HIV Vaccine Development: A Call for Justice
HIV/AIDS: An Introduction
The need for a solution to the current global HIV/AIDS crisis is immediate. While current treatments have helped to curb the pandemic in developed nations, the majority of the world continues to suffer the effects of this deadly virus. Future efforts to resolve the AIDS pandemic should focus on development of an effective vaccine, as that is the only hope for eradication of the disease. Importantly, serious consideration of the common good and the developed world's responsibility to help resolve the AIDS crisis in the developing world are necessary accompaniments to vaccine development.
Since its emergence in 1981, HIV/AIDS has moved to the forefront of global health issues and has become one of the most widespread and publicized pandemics in recent history. Today, approximately 33 million people worldwide are infected with the virus and, despite increased funding for treatment and research in recent years, HIV continues to spread.1 Thanks to extensive efforts in research and development of antiretroviral drugs, HIV/AIDS is now considered by many to be a chronic illness for those with consistent access to the host of pharmaceuticals now available. Unfortunately, many infected people-more than 70% by some estimates-in low- and middle-income countries do not have such access.2 Consequently, millions continue to die each year from untreated AIDS.3
Sub-Saharan Africa is the world's most heavily hit area. In 2007, that region alone accounted for 67% of all people living with HIV and 75% of all AIDS deaths. Five percent of all adults in sub-Saharan Africa are currently infected, compared to the next highest adult prevalence rate of 1.1% in the Caribbean. Despite the huge numbers of infected individuals, worldwide efforts to address the pandemic have fallen short, with only an estimated 30% of people who need treatment in sub-Saharan Africa receiving it.4 Infection rates-which showed 40,000-50,000 new infections in the United States in 2006 as compared to 1.7 million in sub-Saharan Africa5- indicate that the developing world, particularly sub-Saharan Africa, will continue to bear the burden of this disease unless something is done to alter its course.
Before this global problem can be effectively addressed, however, its complexities must be understood. In many ways, the intricate science of HIV and the pharmaceuticals used to treat it contribute to the current problems of drug ineffectiveness and limited access in global AIDS intervention today. HIV's complex retroviral life cycle has made it difficult to treat, because the virus hijacks the infected cell's replication apparatus. Drug development has faced the challenge of finding drug targets that prevent viral activity without also killing the infected host cells.
Human Immunodeficiency Virus (HIV)
The single-stranded RNA genome of HIV consists of only nine genes-three of which are structural-that encode for 15 viral proteins, including the enzymes reverse transcriptase, integrase, and protease. HIV replication begins with fusion of the viral capsid to the host T-cell membrane. Both viral membrane proteins-gp120 and gp41-and integral host cell membrane proteins-CD4 and CCR5 or CXCR4, mediate this fusion. The viral genome, encapsulated by a protein coat, then enters the cytosol, where reverse transcriptase begins transcribing HIV's single-stranded RNA genome into double-stranded DNA. After the newly synthesized viral DNA is transported to the nucleus, integrase inserts the DNA into the host genome. Transcription and translation of the viral DNA are then carried out by the host cell's organelles. The viral enzyme protease eventually cleaves viral protein precursors into functional proteins necessary for the mature HIV virion. Finally, the viral components migrate to the host cell membrane, where they assemble into the virion and use the host cell's transport machinery to bud off from the plasma membrane to infect other cells.6
Antiretrovirals: The Problem of Access
Current antiretroviral treatments aim at blocking the activities of reverse transcriptase, integrase, and protease, as well as thwarting the entry of the HIV virion into the cell. Many of the available antiretroviral drugs are small molecule inhibitors that block the enzymatic activity of these viral proteins. In addition, one class of reverse transcriptase inhibitors uses nucleoside or nucleotide analogs, which compete with the host cell's naturally produced deoxyribonucleotides for the active site of reverse transcriptase. When these analogs, which lack the 3' hydroxyl group needed for DNA strand extension, are incorporated into the DNA, transcription can no longer continue, and consequently viral proteins are not made, preventing assembly of a new virion. 7
The development and use of antiretroviral drugs such as those mentioned above have significantly reduced AIDS mortality worldwide.8 However, the use of these therapies has also been riddled with obstacles. The current standard of treatment is a highly active antiretroviral therapy (HAART), which employs the simultaneous use of multiple antiretroviral drugs.9 Multiple drugs must be used primarily because of the high mutation rate of reverse transcriptase, which lacks effective proofreading and repair mechanisms, leading to one mutation in about every 100,000 base pairs. This high mutation rate allows the HIV virus to quickly develop resistance to drugs because there is an increased likelihood of random mutations that will confer an advantage against drugs, and will therefore allow the virus to survive and most likely be transmitted to other people.10 It was not until the mid- 1990s, when the molecular structure of HIV protease was discovered, that new classes of antiretrovirals started to become readily available to the public. The increased number of available drugs allowed for multi-targeted regimens aimed at different points in the HIV life cycle.11 Today there are over two dozen antiretrovirals on the market and, in developed countries where these drugs are readily available, mortality rates have significantly declined.12 If antiretrovirals continue to be the primary mode of treatment, the continual development of new drugs will be necessary as HIV resistance to these therapies develops. 13
Drug toxicity is also a major challenge in the use of antiretrovirals today. Among the varied toxic side effects are: metabolic abnormalities, mitochondrial toxicity, insulin resistance, and metabolic bone problems, such as osteoporosis.14 Much of the problem of toxicity lies in the fact that drug dosages are often uniformly prescribed based on broad categories such as weight or gender, a strategy that may save time and money but lacks consideration of individuals' unique rates of drug metabolism.15 The timing of the initiation of antiretroviral therapy is also an issue, because the toxicity of the drugs, which is often more pronounced in individuals with higher CD4+ T-cell counts, must be weighed against the need to prevent early viral replication.16 Additionally, there has been evidence showing that proper nutrition is necessary for HAART to be most effective.17 This presents a clear problem in regions such as sub-Saharan Africa, where malnutrition and starvation are perhaps even more devastating problems than AIDS.18
In developing regions with poor medical infrastructure, the limited number of people lucky enough to receive HAART likely obtain the drugs from a clinic or facility that is not equipped to fully meet their general health or AIDS-specific needs.19 In addition to a lack of sophisticated facilities and medical supplies, doctors and medical staff are often under-trained and/or unprepared to work with the local population. Clinic employees may be unable to provide adequate or accurate information to patients about the disease and its treatments.20 Such underdeveloped medical infrastructure exacerbates endemic problems such as the lack of nutritional supplementation and proper drug prescription, as well as the issue of regimen adherence. Because of the specific and multi-faceted targeting of HAART, strict adherence to the drug regimen-which often involves taking multiple pills at specific times each day-is necessary for treatment to be effective . 21 Without proper and continued HIV/AIDS counseling, achieving successful adherence is an unrealistic goal for many. In places without properly trained medical staff or with insufficient medical personnel, drug effectiveness drops dramatically as patients fail to properly adhere to their drug regimens. 22
Most infected people in developing regions, however, do not deal with these issues, because they do not have access to HAART, let alone the additional resources and knowledge necessary for optimal effectiveness. Because HAART is such an expensive treatment, despite falling costs in recent years, universal distribution of these drugs may never be achieved.23 Although there are large financial deficiencies impeding universal access to treatment, the issue of access is much more complex than a simple lack of money and resources. Even in cases where HAART may be available in low-income countries, people may be unaware of this treatment, or how to access it. A 2006 qualitative study in Tanzania found that some people believed that accessing HAART would be too expensive and logistically difficult to obtain, beliefs that most often prevented them from seeking out treatment. And in cases where people are willing to seek treatment, they often face major obstacles obtaining it. The majority of people do not know their HIV status, largely due to lack of education, but also because of prohibitive HIV-testing costs. For those who have tested positive, the money and time needed to travel to distant clinics, the necessity of missing work or household duties to get to the clinic, and the social stigma of being known as HIV-positive are a few of the many reasons people in developing countries do not take advantage of free treatment even when it is available.25
The problems created by antiretrovirals are not limited to the developing world or underserved populations, however. If we are to continue using antiretrovirals as the primary treatment for HIV/AIDS, we must accept that this will likely lead to viral resistance and the emergence of new strains of HIV unresponsive to current first-line drugs.26 Because in most developing countries there is little availability of second-line therapies, in the case of first-line treatment failure, many patients are left to suffer as the virus becomes drug-resistant.27 The patients experiencing drug failure will not be the only ones affected, because as more virulent strains of HIV develop, the rest of the world population is at higher risk of being infected with drug-resistant strains.
The Case for an HIV Vaccine
If we hope to resolve the global AIDS pandemic, we need to begin investing more of our time and resources in the development of a vaccine that will act not as a remedy for damage already caused, but rather as a preventative solution. Most importantly, development of a vaccine would allow for a one-time administration to those who have limited or no access to a stable health care infrastructure. While HAART requires a lifetime of expensive treatments, a vaccine could be delivered in either a single shot or a short series of shots, according to the prime and boost method.28 Eliminating the need for lifetime treatment plans is perhaps the most compelling argument for focusing attention on vaccine development. Obviously a vaccine, which is preventative in nature, would eliminate the cost of living with the disease and of providing years' worth of pricey antiretrovirals. Lowered costs would allow for more people to receive protection, as would the fact that people would only have to go out of their way to receive administration of the vaccine a limited number of times. As mentioned above, a major barrier to accessing antiretrovirals is the need to miss duties at home or work in order to travel to an often distant clinic to receive medication. A vaccine would largely eliminate that obstacle.
Cost and travel are not the only barriers to access of antiretrovirals, however. According to a recent study aimed at identifying and summarizing current barriers to access of HAART in resource-limited regions, social stigma was one of the primary reasons people both avoid getting tested and, if their status is already known, do not seek out treatment. In many developing regions, discrimination against individuals infected with HIV/AIDS is widespread, appearing in the home, at work, and even in faith-based organizations. This discrimination has created a fear in the general population of being stigmatized as HIV-positive. Many, therefore choose not to seek out treatment even in cases where it is available, as they do not want to risk being seen at a clinic and possibly ostracized from their community. Women are particularly susceptible to issues with stigma, as being tagged as HIV-positive could lead to domestic violence or abandonment.29 The development of a vaccine could eliminate many issues associated with social stigma, as receiving the vaccine actually implies that a person is not infected. A vaccine would also prevent people from having to continually risk being seen at an AIDS clinic in order to receive antiretroviral treatment.
In addition to improving accessibility, a vaccine would alleviate many health risks associated with both antiretroviral therapy and AIDS itself. This includes the myriad of HAART-associated abnormalities and infections discussed above, as well as the malnutrition issues associated with antiretroviral therapy and HIV infection. As stated, malnutrition has been seen to decrease the effectiveness of HAART. In addition, HIV infection exacerbates malnutrition, thereby contributing to the already-critical state of nutritional health in developing countries. Because a vaccine would prevent infection, individuals would be at less risk for deteriorating health themselves and less likely to acquire and pass on infectious diseases that often are associated with HIV infection, such as tuberculosis, herpes, Human Papilloma Virus, and pneumonia.30 This would result in an overall improvement in community health.
Of course, we do not yet have an effective HIV vaccine. Some may argue that it will be years before we do, and that we therefore should invest resources primarily in antiretroviral development rather than vaccine research. We must remember, however, that vaccine development often takes time and shouldn't be abandoned simply for the lack of instantaneous results. Antiretrovirals may transform AIDS into a chronic rather than lethal illness for those with access to the drugs; however, we can never hope to eradicate AIDS without a vaccine, because antiretrovirals only address the problem after it has arisen rather than preventing it from arising altogether. And as long as this disease continues to exist, the global health community will suffer.
Recent results from an HIV vaccine trial in Thailand offer promise that research efforts in the field are progressing and that there exists a real possibility of developing an effective vaccine. The Phase III double-blind, placebo-controlled trial lasted for six years and involved more than 16,000 healthy volunteers primarily at risk for heterosexual transmission of HIV. The vaccine, consisting of four priming injections of ALVAC-HIV and two booster injections of AIDSVAX B/E, was administered in a series lasting six months. Participants were then tested for HIV infection and viremia (the appearance of virus in the bloodstream) every six months over the next three years. The vaccine was shown to reduce the chance of HIV infection by 31.2%, but did not affect viremia or CD4+ T cell counts in those who became infected during the study.31
Although this is a modest outcome, these results may help to guide scientists in future research efforts and provide insight as to the type of vaccine that is most likely to be effective against HIV. For instance, both of the vaccine components used in the trial had previously failed to produce any protective effect when administered alone but offered some protection when given together, suggesting that researchers should perhaps focus efforts on using a combinational approach in developing new potential vaccines.32
Importantly, although thirty percent is only a moderate reduction in infection rate, there is evidence that even a partially effective vaccine could have a significant impact on a community's infection rates. A recent study showed that an HIV vaccine with 50% efficacy given to only 30% of the population could result in the decrease of new HIV infections by over a third within fifteen years. 33 This is due to herd immunity, a phenomenon by which one portion of the population's immunity to a disease reduces the risk of others without immunity contracting the disease. This conferred immunity is due to the reduced prevalence of the disease that results from the decreased number of people in the population able to be infected. Considering the effect of herd immunity, we can see that even a partially effective vaccine could offer a substantial opportunity to combat the HIV/AIDS pandemic. The results of the Thailand trial offer promise that some type of vaccine that could be at least partially effective is on the horizon.
Vaccine research must continue full-force. Although funding for HIV/AIDS prevention research-which includes both vaccine and microbicide development-increased by 109 million dollars (14%) between 2005 and 2008, funding fell by 93 million dollars from 2007 to 2008.34 Worldwide, 868 million dollars of public and private funding was directed toward HIV vaccine research in 2008. Currently, over twenty countries are hosting more than thirty ongoing HIV vaccine trials.35 Clearly, many approaches to developing an HIV vaccine are in the pipeline. The majority of current projects, however, are aimed at reducing further HIV infection and promoting the welfare of people in the developed world, rather than those in the more heavily affected developing world.36
Due to its rapid mutation rate and ability to develop resistance to drugs, HIV has a highly variant genome among its subpopulations. HIV-1, which accounts for the vast majority of infections worldwide, is divided into four groups: M, O, N, and P. Within M, the "major" group that accounts for over 90% of HIV-1 cases, there are number of different clades that vary both in their genetic composition and in their geographic distribution. Genetic variation among clades is most notable in the genomic region coding for the viral envelope proteins, where 20-30% nucleotide variation is seen between clades. Other genomic regions that code for proteins crucial to viral function, such as the pol region which contains the genes for reverse transcriptase and protease, show more sequence conservation between clades. Even so, approximately 5-15% of sequence variance is seen in the pol region. 37
This genetic variation among clades is important in the development of treatments, because distinct genetic sequences produce distinct viral proteins, thus requiring targeting of proteins that may differ significantly depending on the viral clade. Luckily, antiretroviral therapies have essentially been effective across clades. This is likely due to the fact that most HIV antiretrovirals target essential viral proteins, such as reverse transcriptase and protease, which tend to display less variance among clades.38 A single vaccine, however, will likely not have the same universal effectiveness as current antiretrovirals due to the fact that vaccines target the highly variable viral envelope proteins mentioned above.
To date, the majority of vaccine research has been targeted at clade B, although it accounts for only about 12% of HIV cases worldwide. This is due to the fact that subtype B is the predominant variety in the United States and Western Europe.39 Conversely, little vaccine research has been done using subtype A, which predominates in central and northern Africa, or subtype C, which is found primarily in southern Africa and India. These two subtypes account for 27% and 47% of global HIV infections, respectively.40 Of the thirty-one HIV vaccine clinical trials currently underway, only five are directed specifically at subtype C; all of these trials were started in the past three years. The Thailand trial targeted subtype B/E, which is unsurprising given that the trial was funded primarily by the U.S. Army.41
In order to resolve the global AIDS crisis, our future efforts must be aimed at targeting the disease where it is most rampant. In the realm of vaccine research and development, this means re-directing funds toward research on the most predominant viral subtypes, namely subtypes A and C. If we hope to one day eradicate AIDS, these subtypes will have to be first addressed. Development of a vaccine effective against only the B subtype will not be sufficient to rid our world of the disease. It may succeed in protecting the developed world from AIDS for a time, but without means to eliminate other, more widespread subtypes, it will only be a matter of time before the developed world is plagued by new, perhaps more virulent strains of HIV. Subtype spreading has in fact already begun. While Europe has historically been a region almost exclusively infected by subtype B, recent years have seen more than 40% of the continent's new infections resulting from a clade other than B.42 This statistic foreshadows continued spread of HIV subtypes that is likely to occur as immigration rates increase and the world experiences the effects of globalization. The possibility for spread highlights why the developed world needs to focus research on subtypes other than its own, if only for the most practical of reasons, self-defense.
The Common Good: A Call to Action
This threat to the developed world's safety, however, cannot be the sole motivation for redirecting our funds and efforts toward developing a vaccine against those subtypes present in the regions carrying the heaviest burden of HIV infection. This must also be driven by a concern for the good of the global community. The common good is a principle based on the idea that societal interdependence forms the basis of ethical reasoning and requires respect and compassion for others, especially for those that are most vulnerable.43 In the global AIDS crisis, the common good calls us to value the well being of all members of the global community, not just those with the ability to access and means to afford expensive treatments. In order to preserve the well being of the global community, those in the developed world with access to the necessary resources have a responsibility to help the vast number of people who do not have the means by which to help themselves. The principle of the common good mandates that we consider and treat all human beings in a manner that shows respect for the fact that we all are of equal worth. Currently those living in the developing world, particularly in regions ravaged by a high prevalence of AIDS, do not have a health status reflective of their human worth. It is clear that those in sub-Saharan Africa and other parts of the developing world are in dire need of services to combat the disastrous effects that AIDS has brought on their communities.
Historically HIV vaccine research, with its focus on clade B, not only has not taken account of the common good, but also has failed to adequately address the issue of the distributive justice, which mandates the distribution of scarce resources according to a just standard. In this case, the distribution of funding for HIV vaccine research must be based on the standards of need and equality. Distributive justice calls for us to address the inequality of disease burden by redirecting the distribution of much-needed resources to the global south in order to foster a more equal and, consequently, more just global community.
In the case of HIV/AIDS, this will require giving preference to those who are most in need. This preference should manifest itself immediately in the distribution of resources and services to heavily affected areas. In the short-term, services must include access to HAART, but this cannot be the only effort to ease the burden of AIDS in highly affected regions. The development of an effective vaccine should be the ultimate goal of current international HIV/AIDS initiatives, such as those of AVAC: Global Advocacy for HIV Prevention, the Global Fund, and International AIDS Vaccine Initiative, as it appears to be our sole hope for eventual eradication of the disease.
The practicalities of funding are, and will continue to be, a key component in the process of vaccine development. Once a vaccine is successfully developed, distribution costs will likely not be an obstacle, as they will most likely be much less than current costs needed for production and distribution of antiretrovirals. Instead, research and development are likely to constitute the majority of vaccine-related to costs, and will most probably necessitate additional funding sources in the near future. Private funding from groups such as the Bill and Melinda Gates Foundation-who contribute significantly to initiatives such as IAVI and The Global Alliance for Vaccination and Immunization (GAVI)-will be important; however, public funding from developed nations, including the United States, must also increase. If future funding from individual nations could be directed to centralized vaccine efforts such as the GAVI, which receives over two billion dollars in public funding from over 50 countries, development efforts may be able to proceed more quickly. 44
We must remember, however, that the developed world's donation of resources cannot be a long-term solution to either the HIV/AIDS crisis or the issues of poverty that exacerbate the severity of this crisis in the global south. Development of local infrastructures in suffering countries will be necessary to the development of a global community that better reflects concern for the common good. To resolve issues with AIDS and other infectious diseases prevalent in the developing world, building a stronger medical infrastructure will be necessary. General national infrastructure must also improve in order to secure a more stable future for these countries. Importantly, development of these infrastructures must be based around local communities and their own knowledge and skill. This will likely require programs aimed at training local community members in order to create a skilled workforce that can hopefully over time take charge of the task of promoting social and economic development within their own country. This is a daunting task, and one that has yet to be achieved despite many humanitarian efforts. The difficulty of the task, however, cannot be a deterrent to us taking action in the present, even if that action seems insignificant, in order to address issues of global inequality and injustice by promoting the common good and distributive justice.
Restoration: A Call to Justice
Interest in the common good and distributive justice are not the only concerns that call the developed world to action in the global AIDS pandemic. In order to resolve the discrepancies that currently exist in the targets of vaccine research efforts, we must also-and with some urgency-recognize how the developed world's past and present actions have contributed to those discrepancies. In addition to the slave trade, decades of colonization, and exploitation of local natural resources, the developed world's inadequate response to the AIDS pandemic in Africa has perpetuated and contributed to the social and economic injustice that now heightens the HIV/AIDS problems on that continent and in the rest of the developing world. Throughout the 1980's, the developed world was not only too slow in acknowledging the emergence of HIV, but also continued to understate the problem in Africa. The World Heath Organization stated that "HIV/AIDS [was] not the predominant health care concern in the region" despite rapidly rising infection rates.
This lack of acknowledgment and urgency to provide treatment to these regions until recently necessitates action from the developed world to repair the harm caused by its prior lack of response to the HIV/AIDS crisis in the global south. The principle of restorative justice calls for peaceful and constructive action to repay past injustices.45
Rather than privileging the law, professionals and the state, restorative resolutions engage those who are harmed, wrongdoers and their affected communities in search of solutions that promote repair, reconciliation and the rebuilding of relationships. Restorative justice seeks to build partnerships to reestablish mutual responsibility for constructive responses to wrongdoing within our communities.46
It is clear that many of our past actions, and lack of action, in Africa have contributed to the every day reality of poverty and disease in the region. We, unfortunately, cannot take back those actions. Instead, we must move forward with constructive action that can hopefully help to repair some of the injustice that we have created and perpetuated.
One example of modern day restorative justice is the creation of the Truth and Reconciliation Commission (TRC) of South Africa in 1995. The aim of the committee was to peacefully reconcile the many human rights violations that occurred during the country's apartheid, which lasted nearly fifty years and severely marginalized the country's majority black population, while granting privilege to the minority white population. In contrast to the Nuremberg Trials that followed the end of World War II and involved the prosecution of those who had taken part in the violation of human rights, the TRC sought instead to give a voice to those who had been silenced for so many years under apartheid. The committee held a series of hearings over a three-year period where both victims and perpetrators were allowed to testify and share their experiences of abuse and injustice. The committee had the power to grant amnesty to perpetrators who were deemed to have been working under government influence and provided full disclosure of their actions. Of course, true justice for human rights violations is difficult, perhaps impossible, to achieve. Despite its imperfection, however, the TRC is a good example of a formal effort to restore human rights and human dignity.47,48
In the case of the global HIV/AIDS crisis, the past injustices run deep and, again, are unlikely to ever be truly resolved. That does not mean, however, that we should not attempt to reconcile with those whose suffering we have helped to perpetuate through our exploitation and ignorance of their humanity. Those of us in the developed world are called to use the many resources at our disposal to assist those in the developing world without access to such resources. Like with the TRC, we need to begin the process of restoring human dignity to those in developing world. Working to eradicate HIV/AIDS is a peaceful strategy for restoring the damage caused by our past injustices. In order to achieve this restoration, however, we must give preference to those in most need. That means that the focus of HIV vaccine research should be redirected to the clades that are most prevalent in the world, rather than the clade most common in the regions that hold the majority of global wealth.
As we continue forward in our efforts to resolve the AIDS pandemic, we must keep in mind consideration for the common good and the principles of distributive and restorative justice that call those of us in the developed world to help resolve the AIDS pandemic in the developing world. These considerations should then guide the actions of future funding and vaccine development decisions. Only then will we fulfill consideration for the common good and the value of global community.
1 UNAIDS 5
2 Bartlett 253
3 UNAIDS 18
4 Bartlett 253
5 UNAIDS 2007
6 Adamson 2-3
7 Porche 95
8 HIV Causal Collaboration
9 Rathbun 1045
10 Mansky 1338
11 Fauci "25 Years of HIV" 290
12 Fauci "HIV/AIDS: 20 Years of Science" 842
13 Adamson 3
14 Heath 13, Herman 555
15 Rodriguez-Novoa 234
16 Curlin 1239
17 Koethe 507
18 World Food Programme
19 Bartlett 256
20 Bartlett 256-7
21 Rathbun 1045
22 Maggiolo 282
24 Mshana 649
25 Bartlett 256-7
26 Jing, Manksy, Mayers
27 Rennie 30
29 Bartlett 257
30 "Infections associated with AIDS"
31 Rerks-Ngarm 2209-2220
32 Cohen "Surprising" 26
33 Stover 1147
34 "Adapting to Realities" 5
35 "Ongoing trials"
37 Spira 239, 241-242
38 Frater 1143
40 Osmanov 186
41 "Ongoing trials…"
42 Spira 230
43 "A Framework for Thinking Ethically"
45 Carael 32
46 Suffolk University
Adamson, C. & Freed, E., 2009. "Novel approaches to inhibiting HIV-1 replication". Antiviral
AVERTing HIV and AIDS, 2009. "AIDS, drug prices and generic drugs."
<http://www.avert.org/generic.htm> 15 May 2010.
Bartlett et al., 2009. "Obstacles and Proposed Solutions to Effective Antiretroviral Therapy in
Resource-Limited Settings". Journal of the International Association of Physicians in AIDS Care 8: 253-265.
Carael, M., 2006. "Twenty years of Intervention and Controversy." The HIV/AIDS epidemic in
sub-Saharan Africa in a Historical Perspective (Denis and Becker eds, online edition):
Cohen, Jon, 2009. "Surprising AIDS vaccine success praised and pondered." Science 326: 26-27.
Cohen, et al., 2008. "The spread, treatment, and prevention of HIV-1: evolution of a global
pandemic." The Journal of Clinical Investigation 118: 1244-1254.
Curlin et al., 2007. "Optimal Timing and Duration of Induction Therapy for HIV-1 Infection".
PLoS Computational Biology 3(7): e133.
Fauci, Anthony, 2003. "HIV and AIDS: 20 years of science". Nature 9(7): 839-843.
Fauci, Anthony, 2008. "25 Years of HIV". Nature 453: 289-90.
Frater, et al., 2002. "Comparative response of African HIV-1-infected individuals to highly
active antiretroviral therapy." AIDS 16(8): 1139-1146.
Gaschen et al., 2002. "Diversity Considerations in HIV-1 Vaccine Selection." Science 296:
Girard et al, 2006. "A review of vaccine research and development: the human
immunodeficiency virus (HIV)." Vaccine 24: 4062-4081.
Global Alliance for Vaccine and Immunization, 2010. "Donor contributions and commitments."
26 May 2010. < http://www.gavialliance.org/support/donors/index.php>
Heath, et al., 2003. "Emerging drug toxicities of highly active antiretroviral therapy for human
immunodeficiency virus (HIV) infection." Current Drug Targets 4(1): 13-22.
Herman, J. & Easterbrook P., 2001. "The metabolic toxicities of antiretroviral therapy". The
International Journal of STD & AIDS 12: 555-564.
Hirschhorn, L. & Skolnik, R., 2008. "Making Universal Access a Reality-What More Do We
Need to Know?". The Journal of Infectious Diseases 197: 1223-5.
HIV Causal Collaboration, 2009. "The effect of combined antiretroviral therapy on the overall
mortality of HIV-infected individuals". AIDS doi: 10.1097/QAD.0b013e3283324283.
AVAC: Global Advocacy for HIV Prevention, 2009. "Ongoing trials of preventive HIV/AIDS
vaccines worldwide (May 2009)." <http://www.avac.org/ht/d/sp/i/3511/pid/3511> 10 May 2010.
HIV Vaccines and Microbicides Resource Tracking Working Group, 2009. "Adapting to
Realities: Trends in HIV Prevention Research Funding 2000 to 2008."
<www.hivresourcetracking.org> 9 May 2010.
"Infections associated with AIDS". UCSF Medical Center. 11 April 2010. University of
California San Francisco. 11 April 2010. <http://www.ucsfhealth.org/adult/medical_ services/infect/hiv/infections.html>
Jing et al., 2005. "Prevalence and evolution of drug resistance HIV-1 variants in Henan, China".
Cell Research 15: 843-849.
Kantor, et al., 2005. "Impact of HIV-1 subtype and antiretroviral therapy on protease and reverse
transcriptase genotype: results of a global collaboration". PLoS Med 2(4): e112. Doi:10.1371/journal.pmed.0020112.
Koethe et al., 2010. "Association between weight gain and clinical outcomes among
malnourished adults initiating antiretroviral therapy in Lusaka, Zambia". Journal of Acquired Immune Deficiency Syndrome 53(4): 507-513.
Leyes, et al., 2008. "Use of diet, nutritional supplements and exercise in HIV-infected patients
receiving combination antiretroviral therapies: a systematic review." Antiviral Therapy
Maggiolo et al., 2007. "Effect of adherence to HAART on virologic outcome and on the
selection of resistance-conferring mutations in NNRTI- or PI-treated patients." HIV
Clinical Trials 8(5): 282-292.
Mansky, Louis, 1998. "Retrovirus mutation rates and their role in genetic variation." Journal of
General Virology 79: 1337-1345.
Markkula Center for Applied Ethics. Santa Clara University. "A Framework for Thinking
Ethically." <http://www.scu.edu/ethics/practicing/decision/framework.html> 9 May 2010.
Martin et al., 2004. "Pharmacogenetics of antiretroviral therapy: genetic variation of response
and toxicity." Pharmacogenetics 5: 643-655.
Mayers, Douglas, 1998. "Drug Resistant HIV-1: The Virus Strikes Back." The Journal of the
American Medical Association 279(24): 2000-02.
Melchior et al., 1999. "Malnutrition and wasting, immunodepression, and chronic inflammation
as independent predictors of survival in HIV-infected patients." Applied Nutritional Investigation 15(11,12): 865-869.
Mshana et al., 2006. "Barriers to accessing antiretroviral therapy in Kisesa, Tanzania: a
qualitative study of early rural referrals to the national program." AIDS Patient Care STDs 20 (9): 649-657.
Osmanov et al., 2002. "Estimated global distribution and regional spread of HIV-1 genetic
subtypes in the year 2000". Journal of Acquired Immune Deficiency Syndromes 29: 184-190.
Porche, D., 1999. "State of the art: antiretroviral and prophylactic treatments in HIV/AIDS". The
Nursing Clinics of North America 34(1): 95-112.
Posse, M. & Baltussen, R., 2009. "Barriers to Access to Antiretroviral Treatment in
Mozambique, as Perceived by Patients and Health Workers in Urban and Rural Settings". Mary Ann Liebert, Inc 23: 23-31.
Potthoff, A. & Brockmeyer, N., 2009. "Current Therapy of HIV". Journal of the German
Society of Dermatology [epub ahead of print].
Rathbun et al., 2006. "Current HIV Treatment Guidelines-An Overview". Current
Pharmaceutical Design 12(9): 1045-63
Rennie, S. & Behets, F., 2006. "AIDS Care and Treatment in Sub-Saharan Africa:
Implementation Ethics". Hastings Center Report 36: 23-31.
Rerks-Ngarm et al., 2009. "Vaccination with ALVAC and AIDSVAX to prevent HIV-1
infection in Thailand." The New England Journal of Medicine 361(23): 2209-2220.
Rodriguez-Novoa et al., 2006. "Overview of the pharmacogenetics of HIV therapy."
Pharmacogenomics 6(4): 234-245.
Sooka, et al, 2003. "Truth and Reconciliation Commission of South Africa Report." South
Spira et al., 2003."Impact of clade diversity on HIV-1 virulence, antiretroviral drug sensitivity
and drug resistance." Journal of Antimicrobial Chemotherapy 51: 229-240.
Storey, Peter, 1997. "A different kind of justice: truth and reconciliation in South Africa." The
Christian Century Sept.: 10-17.
Stover et al., 2007. "The impact of an AIDS vaccine in developing countries: a new model and
initial results." Health Affairs 26(4): 1147-1158.
Suffolk University Center for Restorative Justice, 2010. "What is Restorative Justice."
<http://www.suffolk.edu/research/6953.html> 15 May 2010.
United Nations. Joint United Nations Program on HIV/AIDS, 2007. "AIDS epidemic update:
December 2007." <http://www.unaids.org/en/KnowledgeCentre/HIVData/EpiUpdate /EpiUpdArchive/2007/default.asp> 10 April 2010.
United Nations. Joint United Nations Program on HIV/AIDS, 2008. "Report on the global AIDS
epidemic: executive summary."<http://data.unaids.org/pub/GlobalReport/2008/JC1511_ GR08_ExecutiveSummary_en.pdf> 16 Oct 2009.
Wang, X. & Wu, Z., 2007. "Factors associated with adherence to antiretroviral therapy among
HIV/AIDS patients in rural China." AIDS 12 Suppl 8: S149-55.
Willig, J., 2009. "Durability of Initial Antiretroviral Therapy in a Resource Constrained Setting
and the Potential Need for Zidovudine Weight-Based Dosing." Journal of Acquired
Immune Deficiency Syndrome [ePub ahead of print]
World Food Programme. "The state of food insecurity in the world 2009." Food and
Agricultural Organization of the United Nations. 11 April 2010. <http://www.wfp.org/co
Erin Cleveland wrote this piece as her honors thesis at Santa Clara University.
Jul 1, 2010
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