The AIDS Pandemic Dr. David Wessner

Ask the UN and you’ll get the staggering sum of $10 billion. A year . The annual per capita cost of treating infected Africans, where much of the UN money goes, is around $1,100. One of the major problems facing HIV/AIDS advocates is their inability to lower this number. An estimated $600 is spent on anti-retroviral drugs, while the remaining $500 is spent on other AIDS associated conditions. Even $10 billion wouldn’t cover treatment for the more than 20 million Africans with HIV/AIDS. A considerable portion of the proposed UN budget is directed not towards treatment but towards prevention. A major problem is that no one can seem to agree on the actual cost. Although the UN has held firm to their estimate, other groups have presented vastly different figures. The World Health Organization has presented four different scenarios which vary wildly in both the projected outcome and cost. To merely maintain the current status quo, WHO estimates more than $400 billion will need to be spent over the next 20 years. To significantly reduce annual new HIV infections, WHO’s figure is more than $700 billion. Unfortunately such different figures can sometimes complicate funding by making it hard for donors to decide how much to give. Ask someone who is living with HIV/AIDS and you’ll get a number that’s a lot smaller. The average AIDS patient in America takes a combination of drugs that add up to around $14,000 a year . Much of this cost in the US is defrayed by private insurance, government insurance or sometimes through AIDS drug assistance programs (ADAPs) . These programs are meant to provide access to drugs for low income individuals. Currently 89% of people enrolled in ADAPs make less than 300% of the federal poverty level. However recently the economic conditions have forced many states to scale back their support of these programs. States have either closed enrollment entirely, or narrowed eligibility-forcing people to drop out. Currently the nationwide waiting list is at an all time high of 3,586 people . Ask the companies that manufacture these lifesaving drugs and you’ll be back to huge figures. One of the newest drugs to enter the market, Fuzeon , is produced by the giant Swiss company, Roche. Roche maintains that Fuzeon’s price (nearly $20,000 a year, or three times the next most expensive drug) is due to the $600 million cost of development. The average drug begins to turn a profit in 16 years, but analysts estimate that Fuzeon’s pricing, and anticipated demand, could mean profits for Roche in as little as three years. Ask an economist and you’ll get a couple different figures. By 1995 more than $75 billion had been spent on AIDS. Since then, spending has increased most years, with an average of $10 billion more being spent every year. But money spent directly on AIDS does not even begin to cover the true cost. In addition, economists have tried to measure the costs related to lost productivity, wages, and premature death, due to the disease. Figures vary, but some think that indirect costs account for nearly 80 percent of the total cost of AIDS. Worst case scenario guesses estimate that AIDS robs the world of 1.4% of gross domestic product, or the equivalent of wiping out the economy of Australia . A government study in Uganda found that some companies are hiring and training two employees for a single job in the hope that one will stay healthy. The UN estimates that since 1981 AIDS has reduced Africa’s overall labor force by 25%. Sick days and absenteeism due to AIDS related illness have further reduced productivity in the countries hit hardest by AIDS. Ultimately the cost of HIV/AIDS is extraordinarily difficult to measure. The disease affects so many people worldwide that it would be impossible to assess the impact that it has had on everyone. However it is obvious that unless something drastic changes, the costs will continue to grow until they become unbearable.

Africa. The seed of the world. One of the most beautiful and most scintillating places on earth. From the deserts of the Sahara and the rainforests of the Congo to the bright and bustling metropolis of Cape Town, life is rich everywhere. Yet amidst all this beauty and splendor, a deadly scourge threatens the people of this continent. AIDS. Sub-Saharan Africa is more heavily affected by HIV/AIDS than is any other region in the world. Somewhere around 22.4 million people in the region are currently living with HIV. This makes up a whopping two-thirds of the global number of HIV-infected individuals. Whereas in other areas of the world the disease affects only certain groups, here, HIV/AIDS affects everyone. This affliction picks apart whole extended families one by one. Schools are gradually emptied over time as students are orphaned. Healthcare and economic development have all taken a hard hit because of the impact of HIV/AIDS on the African peoples. Organizations simply don’t have the funds to support or expand prevention, treatment and care efforts and for this reason, it is likely that the death count will continue to rise. Life expectancy has been drastically reduced across the continent, falling to as low as 31 years in some of the worst afflicted areas. HIV/AIDS is present everywhere we look. It is an unavoidable aspect of everyday life. The following dialogue includes excerpts from various interviews. I spoke with a group of college students who lived for six months in South Africa and Zambia, another student who lived 2 years in Nigeria, and a field biologist currently doing research in Cameroon. Their testimonies will enhance the picture of daily life in African countries afflicted with HIV/AIDS. Take the country of Cameroon, for example. As of 2008, the population in Cameroon neared 19 million. Of that, about 600,000 are living with HIV/AIDS. More than half of that is made up of women 15 years and older. While prevalence here is much lower than other countries, HIV/AIDS remains a chief concern. When asked about general knowledge about the disease, most agreed that the “information is very available to middle and upper class citizens, but not necessarily to the lower class citizens and those that are at highest risk.” There is a large focus on prevention here, and the country is littered with billboards promoting abstinence, safer sex practices and condom use. Public Service Announcement in Cameroon “Sex can wait…my future comes first.” South Africa is a key example of a country, of a government that has failed its people. Until very recently, the government took no part in the fight against AIDS. Thabo Mbeki, president from 1999 to 2008 refused to believe that HIV causes AIDS and that condoms can prevent infection. This leadership has fueled outlandish beliefs such as that condoms cause AIDS, or that white people are pushing condoms laced with AIDS to wipe out Africans. When asked about the role of the government in the fight against AIDS, one student said, “The president is not very influential considering he stated that he took a shower after having had sex with someone infected with AIDS, and therefore he would not contract the disease.” Here, she is referring to the current president, Jacob Zuma, who publicly stated that showering after sex with an HIV-positive woman would reduce his risk of being infected. A fellow student added, “NGOs are much more active. They have done a much better job fighting AIDS through their provision of important information and items such as condoms and antiretrovirals.” Incumbent President of South Africa, Jacob Zuma The picture of life here has changed drastically since AIDS exploded on the scene. While treatment and prevention are improving in some areas, the governments of more conservative countries, such as South Africa, need to step up and face this issue with full force so that HIV/AIDS is no longer a shadow looming over the lives of everyone. Facts and

No one can argue that HIV testing is a bad thing. Knowing one’s status allows a person to access treatment earlier, change risky behaviors, or rest assured that he/she is indeed HIV negative. With that said, why not make HIV testing mandatory for everyone? Hello, I am Katie Morris and this is The AIDS Pandemic, a podcast hosted by Dr. Dave Wessner, associate professor of biology, and his students at Davidson College. Compulsory HIV testing—which requires that the entire population, or at least certain high-risk groups, is tested for HIV—has gotten a bad reputation in recent years from human rights activists who argue for a person’s right to choose to know whether or not they have HIV. However, studies have shown that usually, once a person knows he/she is HIV positive he/she will change his/her risky behaviors to avoid transmitting it to anyone else. Would compulsory testing not at least hinder the spread of HIV among populations? I fully support the freedom of choice, however I also support the right to live and if compulsory testing can reduce the number of people dying from AIDS it should at least be considered by policy makers around the globe. One of the largest barriers to HIV research and prevention programs in the developing world is a lack of knowledge of the specific epidemics in each country. By requiring people to be tested for HIV, the public health community would gain valuable information on how many people are infected and what groups are most at risk, significantly aiding prevention programs. Bill Clinton, the former President of the United States and founder of the Clinton foundation, which funds a great number of HIV/AIDS programs around the world, is an advocate for mandatory testing in developing countries with high HIV prevalence rates. In a statement made to Reuters, he said, "[W]e can save people's lives, and we can reduce the stigma. There is no way we are going to reduce the spread of this epidemic without more testing because 90% of the people who are HIV-positive don't know it." Everyone who is sexually active, injecting drugs, receiving blood transfusions, or breastfeeding is at risk for contracting HIV, regardless of their age, skin color, education, financial status, or sexuality. Therefore in order to increase more individuals’ knowledge of their statuses so that they do not unknowingly spread HIV, testing needs to go beyond voluntary clinics. In the aforementioned quote, President Clinton made a statement about reducing the stigma around HIV by implementing mandatory testing. This statement is contrary to what many human rights groups argue. Their concern is primarily with confidentiality breaches, especially in the developing world where the poor infrastructure cannot guarantee secure record keeping and adequate training for counselors. While a valid concern, so much of stigma surrounding HIV in the developing world involves testing itself. People are reluctant to be tested because they associate HIV testing with people who are promiscuous, homosexual, or drug users. By requiring everyone to be tested, the stigma associated with those walking into an HIV testing clinic is eliminated. Also, in places like sub-Saharan Africa where many countries have HIV prevalence rates above 5%, mandatory testing has the possibility to normalize being HIV positive. Of course this requires time and the decision by people to be open about their status but there is potential to show that everyone and anyone can contract HIV and that good things—like treatment, support groups, and advocacy opportunities—can result from knowing your status earlier. Unfortunately, once you get into the implications of such a policy, things do not remain so straightforward. In the developed world, many argue that compulsory testing is simply a waste of money. That same Reuters report found that in order for population-wide mandatory testing to be cost-effective, the prevalence rate should be above 5%. In the United S

“By 2015, let us end the transmission of HIV from mother to child. This is not a dream: we can do it.” Carla Bruni-Sarkozy, The Global Fund Ambassador With that simple statement from Ms. Bruni-Sarkozy as its guiding principle, the Global Fund to Fight AIDS, Tuberculosis, and Malaria has launched Born HIV Free. The goal of this new initiative is straightforward – stop the mother-to-child transmission of HIV. As Ms. Bruni-Sarkozy notes, this goal is achievable. We have at our disposal the means of protecting our children from infection. When an HIV+ woman becomes pregnant and gives birth, the virus can be transmitted to the infant during gestation, during delivery, or through subsequent breast-feeding. These types of transmission collectively are referred to as mother-to-child transmission. The terms vertical transmission and perinatal transmission also may be used. We now know that relatively simple and relatively cheat antiviral regimens can dramatically reduce the rate of mother-to-child transmission. In a 1999 study, Dr. Mary Lou Lindegren and colleagues noted that rates of perinatal transmission dropped significantly in concert with zidovudine (AZT) treatment for the mothers. With the development of better drug regimens, these drops in transmission rates have continued. According to the CDC, an estimated 1,650 HIV-infected infants were born in the US in 1991. In 2004, that number had dropped to less than 200. This success, however, has not been mirrored in developing countries. The causes of this disparity are several-fold. The most important factors affecting the continued problem of mother-to-child transmission of HIV in developing countries include access to treatment and access to testing. In recent years, antiretroviral drugs have become more available throughout the developing world, thanks, in large part, to the influx of money from sources such as the United States PEPFAR program and the United Nation’s Global Fund. Additionally, other groups, most notably the Clinton Foundation, have fought hard to make these drugs more affordable. But we need to do more. Too many HIV+ women still do not have access to the necessary treatments. In addition to making drugs more available, we also must work diligently to increase the levels of testing. Treatment to prevent perinatal transmission requires that women know their HIV status. To find out more about the Born HIV Free campaign, please visit their website at http://www.bornhivfree.org. Let’s join Ms. Bruni-Sarkozy in ending the transmission of HIV from mother to child.

I’m Lindsay Sween, and welcome to this installment of the AIDS Pandemic blog and podcast. Human immunodeficiency virus type 1 (HIV-1) invades a CD4+ (T4) cell through the attachment of the viral protein gp120 to its primary cellular receptor, CD4, and to a transmembrane chemokine coreceptor, usually CCR5 or CXCR4. Agrawal et al. (2007) explain that the removal of 32 base pairs from the CCR5 gene results in the CCR5Δ32 mutation, which produces a shortened, nonfunctional protein that cannot act as a coreceptor due to the fact that it is no longer expressed on the cell membrane. Thus, individuals homozygous for the CCR5 mutation (also known as CCR5 -/- individuals) are extremely resistant to contracting HIV-1, while heterozygous people (aka CCR5+/- people) express fewer CCR5 proteins on the surface of their lymphocytes than wild type individuals, which slows the transition of HIV infection to AIDS. The CCR5Δ32 mutation confers HIV-1 resistance by two mechanisms: the mutated protein cannot be expressed on the lymphocyte surface, and it actively downregulates CXCR4 coreceptor production by causing the formation of heterodimers between CCR5 and CXCR4 proteins that then get trapped in the endoplasmic reticulum. As explained by Nazari and Joshi (2008), individuals with the CCR5Δ32 mutation appear perfectly healthy in all other areas of their immune systems, which seems to indicate that the CCR5 chemokine receptor is not absolutely essential for immune function. Thus, with no selective pressure against the CCR5Δ32 mutation, Agrawal et al. (2007) report that Caucasians carry the mutation relatively frequently, with about 1% of individuals being homozygous for the mutated allele and approximately 10% of the population being heterozygous. Individuals of purely African or Asian descent, however, almost entirely lack the CCR5Δ32 mutation. Figure 1. The CCR5Δ32 mutation results in a nonfunctional protein that cannot serve as a cell surface coreceptor for M-tropic (aka CCR5-tropic or R5) HIV viral isolates and, thus, confers some resistance to HIV-1 infection. The immune cells are still fully receptive to T-tropic (aka CXCR4-tropic or X4) viral isolates, which could bind to their coreceptor, CXCR4 (aka fusin), and transmit HIV-1 infection. From: Samson, Michel. “Human immunodeficiency virus (HIV).” Access Science Online. McGraw-Hill. . There is now a new antiretroviral drug called maraviroc, which was approved by the U.S. Food and Drug Administration U.S. Food and Drug Administration in August 2007 and mimics the natural CCR5Δ32 mutation by acting as an antagonist for the CCR5 receptor and preventing the viral envelope protein gp120 from binding to it. Lieberman-Blum et al. (2008) report the results of two Phase IIb/III clinical trials, MOTIVATE 1 and 2, in which the effects of treatment with 300 mg of maraviroc once or twice daily were compared to placebo treatment in patients who were already being treated with HAART and still had primarily R5 HIV-1 infection. Maraviroc was found to decrease viral load by a greater percentage than placebo. Of the patients receiving maraviroc once or twice daily, 43.2% and 45.5%, respectively, had virus particle counts of less than 50 copies per milliliter, as opposed to 16.7% of patients in the placebo group. After the 48 weeks of the studies, patients demonstrated average viral load reductions of -1.68 log10 copies/mL for the once daily group and -1.84 log10 copies/mL for the twice daily group compared to -0.78 log10 copies/mL for the control group. Figure 2. Most patients given maraviroc once or twice daily had lower HIV-1 viral loads and higher CD4 cell counts at the end of 48 weeks and had a long time period until treatment failure than did patients taking placebo. From: Gulick, R.M., Lalezari, J., Goodrich, J., Clumeck, N., DeJesus, E., Horban, A., Nadler, J., Clotet, B., Karlsson, A., Wohlfeiler, M., Montana, J.B., McHale, M., Sullivan, J., Ridgway, C., Felstead, S., Dunne, M.W., van d

I'm Paige Bates and this is The AIDS Pandemic The RV144 study was a phase III HIV vaccine trial conducted by the US Army and Thai government over seven years on 16,402 volunteers—all HIV negative men and women between the ages of 18 and 30 in parts of Thailand. For ethical reasons, all participants were taught HIV prevention behaviors, given condoms, and promised lifelong antiretroviral treatment if they contracted HIV. Half of the volunteers were given a prime-boost vaccine regimen and half received placebo vaccinations. The prime-boost approach utilizes Sanofi Pasteur’s ALVAC-HIV vaccine as a prime and AIDSVAX (originally made by Genentech) as a boost. ALVAC-HIV is comprised of a canarypox virus with three HIV genes grafted onto it. AIDSVAX contains a recombinant gp120 protein found on the surface of HIV. These vaccinations were combined because one was designed to create antibodies and the other to alert white blood cells. These vaccinations were focused on the two strains of HIV commonly found in Thailand, but it is unclear whether this regimen would have any benefit elsewhere in the world. The participants were regularly tested for HIV for three years following the completion of the vaccine regimen. In September, the companies and agencies which implemented and funded the trial announced in a press release and interviews that new HIV infections were observed in 74 of the 8,198 people who received the placebo, but in only 51 of the 8,187 given the vaccine. They claimed that this was a statistically significant 31.2% reduction in infection. However, the vaccine did not reduce levels of HIV activity in those who became infected and did not appear to produce any neutralizing antibodies. Source: Wall Street Journal, September 25, 2009 In the 1980s, top officials embarrassed themselves by predicting an HIV vaccine in five years. Reminiscent of these overly optimistic declarations, the backers of the RV144 trial claimed that “we now have evidence that a safe and effective HIV vaccine is possible.” In the first wave of press subsequent to the initial press release and interviews, many reputable news sources, such as the San Francisco Chronicle, New York Times, NPR radio and BBC news, suggested that these results were highly encouraging, and some even went so far as to suggest that this regimen might be the forerunner or basis for a usable vaccine in the near future. The LA Times suggested that these findings would “energize and redirect” the HIV vaccine field. Many articles quoted Dr. Anthony S. Fauci, the director of the National Institute of Allergy and Infectious Disease which largely funded the $100 million dollar study, as saying “I don’t want to use a word like breakthrough, but I don’t think that there’s any doubt that this is a very important result.” The Wall Street Journal suggested that this finding could be the second “big game changer in AIDS research since the mid 1990’s” with the advent of drug cocktails. Many articles later qualified with the cautionary statement that much more research is necessary before the vaccine could be available to the public. Phrases urging the public to be “cautious” but “hopeful” and describing the results as “modest” yet “encouraging” rang throughout the media and press releases. However, only days later, the LA Times wrote “By Thursday afternoon, the initial wave of euphoria had given way to the recognition that many vexing questions will have to be answered before researchers can produce a vaccine that will reliably shield people from HIV.” Experts predicted that it would require two to three years of research to unravel how and why the vaccine regimen worked, and then an additional five to ten years to produce a vaccine that was ready to test in people. The fact that this still overly optimistic statement was a step back from the “initial euphoria” shows the extent of the preliminary sensationalism. The media reported that the r