Biomedical Prevention: Has Its Time Now Come?

Biomedical Prevention: Has Its Time Now Come?In the early 1980s, the medical world was thrown into a panic by the appearance of a new and apparently highly contagious infectious disease of unknown etiology. This new illness, that initially seemed to affect only men who have sex with men (MSM), has evolved into a pandemic that has become one of the greatest public health challenges in the last half century. For too long, people infected with HIV were told they had no treatment options and that opportunistic infections and early death were inevitable. Fortunately, clinical researchers and social scientists having been working diligently for more than 25 years to change these circumstances.

Beginning with the use of diagnostic and screening tests for HIV infection in 1985, the spread of HIV in the United States population has dramatically decreased. National HIV-testing programs have led to the testing of about 50% of Americans between the ages of 15 and 44 years.1 Whereas HIV testing promoted individual knowledge of HIV serostatus, identification of HIV-transmission routes reduced unfounded fears about the spread of infection. Prevention programs that provided basic information about HIV and AIDS succeeded in decreasing transmission by promoting risk-reduction strategies for populations at high risk for infection. HIV testing also helped ensure the safety of the nation's blood supply. Since the mid-1980s, blood donor-screening methods and testing technology have reduced the risk of infection from contaminated blood transfusions to about 1 in every 2 million donations.2

The decrease in mother-to-child (perinatal) transmission of HIV was another major milestone in prevention efforts. The number of infants infected through perinatal transmission decreased from 2,000 in 1990 to fewer than 300 by 2002 (see Levison in this issue).3 Multiple interventions contributed to this success: 1) the routine voluntary testing of pregnant women; 2) the use of rapid HIV tests at delivery for women of unknown HIV status; and 3) the use of antiretroviral therapy by HIV-infected women during pregnancy and the treatment of infants after birth. The availability of highly active antiretroviral therapy (HAART) in the 1990s led to a dramatic decline in AIDS-related deaths and the dawn of a new era in which people newly diagnosed with HIV infection could expect to live for decades rather than a few years. The continued research and development of new pharmaceuticals to treat HIV infection means that, at least for people in developed countries, the risk of AIDS-related infections and death are becoming a thing of the past.

Nonetheless, HIV and AIDS have claimed the lives of more than 22 million people worldwide since 1981, including more than 500,000 persons in the United States. By the year 2000, more than 1.4 million cumulative HIV infections were documented in the United States, with an estimated 40,000 new infections occurring per year.4 Estimates of the annual number of new HIV infections have been the same for the past 14 years. This plateau in new cases could mean that a measure of complacency about the HIV epidemic has set into the public consciousness, as well as into the minds of the research community. On the one hand, advances in the treatment of HIV infection have led many to believe that the epidemic is under control and that dying from AIDS-related complications is no longer a problem because it has become a chronic, long-term illness much like diabetes. Whereas there is no question that advances in HIV treatment, particularly in the form of HAART, have greatly improved the lives of those infected with HIV and affected by HIV/AIDS, the promise of drugs that can be used as an HIV-prevention intervention might be overestimated. Evidence suggests that the ready availability of HAART has been accompanied by an increase in sexually transmitted diseases (STDs) and in HIVrelated risk behaviors.4 On the other hand, it is possible that advances in the medical treatment of HIV have resulted in an overreliance on anti-HIV drugs to stave the epidemic. An unforeseen consequence of the latter is that researchers seem to have forgotten that there might not be enough public health resources to ensure that all HIV-infected persons have access to appropriate health care and HIV treatment and prevention services. In reality, prevention programs of all kinds have been hampered by insufficient funding, imperfect targeting strategies, and a problematic policy environment that creates barriers (i.e., abstinence-only sex education programs) to the use of some of these lifesaving interventions.4

The result is that certain subpopulations remain at increased risk of HIV infection or of not receiving adequate treatment when infected. MSM account for about 45% of newly reported HIV/AIDS diagnoses in the United States; a recent survey indicated that in large cities, approximately 1 in every 4 MSM is infected with HIV and nearly 50% of MSM are unaware of their infections.5 Communities of racial and ethnic minorities are also disproportionately affected by HIV/AIDS. For example, between 2001 and 2004, 51% of all new HIV/AIDS diagnoses in the United States occurred among African- Americans; 11% of the African-American men and 54% of the African-American women who were newly diagnosed were infected through heterosexual contact. In 2002, HIV/AIDS was the leading cause of death for African-American women between the ages of 25 and 34 years.6 Today, women in general account for about one quarter of all new HIV/AIDS diagnoses in the United States, reflecting a different transmission pattern than observed during the early years of the epidemic.6

Despite these challenges, there are many opportunities to enhance the effectiveness of both primary and secondary prevention efforts. With regard to primary prevention, the transmission rates of HIV infection among high-risk subpopulations must be further reduced. With regard to secondary prevention, it may be time for a paradigm shift from a strictly clinical approach that directs its resources toward reducing or alleviating adverse health consequences among persons who are living with HIV disease to the biomedical prevention of HIV/AIDS among at-risk groups. This would require the reconceptualization of secondary prevention as a form of primary prevention, in which the principles of the natural sciences (especially biology and physiology) are applied to clinical medicine. In other words, the purpose of antiretroviral treatment would be greater than the medical management of HIV infection alone. Dr. Kevin De Cock, director of the World Health Organization's HIV/AIDS Division, made this point clear when he stated, "Given the slow rate of global access to antiretroviral treatment, the world will not be able to stop HIV/AIDS through medicine alone. We can't treat our way out of this epidemic .... A rebalancing of our perception of the epidemic and reinvigorating prevention is absolutely essential. If there's one big lesson, it's that you cannot separate prevention from treatment."

It is vital to remember that HIV is transmitted in a milieu of social, behavioral, biological, and physiological factors (see Table 1).7 Historically, these different factors have been separated in the design of prevention programs and the implementation of prevention efforts. Today, evidence-based behavioral intervention strategies need to be added to HIV-prevention efforts to complement medical and technological advances.8 Society-wide changes in beliefs about the severity of HIV infection, the emergence of prevention-behavior fatigue, and recent increases in illicit drug use and STDs also present new challenges that must be tackled. Other socioeconomic factors -- such as poverty, homelessness, racism, homophobia, gender inequality, discrimination, and stigma -- should also be factored into the primary prevention equation. In the face of all these factors, the incorporation of biomedical interventions into primary prevention effects could moderate the influence of biological or physiological factors that may increase the infectiousness of an HIV subtype or an individual's susceptibility to HIV infection and prevent the progression of HIV infection after exposure to the virus.

Table 1. Factors Affecting HIV Infection and Prevention

Social and Behavioral FactorsBiological and Physiological Factors
Sociocultural Factors

  • Gender norms
    Attitudes, beliefs, behaviors, customs, display
  • Social structures
    Laws, policies, organizations, institutions
  • Economic arrangements
    Wages, credit, inheritance, employment opportunities

Temporal Factors

  • Epidemiologic stage
    Incidence and prevalence, level of vulnerability, risk
  • Disease stage
    Natural history, clinical course, access and response to treatment and care
  • Comorbidities and infections
  • Lifecourse
    Age at infection, experience of HIV over life course

Interpersonal Factors

  • Relationships
    Long-term vs. short-term, consensual vs. nonconsensual, equitable vs. inequitable
  • Skills
    Communication, negotiation, refusal, technical
  • Social Support
    Family, friends, networks, community

Medical/Technological Factors

  • Directly or indirectly affects risk through scientific advances in medical care and other fields that reduce infectivity or provide new/improved prevention technologies
  • Can affect HIV transmission but depends on other intervention strategies to motivate dissemination and adoption by community members and providers
  • Can affect large numbers of persons but cost and other factors might limit access

Situational

  • Motherhood
    Pregnancy, childbirth, parenthood
  • Geographic location
    Urban vs. rural, high vs. low prevalence, poor vs. rich
  • Social stability
    War, violence, famine, migration
  • Legal status
    Immigrant, migrant, citizen
  • Availability of services
    Access, cost

Biomedical Technologies

  • Rapid HIV testing
  • Screening of blood supply
  • Preventive vaccines
  • Use of antiretroviral therapy
    Postexposure prophylaxis
    Pre-exposure prophylaxis
    Prevention of mother-to-child transmission
  • Microbicides
  • Cervical barrier methods (i.e., diaphragm)
  • Male circumcision
  • Management of sexually transmitted diseases

Adapted from Ickovics JR, Thayaparan B, Ethier KA. Women and AIDS: A contextual analysis. In: Handbook of Health Psychology. 2000. Philadelphia, PA: Psychology Press and from Centers for Disease Control and Prevention. MMWR. 2006;55:597-603.

The ideal prevention tool would be a safe, effective, and accessible vaccine to prevent HIV infection. Such a vaccine would be administered to the entire United States population and would remain viable and 100% effective for a decade or more. Unfortunately, the search for such a vaccine has been hampered by the ways in which the human immune system responds to HIV. Our understanding of HIV-mediated immunopathogenesis has progressed rapidly, however, and there are now more than two dozen HIV vaccine candidates and combinations thereof under investigation.4 Although a vaccine will be the magic bullet that ultimately halts this epidemic, there are other ways to "cure" HIV infection while we wait for that to happen. The good news is that the research and development community has been conducting investigations on several fronts: 1) to prevent transmission from HIV-positive persons to HIV-negative ones; 2) to decrease the risk of reinfection between already infected persons; and 3) to improve the overall quality of life of persons living with HIV/AIDS.

This issue of RI_TA!_ discusses several of the biomedical prevention strategies that are still under development, specifically male circumcision, microbicides, pre-exposure prophylaxis (PrEP), and post-exposure prophylaxis (PEP). But the issue goes one step further by looking at some of the structural factors that cannot be ignored for the HIV epidemic to be conquered. These include gender differences in HIV treatment, STD prevalence and its relation to HIV prevention, the controversy over the newly approved HPV vaccine, and advances in mother-to-child transmission. For the national HIV prevention plan spearheaded by the Centers for Disease Control and Prevention to be realized, HIV prevention and treatment programs must continue to evolve to address the myriad challenges that still exist. An unprecedented mobilization of individual, community, and government resources has been directed at controlling the epidemic. Nevertheless, only by incorporating biomedical advances into traditional clinical approaches to the management of HIV infection.including the development of a vaccine and the amelioration of the effects of antiviral treatment on infectivity.will the course of this epidemic be controlled.

References

  1. Anderson JE, Chandra A, Mosher WD. Adv Data. 2005;363:1-32.
  2. Dodd RY, Notari EP, Stramer SL. Transfusion. 2002;42:975-9.
  3. Centers for Disease Control and Prevention. MMWR. 2006;55(21):592-597.
  4. Holtgrave, DR, Curran JW. Annu Rev Public Health. 2006;27:261-275.
  5. Centers for Disease Control and Prevention. MMWR. 2005;55(21):585-589.
  6. Centers for Disease Control and Prevention. MMWR. 2006;55(21):589-592.
  7. Auerbach JD. HIV Prevention Strategies for Women. WORLD's Community Summit on Women and HIV. Nov. 2007. Oakland, CA.
  8. Wolitski RJ, Janssen RS, Holtgrave DR, et al. The public health response to the HIV epidemic in the U.S. In Wormser GP, ed. AIDS and Other Manifestations of HIV Infection. 2004. 4th ed. San Diego, CA: Elsevier Academic Press.