Author: Ng Elizabeth
Date: December 2007
Despite twenty-six years of research, activism, and education, the HIV/AIDS pandemic continues to affect the lives of millions worldwide. The Joint United Nations Programme on HIV/AIDS (UNAIDS), estimates that by the end of 2006, approximately 32.7 million adults and 2.3 million children were living with HIV. Sadly the same year, UNAIDS also estimates that 4.3 million people were newly infected with HIV, and that about 2.9 million people died from AIDS. (1) Although, the treatment and prevention plans of today offer hope to some, there is still much to be done to combat this deadly disease.
"A cure for HIV infection remains an elusive goal despite the significant impact of current treatments. This is because of the virus' ability to adapt to and resist those treatments, and bypass the immune system's natural defenses," said Robert J. Suhadolnik, Ph.D., a professor of biochemistry at Temple University School of Medicine in Philadelphia. (2)
For these reasons, HIV poses a daunting challenge for researchers, forcing them to approach treatment and vaccination with creativity and tenacity. In the following segments, I will take a look at the shortcoming and challenges of today's treatments, the status of the ellusive HIV vaccine, and the steps researchers are taking to improve the lives of those with and without HIV/AIDS.
What are HIV and AIDS?
The human immunodeficiency virus, known as HIV, is transmitted primarily through unprotected sexual intercourse, sharing of contaminated needles, contact with infected blood, and from mother to child. HIV is a debilitating retrovirus that preys on the body's immune system, attacking a specific kind of helper T-cell called CD4+ T-cells. HIV is a retrovirus, meaning that it is able to inject RNA and enzymes into the T-cell, and hijack the cell's DNA replicating machinery to churn out new viruses. This causes T-cell death, either by direct viral killing, protective programmed cell death in which the cell destroys itself to prevent further infection, or destruction by the healthy immune system.
HIV usually goes through asymptomatic period, during which the virus continues to attack T-cells and replicate, but during which there is not visible immune system deterioration. Basically the virus lays dormant in the cells, replicating and building up its forces for a future attack. It is also during this time that HIV can sequester itself in tissues, becoming inactive and undetectable. As this asymptomatic phase progresses, more CD4+ cells become destroyed. At the same time, the number of infected cells increases, progressively weakening the immune system of the infected person. In many cases, this weakening of the immune system no longer allows the body to fight other illnesses, such as pneumonia, tuberculosis, and tumors. This collection of opportunistic infections, preying on an HIV weakened immune system, is known as acquired immune deficiency syndrome, or AIDS.
The Vaccine
Vaccines are vital for the prevention of many diseases. In general, a vaccine works by introducing a dead or disabled pathogen into the body. The person's immune system is able to fight off and destroy these weakened viruses or bacteria much more easily than it could live ones. During this process, the body's immune system remembers what these pathogens were and develops specific defenses against them; so when live bacteria or viruses attack the body later, the immune system will already have defenses, or immunity, against the attacking microorganisms. An effective HIV vaccine, therefore, is one of the main objectives in HIV research.
A successful vaccine would help curtail the spread of HIV, giving health workers a vital tool in stopping the HIV/AIDS pandemic. As researchers from the Fred Hutchinson Cancer Research Center state in a 2006 paper, "[an HIV] vaccine is the most promising and feasible strategy to prevent the events during acute infection that simultaneously set the course of the epidemic in the community and the course of the disease for the individual." (3)
However, there are many aspects of HIV that make it very difficult to develop a vaccine or cure. As of 2005, there had been about 49 phase I trials for vaccines, of which only two vaccines made it to phase II and phase III trials. (4) The development of an HIV vaccine is impeded by three main characteristics of the virus. The first problem is that as a retrovirus, HIV is capable of inserting its DNA into a strand of human DNA, thereby giving it a permanent foothold in the host organism from which it can launch future attacks. Secondly, since HIV attacks the cells of the immune system, many potential vaccines must also target the body's defense system. However, traditional vaccines, such as those for the flu, polio or smallpox, rely on training the body's existing defenses to recognize and attack invading diseases. This method will obviously be inefficient for a virus that naturally destroys the immune system.
"Schematic Representation of the Key Structural Features of SIV and HIV-1 Entry into T Cells." (A) Different stages of viral entry from budding, to maturation, to entry claw formation. (B and C) Two alternative models for viral entry. Image Courtesy of Electron Tomography of the Contact between T Cells and SIV/HIV-1: Implications for Viral Entry Sougrat R, Bartesaghi A, Lifson JD, Bennett AE, Bess JW, et al. PLoS Pathogens Vol. 3, No. 5, e63
The third, and most difficult challenge, is that HIV is a continuously mutating and evolving disease. Since the enzymes that copy the viral RNA and insert it into the host's chromosome are very inaccurate, the possibility for mutation is very high. As HIV mutates, the virus itself can change in structure and in what kinds of proteins it produces. Since these changes are completely random, there is a great deal of variation between different strains of HIV. Some of these changes can even cause strains of HIV to be resistant to treatments that are effective against other strains. This has lead many researchers to conclude that no vaccine will ever be able to effectively protect against all strains of HIV. (5)
Despite these setbacks, researchers are making headway on potential vaccines, especially as more detailed information on the structure of the virus and its enzymes become available. One promising approach is to target the parts of the virus that must remain relatively unchanged in order to allow binding to T-cells. This may allow scientists and doctors to create an arsenal of antibodies that target these weak spots. (6)
Another approach to the vaccination dilemma is to avoid the problem of creating global vaccinations- or vaccinating every person against every strain of HIV- by using an alternative method, known as altruistic vaccination. In this system, a vaccine that is not 100 percent effective is administered with the hope that the protection gained by those with immunity will extend to those without immunity, since fewer people will be able to spread the disease. If the population of people without immunity is small enough, the virus will not have ready access to new hosts, and will hopefully disappear.
The Treatment
As there is no highly effective HIV vaccine in the near future, the most common way of combating HIV and AIDS is with Highly Active Anti-Retroviral Therapy (HAART). HAART is a cocktail of three different types of drugs: reverse transcriptase inhibitors, protease inhibitors, and fusion inhibitors. Reverse transcriptase inhibitors interfere with the virus's ability to translate its RNA into DNA by interfering with nucleotide addition, or by binding to the actual enzyme. Protease inhibitors stop HIV from breaking down cellular proteins used in the construction of new viruses, thereby stopping virus reproduction. Finally, fusion inhibitors reduce HIV infection by preventing it from binding to and merging with target cells. (7)
Because HIV can develop a resistance to any one of these drugs, they must be used in combination to effectively suppress the disease. Although HAART cannot cure a patient of HIV, it can suppress nearly all symptoms of AIDS, and has been highly successful at reducing AIDS related deaths in developed countries like the United States. Despite these lifesaving qualities, there are several problems with HAART that motivate doctors and scientists to seek other options.
The first problem is that the side effects of HAART can be devastating. These can range from nausea and diarrhea, to severe allergic reactions, to inflammation of the pancreas and nerve damage. (8) Abigail Zuger, a doctor in an AIDS clinic, illustrates the tension between the lifesaving aspects of HAART and the destructive side-effects:
That skeletal fellow reading a magazine, skin pulled taut over his skull, folds of denim covering his wasted legs, is actually one of our big successes. He is perfectly well, at least as far as his H.I.V. infection goes. Ten years ago he was dying of AIDS; now he is living with it , or, more accurately, living almost without it, his immune system normal, no trace of virus detectable in his blood. It is the lifesaving drugs that have transformed his appearance like this, leaching the fat from his body even as they clear the virus from his blood. (9)
Not all HAART patients react in quite the same way, but many suffer from some form of adverse reaction.
The second problem with HAART is its cost. Although the cost of HAART has dropped to about $800 a year from about $11,000 a year in 2000, continuous reliable treatment is still far out of reach for many AIDS patients in the developing world. Although organizations like UNAIDS are working to raise money to lower the cost of retroviral treatment, other steps must be taken. (10)
Interestingly, one solution to both of these problems is to use HAART periodically, in short breaks without drugs. These breaks not only give the body a respite from the side affects of drug usage, but also reduce cost because less medicine is needed. Many doctors believe that such breaks are beneficial, and do not increase the rate of drug resistance or reduce efficacy.
Better informed and more prepared, the researchers, activists, and doctors of today continue to fight HIV and AIDS. Despite the benefits and successes of many of the breakthroughs mentioned above, prevention must also remain a high priority. For example, in 2007, the results from large scale studies showed that male circumcision could reduce HIV infection by up to 76 percent compared to uncircumcised men, and could possibly reduce transmission to female partners. (11) Circumcision seems to reduce HIV transmission since the foreskin is more susceptible to small tears that could allow the entry of virus. It has also been proposed that the unretracted foreskin provides a shelter for viruses. Although, there is some risk with circumcision, and it is unethical to implement mandatory circumcision, in conjunction with other preventative measures, it could be a cost effective addition to the prevention of HIV transmission. Aside from this, the most important preventative measure is education. It is only by learning about HIV and how it is transmitted that people can take responsibility of their own protection.
Works Cited
1. United Nations. UNAIDS. Report on the Global AIDS Epidemic 2006. May 2006. 15 Oct. 2007
2. Suhadolnik, Robert J. et al "New Compound Shows Promise in Halting HIV Spread." AIDS Research and Human Retroviruses 31 Jan. 2007. 15 Oct. 2007.
3. Duerr, Ann, Judith N. Wasserheit, and Lawrence Corey. "HIV Vaccines: New Frontiers in Vaccine Development." Infectious Diseases Society of America 43 (2006): 500-503. 14 Oct. 2007
4. Griard, Mp. "The Quest for an HIV Vaccine." Bull Acad Natl Med 5 (2005): 831-844. PubMed. 15 Oct. 2007
5. Duerr, Ann, Judith N. Wasserheit, and Lawrence Corey. "HIV Vaccines: New Frontiers in Vaccine Development." Infectious Diseases Society of America 43 (2006): 500-503. 14 Oct. 2007
6. "Scientists Expose HIV Weak Spot." BBC News 15 Feb. 2007. 16 Oct. 2007
7. HIV Infection and AIDS: an Overview. National Institute of Allergy and Infectious Diseases. National Institute of Health. 8 Oct. 2007. 15 Oct. 2007
8. HIV Infection and AIDS: an Overview. National Institute of Allergy and Infectious Diseases. National Institute of Health. 8 Oct. 2007. 15 Oct. 2007
9. Zuger, Abigail. "AIDS, At 25, Offers No Easy Answers." The New York Times 6 June 2006. 17 Oct. 2007
10. United Nations. UNAIDS. Report on the Global AIDS Epidemic 2006. May 2006. 15 Oct. 2007
11. Male Circumcision and Risk for HIV Transmission: Implications for the United States. Centers for Disease Control and Prevention. 2007. 17 Oct. 2007
Written by Elizabeth Ng
Reviewed by Nira Datta, Pooja Ghatalia
Published by Pooja Ghatalia