Comprehensive, up-to-date information on HIV/AIDS treatment and prevention from the University of California San Francisco

In the United States, all medical information generally is considered confidential and protected under the law. Because of the sensitivity of HIV-related information, many states in the U.S. have adopted laws that provide additional protection to HIV-related medical records. For example, in many states, HIV information may not be disclosed based on a general release of medical information-specific authorization for release of HIV-related information must be obtained.

Exceptions to the legal and ethical obligation to maintain the confidentiality of HIV-related information exist. For example, health care providers in the U.S. have a duty to report HIV infections and AIDS cases to public health authorities. The benefits to the public health of this reporting are felt to outweigh the risk to individuals.(9) Reporting of AIDS cases has always included the patient's name and other identifying information. Although reporting of HIV infections initially was not done by name, there has been a recent and controversial movement in the U.S. toward name-based reporting of HIV infection.(10) The debate over name-based reporting has focused on the need for more accurate epidemiological information regarding the spread of the epidemic-especially as antiretroviral therapies have proven successful in delaying progression to AIDS-versus concerns about deterring testing and the risk of discrimination. The Centers for Disease Control and Prevention (CDC) has made specific recommendations for keeping reporting confidential.(11) However, because HIV testing carries the risk of discrimination if confidentiality is breached, the CDC and commentators on this issue have recommended that anonymous testing, from which name reporting is not possible, continue to be offered.(9-11)

Health care providers may also be permitted to disclose a patient's HIV infection to persons at risk of infection without legal penalty.(9) In some states, such as California, a health care provider may not warn sexual or drug-using partners of infected patients without first informing the patient of the intended disclosure.(12) This exception to confidentiality is justified on the grounds that (a) breaching confidentiality will help prevent serious harm to an identifiable person, (b) there is no other effective means to achieving the goal, and (c) the breach of confidentiality is minimized.(9,13)

Another exception to the general rule of confidentiality of HIV-related information concerns HIV-infected health care workers. U.S. government policy has recommended that HIV-infected health care workers who perform exposure-prone invasive procedures have their cases reviewed by an expert panel, which will decide whether they may continue to perform such procedures and whether they must inform patients of their infection. States are required to adopt this policy or its "equivalent." Because the government has taken a flexible view on "equivalency," there is wide variation in state law and not all states require disclosure of HIV infection by health care workers.(14) Those who favor the federal policy argue that disclosure of health care worker HIV infection is necessary to meet the obligation of informed consent. They also argue that the health care workers' obligations to act in patients' best interests also mandate disclosure of HIV infection and, in some cases, restrictions on clinical activities.(15) Those who are against the federal policy argue that such disclosure or restrictions are inappropriate because they violate health care workers' privacy and because the risks to health care workers, for example from discrimination, far outweigh the benefits to patients, given that the risk of infection from a seropositive health care worker is very small.(15) Some have suggested that the federal policy should be revised in light of the data demonstrating that the risks of transmission in the health care setting are exceedingly low.(14)

Special Procedures for HIV Testing

Because the physical risks are minimal, blood tests in the U.S. typically do not require extensive informed consent discussions, and consent often is implied rather than explicit. However, early in the AIDS epidemic, HIV testing was recognized as different from other blood tests because it presented serious psychosocial risks, such as rejection by family; discrimination in employment; and/or restricted or no access to health care, insurance, and housing.(16) Moreover, because there was no proven treatment at that time, the benefits of early diagnosis to individual patients were uncertain. In recognition of these circumstances and to encourage testing, special procedures were adopted for obtaining consent for an HIV test, such as pretest counseling and specific informed consent.(17) Special protections for confidentiality of HIV test results also were enacted.(18-21) For the most part, these special requirements remain in effect. Nearly one-fifth of states require pretest counseling, and many of these specify the information that must be covered, including the nature of the test, the risks and benefits of testing, how to prevent transmission, and the confidentiality of HIV test results. The pretest counseling requirement typically is in addition to any requirements for informed consent. The majority of states require specific informed consent to HIV testing, and many of these require that consent be written. In addition, a number of these states specify the information that must be conveyed during the informed consent process, including information about the nature of the test, the nature of the illness caused by HIV, risk behaviors and prevention measures, the confidentiality of test results, reporting requirements and other circumstances under which test results may be disclosed, the voluntary nature of the test, the ability to withdraw consent, and the availability of anonymous testing. Some of these states require that written information also be provided during the consent process.

Exceptions to Informed Consent

Some states permit HIV testing without informed consent under specified circumstances. For example, many states permit testing of patients without permission after a significant exposure to emergency response workers or health care workers occurs, although permission generally must be sought. In addition, some states permit the testing of prisoners and persons accused of sex crimes. Connecticut and New York also require mandatory HIV testing of newborns,(22,23) which indirectly reveals maternal HIV status.

Prenatal HIV Testing

Mother-to-child transmission of HIV has been a priority area for earlier detection because transmission is significantly reduced if pregnant women identified as seropositive take antiretroviral therapy.(24-28) In 1999, an Institute of Medicine panel on reducing perinatal HIV transmission concluded that pretest counseling and written informed consent requirements for HIV testing were barriers to prenatal HIV testing. To take advantage of the proven effectiveness of antiretroviral therapy for preventing perinatal HIV transmission, the panel proposed significant changes in HIV testing policies for pregnant women in the United States. It recommended that all pregnant women be tested for HIV as a routine part of prenatal care. Under its recommendations, women would be informed that an HIV test would be conducted, along with other prenatal blood tests, but would not be required to consent specifically to the HIV test.(29) The American College of Obstetrics and Gynecology and the American Academy of Pediatrics have supported routine universal prenatal HIV testing.(30)

Whether the IOM recommendations are adopted remains to be seen. In October 2000, the U.S. Public Health Service (USPHS) issued draft revised guidelines for prenatal HIV testing that stop short of the IOM recommendations.(31) The USPHS recommended that health care providers recommend HIV testing to all of their pregnant patients, but embraced the requirements for specific written informed consent required by many states. It did note that verbal consent may be used, where permitted by state law, if written consent is deemed a barrier to testing.(31)

The proposals to make HIV testing a routine part of prenatal care raise several concerns.(32) First, it is unknown whether such testing would be acceptable to pregnant women. Second, there is a danger that, if HIV testing becomes routine, it will become so habitual or mechanical that pregnant women may not realize that they have the option to decline testing. Thus, the decision to be tested may not really be an autonomous one. Third, caregivers and patients may forget that HIV testing entails much greater psychosocial risks than other blood tests and that prenatal HIV testing differs from HIV testing in other settings. Additional procedures or protections may be necessary to safeguard pregnant women's autonomous choices. Fourth, by foregoing opportunities for education and counseling, routine testing may undermine prevention efforts. Finally, routine HIV testing in the prenatal context may affect adherence to the norms of pretest counseling and informed consent for HIV testing in other contexts.

The ethical concerns surrounding prenatal HIV testing are different in developing countries. To date, the cost of antiretroviral prophylaxis has been prohibitive and therefore, for the most part, pregnant women do not receive it.(33,34) Although knowing their HIV status may be helpful in guiding decisions concerning breastfeeding, in many circumstances, bottle-feeding is not a feasible option because of cost and lack of access to clean water(35). Accordingly, determining HIV status may be of limited benefit. Moreover, such determination could subject women to risk of physical harm or loss of housing and support.(36,37) The benefits of testing will increase as prenatal antiretroviral prophylaxis, along with support services, becomes increasingly available.(38)

Early in the U.S. epidemic, before antiretroviral therapy was developed and shown to be effective, HIV infection often quickly progressed to a terminal illness. However, because the availability of highly active antiretroviral therapy has prolonged survival, end-of-life care in HIV infection has become a less prominent issue in the U.S. However, in the developing world, where antiretroviral therapy is generally not available, palliative care, which focuses on relief from suffering, is the only tenable goal. Severe resource constraints may render it difficult to provide palliative measures such as opioids for pain control. Under those circumstances, care may be limited to psychosocial support and helping patients make plans for such practical issues as burial and child custody and support. This focus will need to change as highly active antiretroviral therapy becomes increasingly available in developing countries. There have been many efforts to make HIV medications more available to the developing world by pressuring pharmaceutical manufacturers to reduce prices,(33,39,40) permitting production of generic versions of effective therapies,(41) and providing funds for drug purchases(40,42,43).

It is unethical to expose subjects to the risks of participating in a research study unless the design is sufficiently rigorous that the results will be valid and generalizable(3). To meet the ethical obligations for research, the study size must be adequate and appropriate study endpoints must be chosen. Clinical trials usually require preliminary laboratory and animal research.(44)

The expectations of potential research participants may complicate obtaining informed consent in the research context.(45) Although the goal of research is to test a hypothesis and develop generalizable knowledge, many participants enter research studies to benefit personally(46,47). The language that investigators use (e.g., "experiment" vs. "research") may have significantly different meanings for participants and affect their understanding of their participation.(46) Many participants also do not understand randomization and expect that decisions about which intervention they receive will be based on their individual clinical needs.(46) Some may not even be aware that they are participating in research.(46,48) Some of these misconceptions may arise because patients apply their own experience with health care providers, who have an ethical obligation to place patients' interests first, to the research setting, which must take responsibility for the scientific and logistical aspects of the research as well as the interests of the individual participant. Because of such hopes and misconceptions, patients may misinterpret the information given to them about the study.(46)

The role of health care providers in research may contribute to participants' misunderstanding.(45) Health care providers exert considerable power in their relationships with patients, and patients are inclined to follow their health care providers' advice.(47) Patients often understand offers to participate in research as recommendations for their care.(47) Patients also may agree to participate in research if their health care providers ask because they want to please their providers or fear that the quality of their care will be negatively affected if they refuse.(49) In addition, patients' trust in their health care providers, medical institutions, and the research enterprise may lead them to agree to participate in research without critically reviewing information about the trial.(47) Health care providers themselves frequently overestimate the benefits of experimental interventions and participation in clinical trials.(47) When health care providers also are investigators, special care must be taken to (a) ensure that the patient/participant understands the health care provider's/investigator's divided interests and (b) where possible, separate these roles.(47,50)

Health care providers can help address these potential problems by:(45)

• clarifying that participation in a clinical trial is voluntary and will not influence a patient's care

• making clear whether they are recommending the patient participate in a trial or merely offering the opportunity

• checking that patients have understood the key aspects of the trial and correcting any misunderstandings

If the health care provider is also the investigator, another member of the research team-if possible-should handle consent discussions and follow-up visits that are part of the study.

Some people may be at greater risk from research and are considered vulnerable. Traditionally, vulnerability in research has been defined by categories. For example, the U.S. federal regulations identify children, prisoners, pregnant women, mentally disabled persons, and economically or educationally disadvantaged persons as vulnerable populations.(51) The May 2001 report from the U.S. National Bioethics Advisory Commission (NBAC) on research with human participants recommended that vulnerability should be based on characteristics of individuals, rather than on group membership.(52) NBAC proposed six categories of vulnerability: cognitive, institutional, deferential, medical, economic, and social. Both the U.S. federal and NBAC approaches conclude that vulnerable people require special protection from research risks.(51,52) Such vulnerability must be taken into account in research design.(33,53)

Vulnerability is particularly important in the context of HIV-related research. Those infected with HIV may be medically vulnerable because of their infection. In addition, homosexuals, injection drug users, minorities, and women, who, for various reasons, may be at higher risk of HIV infection, are more likely to be socially and economically vulnerable because of historical attitudes and discrimination. Accordingly, investigators conducting HIV-related research must pay particular attention to vulnerability and take steps to protect potentially vulnerable research participants.

Some conflicting interests are inherent in research. For example, health care providers gain prestige, grants, and promotions through their research and publication of their work. Accordingly, they have a personal interest in recruiting and maintaining participants in their studies. Although this interest may sometimes conflict with the best interests of participants, it is an accepted element of research, in part, because it is open and acknowledged.(45,54) However, some conflicting interests, particularly financial ones, create ethical problems because they may influence the myriad decisions researchers make over the course of a study. For example, such interests may lead researchers to overestimate the benefits of a study, underestimate the risks, fail to objectively review existing evidence, and, if necessary, halt an on-going study.(45,54)

Some steps can be taken to minimize conflicting interests.(1,45) These include:

• openly discussing research plans with colleagues and ensuring peer review of research protocols

• blinding investigators and participants to which intervention participants are receiving

• using an independent data safety monitoring board to interpret interim data and assess reports of adverse events

Disclosing conflicting interests may also be necessary. In California, for example, such disclosure is legally mandated by a 1990 California Supreme Court decision in Moore v. Regents of University of California, which declared that health care providers need to "disclose personal interests unrelated to the patient's health, whether research or economic, that may affect the health care provider's professional judgment."(55) The courts of other states have not confronted the issue posed by Moore; however, there are strong reasons, both ethical and legal, for requiring such disclosures. They allow people to make informed decisions about participating in a clinical trial and to evaluate study results in which investigators have a financial stake(1,45). Some conflicts of interest are so problematic that they should be prohibited, not merely disclosed.(1,45,54) In particular, all researchers in clinical trials, and their immediate families, should be prohibited from holding stock, options, or management positions in the company making the product or technology tested, its competitors, or the sponsor of the study.(54)

Some of the requirements for ethical research design present difficulties in HIV vaccine research because (a) a good animal model does not exist, (b) HIV is highly variable and undergoes rapid mutation, and (c) there is currently little information about how to build protection against HIV.(56) However, because of the enormous disease burdens of HIV, it is ethically appropriate to begin trials without fully understanding the correlates of viral immunity, provided the other requirements are met.(44)

Vaccine trial participants may mistakenly believe that they will receive protection from the vaccine and, therefore, may increase their risky behaviors.(57) Although researchers need outcomes (i.e., seroconversions) to evaluate the efficacy of the vaccine candidate, they also have an obligation to protect research participants. Accordingly, researchers must provide high-quality risk reduction counseling and emphasize the uncertainty about the effectiveness of the vaccine candidate to all participants, while hoping that such counseling is not fully effective in reducing risk. Because of this conflict between researchers' obligations to carry out sound research and their obligations to protect their subjects, it may be necessary to have separate counseling and vaccine staff.(44)

HIV vaccine trials pose unique risks to participants. Participants may be prevented from participating in future vaccine trials, and vaccines developed later may be less effective for them. In addition, because participants may react positively to certain HIV antibody tests, they may also face limits on international travel and on eligibility for certain governmental jobs (in the U.S., e.g., Peace Corp, foreign service, Job Corps, and the military) even if their seroconversion does not represent true infection.(56) Subjects may also face stigmatization from family or friends to whom they disclose information. Participation in some trials (e.g., Phase III trials) may identify the subject as someone at high risk of contracting HIV, an identification that may entail numerous difficulties. Although researchers always have an obligation to protect the confidentiality of the information they collect, this duty is particularly important in HIV vaccine trials because of the high stakes if confidentiality is breached.(44)

In May 2000, the Joint United Nations Programme on HIV/AIDS (UNAIDS) issued a guidance document regarding HIV preventive vaccine research.(53) The document contains 18 specific guidance points regarding the conduct of this research. Among the key points:

• Early phase clinical trials should take place in sponsor (developed) countries, unless there are specific scientific and public health reasons to justify conducting such trials in a host (developing) country (Point 8).

• Placebo-controlled vaccine trials are ethically acceptable as long as there is no known effective HIV preventive vaccine (Point 11).

• All vaccine trial participants should have access to appropriate risk-reduction counseling and access to prevention methods (Point 14).

• An appropriate monitoring system must be in place (Point 15).

• Participants in HIV preventive vaccine trials should be provided with care and treatment for HIV/AIDS and its associated complications, with the ideal being to provide the best proven therapy, and the minimum to provide the highest level of care attainable in the host country in light of:

• the level of care and treatment available in the sponsor country

• highest level of care available in the host country

• availability of infrastructure to provide care and treatment in the context of research

• potential duration and sustainability of care and treatment for the trial participant (Point 16).

There has been considerable dispute over whether researchers are obligated to provide state-of-the-art care, and, particularly, for international studies, which standard of care should govern. The debate was driven, in part, by language in the World Medical Association's Declaration of Helsinki (first adopted in 1964), which set forth ethical principles for medical research involving human subjects and stated that "[I]n any medical study, every patient-including those of a control group, if any-should be assured the best proven diagnostic and therapeutic methods"(8). Relying on this language, some have argued that placebo-controlled trials in developing countries are unethical when a proven effective treatment exists, even if the treatment is not available in the country because of cost or other reasons.(58,59) Others have argued that such placebo-controlled trials may be appropriate because they provide information that responds to local needs.(60) A developing country needs to know whether a simpler, cheaper therapeutic regimen is superior to what is currently available in the country (generally no therapy). It may not be relevant to the developing country whether a simpler, cheaper treatment is as effective as the best proven treatment, which the country cannot afford. Participation of local government, investigators, and community members helps ensure that the research is ethical(33,53,60) and that the standard of care is the highest standard "practically attainable" in that country.(61-63)

The World Medical Association revised the Declaration of Helsinki in 2000(64). After considerable debate about the role of placebo-controlled trials(65), the final version reads: "[T]he benefits, risks, burdens and effectiveness of a new method should be tested against those of the best current prophylactic, diagnostic and therapeutic methods. This does not exclude the use of placebo, or no treatment, in studies where no proven prophylactic, diagnostic or therapeutic methods exists." The "highest attainable and sustainable" standard was explicitly rejected. Although the Declaration of Helsinki serves an important symbolic role, it has no enforcement mechanism and may conflict with national laws and regulations.(65)

Another issue in international research is making therapies available to developing countries once they are shown to be effective there. Researchers, research sponsors, and international organizations are trying to negotiate with drug manufacturers and host country governments to make therapies available at affordable prices. This may entail discounted prices, licensing agreements to manufacture the drug in a developing country, or other strategies. However, the appropriateness of providing antiretroviral therapies in developing countries, particularly Africa, has been the subject of debate. Some have argued that the severity of the AIDS epidemic in the developing world requires that antiretroviral therapies be provided to those affected by it. Others have argued that the lack of health care infrastructure makes provision of these drugs inappropriate at this time.(39) In conjunction with the June 2001 United Nations Special Session on HIV/AIDS, United Nations Secretary General Kofi Annan proposed a $7 to $10 billion fund to combat AIDS globally, although, to date, funding has fallen well short of this goal.(42,66,67)

In the United States, the National Bioethics Advisory Commission (NBAC) issued a report in April 2001 entitled Ethical and Policy Issues in International Research: Clinical Trials in Developing Countries.(33) Among the key points and recommendations:

• All research sponsored or conducted by the United States must, at a minimum, meet the following criteria:

• prior review by an ethics review committee(s)

• minimization of risks to research participants

• risks of harm that are reasonable in relation to potential benefits

• adequate care of and compensation to participants for injuries directly sustained during research

• individual informed consent from all competent adult participants in research

• equal regard for all participants

• equitable distribution of the burdens and benefits of research.

• Ethics review by the host country that meets these standards should be sufficient, and steps should be taken to determine when a host country meets these standards. If a host country does not meet these standards, review should be conducted by both the host country and the appropriate U.S. ethics review committee.

• Only those studies that are responsive to the health needs of the host country are permissible.

• Members of any control group should be provided with an established effective treatment, whether or not such treatment is available in the host country. An alternative design that would not provide such treatment requires strong justification based on the health needs of the host country.

• Community representatives should be involved throughout the design and implementation of research projects.

• Researchers, in consultation with community members, should develop culturally appropriate ways to meet the standard of voluntary informed consent. This may include culturally appropriate methods of disclosing information, seeking permission for research participation from a community representative or family member, and assessing participants' understanding of information disclosed. However, where such permission is sought, it may not substitute for individual informed consent.

• U.S. research regulations should be amended to permit ethics review committees to waive the requirements for written and signed consent documents in accordance with local cultural norms.

• Researchers and sponsors in clinical trials "should make reasonable, good faith efforts" to ensure continued access for all participants to experimental interventions that have proven effective

• Where possible, researchers should negotiate agreements to provide interventions that are proven effective to others within the host country prior to starting the research and should discuss plans to provide such access in their research proposals for evaluation by ethics review committees.

References

1.		Lo B. Overview of Conflicts of Interest. In Resolving Ethical Dilemmas: A Guide for Clinicians. 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2000.

2.		Beauchamp TL, Childress JF. Principles of Biomedical Ethics. 4th ed. New York: Oxford University Press, 1994.

3.		U.S. National Commission for the Protection of Human Subjects of Biomedical and Behavioral Research. The Belmont Report: Ethical Principles and Guidelines for the Protection of Human Subjects of Research. Washington, D.C.: Dept. of Health, Education and Welfare, 1978.

4.		Angell M. Ethical imperialism? Ethics in international collaborative clinical research. N Engl J Med. 1988 Oct 20;319(16):1081-3.

5.		Marshall PA. The Relevance of Culture for Informed Consent in U.S.-Funded International Health Research. In: Ethical and Policy Issues in International Research: Clinical Trials in Developing Countries, Vol. II. Bethesda, Md.: National Bioethics Advisory Commission, 2001. Commissioned papers and staff analysis.

6.		Macklin R. A Against Relativism: Cultural Diversity and the Search for Ethical Universals in Medicine. New York: Oxford University Press, 1999.

7.		Council for International Organizations of Medical Sciences (CIOMS). International Ethical Guidelines for Biomedical Research Involving Human Subjects. Geneva: 1993.

8.		World Medical Association (WMA). Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. Ferney-Voltaire, France: Adopted 18th WMA General Assembly, Helskinki, Finland, June 1964; amended: 29th WMA General Assembly, Tokyo, Japan, October 1975; 35th WMA General Assembly, Venice, Italy, October 1983; 41st WMA General Assembly, Hong Kong, September 1989; 48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996; and 52nd WMA General Assembly, Edinburgh, Scotland, October 2000. http://www.wma.net/e/policy/17-c_e.html

9.		Lo B. Confidentiality. In: Resolving Ethical Dilemmas: A Guide for Clinicians. Philadelphia: Lippincott Williams & Wilkins, 2000.

10.		Gostin LO, Ward JW, Baker AC. National HIV case reporting for the United States. A defining moment in the history of the epidemic. N Engl J Med. 1997 Oct 16;337(16):1162-7.

11.		Centers for Disease Control and Prevention. Guidelines for national human immunodeficiency virus case surveillance, including monitoring for human immunodeficiency virus infection and acquired immunodeficiency syndrome. Centers for Disease Control and Prevention. MMWR Morb Mortal Wkly Rep. 1999 Dec 10;48(RR-13):1-27, 29-31.

12.		Cal. Health and Safety Code §§ 120975-121020 (2000).

13.		Tarasoff v. Regents of the University of California, 551 P.2d 334 (Cal. 1976).

14.		Gostin LO. A proposed national policy on health care workers living with HIV/AIDS and other blood-borne pathogens. JAMA. 2000 Oct 18;284(15):1965-70.

15.		Lo B. HIV Transmission in Health Care Settings. In: Resolving Ethical Dilemmas: A Guide for Clinicians. Philadelphia: Lippincott Williams & Wilkins, 2000.

16.		Lo B, Steinbrook RL, Cooke M, Coates TJ, Walters EJ, Hulley SB. Voluntary screening for human immunodeficiency virus (HIV) infection. Weighing the benefits and harms. Ann Intern Med. 1989 May 1;110(9):727-33.

17.		Gostin LO, Webber DW. HIV infection and AIDS in the public health and health care systems: the role of law and litigation. JAMA. 1998 Apr 8;279(14):1108-13.

18.		Gostin LO. Public health strategies for confronting AIDS. Legislative and regulatory policy in the United States. JAMA. 1989 Mar 17;261(11):1621-30.

19.		Gostin L, Curran WJ. Legal control measures for AIDS: reporting requirements, surveillance, quarantine, and regulation of public meeting places. Am J Public Health. 1987 Feb;77(2):214-8.

20.		Gostin L, Curran WJ. AIDS screening, confidentiality, and the duty to warn. Am J Public Health. 1987 Mar;77(3):361-5.

21.		Bayer R. Public health policy and the AIDS epidemic. An end to HIV exceptionalism? N Engl J Med. 1991 May 23;324(21):1500-4.

22.		Conn. Gen. Stat. § 19a-55 (1999).

23.		10 NYCRR § 69-1.1 - 1.5 (1999).

24.		Altman L. Spare AIDS Regime Is Found to Reduce Risk to Newborns. The New York Times 1999 Feb. 2;Sect. 1A.

25.		Department of Health and Human Services. Researchers Identify a Simple, Affordable Drug Regimen That Is Highly Effective in Preventing HIV Infection in Infants of Mothers with the Disease. Washington, D.C.: 1999 July 14. Press release.

26.		Blanche S, Rouzioux C, Mandelbrot L, et al. Zidovudine-lamivudine for Prevention of Mother to Child HIV-1 Transmission. In: 6th Conference on Retroviruses and Opportunistic Infections, Chicago, Ill.: 1999 January 31-February 4. Abstract 267.

27.		Saba J. Interim Analysis of Early Efficacy of Three Short ZDV/3TC Combination Regimens to Prevent Mother-to-Child Transmission of HIV-1: The PETRA Trial. In: 6th Conference on Retroviruses and Opportunistic Infections, Chicago, Ill.: 1999 January 31-February 4. Abstract S7.

28.		Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O'Sullivan MJ, VanDyke R, Bey M, Shearer W, Jacobson RL, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group.N Engl J Med. 1994 Nov 3;331(18):1173-80.

29.		Stoto MA, Almario DA, McCormick MC (U.S. Institute of Medicine, Committee on Perinatal Transmission of HIV, Board on Children Youth and Families). Reducing the Odds: Preventing Perinatal Transmission of HIV in the United States. Washington, D.C.: National Academy Press, 1999.

30.		Human immunodeficiency virus screening. Joint statement of the American Academy of Pediatrics and the American College of Obstetricians and Gynecologists. Pediatrics. 1999 Jul;104(1 Pt 1):128.

31.		U.S. Public Health Service. Revised US Public Health Service Recommendations for Human Immunodeficiency Virus Screening of Pregnant Women. Washington, D.C.: 2000 October 20.

32.		Lo B, Wolf LE, Sengupta S. Ethical issues in early detection of HIV infection to reduce vertical transmission. AIDS. In press.

33.		U.S. National Bioethics Advisory Commission. Ethical and Policy Issues in International Research: Clinical Trials in Developing Countries. Vol 1. Report and Recommendations of the National Bioethics Advisory Commission. Bethesda, Md.: 2001. http://bioethics.gov/clinical/Vol1.pdf

34.		Jimoh A. Raise the Alarm Loudly. Dollars & Sense 2001 May;Sect. 16.

35.		Sargent J. Should all mothers breast-feed? Eff Clin Pract. 2000 May-Jun;3(3):141-3.

36.		North RL, Rothenberg KH. Partner notification and the threat of domestic violence against women with HIV infection. N Engl J Med. 1993 Oct 14;329(16):1194-6.

37.		White E. The Fears Driving Women's Infant Feeding Decisions. In Breastfeeding and HIV/AIDS: The Research, the Politics, the Women's Responses. Jefferson, N.C.: McFarland & Company Inc., 1999.

38.		Lederer E. Nigeria Launching Largest AIDS Program. The Washington Post 2001 July 31.

39.		Ferriman A. Doctors demand immediate access to antiretroviral drugs in Africa. BMJ. 2001 Apr 28;322(7293):1012.

40.		Gellman B. An Unequal Calculus of Life and Death; As Millions Perished in Pandemic, Firms Debated Access to Drugs; Players in the Debate over Drug Availability and Pricing. The Washington Post 2000 December 27;Sect. A01.

41.		Kallings L, Stefano V. Access to HIV/AIDS care and treatment in the south of the world. AIDS 001;15:IAS1-IAS3.

42.		Annan K. We Can Beat AIDS. The New York Times 2001 June 25;Sect. A17.

43.		Crossette B. In the War on AIDS, a U.N. Official Aaccents Prevention as a Battle Plan Takes Shape. The New York Times 2001 May 28;Sect. A6.

44.		Wolf LE, Lo B. What about the ethics? West J Med. 1999 Nov-Dec;171(5-6):365-6.

45.		Wolf LE, Lo B Association of Professors of Medicine. Ethical issues in clinical research: an issue for all internists. Am J Med. 2000 Jul;109(1):82-5.

46.		Appelbaum PS, Roth LH, Lidz CW, Benson P, Winslade W. False hopes and best data: consent to research and the therapeutic misconception. Hastings Cent Rep. 1987 Apr;17(2):20-4.

47.		Kass NE, Sugarman J, Faden R, Schoch-Spana M. Trust, The fragile foundation of contemporary biomedical research. Hastings Cent Rep. 1996 Sep-Oct;26(5):25-9.

48.		U.S. Advisory Committee on Human Radiation Experiments. Final Report. Washington, D.C.: Supt. of Docs., U.S. G.P.O., 1995.

49.		Eichenwald K, Kolata G. Drug Trials Hide Conflicts for Doctors. The New York Times 1999 May 16;Sect. 1.

50.		Lo B. Ethical Issues in Clinical Research. In Hulley S, ed. Designing Clinical Research. 2nd ed. Philadelphia: Lippincott Williams & Wilkins, 2000.

51.		45 CFR § 46.111(a) (2000).

52.		U.S. National Bioethics Advisory Commission. Ethical and Policy Issues in Research Involving Human Participants. Bethesda, Md.: May 2001. http://bioethics.gov/press/finalrecomm5-18.html

53.		Joint United Nations Programme on HIV/AIDS (UNAIDS). Ethical Considerations in HIV Preventive Vaccine Research. Geneva: May 2000.

54.		Lo B, Wolf LE, Berkeley A. Conflict-of-interest policies for investigators in clinical trials. N Engl J Med. 2000 Nov 30;343(22):1616-20.

55.		Moore v. Regents of University of California, 793 P.2d 479 (Cal. 1990).

56.		Langan M, Collins C. Paving the Road to an HIV Vaccine: Employing Tools of Public Policy to Overcome Scientific, Economic, Social and Ethical Obstacles. San Francisco: Center for AIDS Prevention Studies, AIDS Research Institute, University of California San Francisco, 1998 December 1.

57.		Chesney MA, Lurie P, Coates TJ. Strategies for addressing the social and behavioral challenges of prophylactic HIV vaccine trials. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 May 1;9(1):30-5.

58.		Angell M. The ethics of clinical research in the Third World. N Engl J Med. 1997 Sep 18;337(12):847-9.

59.		Lurie P, Wolfe SM. Unethical trials of interventions to reduce perinatal transmission of the human immunodeficiency virus in developing countries. N Engl J Med. 1997 Sep 18;337(12):853-6.

60.		Varmus H, Satcher D. Ethical complexities of conducting research in developing countries. N Engl J Med. 1997 Oct 2;337(14):1003-5.

61.		Levine RJ. The "best proven therapeutic method" standard in clinical trials in technologically developing countries. J Clin Ethics. 1998 Summer;9(2):167-72.

62.		Levine RJ. The need to revise the Declaration of Helsinki. N Engl J Med. 1999 Aug 12;341(7):531-4.

63.		Science, ethics, and the future of research into maternal infant transmission of HIV-1. Perinatal HIV Intervention Research in Developing Countries Workshop participants. Lancet. 1999 Mar 6;353(9155):832-5.

64.		World Medical Association (WMA). Declaration of Helsinki: Ethical Principles for Medical Research Involving Human Subjects. Ferney-Voltaire, France: Adopted 18th WMA General Assembly, Helskinki, Finland, June 1964; amended: 29th WMA General Assembly, Tokyo, Japan, October 1975; 35th WMA General Assembly, Venice, Italy, October 1983; 41st WMA General Assembly, Hong Kong, September 1989; 48th WMA General Assembly, Somerset West, Republic of South Africa, October 1996; and 52nd WMA General Assembly, Edinburgh, Scotland, October 2000. http://www.wma.net/e/policy/17-c_e.html.

65.		Enserink M. Helsinki. Bioethics. Helsinki's new clinical rules: fewer placebos, more disclosure. Science. 2000 Oct 20;290(5491):418-9.

66.		Sanger DE. Genoa Summit Meeting: The Haves and the Have-Nots; Rich Nations Offer a Hand, but the Poor Hope for More. The New York Times 2001 July 21;Sect. A7.

67.		Crossette B, Sanger DE. Annan in Washington to Seek AIDS Funds. The New York Times 2001 May 10;Sect. A16.