Opportunistic Infections in Developing Nations: A World Away

In the United States and other developed nations, for many people, AIDS has become a manageable disease. With adequate care and lots of medication, HIV positive individuals can live with relatively few serious complications for a long time. In the US, 71% of HIV-infected individuals have at least started HAART therapy, decreasing deaths per infected individuals per year from 30/100 to 5/100 since the 1980’s. In developed nations, however, HIV positive individuals do not have the luxury of adequate care. In areas like Africa where the burden of disease is highest, HIV positive individuals must face an array of opportunistic infections as their CD4 counts dip lower and lower.

Because these opportunistic infections are generally localized to areas where HAART is not available, it is both hard for us to understand the difficulties in treatment and to determine which infections are endemic to what populations. For example, MAC (for Mycobacterium avium complex) is a common, life-threatening opportunistic infection in Asia causing a significant portion of AIDS-related mortalities. In Africa, however, MAC is rare. In addition, tuberculosis is a particularly life-threatening coinfection that is particularly common in many developing areas, especially Sub-Saharan Africa and Asia. Many opportunistic infections in these nations have developed resistance to the drugs typically used to treat them. Determining which disease populations have resistance to what medications can be exceptionally difficult given how isolated some of these areas are.

The HIV/IDS prevalence is highest in sub-Saharan Africa

The most reputable source for information like this is undoubtedly the World Health Organization. The WHO publishes information on the geography, morbidity, symptoms and treatment of various opportunistic infections for different nations and settings. While it is hard to determine where exactly the WHO gets their sources for information from developing nations, it is clear that they get their information from all parts of the globe. However, it is also hard to pick apart the complicated interactions of HIV and opportunistic infections in a multitude of settings, and even harder when there are additional complicating factors such as malnutrition, social unrest, and a lack of medical infrastructure for reporting treatment schemes. Many times, the WHO provides useful information about the scope of opportunistic infections in developing nations, but they often miss the deeper and more individual issues that a given region may have. If first-line drugs for opportunistic infections are not available in these developing areas (due to oppressively high costs or restrictive storage conditions), the WHO lacks vital information on how to cope.

The availability of antiretrovirals in lowest in sub-Saharan Africa

While it is not the fault of the WHO that there is a dearth of useable information for medical workers in low-resource environments, it is clear that there is a lack of necessary medical care in these nations that perpetuates a cycle of poverty and illness and that millions of HIV-positive individuals are dying as a result of a lack of ARVs. In a situation where prohibitively high costs of necessary drugs prevents individuals from being treated for HIV, we need to focus more on preventative efforts and HIV prophylaxis in the form of vaccines or microbicides. In this sense, the US and other developed nations are providing a massive amount of resources in trying to find a vaccine and developing useful microbicides to prevent HIV infection from happening in the first place. Because of the massive amount of people infected in areas that lack the resources to treat them, the disease needs to be treated when it is least expensive to do so. While it is hard to know what the future holds for those with HIV in developing nations, it is sure that we need to develop better ways of treating opportunistic infections and preventing the development of AIDS from HIV.

For more information on the global context of the AIDS pandemic, please visit:
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Testing and Treatment of HIV/AIDS in Children

According to a 2006 UNAIDS/WHO AIDS Epidemic Update, there are approximately 39.5 million people living with HIV/AIDS throughout the world. Of those infected, 2.3 million are aged 15 or younger. Approximately 90% of children infected with HIV acquire the virus perinatally, meaning it is transmitted from a mother to her child during pregnancy, labor, delivery or through breastfeeding. According to the CDC, the prevalence of mother-to-child transmission of AIDS in the US has dropped significantly due to effective testing of pregnant women and treatment of those found to be infected; in resource poor settings, however, the testing and treatment of infected women is far less common. In 2005, the UNAIDS/WHO AIDS Epidemic Update found that only 9% of pregnant women in resource poor countries were offered any sort of prevention services, leading to a higher prevalence of pediatric HIV/AIDS infection in less developed countries. As the prevalence of women of childbearing age who are infected with HIV increases in resource poor settings, it can be expected that the number of babies infected from mother-to-child transmission will likewise increase.

Children infected with HIV/AIDS are confronted with an extremely high rate of illness and death. The World Health Organization has found that because of their unique metabolic and immunologic circumstances, HIV progresses rapidly in children, with an estimated one third of infants dying by the time they reach their first birthday and half dying by their second birthday. Although in most developed countries identification and treatment of HIV infected babies is quite successful, which allows those children to lead healthier and longer lives, the situation is quite different in resource poor countries where testing, much less treatment of infants and children is relatively unavailable. To begin with, testing may be unavailable to individuals in developing countries due to the distance, expense and impracticality of reaching those hospitals and clinics that provide testing. Even when testing is locally available, parents may be unwilling to test their babies for fear of stigma and prejudice associated with an HIV positive status. Furthermore, testing of infants in developing countries can require far more time than in developed countries. PCR tests are among the fastest and most effective ways to diagnose infants as they can be done within 48 hours of birth and results are available to the mother within 6 weeks of the completion of the test. PCR tests are rarely accessible and prohibitively expensive in resource poor settings where antibody tests are the norm. These antibody tests only begin to give accurate results 18 months after birth, and so babies in developing countries are oftentimes diagnosed far later than in developed countries, if they are diagnosed at all.

Aside from the difficulties in testing infants and children for HIV in resource poor settings, there continues to be a dearth of treatment for children found to be positive for the virus. Although both prophylaxis and HAART or highly active antiretroviral therapy can be extremely effective in treating HIV/AIDS and preventing opportunistic infections in children, the unique difficulties associated with treating children in resource poor settings mean that these therapies are widely underused. UNAIDS found in 2006 that “an estimated 380,000 children died of AIDS-related causes” and that, “the vast majority of these deaths could have been prevented either by treating opportunistic infections or providing HAART.” Similarly, a UNAIDS/WHO report found that nearly 90% of children who could benefit from ARV treatments are not currently receiving it. This lack of treatment can be attributed to several factors.

In many resource poor settings, antiretroviral treatment may simply be unavailable. Those countries where the HIV/AIDS burden is greatest such as in Sub-Saharan Africa are oftentimes the least able to provide treatment, and so a lack of resources oftentimes translates into a lack of prophylaxis and/or antiretrovirals. Prophylaxis has been found to be extremely effective in staving off opportunistic infections in HIV positive children and is useful in delaying the need for HAART in pediatric populations. Although prophylactic drugs are widely available and relatively cheap, a UNAIDS/WHO study has found that currently nearly 4 million children who could benefit from such treatment are not receiving it. This is probably the result of lack of available treatment sites and infrastructure in resource poor settings. This dearth of available treatment translates to ARVs as well as prophylactic treatments. Even in areas where adult ARV treatment is present, there is rarely a comparable pediatric treatment site. This is due to the fact that suitable pediatric drug formulations are oftentimes prohibitively expensive and impractical. Little research had been conducted in the area of pediatric dosages because in the developed world effective mother to child prevention had limited the need for pediatric ARVs. Because so few drugs are available in pediatric dosages, and those that are available tend to be far more expensive than those made for adults, most caregivers in resource poor settings are limited to providing either expensive and unpleasant tasting syrup formulas or cutting and crushing adult tablets to provide ARVs for their pediatric patients. Crushing the pills provides an inexact measure of the amount of medication that is administered. Since under dosage can result in resistance of the virus to the drugs, and over dosage can result in amplified side-effects, the lack of correct dosages inherent in using adult drugs for pediatric patients means this mode of drug administration is far from ideal.

Important steps have been taken to begin to provide better treatment for pediatric AIDS patients. In August of 2007 the US Food and Drug Administration (FDA) approved a special tablet for children with HIV that combines three antiretroviral drugs into one pill. The tablet can be dissolved in water for ease of administration which is required only twice a day. The drug is produced by the manufacturer Cipla Limited, a generic pharmaceutical company based in India. Though unapproved for use in the US, the drug has been authorized for use in developing countries where the need and demand is greatest. Despite the enormous implications for successful treatment of pediatric AIDS that this drug will bring, there are still substantial obstacles to be overcome before pediatric care and treatment of AIDS is fully complete. Mother-to-child transmission must be diminished in resource poor settings. In situations where prevention of mother-to-child transmission is not achieved, suitable infrastructure for administration of prophylactic and antiretroviral drugs to pediatric patients must be established. Movements and groups such as the “Stop AIDS in Children” campaign are working towards prevention of mother-to-child transmission and improvement of treatment for infected children. With support of both developed and resource poor countries, the relatively ignored problem of HIV/AIDS in children can be successfully addressed.

Until next time, this is Dominique Maietta for the AIDS Pandemic Podcast.

PRODUCT(RED): Philanthropy or Exploitation?

Product(RED)



An earlier installment of this podcast from a year ago called attention to the launch of PRODUCT(RED) in the United States. Since the brand’s introduction, (RED) watches, sunglasses, t-shirts, cell phones, and iPods have been extensively marketed and sold, with some of the revenues going to support the fight against AIDS in Africa. Nevertheless, the (RED) brand has been a target of criticism for its commercial approach to a philanthropic endeavor. In this installment, I intend to take a close look at PRODUCT(RED) and its impact on the AIDS pandemic.

(RED)’s business model embodies the strategy of cause marketing, where for-profit companies and non-profit organizations collaborate in a joint initiative for their mutual benefit. (RED) currently has partnerships with several distinctive consumer goods companies, including Motorola, The Gap, Converse, Apple, and Emporio Armani. PRODUCT(RED) gives its partners permission to brand certain products as (RED), and in return the partners send a share of their profits from those products to the Global Fund to Fight AIDS, Tuberculosis, and Malaria. Hip, humanitarian, and business-savvy, PRODUCT(RED) panders simultaneously to Americans’ munificence and to their conspicuous consumption.

According to the PRODUCT(RED) website, as of September 2007 the sale of (RED) products has generated more than $45 million for the Global Fund. This money has been directed toward AIDS treatment and prevention programs for women and children in Ghana, Swaziland, and Rwanda. (RED) points out that its contribution to the Global Fund will be a steady, constant stream of revenue rather than a one-time lump sum donation, ensuring that the brand will have a sustained impact on its beneficiaries.

Most criticism against the brand has centered on the belief that its partners are taking advantage of the AIDS problem in order to turn a profit. Early detractors of the brand encouraged consumers to donate their money directly to charity and thereby bypass the middle-men (RED) partners siphoning off most of the revenues. Later, a particularly scathing article in the magazine Advertising Age cited the disproportionately large amount of money spent by the brand’s partners promoting their (RED) products compared to the amount the partners actually raised for the Global Fund from the product sales. More recently, Ben Davis, creator of a parody campaign called BUY(LESS), has written an open letter to (RED) CEO Bobby Shriver requesting both more transparency in the distribution of profits from (RED) products and a more direct way for consumers to contribute directly to the Global Fund without having to buy (RED)-branded products.

In the end, it is important to consider what PRODUCT(RED) really is. It is not a charity, but “an economic initiative”, according to its website. Accordingly, its partners’ financial interest in the (RED) brand gives them an incentive to ensure its continued success. So what if the amount of money spent by the partners promoting their (RED) products exceeds the amount they turn over to the Global Fund? The money is already designated for their advertising budgets and would be spent anyway. This way, it at least goes toward publicizing a good cause. And besides, strictly fiscal measurements of PRODUCT(RED)’s impact (in terms of dollars alone) understate the heightened general awareness that the brand engenders among consumers.

Debating whether (RED) is more philanthropic or exploitative in nature misses the point. Even its most ardent critics would agree that the brand is making a positive contribution to the fight against AIDS. The question is, could PRODUCT(RED) do more to achieve its stated goal to “expand opportunities for the people of Africa”? I think it could.

Thanks for listening. I’m Bill Stokes.


References:
Bennett, J. Does Shopping for a Good Cause Really Help?. Newsweek. 14 March 2007.
Davis, B. Buy (Less), Give More. accessed 09 October 2007.
Kim, R. Africa’s Poor Had the Best Week Ever. The Nation. 15 October 2006.
The Persuaders, LLC. 2006. (RED). accessed 09 October 2007.
Vallely, P. The Big Question: Does the RED campaign help big Western brands more than Africa?. The Independent. 09 March 2007.

Integrase Inhibitors: A New Hope

I’m Bevin English.

On October 12th, the Food and Drug Administration (the FDA) announced that it had approved a New Drug Application for a completely new kind of medication in the fight against AIDS. This drug, called IsentressTM, is the first integrase inhibitor and comes in 400 mg tablets that are taken twice daily. Produced by Merck & Co., Inc., Isentress, whose generic name is raltegravir and whose in-development name was MK-0518, has impressed many leading AIDS researchers, including Dr. Amneris Luque, medical director of the AIDS Center at the University of Rochester, who called the new drug “the road to hope for people who have failed all other AIDS medications.”

Before raltegravir’s approval, there were three oral anti-retroviral drug classes approved by the FDA: nucleoside reverse transcriptase inhibitors (also called NRTIs), non-nucleoside reverse transcriptase inhibitors (also called NNRTIs), and protease inhibitors (also called PIs). These drugs block two of HIV’s three enzymes that are necessary for infection: reverse transcriptase and protease. When HIV infects a cell, reverse transcriptase converts the viral genetic information from RNA to DNA. Integrase then inserts this viral DNA into the host cell’s genome. After the viral DNA has been translated by the host cell, protease cleaves the proteins into the functional units that come together to form protein coats for new viruses. These three classes of drugs have been used to treat HIV positive patients for many years. Nucleoside reverse transcriptase inhibitors have been used since 1987, when the FDA approved AZT. One of the most prominent non-nucleoside reverse transcriptase inhibitors, efavirenz, has been in use since 1998. And three common protease inhibitors, saquinavir, indinavir, and ritonavir, were approved by the FDA in 1996.

In Phase III clinical trials, raltegravir was administered to over 600 people who had viral loads greater than 1000 copies/mL and resistance to at least one drug in each of the three oral antiretroviral classes. In all trial groups, patients receiving raltegravir tended to have lower viral loads and higher CD4 cell counts than the control group, which consisted of patients receiving optimized background therapy (OBT) and a placebo. OBT is a personalized combination of different antiretroviral drugs that will most effectively increase an individual’s CD4 count and decrease his or her viral load; OBT is based on the patient’s history, current viral load and CD4 count, and any resistance tests. In raltegravir’s Phase III trial, the most dramatic result was seen when the drug was combined with one or two other active drugs, with 98% of patients’ viral loads below 400 copies/mL after 16 weeks. Data from on-going Phase II clinical trials show that raltegravir in combination with OBT maintains low viral loads over an extended period of time, with 64-71% of individuals achieving loads below 400 copies/mL and 46-64% of patients having loads less than 50 copies/mL after 48 weeks of the therapy.

Side effects of raltegravir were generally reported as mild to moderate and caused fewer than 2% of participants to discontinue therapy; nausea, headache, and diarrhea were the most common. Currently, there are no known drug interactions, although further studies must be conducted to investigate any possible drug interaction issues. Because of raltegravir’s efficacy, safety, and tolerability, the FDA gave this new drug priority review status, meaning that the Administration promised to review the drug within six months of their reception of the New Drug Application because it could potentially help with unmet medical needs.

However, it is important to note that “[t]he fight will not end with raltegravir,” as AIDS activist and participant in raltegravir clinical trials Matt Sharp stated to the FDA. One problem is that the drug simply has not been around long enough for scientists to understand its long-term effects in vivo. It has been less than four years since the drug was first used in humans and less than three years since it was first used in HIV positive individuals. During clinical trials, researchers observed more cases of different cancers, including lymphoma, squamous cell carcinoma, and hepatocellular cancer, among individuals who received raltegravir. Upon analysis, researchers claimed that the increase in the occurrence of cancers was not significant. However, any patient receiving raltegravir must be observed for the long-term to ensure that the drug does not lead to an increased risk of cancer.

Another important issue that must be taken into consideration is viral resistance to the new drug. In vitro data has shown that HIV can become resistant to raltegravir, but resistance generally occurs after serial passage in cell culture for several months. During clinical trials, 16% of patients were virological failures in the raltegravir group after 24 weeks. However, researchers remain hopeful that second-generation integrase inhibitors, such as Gilead’s elvitegravir, which is currently undergoing Phase II clinical trials, may help overcome resistance.

Despite the uncertainty of raltegravir’s long-term effects in vivo and the possibility of resistance, this breakthrough drug marks a milestone in AIDS treatment. The first integrase inhibitor, raltegravir, in combination with other drugs, has shown to be extremely effective in reducing viral loads and increasing CD4 counts, even in patients whose treatment options are severely limited by multi-class resistance.

Integrase Inhibitor Isentress Provides a New Way to Treat AIDS Patients

Welcome to this installment of The AIDS Pandemic, a podcast hosted by Dr. David Wessner from the Department of Biology at Davidson College. I’m Mike Neri.

In this podcast, I will talk about the optimism surrounding the recently FDA approved AIDS drug Isentress, including how it works, what step in the HIV replication cycle it affects, and what preliminary data show about the drug’s effectiveness and side effects. Ever since the discovery of HIV as the causative agent of AIDS, scientists have searched for weaknesses in its life cycle that they can exploit. As early as 1990, scientists had identified 13 pathways in the life cycle of HIV where the virus was susceptible to treatment. Unfortunately, due to the years of trial and error necessary to produce safe and effective drugs, new AIDS medications are developed slowly, and often have many side effects.




But optimism is high after the new drug Isentress showed very promising results when acting on a novel pathway to inhibit HIV replication. Isentress, also called Raltegravir, was developed by the Merck Corporation. It’s the first drug in a new line of AIDS medications called integrase inhibitors. As the name suggests, these drugs target an enzyme called integrase that the virus brings with it into an infected cell. Integrase, along with two other enzymes called reverse transcriptase and protease, is essential for HIV’s replication within the host. Therefore, scientists believe that if they can find a compound that stops integrase, they may be able to stop HIV from replicating.

After HIV has entered the cell by fusing with the membrane of its target cell, the virus dumps its genetic material and enzymes inside. It then makes copies of its own genetic material and uses integrase to insert them into the DNA of its host. This allows the virus to replicate its genome using the host’s machinery, and essentially take over the infected cell for its own reproductive purposes. The goal of integrase inhibitors is to prevent integrase from working correctly, therefore keeping the HIV genetic material out of the host’s genome and hindering viral replication. Previously, there had been only four pathways that drugs target in the HIV life cycle, and none of them had targeted integrase. However, integrase is an attractive target molecule for drug development for a number of reasons. First of all, integrase does not resemble any known human proteins, meaning the chances of side effects are reduced. In addition, by going after a new viral pathway for infection, doctors can combine integrase inhibitors with drugs targeting different pathways, which prevent the virus from becoming resistant to an entire class of drugs.

Scientists have long wanted to develop an integrase inhibitor, but the road to creating an effective drug and gaining FDA approval for it is a long one. According to Merck’s website, research into integrase inhibitors began in 1993 and eventually resulted in the identification of a class of compounds that could impede the function of the enzyme. These compounds work by binding to the active site of the integrase, thus preventing it from binding and cutting the host DNA, which prevents the viral genome from being inserted. After this discovery, researchers worked with these compounds in the lab to create the best integrase inhibitor, and tested it in virus cultures and animals. The use of animals allowed them to get an idea of the severity of the side effects and an approximate idea of the appropriate drug dosage. The final product of this drug testing was named Isentress. After emerging from the laboratory phase, Isentress was put through three phases of clinical studies involving groups of healthy and sick people. Results from the studies of Isentress given with a combination of other AIDS drugs were compared to a placebo given with the same drugs. From these data, researchers were able to get an idea of the effectiveness of the drug in treating the virus and fine-tune dosage information, all while closely monitoring side effects. At the end of this process, Merck submitted the data from all of the tests and clinical studies to the FDA for it to decide whether the drug was safe to be offered on the market. And on October 12, 2007, Isentress was officially approved by the FDA for treatment in AIDS patients, specifically those with HIV strains resistant to all other drugs. Most of the optimism surrounding the approval and release of the drug comes from the data obtained in the clinical studies. In the later phases of these trials, Isentress and a standard combination of other drugs were given to the most drug-resistant patients and compared to a placebo group. After 16 weeks, the Isentress treatment reduced the viral load to almost undetectable amounts in nearly 80% of patients, compared to only 43% in the placebo group.

While questions concerning Isentress still remain, such as whether the drug will work over longer periods of time and what the long term side effects might be, the preliminary results suggest that Isentress will have a significant impact on the treatment of AIDS immediately. As mentioned before, Isentress is initially expected to be used in patients who have exhausted all other drug treatment options. However, the overwhelming success of the drug so far has medical professionals wondering whether it can eventually be used as a front-line treatment against HIV. The true impact of Isentress cannot be known until it has been used by all types of AIDS patients over long periods of time. Nevertheless, the approval of Isentress is a sure sign for optimism in the AIDS community and a great success for the drug and pharmaceutical companies that have spent years producing and testing it.

I’m Mike Neri, and thanks for listening.

HIV/AIDS: The Brazilian Response

In the arena of HIV/AIDS prevention and treatment, Brazil has become a beacon of hope, particularly among developing countries. Countries around the globe are now looking towards their system of universal AIDS care for guidance.

In the early 90’s it was estimated that within a decade, the number of HIV+ people in Brazil would be near 1.2 million. Instead, recent estimates suggest that only half that amount (about 660,000 people) are infected. How have they been so successful in limiting the spread of this deadly disease? With a three pronged government program focusing on prevention, treatment, and reducing the stigma associated with AIDS patients.

The first aspect of Brazil’s plan hopes to prevent the spread of HIV, particularly among the highest risk groups. After a brief stint of abstinence education failed early in the epidemic, the government looked towards other alternatives. Surprisingly, even in a country that is dominated by the Catholic Church, promoting condoms has proven very effective. The government has plans to distribute millions of condoms through local clinics, particularly to those involved in the commercial sex industry. Condom distribution is intensified during Carnival, a lively celebration before Lent where “free condoms are passed out like candy.” They have even encouraged the adult films industry to incorporate condoms into their films, and have produced prime time TV ads promoting condom usage in homosexuals. Additionally, a government funded needle exchange program hopes to slow down the spread among IV drug users.

A particularly intriguing aspect of Brazil’s treatment program has been their ability to supply anti-retroviral drugs to any AIDS patient needing them. As of September 2005, over 170,000 patients who required treatment were receiving it for free from the government. On a recent visit, the head of Uganda’s Parliamentary Committee on HIV/AIDS affirmed that “being able to provide the same standards of care to all citizens irrespective of their status in society is something to emulate.” This program, which began in 1997 as the first of its kind in the developing world, has lead Brazil to seek cheaper prices in order to keep costs down. A government sponsored company produces generic forms for many of the most widely used drugs. They have even broke patents on some of the newer drugs as costs have continued to skyrocket. Under fear that the Brazilian government will bypass the patent system, many companies have opted to cooperate and lower their prices. Even still, treatment makes up about 80% of their AIDS budget.

Contrary to many aspects of the US AIDS program, the Brazilian government has worked to gain the support of many of the most at risk groups. In 2005, Brazil rejected over $40 million from the United States because they would have had to pledge that they oppose commercial sex work; having the support of the sex industry has been integral in their fight against AIDS. Additionally, focusing on treatment instead of solely on prevention has encouraged testing and reduced stigma for those suffering with AIDS.

The model system that Brazil has implemented is envied by many countries around the world. Even the United States could learn from Brazil’s focus on condom distribution and treatment, as well as their support for constructive dialogue about the disease.

For more information about the current status of HIV/AIDS in Brazil, go to Brazil’s page of the UNAIDS website.

I’m Ben Young, thanks for listening.

VIRIP: A new anti-HIV compound?

Welcome to this installment of The AIDS Pandemic. I’m Dave Wessner.

Could our own bodies be producing potent inhibitors of HIV? According to research published in today’s issue of Cell, the answer may be ‘Yes.’ And these interesting findings eventually may lead to the development of new anti-retroviral drugs.

Since the isolation of HIV in 1983, numerous naturally occurring human factors have been postulated to have anti-HIV properties. Today, a group of researchers in Germany have added another factor to this list. By studying hundreds of small molecules isolated from human blood, the researchers identified a short peptide, or protein fragment, that effectively blocked HIV from infecting cells. Termed Virus-Inhibitory Peptide, or VIRIP, this peptide represents a small piece of a larger protein normally found in our blood – alpha1-anti-trypsin.

To demonstrate the inhibitory effects of VIRIP, the researchers infected cell lines with HIV-1, added VIRIP to the cells, and then determined how many additional cells subsequently became infected. VIRIP decreased the infection rate in a dose-dependent manner. In other words, when higher concentrations of VIRIP were used, the effect was greater. The effect also was very specific for HIV; the peptide did not block the infectivity of other types of viruses. Interestingly, the researchers showed that if they altered the VIRIP peptide slightly, it’s inhibitory properties increased dramatically. Finally, VIRIP was equally effective against strains of HIV that were resistant to other anti-retroviral drugs, yet resistance to VIRIP was not observed.

Mechanistically, it appears that VIRIP blocks HIV infection by binding to the viral protein gp41 and preventing fusion between the viral envelope and the cell membrane. An existing drug, T20, or Fuzeon, works in a similar manner.

The path from an initial discovery like this and a marketable drug is a long and winding path, filled with potholes. Promising candidate molecules rarely become FDA-approved drugs. So, the odds are against VIRIP. But, based on this report, it’s certainly worth keeping our eye on it.

Until next time, I’m Dave Wessner.

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.