Infectious disease and the evolution of AIDS

Thirty years since “patient zero,” how the world’s worst epidemic forever changed the specialty.

The June 1981 advent in America of the AIDS virus, and the subsequent 15 years when contracting it was essentially a death sentence, forced infectious disease specialists to quickly learn new skills, adapt new perspectives, examine their fears and prejudices, and make acute decisions about their private lives.

Although antiretroviral drugs were available before 1996, it was not until then that treatments capable of managing the disease meant that what was once an automatic death sentence was now a chronic disease. At that point, infectious disease specialists’ focus shifted from crisis management to finding a cure or a vaccine or both, and to working within structures of care that had not existed in the field before the epidemic.

For infectious disease specialists who had chosen the field believing that the bygone era of mass contagion would not revisit modern times, AIDS was “an absolute shock,” according Michael Tapper, MD, chief epidemiologist at Lenox Hill Hospital in Manhattan and Infectious Disease News Editorial Board member. “There was enormous fear of contagion early on,” Tapper said. “The routes of transmission were not known. All we knew is that patients were coming in with a disease they were dying of, and we hadn’t any idea how it was transmitted. And in the bigger cities, it just kept coming. It never stopped. Every day, more and more patients would just roll in.”

Some physicians balked at treating this unexpected cohort. A survey of house officers in a 1988 issue of the American Journal of Public Health stated that, “Twenty-five percent of all respondents reported that they would not continue to care for AIDS patients if given a choice.” In 1991, the Journal of the American Medical Association reported that half of all primary care providers would not treat AIDS patients if they could avoid it.

“I can remember house officers in effect saying they loved the field, but that they didn’t particularly want to spend their entire careers taking care of AIDS patients,” Tapper said. “There were some pretty scary cases where people had sharps exposures or had needle sticks and contracted the virus. Most people didn’t go into this field thinking that would happen to them — the days of communicable diseases were over. The concept that you were putting your life at risk by doing something as simple as drawing blood from patients was upsetting to a lot of people.”

“I don’t think there is anything wrong with being afraid. I was afraid,” said Lisa Capaldini, MD, who at the time the disease struck was in residence at San Francisco General Hospital, the epicenter of the nascent disease in America. “In a sense, having HIV to deal with was a throwback to the pre-antibiotic days when doctors were obligated to be risk-takers.”

Further complicating the treating physicians’ response was that AIDS first manifested in the gay and IV drug-user communities.

“It’s not that it was an explicitly stated view, but there was this sense that some people thought that these people deserved what was happening,” Capaldini said.

This presented a crossroads for physicians such as Capaldini, who is gay. “The disease helped a lot of lesbian and gay men working in health care to come out because now they were taking care of their own community and educating their colleagues. AIDS allowed people who were unfamiliar with gay people to see them as people. It broke down the barriers, the phobias. My sexuality became an asset. I felt this responsibility to be an advocate, in a way. Now gay people weren’t just the patients, they were ‘one of us.’”

Ultimately, the “warmth, sympathy and understanding” physicians are bound to under the Hippocratic Oath triumphed. “AIDS required a dialing up of doctors’ compassion and pragmatism — these people needed care, and we had to find the best way to deliver it,” Capaldini said.

Losing patients, losing friends

For those in the trenches, staying emotionally fortified was difficult. “I don’t know anyone who exited the field as a result of this, but especially in communities that were directly affected by the disease, there was a high degree of burn out because they were not only losing their patients, but also they were losing their friends,” Tapper said.

Elizabeth Connick, MD, associate professor of infectious diseases at the University of Colorado School of Medicine in Denver, and Infectious Disease News Editorial Board member, was in residence at Columbia Presbyterian in Manhattan when AIDS was emerging into the gay and IV drug-user communities in New York City.

“Those of us who entered the profession at the same time that HIV emerged didn’t know what it was like when it wasn’t that a third of your patients were dying,” Connick said. “It’s hard to imagine how desperate those times were.”

The intensity of constantly taking care of young people who were dying had a resounding effect on the infectious disease community, according to Tapper. “It was hard on many people emotionally, taking care of young people who were dying all the time and you knew there was nothing you could do about it. It was devastating. It turned off a lot of people to infectious disease careers. Not necessarily the people who were already in it, but it had a somewhat negative effect on recruiting new graduates from the internal medicine training programs into infectious disease fellowships, but it probably also excited some people who wanted to get into AIDS work.”

Besides learning to live with the constant death of their patients, infectious disease specialists were tasked with attending to patients in ways they had never intended.

“Not all departments wanted to deal with this,” Connick said. “In some places, it was infectious disease physicians, in others it was hematologists/oncologists. But no matter what happened in the beginning, it completely changed the field of ID because now a significant portion of the clinical activities of infectious disease specialists occur on an outpatient basis, whereas in the past, we would have spent most of our time in the hospital.”

Today, Capaldini, an internist, practices in an outpatient AIDS/HIV clinic in San Francisco’s Castro district. “The care tasks involved with managing HIV (adherance promotion, diagnosing and treating mental health issues, dealing with medical comorbidites) is something that primary care clinicians are used to doing and because of this, primary care clinicians have an important role in managing HIV. So, in the early days, I had to learn about infectious disease, and now, ID doctors have to either learn primary care skills or team up with a primary care provider. One of the things I have enjoyed most about my practice is this way of working together.”

Collaboration and activism

The overwhelming nature of the disease necessitated this collaborative spirit. Capaldini said she believes that AIDS taught patients to be responsible for themselves. “They want to collaborate, they get their health markers taken. They are health literate.”

But when it came to partnering with the patient, “It was a little bit like Alice in Wonderland,” Capaldini said. “Having the patient telling me, the doctor, what they wanted was strange. But, the reality is, collaborative relationships get better results and the patients feel better.”

“The idea that the medical community should be in collaboration with the patient wasn’t invented during the AIDS epidemic,” said Paul Volberding, MD, Infectious Disease News Editorial Board member and professor and vice chair in the department of medicine at University of California, San Francisco. “But it was during that time that we learned how important patient-centered care is, how you shouldn’t force-fit patients into a system.”

As multitudes of patients were routinely dying, doctors collaborating closely with nurses also became standard. “Once you start doing palliative care, you are much more aligned with the nurses,” Capaldini said. “AIDS hit so hard, it gave nurses a chance to have an enormous impact on the way doctors practiced medicine. It softened doctors, in a good way.”

AIDS activists also sought to engage the infectious disease community and various government officials who, particularly at the federal level, had largely ignored the crisis. “There was a real refusal to deal with it in the Reagan administration,” Tapper said.

“In the face of stigma, discrimination and indifference to their friends dying, affected communities organized to provide prevention advice, care and support,” wrote the CDC’s Kevin M. De Cock, MD, Harold W. Jaffe, MD, and James W. Curran, MD, in “Reflections on 30 Years of AIDS,” published in the May issue of Emerging Infectious Diseases. ACT UP undertook acts of civil disobedience to influence the research agenda, improve access to HIV drugs, and lower the cost of treatment, the researchers wrote.

“There was a coming together of groups advocating for more aggressive public policies,” Tapper said. “AIDS activism was a model for patient empowerment.”

The activism affected public policy as well as health care delivery in large systems, according to Jonathan Mermin, MD, director of HIV/AIDS prevention at the CDC. “Taking into account the perspectives of patients and their communities has become a part of the foundation of good clinical care and best research practices. This has, in many ways, been built on the experience with HIV,” Mermin said.

Fast-tracking therapies

One of the activists’ most enduring legacies was how they affected drug research. “We couldn’t wait 20 years for a drug to be developed. There was a great need to rapidly identify good drugs, to rapidly test them in people, and rapidly get the results out, and that required an infrastructure, people knowledgeable in how to conduct clinical trials, and collaborative relationships with pharmaceutical companies,” Connick said. “The activists promoted a lot of this. It was a huge advance in medical research with far-reaching implications not only for HIV, but in other fields as well.”

“It was important to have community-based organizations partnering with medicine,” Volberding said. “When something frightening happens, people need to ask questions. So we started doing research, which gave hope to the patients. And we saw the importance of having a public dialogue and not pretending that something was known when it wasn’t.”

This candor led to a productive partnership between activists, patients, researchers and various agencies such as the FDA. “Pressure from the AIDS community helped to change the way that people within the [FDA] thought about drug development and approval,” Richard Klein, director of the HIV/AIDS Program within the FDA’s Office of Special Health Issues, told Infectious Disease News.

The more activists learned about research, clinical testing and analysis, the greater their value became to the entire process, according to Klein. “Activists challenged regulators to think in new ways, to reconsider risk/benefit analyses in ways that might have shifted greater risk to patients, but realizing that patients were willing to accept that risk for the potential benefits of treatment access.”

With their emphasis on human rights for AIDS victims, the activists created a fundamental shift not only in how FDA researchers and policymakers viewed the treatment of infectious disease, but how the American public did as well. “Ultimately, HIV changed the relationship Americans have with sex, drugs, and issues of public health justice,” Mermin said.

Evolution of an epidemic

Once the epidemic was brought under control, however, interest in its devastating effects waned. “The nation is experiencing a type of ‘HIV fatigue,’” Mermin said. “Effective treatment allows most people with HIV to live decades after their diagnosis, and the American public’s increased understanding of transmission risk and their increased comfort living and working alongside people with HIV — both very welcome outcomes — have in fact resulted in the perception that AIDS is less important of a health issue than it is.”

According to the White House National HIV/AIDS Strategy, in 1995, 44% of the American public said AIDS was the nation’s most pressing health problem vs. 6% in 2009.

“The euphoric days of the early ’90s when we thought we were going to cure the disease have settled into a more mature pattern of recognizing that now we have good therapies that, as far as we know, can cause life-long disease suppression for those who take their medications reliably,” Tapper said.

The latest statistics from the CDC (October 2010) indicate that despite an increase in the total number of people living with HIV in the US, the number of new infections has remained static, with about 56,300 cases reported annually. White men who have sex with men account for 53% of new infections. An FAQ sheet provided by the CDC to Infectious Disease News stated that, “White MSM account for the largest number of annual new HIV infections of any group in the United States, followed by black MSM.”

Connick said, “Yes, AIDS transmission is higher in the MSM cohort, and this clearly deserves resources. However, 27% of new infections in 2006 occurred in women, and American women are largely neglected by CDC prevention efforts.”

New HIV infections in black women reported by the CDC in 2006 totaled 7,340, 15 times higher than the rate of infection in white women and four times that of Hispanic women.

“HIV-infected women are often poor, from minority groups and uneducated, and they have little political clout,” Connick said. “Currently, there is enormous emphasis on global health initiatives, which are indisputably important. It’s an enormous irony that it’s in vogue for American researchers to fly off to Africa to help women there, but it is not glamorous to get in their cars and drive down the street to help American women with HIV. More resources need to be devoted to HIV prevention and treatment in American women, such as studies of [pre-exposure prophylaxis]. Meanwhile, The White House Office of National AIDS policy has stated as among its goals for 2015, “reducing HIV-related health disparities” including improving “access to prevention and care services for all Americans…[and increasing] the proportion of HIV-diagnosed Blacks with undetectable viral load by 20%.”

AIDS and the future of ID

“A safe and effective vaccine would be an important addition to the armamentarium of combination prevention strategies,” according to Carl Dieffenbach, PhD and Anthony S. Fauci, MD of the NIH, authors of a paper about the future of AIDS published in this month’s Annals of Internal Medicine.

Building on the established foundations of collaboration, the infectious disease field now has the opportunity to partner with a scientist who studies gene therapy to quash AIDS. Philip Johnson, MD, director of the Joseph Stokes, Jr. Research Institute at The Children’s Hospital of Pennsylvania, recently identified a neutralizing antibody in the genes of macaques, leading to a vector-mediated gene transfer that produced an antibody-like immunoadhesin that neutralized the simian immunodeficiency virus in infected monkeys. “The strategy bypasses the adaptive immune system and holds significant promise as a novel approach to an effective HIV vaccine,” Johnson and colleagues wrote in a 2009 issue of Nature Medicine.

Regarding the infectious disease field’s reaction to his research, Johnson said, “For a while, the response was, ‘You can’t do that.’ Now the response is, ‘Can you really do that?’” The interest in his work, he said, means there is potential to collaborate with infectious disease specialists to find “HIV-infected humans who have very high titers of neutralizing antibodies [in order to] isolate more and better human monoclonal antibodies.” Phase 1 trials of the vaccine, according to Johnson, are set to begin in late 2012.

As for eradicating the disease altogether, this summer, the NIH’s National Institute of Allergy and Infectious Diseases and National Institute of Mental Health are expected to announce the winners of up to $8.5 million in grant monies for finding an AIDS cure. Other developing aspects of AIDS research include the application of the CAPRISA trial findings, which show that treatment is an effective form of prevention, and studying the long-term consequences on AIDS patients of taking antiretroviral drugs over the course of many years.

About these developments, Tapper said that for him, “[AIDS] is still the most exciting field in infectious disease.” – by Whitney McKnight

For more information:

• CDC. Estimates of new HIV infections in the US. Available at: www.cdc.gov/nchhstp/newsroom/docs/Fact-Sheet-on-HIV-Estimates.pdf Accessed May 10, 2011.
• CDC. HIV and AIDS in America: a snapshot. Available at: www.cdc.gov/nchhstp/newsroom/docs/HIVandAIDSinAmericaSnapshotFINAL70710508COMP.pdf
• COMP.pdf. Accessed May 10, 2011.
• De Cock K. Emerg Infect Dis. 2011;doi:10.3201/eid1706.100184.
• Dieffenbach C. Ann Intern Med. 2011; 154
• Gerbert B. JAMA.1991;266:2837-2842.
• Johnson PR. Nat Med. 2009;15:901-906.
• Link RN. Am J Public Health.1988;78:455-459.
• NIH. Martin Delaney Collaboratory: towards an HIV-1 cure (U19). Available at: http://grants.nih.gov/grants/guide/rfa-files/RFA-AI-10-009.html. Accessed May 12, 2011.
• The White House Office of National AIDS Policy. National HIV/AIDS Strategy for the United States. July 2010. Accessed at www.aids.gov/federal-resources/policies/national-hiv-aids-strategy/nhas-fact-sheet.pdf on May 25, 2011.

Disclosures: Drs. Capaldini, Connick, Mermin, Tapper and Volberding reported no relevant financial disclosures.

Does the White House National HIV/AIDS Strategy make the best use of resources to help those affected by the disease?

We should make higher investments in black communities.

One of the things the National HIV/AIDS Strategy calls for is to invest where the epidemic actually is — that means we should be making higher investments in black communities.

Black Americans represent nearly 50% of all new cases of AIDS nationwide, even though they are only 12% of the US population. When you look at the disease through the lens of gay men, 30% of them are black, and they are the largest gay population affected by AIDS. But they don’t tend to live in the predominately white ‘gay ghettoes,’ like Chelsea [in Manhattan] or the Castro [in San Francisco], so when resources are placed there, they aren’t utilized by black gay men as much.

Black men with AIDS tend to live in black communities. But in those communities, there are women and children and IV drug users who have AIDS, too. Their needs are different than infected black gay men. These silos make it hard to address the epidemic in blacks, but what I expect to happen now with the National HIV/AIDS Strategy is that we will formulate our response to the disease based on science and not on politics and morality. That means we will help those most at risk, and that’s going to be people of color.

Phill Wilson is the president and CEO of the Black AIDS Institute. Disclosure: Mr. Wilson reports no relevant financial disclosures.

The National HIV/AIDS Strategy says resources have to be appropriately aligned.

Although there are a number of issues, there are two key changes. The first and foremost is to concentrate our resources where the burden of the epidemic is most severe, in terms of geography and where the majority of new infections are taking place.

The other change is to make sure the resources are not only scaled geographically, but to make sure that they have the biggest pay off in reducing infections and to getting high-quality care for those who are infected. So you’ll see the National HIV/AIDS Strategy talk about African Americans and Latinos, but it also talks about the high burden of infection of gay men of all races and ethnicities.

We probably need to do more of some kinds of activities and less of others. There is no magic formula, but there is a much greater focus on interventions that will have greater pay off. For example, we know based on very sound CDC epidemiology that of all people infected with AIDS, nearly 20% are unaware of their infection. So, we need to make sure they get diagnosed and then make sure they are actively linked into a system of care.

Ronald O. Valdiserri, MD, MPH, is the deputy assistant secretary for health, infectious diseases in the US Department of Health and Human Services. Disclosure: Dr. Valdiserri reports no relevant financial disclosures.

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