Friday, September 19, 2008

AIDS-related dementia

I’m Bevin English

Since the early stages of the AIDS pandemic, doctors have known about an important neurological complication of HIV infection. This condition, known as AIDS-related dementia, AIDS dementia complex (ADC), or HIV-associated dementia (HAD), is a complex and poorly understood disease, and has the potential to greatly impact many people’s lives, including HIV-positive individuals and their families and close friends. In the United States, HIV-1 is the most common cause of dementia in adults under the age of 40. Also, neurological impairment affects roughly 60% of HIV-positive patients throughout the world. The major causes of neurological impairment include opportunistic infections, such the parasite toxoplasmosis, and AIDS-related dementia.

The primary symptoms of AIDS-related dementia include cognitive impairment, such as the inability to concentrate and impaired short-term memory; motor dysfunction, including leg weakness, affected gait, and slow hand movements; and behavioral changes, such as depression, apathy, and social withdrawal. In rare cases, the dementia progresses so that the patient is in a nearly vegetative and mute state. Before the introduction of highly active antiretroviral therapy (HAART) in the mid-1990s, AIDS-related dementia affected up to 30% of HIV-positive individuals, but the current prevalence has dropped to approximately 10% in areas with high HAART availability. However, a less-severe form of the disease, called minor cognitive motor disorder (MCMD), has become more prevalent in regions where HAART is widely available, with estimates ranging up to a 30% prevalence rate. This high prevalence rate shows that HAART is not sufficient in reducing neurological impairment in HIV-positive individuals.

Despite years of research and progress, much remains unknown about HIV’s interaction with central nervous system (abbreviated CNS; this includes the brain and spinal cord), and this lack of knowledge has serious implications for treatment. HIV is found in the CNS of all AIDS-related dementia patients, but there is still controversy regarding how HIV enters the CNS. The brain is protected by the blood-brain barrier, which is a selectively permeable layer of tightly-linked endothelial cells that carefully regulate what enters and exits the CNS. While many things are excluded from the brain by the blood-brain barrier, some immune system cells are allowed to cross the barrier. The most widely accepted theory to explain HIV’s entry into the brain is the “Trojan horse hypothesis,” which states that infected monocytes (cells that later mature into macrophages) cross the barrier and carry HIV into the CNS. However, there are other possible explanations for the presence of HIV in the brain. For example, infected CD4+ T-cells may also carry the virus into the brain. It is also possible that the virus may be able to directly cross the blood brain barrier, especially if the barrier’s integrity is compromised, or that the cells that make up the barrier ingest the virus and expel it in the brain in a process called transcytosis. Because the virus may enter the CNS through many pathways, most of which are not fully understood, it will be difficult for scientists to come up with treatments to prevent the entry of HIV into the brain in the near future.

Once in the CNS, HIV’s most devastating effect is the sheer loss of neurons. For example, 20-40% of neurons are lost in the frontal cortex, a region of the brain that is involved in planning, coordinating, controlling, and executing behavior (or more specifically, impulse control, judgement, language production, working memory, motor function, and socialization). This large loss in neurons can be seen in the CT scans below (image courtesy of AIDS Images Library )

However, HIV cannot infect neurons because they do not express CD4, but instead HIV persists in the CNS by infecting other cells; thus, neurodegeneration is not a result of active infection of neurons. There are two major pathways for neuropathogenesis in AIDS-related dementia: direct and indirect. The direct pathway includes the effects of different viral proteins on neurons. For example, three HIV proteins, gp120, Tat, and Vpr, have been shown to cause neuronal cell death through many different pathways. Further, Tat has been shown to increase the permeability of the blood-brain barrier, thus increasing the amount of HIV that can enter the CNS. The indirect pathway of neuropathogenesis involves infected cells’ secretion of chemicals that harm neurons. For example, when activated by infected macrophages, astrocytes, which normally provide support for neurons, actually secrete neurotoxins. Thus, HIV causes neuronal cell death through many different mechanisms, making AIDS dementia extremely difficult to treat.

Despite these difficulties, many scientists have been investigating treatments to prevent or slow the progession of AIDS-dementia. Many antiretroviral treatments currently in use cannot penetrate the blood brain barrier, and the few that can enter the CNS do so very inefficiently. For example, protease inhibitors, an entire class of drugs, are actively pumped out of the CNS. The ineffectiveness of current antiretroviral treatments in penetrating the blood-brain barrier has led scientists to investigate other means of preventing neuronal cell death. Many different compounds that block different steps in the pathways that cause neuronal death have been tested in AIDS-related dementia patients, but so far none have shown any significant therapeutic benefits. However, progress is being made in understanding the processes involved in HIV’s interaction with the CNS, and these new discoveries may open the door for new treatments for AIDS-related dementia.

Thursday, September 11, 2008

The Presence of HIV/AIDS in Prison Populations

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

U.S. prison populations are at a record high today, with barely enough room to house incarcerated individuals. Due to the close proximity and high-risk behaviors of inmates, as well as a lack of intervention from authorities, the transmission of HIV in prisons is a major problem today. A combination of both pre-existing and new infections plague prison populations, making them one of UNAIDS’ four major at-risk groups for HIV/AIDS.

In 2005, 1.8% of all state inmates and 1.0% of all federal prison inmates in the U.S. were believed to be HIV positive, leading to a total of 22,480 infected individuals behind bars. These percentages are disproportionate to the rest of the general population, making HIV/AIDS about four times as common among inmates than the population at large. Around 25% of all HIV infected people have spent time in a correctional facility, and these HIV infections are often accompanied and exacerbated by high rates of hepatitis and tuberculosis.

There are several means of transmission regarding the spread of HIV/AIDS in prisons, both primary and secondary. Injection drug use is one major cause of transmission, as sharing of dirty needles and syringes (estimated to be greater than 70%) is a common practice. Sharing items such as razors and toothbrushes contributes to the spread of other germs. Along with injection drug use there is tattooing and body piercing, a widespread activity among many inmates. Typically, it is performed through multiple skin-punctures and without sterile instruments, causing the inmates to resort to recycled, make-shift tools such as staples, paper clips, and plastic ink tubes from ballpoint pens. Finally, various sexual activities and rape directly contribute towards the problem. It is difficult to obtain accurate statistics regarding this area, due to fear and embarrassment, but consensual and non-consensual sex are both quite prevalent among prisoners. Boredom, identity issues, and the desire to assert dominance all contribute towards sexual activity. Types of sexual activities include consensual same-sex activity, sex between prisoners and staff, conjugal visits, and rape or other forms of sexual violence. Rape is a particularly complex problem, often brutal and gang related, and the violent nature of it makes recipients more prone to vaginal or anal tears, and thus increases the chances of HIV transmission.

Also contributing to the spread of HIV/AIDS, and co-infection with other STI’s, is the absence of condoms or clean needles. Additionally, a lack of information is a major problem, with many inmates being forced to live in a state of silence and fear, and a third major confounding factor is the lack of people getting tested. Currently, very few inmates get tested due to the large stigma surrounding it and fear of ridicule or violence if their test results confidentiality were to be violated. Additionally, the prison lifestyle and rapid turnover of inmates makes consistently adhering to ARV therapy difficult. Thus, the major hesitations to reform in U.S. prisons come from a lack of political will, security concerns, and false assumptions that such programs will encourage injection drug use and sexually risky behavior. Also, many opponents believe there is a lack of resources and technology to meet the overwhelming need in prisons.

In recognizing these problems, many ideas have been proposed for prevention and change. The main goal would be to develop a multi-pronged approach to enhance detection, prevention, and the reduction of sexual violence. Next, condoms, clean needles and syringes, and bleach kits must be distributed. Many advocates of reform also believe post-exposure prophylaxis (PEP) should be made available to victims of sexual encounters. Additionally, health education and support programs, and the strong encouragement to get tested would both serve to be useful. Finally, once diagnosed, HIV positive individuals must be able to receive consistent drug treatment.

Many model prisons show promising results in their quest to enact some of these changes, including the Hampden Country, MA, Correctional Center and Brown University’s Rhode Island Prison. Further lessons can be learned from countries like England who successfully prevented problems by targeting injection drug users early on in the epidemic, and Cuba, who was able to keep HIV under control through superb penitentiary health and clean conditions.

Overall, change is a daunting challenge due to the rapid turnover of inmates and the large sense of stigma and secrecy within prison walls. In order for change to be effective, it must occur on multiple levels. Officials can no longer turn a blind eye to this problem. Prisoners are ethically entitled to the same safety, health care, treatment, and support as the rest of society. Reforming the current state of correctional facilities would not only help these facilities run smoother, but according to the UNAIDS and WHO Framework, good prison health would equate to good public health. The vast majority of all incarcerated individuals will eventually return to society, bringing with them any known and unknown diseases they may have acquired in prison. If officials can bridge these barriers, they can indeed have a lasting impact on the spread of HIV/AIDS in the U.S. as a whole.

Thanks for listening. Until next time, this is Ali Cundari.

For more information:
• J├╝rgens, Ralf. “Interventions to Address HIV in Prisons – Prevention of Sexual Transmission.” World Health Organization. . 2007.
• Kanter, Elizabeth. “HIV Transmission and Prevention in Prisons.” HIV InSite Knowledge Base Chapter. . April, 2006.
• Lines, Rick, et al. “HIV/AIDS Prevention, Care, Treatment, and Support in Prison Settings.” WHO & UNAIDS Framework for an Effective National Response. . 2006.
• Maruschak, Laura. “HIV in Prisons, 2005.” Bureau of Justice Statistics Bulletin. . September, 2007.
• Polonsky, S., et al. “HIV Prevention in Prisons and Jails: Obstacles and Opportunities.” Public Health Rep. 109(5): 615–625. . September-October, 1994.
• “Prisons.” Joint United Nations Programme on HIV/AIDS. .