Friday, March 30, 2007

Refrigeration and HIV Meds in Resource-limited Settings

I'm Charlie Raver.

One of the distinguishing characteristics between the AIDS epidemic in the developed world and that in Africa and the developing world is a simple lack of the infrastructure to deal with the disease. Infrastructure includes everything from roads to electricity to hospitals. One example that most of us rarely think of as a gift, couldn’t dream of walking into a home and not finding, and would be lost without is something to which many in the developing world do not have access. What am I talking about? Refrigeration. Without this amazing piece of technology we would not be able to easily enjoy fresh meats, fish, dairy, and many simple nutritional luxuries that we as Americans take for granted. In addition to problems with food preservation, hospitals and health clinics would be unable to store blood, vaccines, heat intolerant medicines, and many laboratory supplies.

For many in the developing world that is exactly the problem. Without refrigeration they have no means to store many of the supplies necessary for maintaining a health clinic. Without this infrastructure, access to basic care, essential for the treatment of AIDS, is extremely limited. Recently, the WHO recommended the use of a ritonavir boosted protease inhibitor as part of the drug regimen. Aside from being able to obtain the drug, one problem is that ritonavir requires refrigeration in hot climates. Currently only one of the ritonavir boosted PIs is available in a heat stable form which, obviously puts a huge constraint on the availability of the drug in the developing world. A confounding issue is the high rates of coinfection of diseases such as tuberculosis and malaria in these resource poor areas. In addition to proper care, access to testing for HIV and TB has been cited as one of the first obstacles to fighting the epidemic. The WHO estimates that less than 10% of people living with HIV/AIDS in parts of Sub-Saharan Africa are aware of their HIV status.

In addition to poor access to health care, the epidemic is only made worse by the staggering rates of malnutrition. In their recommendations for antiretroviral therapy, the WHO emphasized the importance of nutrition not just for the overall health of the affected individuals but also because of the link between nutrition and the effectiveness of ART. However, in some parts of Sub-Saharan Africa, it is estimated that as much as 50% of the population is malnourished. Many Africans do not even have the means to buy or grow the most basic foods. This problem is again only made worse by the lack of refrigeration. Some form of food preservation could allow rural communities and individuals to grow crops in excess and store the surplus to either sell and trade with other communities or even just maintain a supply during the non-productive parts of the year. However, when you consider that over 500 million people in Sub-Saharan Africa do not have access to electricity the idea of refrigeration is a long shot.

Unfortunately providing those in rural Africa with electricity is a problem unto itself. Without economic stability there is little room for expansion and improvement of infrastructure whether it is roads, electricity or health care. These lacks in infrastructure only make the AIDS epidemic harder to fight which further hinders economic growth. However, small improvements like access to refrigeration could be a catalyst for change.

One type of refrigeration that requires no electricity is sorption refrigeration. This form of refrigeration works by having two chambers connected by some type of tube. One chamber, the hot side, contains an absorbent material. The other chamber, the cold side, contains a refrigerant. The tube connecting the two would be filled with refrigerant vapor. The vapor in the tube is then absorbed on the hot side causing a drop in pressure in the connecting tube. This causes evaporation of the refrigerant which in the process absorbs heat and causes cooling on the cold side. This continues until all the refrigerant has vaporized and been absorbed on the hot side. To restart the cooling process, the hot side must be heated gently to drive the refrigerant vapor out of the absorbent material and back to the cold side. In the late 1920s, Powell Crosley Jr. developed a commercial version using ammonia and water that was used throughout the rural United States prior to wide-spread access to electricity. Although this is by no means a large scale solution to the infrastructure problem, adaptation of these ideas for use in the developing world could provide one of the basic necessities for health care and food preservation.

Friday, March 23, 2007

AIDS Orphans in Sub-Saharan Africa

I'm Christie Brough

According to the AIDS Epidemic Update of December 2006, about 25 million people are living with HIV in sub-Saharan Africa, comprising 63 percent of all individuals with HIV globally. Approximately 13.3 million, or 59 percent, of these individuals are women, most of whom have children. Although considerable efforts have been made to provide these individuals increased access to antiretroviral therapy, 2.1 million Africans died in 2006, resulting in an increased number of AIDS orphans.

In 2001, 14 million children had already lost one or both of their parents to AIDS. Because of the difficulty of obtaining antiretroviral therapy, many more children will be affected. In fact, one estimate projects that the number of AIDS orphans will increase by approximately 150 percent by the year 2010, leaving 20 million children to raise themselves.

As children watch their parents succumb to AIDS, they often suffer psychological and emotional harm. Once a parent becomes too sick to work, children are forced to work themselves in order to raise money for their families or to take care of younger siblings, causing them to drop out of school. Another factor forcing children to drop out of school is their inability to pay for required items, like school uniforms, pencils, textbooks, and exam fees, which they no longer can afford. If they do not have these items for school every day, they may be sent home and told not to return until they have the proper materials. Children that continue to attend school despite their parent’s illness often display a lack of attention or inappropriate behavior in the classroom, which is thought to result from emotional stress. Academic performance is also negatively affected by child malnutrition. Malnutrition is common in AIDS-related poverty since most of the family’s resources must be spent on medication for the ill parent. As a result, school enrollment rates in sub-Saharan Africa are dropping as the death toll from AIDS continues to rise.

Children that grow up without parents and without an education are “trapped in a social and pedagogical vacuum.” These children are not only more vulnerable to contract HIV/AIDS, but they are also at higher risk of unemployment, exploitation, and other forms of social inequalities. In order to change the outlook for AIDS orphans in sub-Saharan Africa, international and national agencies must aid in providing greater access to antiretroviral treatment. One relatively successful example is the World Heath Organization’s 3-by-5 program. The 3-by-5 plan aimed at providing 3 million individuals worldwide antiretroviral treatment by 2005. Although the program did not meet its goal of treating 3 million HIV positive individuals in the 2-year period, the program successfully provided access to many individuals who were not receiving treatment before. According to the World Health Organization, the number of individuals receiving treatment in sub-Saharan Africa increased by more than 800 percent, increasing the distribution of antiretroviral drugs from 100,000 individuals to 810,000 individuals.

Although the success of the 3-by-5 program will decrease the number of AIDS orphans in future generations, programs must be implemented to save current AIDS orphans. One option is the development of vocational training programs, which could help orphans stay off the streets (especially, young girls who are forced into sex work). If funds from debt relief programs are channeled directly into schools, school enrollment might increase. Another option is to offer government subsidies to extended families, which might help children stay out of work and stay in school. Additionally, providing government subsidies would maintain a family structure for children, keeping them out of orphanages. While these appear to be wonderful programs, the effectiveness of these programs would be difficult to monitor. Thus, before any programs are employed, local, national, and international governments and agencies want to ensure their success. However, it is imperative that these agencies act quickly before it is too late.

Friday, March 16, 2007

Stigma in the Lives of HIV+ Healthcare Workers

I'm Pete Levandoski

Advances in HIV related pharmacology have given HIV patients extended lifetimes, turning them from dead men walking to living individuals with a debilitating condition. In treating any patient, HIV status not withstanding, the American Dental Association states that dentists should practice, “high ethical standards which have the benefit of the patient as their primary goal” (Rhode Island Dental Association, 2006). If the maxim is adhered to, dentists should have no problems treating HIV positive individuals who come to them seeking care. The fear of exposure to the virus however, has led some dentists to refuse treatment. In these instances, the Supreme Court has stepped in, ordering treatment and protecting the rights of patients. However, in jumping to the aid of patients, the High Court may have inadvertently aided efforts to discriminate against those living with HIV.

A landmark case for HIV patients was the 1998 affirmation of the ruling in Abbott vs. Bragdon. Sidney Abbott, an HIV positive individual, successfully argued that in refusing to treat him because he was HIV positive, Dr. Rondon Bragdon had violated the Americans with Disabilities Act. Bragdon’s unsuccessful defense was that Abbott’s HIV represented a “direct threat” to his own health (Sfikas, 2002).

In May of 2002, the “direct threat” defense was again used, this time in the case of Waddell vs. Valley Forge. The Court ruled that Spencer Waddell, an HIV positive dental hygienist, could be removed from his job because his disease was a “direct threat” to the health of his patients (Sfikas, 2002). The sum of these two decisions is that the idea of “direct threat” can legally be used to protect patients but not to protect dentists.

The same code of ethics that puts patients first also claims that this goal has lead to, “…society affording to the profession the privilege and obligation of self-government” (Rhode Island Dental Association, 2006). Above all, dentists want to retain autonomy and self regulation. In the process of trying to protect patients, these two court decisions have reduced the autonomy of dentists. Decisions in the cases of Waddell and Abbott should have been made by dental professionals, argues Peter Sfikas in his article in the March 2002 Journal of the American Dental Association (Sfikas, 2002).

In the Abbott case, the procedure being performed was a cavity filling, which involves little to no blood. In the Waddell case, root planning, which involves a large amount of blood, was being done. The courts made the correct decision in siding with the patient when looking at the evidence in each specific case (Sfikas, 2002). However, instead of maintaining a case by case system, the courts have set precedents which issue blanket statements without regard for case specifics. This has lead to the reality that the only way a dentist can refuse treatment is by preemptively providing evidence of a “direct threat” to his or her health from the patient (Sfikas, 2002).

These two court cases have gone a long way to advancing the rights of HIV positive patients. The Supreme Court stepped in and set a precedent to prevent HIV positive individuals from being denied healthcare. The Waddell case however, could be spun to deny rights to HIV positive individuals (Sfikas, 2002). The Court gave Spencer Waddell’s employer the right to fire him because he was HIV positive. In trying to protect the rights of patients, the court system has set a legal precedent which discriminates against HIV positive workers if they pose a “direct threat” to the health of their customers (Sfikas, 2002).
Waddell’s case was denied writ of certiorari by the Supreme Court, so it will be up to future cases to decide whether or not firing an employee because they have HIV is legal (Waddell v. Valley Forge Dental Assocs. 2002). Whatever decisions are made in future cases; these two examples highlight the complex interplay between human rights and stigma that HIV positive individuals still face in the United States today.


Sources
Sfikas PM. “HIV and discrimination: A review of the Waddell case and its implications for health care professionals”. The Journal of the American Dental Association. Vol. 133, March 2002. (pp. 372-374).
Rhode Island Dental Association. “Principles of Ethics & Code of Professional Conduct”. 2006.< http://www.ridental.com/ethics.cfm>. (29 November 2006).
Waddell v. Valley Forge Dental Assocs. 535 U.S. 1096. US Supreme Court. 2002.

Friday, March 09, 2007

AIDS dementia: Current findings

Welcome to The AIDS Pandemic, a podcast hosted by Dr. David Wessner from the Department of Biology at Davidson College. I'm Steve Halliday.

One of my most striking memories from my time spent in the hospital in Mwandi was towards the end of my stay when I saw a woman suffering from AIDS dementia who was in the courtyard screaming at the top of her lungs. I asked one of the hospital employees what was going on, and he responded “oh, she is confused.” Since that moment I’ve been interested in this symptom of late stage AIDS, and in today’s installment I am going to look at a paper that examines one possible cause of AIDS dementia, titled HIV-1 Promotes Quiescence in Human Neural Progenitor Cells by Krathwohl and Kaiser.

AIDS dementia is a purely clinical diagnosis, based on observations of cognitive decline and motor dysfunction, and occurs in approximately 6-15% of AIDS patients. The pathology of AIDS dementia remains elusive, however, and this article represents only one theory of how it is caused.

The article examines the possibility that HIV could inhibit the activity of recently discovered neural progenitor cells. These cells have been found to be capable of differentiating into new astrocytes and neurons, which are thought to then form synaptic connections with other neurons, increasing memory and replacing lost neurons in the hippocampus.
These progenitor cells exist in quiescent states until they are needed, and it has been found that these cells can be forced into quiescence by chemokines, which can be mediated by CXCR4 or CCR3. Because HIV-1 uses chemokine coreceptors it is thought that it may inhibit proliferation of progenitor cells and force them into quiescence.

To test whether HIV-1 could induce quiescence, the researchers used purified recombinant coat proteins from several stains of HIV-1 using proteins that signal through either CXCR4 or CCR3. They found that two strains caused plated progenitor cells to enter a quiescent state, reducing proliferation by 67 and 74%, while a third strain had no visible effect. They also discovered that by washing the plates the cells were able to begin differentiating again. The researchers went on to determine that the coat proteins of the effective strains induced expression of cyclin-dependent kinase inhibitors p21 and p27.

The researchers then sought to prove the HIV-1 coat proteins were mediated by chemokine receptor binding. They found that by adding pertussis toxin, which affects the G-proteins linked to chemokine receptors, the inhibitory effects of both effective strains were blocked, suggesting the suppressive effects of HIV-1 are mediated by chemokine receptors.
In addition to direct inhibition, HIV-1 was found to suppress phosphorylation of ERK, which stimulates neural progenitor cells. The two effective strains of HIV-1 were found on to inhibit ERK by 34 nad 77%. This was also shown to occur by signaling through chemokine receptors.

Having established that HIV-1 can inhibit neural progenitor cell differentiation, the researchers examined CerebroSpinal Fluid from patients suffering from AIDS dementia, and discovered that the CSF from patients suffering from dementia was able to suppress progenitor cells by 67% whereas CSF from patients without dementia showed no inhibitor effect.
They also determined that gp120 was responsible for this inhibition. Furthermore they determined that viral load for patients with and without dementia was similar, and presence or absence of antiretroviral therapy had no effect on the inhibitory effect of the CerebroSpinal Fluid.

The researchers then proved that both the HIV-1 coat proteins and the CSF from patients with dementia could reduce neural cell proliferation in human hippocampal tissue in vitro, and that autopsied hippocampal tissue from patients with dementia was found to contain 75% fewer neural progenitor cells than in patients without dementia.

This paper provides seemingly very conclusive evidence for the role of neural progenitor cells in AIDS dementia, but this is by no means the only area of research going on in AIDS dementia. Another paper, Pharmacological frontiers in the treatment of AIDS dementia by McGuire and Marder, discusses possibilities that reactants to viral products and macrophages may cause neuronal cell death, leading to dementia via a more direct route.

The pathology of AIDS dementia is complex and not easily deciphered, but hopefully with this continuing research an effective treatment can be found for this devastating AIDS related illness.

This is Steve Halliday signing off.

Friday, March 02, 2007

HIV/AIDS in Prisons

Welcome to this installment of the AIDS Pandemic, a podcast hosted by Dave Wessner of the Department of Biology at Davidson College. I am Justin Fried.

Prisons have become a fertile ground for the HIV epidemic in the United States. In fact the Joint United Nation Programme on AIDS (UNAIDS) listed prisoners as one of the four "major at-risk and neglected populations" in the HIV/AIDS pandemic (2006 Report on the Global AIDS Epidemic). The other three categories included men who have sex with men, injection drug users, and sex workers (2006 Report on the Global AIDS Epidemic). Recent figures show that 2.3 percent of state prison inmates, and 1.0 percent of federal prison inmates in the United States are HIV positive, and an estimated 20 to 26 percent of people living with HIV have spent time in the correctional system (2006 Report on the Global AIDS Epidemic and Kantor 2006). The overcrowded and typically understaffed prisons in the United States are ideal breeding grounds for HIV. HIV is transmitted through bodily fluids with sharing needles and unprotected sex being the leading causes of virus transmission. Despite strict regulations against drugs in prisons, intravenous drug use still occurs. Clean needles are almost impossible to find and needles or improvised injection devices are often shared by inmates. These needles may also be shared for tattooing, another common practice in prisons. In addition to drugs, many inmates turn to sex to escape the boredom of prison life. Because distribution of condoms is prohibited in most penal institutions across the United States, safe sex is not even an option for most inmates. Sexual assault and rape, which are common intimidation tactics used by inmates, are also potential sources of transmission of HIV in correctional facilities (2006 Report on the Global AIDS Epidemic).

While high risk behaviors common to prisons put inmates at a higher risk for HIV infection while incarcerated, most HIV positive prisoners were infected before being sent to prison (HIV/AIDS Prevention). Indeed, the populations most vulnerable to the HIV infection are the same communities at high risk for criminalization and incarceration (HIV/AIDS Prevention). Fear of discrimination deters prisoners from accessing the voluntary HIV testing available in most prisons. Test result confidentiality is a major issue in a prison environment where even the suspicion of a positive test result can lead to stigmatization, bringing social isolation and violence from other inmates and sometimes even prison staff. The fear of stigmatization also discourages many inmates living with HIV from seeking medical services and treatment. Prison conditions also undermine the dosing schedules that are important for the effectiveness of antiretroviral therapy. Transfers of inmates to different correctional institutions or to and from courthouses can cause gaps in treatment. Searches for contraband may also result in medicine confiscation (Kantor 2006).

Addressing the problem of HIV and AIDS in prisons requires a multifaceted approach. UNAIDS believes that it is essential that prisoners be allowed access to prevention materials, including condoms, safer-sex supplies, and bleach kits for cleaning needles (HIV/AIDS Prevention). Increasing HIV and AIDS awareness through prisoner health education programs is crucial to decreasing the stigmatization of HIV inside prisons that prevents many inmates from seeking testing or treatment. For inmates living with HIV, provisions must be taken to ensure the regular interruptions of a prisoner’s life do not interrupt his or her antiretroviral therapy.

The Hampden County Correctional Facility in Massachusetts is a prison which is taking steps towards providing preventive education and effective health care to its inmates. This prison has adopted a health care program based on a public health model that provides inmates with a community-based standard of care (Kahn 2000). This program is based around five basic tenets: detection, effective and prompt treatment, education, prevention, and continuity of care. Prisoners undergo a three-day orientation upon admission and are given a full physical exam including tests for common communicable diseases. After attending an intensive peer-led educational session on HIV and AIDS, new inmates are encouraged to take an HIV test. Inmates that test positive for HIV then undergo additional tests to determine how best to proceed with treatment. Doctors, nurses, and case managers from the community are brought into the jail to deliver services to inmates. After the prisoners are released they have the option of continuing with the same primary care providers through a comprehensive discharge plan that includes Medicaid benefits and other supportive services (Kahn 2000).

The Hampden County Correctional facility is taking steps in the right direction, but fighting HIV in prisons is an uphill battle that will require revolutionizing prison health care. For changes to be made, Americans must first recognize that prisons are not isolated from the world, and that most inmates will eventually be released and infections acquired inside prison walls can be transmitted to the society outside. Preventing and treating HIV in prisons will benefit society as a whole and is important in the fight against AIDS.

Until next time, I am Justin Fried.
References

At Risk and Neglected: Four Key Populations. 2006 Report on the Global AIDS Epidemic. Joint United Nation Programme on AIDS. 2006. Retrieved Dec 2, 2006 from http://data.unaids.org/pub/GlobalReport/2006/2006_GR_CH05_en.pdf

HIV/AIDS Prevention, Care, and Treatment in Prison Settings: A Framework for an Effective National Response. Health Organization and Joint United Nation Programme on AIDS. 2006. Retrieved Dec 2, 2006 from
http://data.unaids.org/pub/Report/2006/20060701_HIV-AIDS_prisons_en.pdf.

Kahn, Stanya. Fire in the belly: A model program stresses community involvement. AIDS Info NYC. January 2000. Retrieved Dec 2, 2006 from http://www.aidsinfonyc.org/hivplus/issue6/report/model.html.

Kantor, Elizabeth. HIV Transmission and Prevention in Prisons. HIV Insight. April 2006. Retrieved Dec 2, 2006 from http://hivinsite.ucsf.edu/InSite?page=kb-07-04-13