking away health insurance from children who now have it?” the editors ask …  

What I don’t read is, that the Bush administration plans on 30 Mio. USD for the following 5 years, whereas the first 10 years did cost 40 Mio. USD, while deputies and experts estimate 50 Mio. USD necessary to maintain the momentary insurance situation. Convincing as those figures are for national economists, I want to hear one parent among deputies using them to argue against medical assistance for his own child.

Like the discussion were not about children’s access to necessary healthcare - we are not discussing subsidies to Ben&Jerry’s icecream production - I read that asthmatic children profiting from medical assistance regularly, are 70% less likely to have an attack and need 60% less medical consultations.

I read, that President Bush said he would veto the Schip expansion bill on “philosophical” grounds. That is scary. When did GWB put hands on philosophy, and ”what kind of philosophy says that it’s O.K. to subsidize insurance companies, but not to provide health care to children?”, as NYT columnist Paul Krugman is asking. The way the president presented himself so far, makes the problem even more dangerous. What has he put hands on altogether, as he is hardly able to tell what philosophy is in fact?

Ironically enough, if Bush expresses his veto and his party offers even token support, it might be better for children benefiting from the programme as well as for those left outside. Democratic sweep in 2008 would be then even more likely, after all the Iraqui-war “successes” recently presented to the public; they would bring with them a mandate for serious reform — universal coverage, simplified reimbursement, first-dollar coverage for preventive and chronic care…

There are two distinct, but related, HIV viruses that humans can become infected with — HIV-1 and HIV-2. Individuals infected with HIV-2 progress to AIDS at a dramatically reduced rate compared with individuals infected with HIV-1; in fact, most individuals infected with HIV-2 die of unrelated causes.

It is hoped that understanding why individuals infected with HIV-2 rarely progress to AIDS will help with the design of therapeutics and vaccine strategies for the treatment and prevention, respectively, of infection with HIV-1.

A new study by Aleksandra Leligdowicz and colleagues at the Weatherall Institute of Molecular Medicine, Oxford, demonstrates that individuals infected with HIV-2 mount a strong immune response to a specific region of the viral protein Gag.

The robustness of this response was inversely correlated with the amount of virus detected in the individual. In turn, individuals with high levels of detectable virus had fewer CD4+ T cells, indicating that they were progressing towards AIDS. The authors therefore suggest that T cell responses to Gag are important in determining the better outcome of infection with HIV-2 than infection with HIV-1.

J Clin Invest. 2007 Sep 6; [Epub ahead of print]

Robust Gag-specific T cell responses characterize viremia control in HIV-2 infection.

Leligdowicz A, Yindom LM, Onyango C, Sarge-Njie R, Alabi A, Cotten M, Vincent T, da Costa C, Aaby P, Jaye A, Dong T, McMichael A, Whittle H, Rowland-Jones S.

Pharmindustry lately seems to love funding research about bad HIV guys, who do not take their pills regularly. I assume, it is because those guys ruin the last bits of ROI that can be squeezed out of market in the Western world. That same industry is ways less interested in AIDS-related health issues in what is called the Third World. These studies do find out everytime so amazing things! This time we learn, that unstable and unpredictable lifestyles are significant factors in determining access to health care among low-income HIV-positive people, from a new UCLA study.

The study mirculously found that when HIV patients lead chaotic lives — meaning they are disorganized or experience too many unexpected events — that chaos can act as a barrier to regular medical care. The ingenious researchers even tailored a new scale to gauge the level of chaos in an adult’s life (in case you wanna try?).

The findings suggest a possible new alternative to help ensure that low-income patients get the care they need, said the study’s lead author, Dr. Mitchell Wong, an assistant professor of general internal medicine and health services research at the David Geffen School of Medicine at UCLA. (The study also finds interesting odds concerning racial provenance among participants. But these were less likely to be leading to “new help alternatives” and hence are amiss in the discussion of results.)

“Many people have barriers to care, such as problems with transportation, housing, child care and health insurance. Traditionally, we look to solve these problems with case managers who can help reduce these barriers,” Wong said. “But there’s a whole potential other mechanism which might be happening — that people are just having trouble managing and organizing their lives. I think many of us take for granted the support mechanisms that we have, but many people who are living in poverty don’t have that support network. They don’t have that buffer zone to cope with the unexpected things. Perhaps enhancing stability and organization in people’s lives can also help them get the regular care that they need.”

Some 220 low-income HIV-positive patients participated in the study. Of those, 45 percent were African American, 40 percent were Latino and 20 percent were women. About one-third did not graduate from high school, approximately 75 percent had a history of homelessness and half had used drugs in the previous 30 days. In addition, 45 percent were uninsured and 75 percent had one or more unmet social-service need. In the six months prior to the study, 83 percent had seen a physician for HIV care at least twice, 46 percent missed two or more visits, and one-third had gone to a hospital emergency room at least once.

In developing the new scale to measure chaos in adults’ lives, the researchers took as their model the 15-item Confusion, Hubbub, and Order Scale (CHAOS), designed for parents to assess chaos affecting children’s home lives. The researchers changed some questions in the CHAOS scale to reflect a person’s life in general and whittled the assessment down to six simple statements designed to key in on the level of chaos in patients’ lives. These statements had a five-point response ranging from “strongly agree” to “strongly disagree.”

The statements were:

• My life is organized.
• My life is unstable.
• My routine is the same from week to week.
• My daily activities from week to week are unpredictable.
• Keeping a schedule is difficult for me.
• I do not like to make appointments too far in advance because I do not know what might come up.

The researchers found that those patients who did not have spouses or partners and those with at least one unmet social-service need, such as transportation or housing, scored highest on the chaos scale.

They also found that patients with more chaos in their lives were less likely to have had two or more outpatient HIV care visits and were more likely to have missed two or more visits in the six months prior to enrolling in the study. These patients also had lower mental health status, both when they enrolled in the survey and at follow-up. The researchers, however, did not find an association between life chaos and emergency department visits or physical health status.

The Health Resources and Services Administration, the National Institute on Aging, the Pfizer Foundation, the National Center on Minority Health and Health Disparities, and the National Institute of Mental Health funded the study.

J Gen Intern Med. 2007 Sep;22(9):1286-91. Epub 2007 Jun 28.

The association between life chaos, health care use, and health status among HIV-infected persons.

Wong MD, Sarkisian CA, Davis C, Kinsler J, Cunningham WE.

Virological evidence cannot prove transmission in HIV criminal cases, warn experts in the British Medical Journal.

Viral phylogenetics provides a way of assessing the relations between viruses from different people. It allows us to estimate the probability that viruses from two particular people have a recent common origin. But there are serious limitations on what can and cannot be inferred using this technique.

The recent flurry of criminal cases brought against people in the United Kingdom accused of infecting their sexual partner(s) with HIV has resulted in several convictions, write Professor Deenan Pillay and colleagues in an editorial.

This has caused concern amongst health professionals and community groups about the detrimental effect such cases may have on disclosure of HIV infection and uptake of voluntary HIV testing.

In some cases, attempts have been made to present evidence on HIV viral sequence data in a similar way to DNA fingerprinting.

In our view, this analogy is seriously misleading, say the authors. When attempting to establish that transmission occurred between specific people, virological evidence should be used with caution and only in conjunction with the clinical and epidemiological evidence.

The greatest difficulty lies with the nature of the data, they write. Identifying a link between viruses from two people on its own says nothing about who infected whom. Other difficulties include the unlikelihood that all sexual contacts of all HIV infected people will be available for viral testing, co-infection with genetically diverse strains, and similarities in two virus genomes as a result of convergent or parallel evolution.

They advise caution when interpreting such data because the strength of any apparent linkage between viruses will never approach the degree of certainty generally expected of DNA data in a criminal court.

Phylogenetic evidence — together with clinical and epidemiological evidence regarding likely duration of infection, sexual history, and other relevant factors — can provide support for linkage between cases but cannot prove transmission, they say.

Despite the difficulty in determining linkage between specific individuals, phylogenetics can provide important new insights in investigations, they say. A recent example is a study of the timing of HIV-1 infections among Libyan children in hospital, which showed that most infections occurred before the arrival of the accused medical workers in the country.

It will be important that sufficient checks and balances are in place to allow full use of HIV surveillance data for public health benefit, without concern that the underlying purpose for identifying possible viral genetic linkage between people will be to support criminal proceedings, they conclude.

BMJ  2007;335:460-461 (8 September), doi:10.1136/bmj.39315.398843.BE

HIV phylogenetics

Criminal convictions relying solely on this to establish transmission are unsafe

Deenan Pillay, Andrew Rambaut, Anna Maria Geretti, and Andrew J Leigh Brown
No Abstract availabe - the first 150 words of the full text of this article appear below.

The recent flurry of criminal cases brought against people in the United Kingdom accused of infecting their sexual partner(s) with HIV has resulted in several convictions. This has caused concern among health professionals and community groups about the detrimental effect such cases may have on disclosure of HIV infection and uptake of voluntary HIV testing, which contrasts with the move to normalise HIV testing and clinical care. The potential negative effect of this on the public health programme to reduce transmission of HIV has been widely discussed in these pages^{1 2} and elsewhere.³

Virological evidence, specifically HIV gene sequence data obtained from the defendant and complainant, has been used in these cases because a prerequisite for establishing criminal liability is that the defendant caused the complainant’s infection. Because HIV-1, like other RNA viruses, evolves rapidly, the virus isolated from independently infected people is typically distinct. The extent of similarity between viruses . . . [Full text of this article]

… as it appears in three related papers, providing new insights into the complexity of HIV/AIDS.

Don Sodora, Ph.D., a principal investigator in SBRI’s Viral Vaccines Program who recently joined SBRI from the University of Texas, Southwestern Medical Center, is senior author on one of three papers that collectively show CD4 T-cell depletion, a critical symptom of AIDS, is likely a part of a multifaceted scenario that triggers disease rather than the only cause.

In an HIV-infected person, CD4 T-cells (white blood cells that play a central role in creating immunity) decline and, at a certain point, the person gets sick and dies. This rapid and dramatic loss of CD4 T-cells is considered to be a key determinant of AIDS disease. However, in natural hosts, like the sooty mangabey (an African monkey species), simian immunodeficiency virus (SIV) induced CD4 T-cell depletion can be comparable to that in humans, but the monkeys do not show clinical signs of AIDS. “Our assessment of these natural hosts like mangabeys offers insight into the disease and shows us that progression to AIDS likely results from the cumulative effects of HIV/SIV replication, CD4 T-cell depletion, generalized immune activation and non-CD4 T-cells depletion or dysfunction,” said Sodora.

Sodora’s paper provides evidence, using the sooty mangabey SIV natural host, that virally induced CD4 T-cell depletion, by itself, is not sufficient to induce AIDS in a natural host. “When we first observed the dramatic CD4 depletion in all the tissues we examined in these monkeys, we were concerned that they might begin to exhibit clinical signs of AIDS,” said Jeffrey Milush, Ph.D., lead author on the paper. “But after more than six years, we are sure that CD4 depletion by itself does not necessarily result in progression to AIDS”.

Sodora contributed to a second paper, with senior author Guido Silvestri, M.D., of the University of Pennsylvania. In a study of disease free SIV–infected sooty mangabeys, Silvestri proposes that these African monkeys preserve immune function despite a major loss of mucosal CD4 T-cells as a result of an evolutionary adaptation to reduce immune activation in response to virus replication.

The third of the three papers published this week in The Journal of Immunology, with Ivona Pandrea, M.D., Ph.D., and Cristian Apetrei, M.D., Ph.D., from Tulane University as lead authors, shows that a severe loss of intestinal CD4 T-cells in another natural host, the African green monkey, is also not predictive of SIV virulence.

“These three papers published together indicate that CD4 T-cell depletion is one part of a more complex scenario that results in the clinical signs identified as AIDS,” Sodora said. “We hope that studies in these natural host models will lead to improved HIV vaccines or new therapeutics that might someday make HIV-infected people more like these disease-resistant sooty mangabeys.”

J Immunol. 2007 Sep 1;179(5):3047-56.

Virally Induced CD4+ T Cell Depletion Is Not Sufficient to Induce AIDS in a Natural Host.

Milush JM, Reeves JD, Gordon SN, Zhou D, Muthukumar A, Kosub DA, Chacko E, Giavedoni LD, Ibegbu CC, Cole KS, Miamidian JL, Paiardini M, Barry AP, Staprans SI, Silvestri G, Sodora DL.

J Immunol. 2007 Sep 1;179(5):3026-34.

Severe Depletion of Mucosal CD4+ T Cells in AIDS-Free Simian Immunodeficiency Virus-Infected Sooty Mangabeys.

Gordon SN, Klatt NR, Bosinger SE, Brenchley JM, Milush JM, Engram JC, Dunham RM, Paiardini M, Klucking S, Danesh A, Strobert EA, Apetrei C, Pandrea IV, Kelvin D, Douek DC, Staprans SI, Sodora DL, Silvestri G.

Acute Loss of Intestinal CD4+ T Cells Is Not Predictive of Simian Immunodeficiency Virus Virulence.

Pandrea IV, Gautam R, Ribeiro RM, Brenchley JM, Butler IF, Pattison M, Rasmussen T, Marx PA, Silvestri G, Lackner AA, Perelson AS, Douek DC, Veazey RS, Apetrei C.

see also:

J Exp Med. 2007 Sep 3;204(9):2171-85. Epub 2007 Aug 27.

Progressive CD4+ central memory T cell decline results in CD4+ effector memory insufficiency and overt disease in chronic SIV infection.

Okoye A, Meier-Schellersheim M, Brenchley JM, Hagen SI, Walker JM, Rohankhedkar M, Lum R, Edgar JB, Planer SL, Legasse A, Sylwester AW, Piatak M Jr, Lifson JD, Maino VC, Sodora DL, Douek DC, Axthelm MK, Grossman Z, Picker LJ.

Socioeconomic position is a determinant of antiretroviral treatment effectiveness during initial therapy for HIV-1 infection. The effect was found in a study from Harvard School of Public Health (HSPH), Massachusetts General Hospital, Stanford University Medical School, and the American Psychological Association, even among subjects with high rates of drug adherence, according to a study published in the August 1 issue of the Journal of Psychosomatic Research. One probably has to live in Harvard to wonder how this is possible. And one does not have to wonder that there are means for such amazing research, as the study was supported by grants from GlaxoSmithKline, Pfizer, and Novartis. In case you wonder why those companies are interested in behavioral factors influencing patient’s compliance see: with adequate profit, capital is very bold - HIV market to top $10 billion

The researchers used data from a clinical trial that recruited HIV-positive men and women in the U.S. and Italy who had not previously taken any HIV medications. The study participants were being treated with highly active antiretroviral treatment (HAART), a combination of antiretroviral drugs sometimes referred to as an AIDS “cocktail.”

Scientific literature suggests that stress and emotional distress predict a faster decline in the immune system cells that can fight HIV progression. Previous studies have shown that people at lower socioeconomic positions often report chronic life stressors. The HSPH team and its collaborators wanted to examine whether socioeconomic position would influence immune functioning and response to antiretroviral treatments, even if patients adhered to their antiretroviral drugs. The researchers used the educational level of subjects as a measure for socioeconomic position.

The study’s authors documented the length of time until a participant first experienced a regimen failure, meaning that the drug combination had failed to maintain low HIV levels in the bloodstream or that HIV drugs had been changed or stopped. The researchers found that participants with lower levels of education reached initial regimen failure faster than participants with a college- or graduate-level degree.

However, participants with high levels of so-called “adherence self-efficacy,” despite lower education levels, experienced a reduction in initial regimen failure by 15 to 17 percent. Adherence self-efficacy was described by the authors as a coping resource that reflected the strength of the patient’s belief in the effectiveness of their medication and their ability to adhere to their treatment regimen. The authors suggest that one reason behind this association may be that coping styles are known to be associated with better immune functioning in individuals with HIV disease.

“These findings support health promotion programs focusing on psychological and behavioral aspects associated with therapeutic regimens, which might not otherwise be considered in the treatment of HIV,” said Linda Marc, who led the research project while a Doctor of Science candidate in the Department of Society, Human Development, and Health at HSPH. Marc is now a lecturer at Yale School of Public Health and chair of the HIV/AIDS Special Interest Group for the International Society for Quality of Life Research.

Marc and her team also point out that the study’s results may be particularly relevant to HIV care in the developing world. However, Marc noted, it is unknown if these results can be extrapolated to resource-poor settings because the trial was conducted with participants who live in developed nations. Marc added that since little is known about the impact of stressors on immune functioning in resource-poor settings, she believes there is a need to promote research methods in these parts of the world that simultaneously examine biological and social factors.

“In this way, researchers can better understand the variations of immune functioning and determine what proportion of treatment failure is modifiable through social variables, in contrast to known biological factors of HIV treatment effectiveness,” she said.

J Psychosom Res. 2007 Aug;63(2):207-16.

Educational attainment and response to HAART during initial therapy for HIV-1 infection.

Marc LG, Testa MA, Walker AM, Robbins GK, Shafer RW, Anderson NB, Berkman LF; for the ACTG Data Analysis Concept Sheet Study Team.

By furthering scientists’ understanding of the molecular mechanisms that separate the minority of successful HIV antibodies from the majority of ineffective antibodies, the work may have implications for future attempts to design an HIV vaccine. The study was published on September 6, 2007, in the journal Nature,

“This study is part of the effort to understand how protection against HIV occurs,” says Dennis Burton, a professor at The Scripps Research Institute. “If we really understand this, then we can design tailor-made vaccines in a way that has never been done before.”

Although vaccines have long been used with great success to prevent diseases, scientists are still learning about the exact mechanisms of how vaccines work and how the antibodies that vaccines prompt the body to create can neutralize a pathogen. The spread of HIV, which is resistant to most antibodies the body produces against it, has made fully understanding this method of action more urgent.

With this in mind, Burton and colleagues sought to tease apart the action of the b12 antibody-one of the rare antibodies that protects against the HIV virus. The antibody, first identified by Burton, Scripps Research Professor Carlos Barbas III, and colleagues in 1992, originally came from the bone marrow of a 31-year-old male who had been HIV positive without symptoms for six years.

In the current study, researchers created mutated versions of b12 to see what effect various changes would have on the antibody’s effectiveness.

“Hopefully, we can work backwards towards a vaccine, using b12 and the very few other really great, broadly neutralizing antibodies against HIV that have been found,” says Scripps Research Senior Research Associate Ann Hessell, who was first author of the Nature paper jointly with Lars Hangartner, a Scripps Research postdoctoral fellow.

Results from the new study suggest the importance of antibody activity against both infected cells and free virus for effective protection. As well as simply binding to HIV, protection was dependent upon the ability of antibodies to interact with immune cell Fc receptors.

Fc receptors are found on the surface of immune cells, such as natural killer cells. The Fc receptor binds to the Fc region of an antibody after an antibody binds to a pathogen, targeting the pathogen for attack by the immune system. Although Fc receptor function was known to be important for the function of antibodies against other diseases, a role in protecting against HIV had never before been demonstrated.

Burton’s team examined the ability of two antibodies mutated from b12, dubbed KA and LALA, to prevent infection using the SHIV/macaque model, in which macaques are challenged with a hybrid human-simian virus that infects the model but is recognized by human antibodies. The KA antibody contained a mutation that prevented it from interacting with the complement cascade, a major component of the immune system responsible for destroying invading pathogens. The LALA antibody contained a mutation that rendered it unable to interact with either the complement pathway or the Fc receptor.

In both mutants, the site where the antibody binds to free-floating virus was unaltered, allowing the researchers specifically to investigate the importance of the complement cascade and Fc receptor system for preventing infection.

“We saw that the KA antibody, which could still bind to the Fc receptors on the immune cells but not to the complement cascade, protected the animals from becoming infected just as the wild type b12 antibody,” says Hessell. “In contrast, the LALA group became infected much like the controls.”

The results provide the first evidence that the Fc receptor, but not the complement cascade, is important to the function of the b12 antibody in preventing HIV infection.

Additional in vitro experiments revealed that the wild type and KA antibodies, but not the LALA antibody, blocked infection more efficiently in the presence of other effector cells of the immune system.

“Our results are fully consistent with the antibody doing two jobs,” says Burton, “job one, stick to the virus; job two, recruit immune cells to come and kill infected cells.”

Nature. 2007 Sep 6;449(7158):101-4.

Fc receptor but not complement binding is important in antibody protection against HIV.

Hessell AJ, Hangartner L, Hunter M, Havenith CE, Beurskens FJ, Bakker JM, Lanigan CM, Landucci G, Forthal DN, Parren PW, Marx PA, Burton DR.

J Immunol. 2007 Sep 1;179(5):3144-52.

Inhibition of HIV-1 Infectivity and Epithelial Cell Transfer by Human Monoclonal IgG and IgA Antibodies Carrying the b12 V Region.

Mantis NJ, Palaia J, Hessell AJ, Mehta S, Zhu Z, Corthésy B, Neutra MR, Burton DR, Janoff EN.

Physicians might want to be extra careful about how they treat HIV-infected patients –not just in the clinical sense but in the way they behave toward them.

Even the perception that physicians are stigmatizing patients for carrying the virus that causes AIDS can discourage these individuals from seeking proper medical care, according to a new UCLA study.

The mentioned study found that up to one-fourth of patients surveyed in the Los Angeles area reported feeling stigmatized by their health care providers. This perception was also linked to low access to care among these patients, a large proportion of whom are low-income and minorities.

“Whether or not it is actual stigmatization is hard to measure, because it’s coming from the patients that we interviewed,” said UCLA researcher Janni J. Kinsler, the study’s project director and lead researcher. “The point is that these people feel that way, and that’s bad enough, because they’re less likely to seek the care they need.”

The study results were based on surveys of 223 HIV-positive individuals in Los Angeles County, with initial baseline interviews taking place between May 2004 and June 2005 and follow-up interviews conducted six months later, from November 2004 to December 2005. Of the respondents, 80 percent were male, 46 percent were African American and 40 percent were Latino.

Nearly three-quarters had a high school education or less, half had annual incomes below $8,000 and 46 percent did not have insurance. In addition, 54 percent of the patients reported that they became infected through homosexual contact, 30 percent through heterosexual contact and 16 percent through intravenous drug use.

There are two types of stigma: external, or “public,” stigma and personal, or “perceived,” stigma. The latter refers to individuals’ anticipated fears of societal attitudes or discrimination because their HIV infection.

Researchers questioned 223 patients during the baseline interviews and 171 during the follow-up. They were asked the following questions about stigmatization:

Since you contracted HIV, has any health care provider:

• Been uncomfortable with you?
• Treated you as inferior or in an inferior manner?
• Preferred to avoid you?
• Refused to serve you?

Patients were also asked six questions related to their access to health care: whether they had gone without medical care due to expense, if medical care was conveniently located, whether they could obtain medical care whenever they needed it, if they had easy access to medical specialists, if emergency care was easily obtainable and if they could be admitted to hospitals with no trouble.

The researchers found that at baseline 26 percent of the patients reported at least one of the four types of perceived stigma from a health care provider, and 19 percent reported the same at follow-up. Also, 58 percent claimed low access to care on at least one of the six relevant questions at baseline, as did 57 percent at follow-up.

“Most importantly, we found that those who perceived stigma from a health care provider had more than twice the odds of reporting low access to care, even after examining the effect prospectively and adjusting for a host of sociodemographic and clinical characteristics,” the researchers said.

Researchers noted the significance that perceived stigma “could greatly affect [patients'] use of needed medical services, including antiretroviral therapy.” Because of this, patients may seek medical care only when their illness has progressed to a more severe stage, leading to more intensive medical interventions, hospitalization and earlier death.

The next step is to investigate whether physicians are in fact stigmatizing these patients, Kinsler said.

AIDS Patient Care STDS. 2007 Aug;21(8):584-92.

The Effect of Perceived Stigma from a Health Care Provider on Access to Care Among a Low-Income HIV-Positive Population.

Kinsler JJ, Wong MD, Sayles JN, Davis C, Cunningham WE.

 see also:

Stigma