• Untitled The Future of the AIDS Epidemic

    The dramatic successes in prevention and medical breakthroughs -- during the two-decade long AIDS epidemic in the United States -- hide some forebodding clouds in the horizon.

    Antiretroviral agents and HIV resistance . Better antiretroviral and combination drug therapies coupled with improved health care to manage AIDS-related illnesses and other opportunistic infections either delayed the transition from HIV positive to AIDS status or allowed people living AIDS to "manage the disease", and thus live longer. These medical developments contributed to the sharp decline in AIDS deaths since 1995.
    Incidence, prevalence and deaths among persons with AIDS, 1985 - 2001 (US)
    Incidence, prevalence and deaths among persons with AIDS, 1985 - 2001 (US)

    The euphoria however was short-lived; the rate of decline in AIDS deaths has begun to level off since 1998. Several factors contributed to this leveling off.

    First, the current arsenal of antiretroviral and combination drug therapies work only for a significant number, but not all, of those living with HIV/AIDS. Thus, as the number of receptive patients are saturated, the remaining who do not respond, i.e., "refractory", to an antiretroviral drug are likely to die, unless other antiretroviral agents or medical regimens become available.

    The sinister reason why some patients are "refractory" , i.e., do not respond, to a drug treatment is due to development of "resistance" to the antiretroviral drug in use. Development of "resistance" to a drug is responsible for why some antiretroviral drugs work only for a significant number but not all of those living with HIV/AIDS. An HIV positive patient who does not respond, i.e., "refractory", to a specific antiretroviral drug has been infected already with an HIV strain that is resistant to the specific drug.

    Alternatively, as a patient keeps on using a specific antiretroviral agent, the specific HIV strain in the person's body can evolve to develop resistance to the drug being used. The patient can be shifted to a new antiretroviral drug; but again, in due time, the HIV strain in the person's body can evolve and become resistant to the new antiretroviral agent. Thus, the patient would become "refractory" to any drug in the long run.

    In fact, it is even possible that the new HIV strain that would evolve in the patient's body would be resistant to both antiretroviral agents; and the patient becomes "refractory" to both antiretroviral drugs. The latter phenomenon, termed as development of "multiple resistance", is the underlying reason why physicians avoid unnecessary shift or delay shift from one antiretroviral drug to another.

    The arsenal of "new" highly potent antiretroviral agents therefore is a "double-edged sword". In effect, the combination drug therapies have allowed people living with HIV/AIDS to "manage the disease"; thus, live longer. However, as discussed in aforementioned "development of resistance", these people living with HIV/AIDS are also "walking reservoirs" of mutant HIV strains that are gradually becoming resistant to antiretroviral agents the patients are using. These people living with HIV/AIDS under antiretroviral drug treatment can infect other individuals with their mutant HIV strains. In effect, the newly infected person can readily become "refractory", i.e., do not respond, to specific antiretroviral drugs.

    The rapid reproduction rate of the HIV strains have already resulted in a plethora of mutant HIV strains that have " specific" or "multiple" drug resistance to the existing library of antiretroviral agents:
    The aforementioned links provide more comprehensive databases of the molecular basis of the resistance of specific HIV strains to the library of antiretroviral agents.

    Since viruses can reproduce quite rapidly, it is unclear whether scientists and pharmaceutical companies can discover or synthesize new and more potent drugs that can keep pace with the continuously and rapidly evolving HIV strains.

    Globalization of HIV strains. Current antiretroviral drugs were developed mainly against the HIV strains predominant in the United States and other Western countries. Other HIV strains are found in other parts of the world. The HIV-2 strain for example is common in some regions of Africa, but is still very rare in the United States and other countries. With increasing globalization and mobility, other HIV strains, that were once localized, are being introduced in other parts of the world. It is grim to imagine a new round of AIDS epidemic in the future, where even more resistant or new strains of HIVs may come into play.

    Resurgence of HIV infection in Western countries. More troubling, those who were not around during the height of the AIDS epidemic in the 1980's have been found to engage in substance abuse and sexual practices that could lead to HIV infection. Coupled with this, many are not aware that they may have already been infected with HIV and thus could pass on the virus to their partners. These developments are behind the resurgence of HIV infection and AIDS among younger people in the United States and other Western countries. If the backdrop of evolving resistance to current antiretroviral agents is introduced in the equation, a future resurgence of an AIDS epidemic may be more difficult to control.

    Because of the gestation period and the progression of the disease, it is unclear whether these new developments could lead to future resurgence of the AIDS epidemic here in the United States.

    Equally disconcerting, the disease is no longer just a "white gay male disease". It is significantly invading the heterosexual population, especially specific minority populations, including African-Americans and Hispanics. The latter development is following the past trend of the AIDS epidemic in other parts of the world. So far, the visible political leaders in these communities in the United States have only given tepid acknowledgement and response to the encroaching impact of the AIDS epidemic in their respective communities. This seeming apathy parallels the previous behaviors of some political leaders in the less developed countries who then considered AIDS to be mainly a "Western" disease.

    Complacency. In the age of internet and mass-media saturation, it brings pause as to whether these target populations are indeed reached by the HIV/AIDS education campaign. If the education programs succeeded in informing these groups about the modes of transmission of HIV, what is behind the complacency of the younger population, certain minority groups and political leaders?

    Understanding this apathy may lead to more effective educational outreach education programs in the continuing fight against the spread of HIV/AIDS.

    Natural resistance to the AIDS virus? It is true based on the principles of evolution, that man, as a "collective species", can evolve also in response to an environmental assault, including diseases and pests. The most remarkable demonstration of this selection procedure, for example, is the preferential survival of individuals with genetic predisposition to "sickle cell anemia", in response to malaria caused by a plasmodium parasite. In this case, "cell sickling" can induced by the metabolites of the plasmodium parasite itself, cause dramatic lowering of "pH" and concomittant drop in potassium level -- conditions that are not favorable for the plasmodium itself. This process occurs quite rapidly among members of the population already with the mutated genes that predispose them to " cell sickling"; thereby surviving malaria. At the same time, the tragic reality is that most individuals in the population do not have this predisposition explaining why malaria is still one of the highest cause of death in less developed countries (LDCs) -- in effect increasing the % ratio of surviving individuals with predisposition to " cell sickling"; thereby surviving malaria.

    The latter explains why human populations where malaria is endemic also have high preponderance to "sickle cell anemia". In the case of of individuals who inherit the predisposition to cell sickling, the surviving population in the species suffer from the debilitating effects of sickle cell anemia. Also, the predisposition to " cell sickling" does not necessarily ensure protection from to other specific types of environmental assault; in fact, it may render the individual susceptible to specific adverse conditions. For example, those who are predisposed suffer from " cell sickling" at high altitudes, making this predisposition undesirable in the age of globalization and international travel through air transport.

    In due time, what was observed with malaria would be the natural direction of evolution in the case of AIDS. Already, there are individuals with the genetic predisposition to "survive" HIV infection without any medication. But, like the situation with other "acquired resistance", a genetic predisposition to resist the complications of "HIV/AIDS" does not guarantee resistance or survival from other environmental assaults, including other diseases that may visit mankind in the future.