When it emerged in the 1980s and into the early 1990s, HIV/AIDS was a universally fatal disease. Now, thanks to decades of basic science research, clinical trials and consistent patient care – much of it involving UNC School of Medicine researchers and physicians -- it is considered a chronic disease, and experts can see a way to end the epidemic.
“It is clear that North Carolina’s statewide HIV prevention strategy to encourage early HIV testing and linkage to care and treatment is working,” said Evelyn Foust, director of the N.C. Division of Public Health Communicable Disease Branch.They know what works thanks in part to the patience and perseverance of thousands of patients – patients were honored Sept. 12, when the UNC Hospitals Infectious Diseases Clinic hosted a first-of-its-kind celebration gala to pay tribute to those who have been living with HIV infection for more than 20 years. The event was co-sponsored by the Foundation for AIDS Research (AmfAR), and it brought together patients, doctors, researchers, state officials and individuals from industry.
In 2008 the state of North Carolina reported a reduction in the rate of new HIV infections; this decrease has continued over recent years.
That reduction – and the optimism for the end of HIV/AIDS -- is based on effective drugs that reduce the amount of virus present in an HIV positive individual.
“We want to increase the number of patients with viral suppression because we know that when their viral load is controlled, not only are they healthy, but they are much less likely to transmit the virus to others,” said Foust.
This concept was demonstrated during a clinical trial called HPTN052, led by Myron Cohen, Vice Chancellor for Global Health and head of infectious diseases at UNC-Chapel Hill. The results of that study were published in 2011, and “Science” named the study the “Breakthrough of the Year.”
These advances in treatment are the result of decades of research in labs and then in large clinical trials like HPTN052.
“How did I get here? How did medicine get here?” asked Annie, who has been a patient at the UNC Hospitals Infectious Diseases Clinic since 1997 and has participated in clinical trials; she asked to be identified by an alias. “Through a study or research that was done a couple years. So, that’s how I give back.”
It has been a long, sometimes painful journey, though.
“Prior to 1995, we saw a lot of death,” said Lynda Bell, Adult Nurse Practitioner and Associate Director of the UNC Health Care Infectious Diseases Clinic.
But then in 1995, highly active antiretroviral therapies became available -- and they worked: “Suddenly, I saw a change in my patients,’’ Bell said. “They had a new perspective on life.”
The gala, Bell’s inspiration, was about celebrating those patients who survived and honoring those who did not. Bell witnessed the courage it took for patients to continue with their medications, despite extremely unpleasant side effects. She also witnessed patients overcoming barriers to treatment, from the practical -- dealing with transportation and childcare issues -- to the emotional -- most prominently, the stigma associated with living with HIV.
What she’d like to witness next: an end to the disease.“I predict, although my colleagues think I’m crazy, I predict that within the next 10 years we’re going to see a cure,” she said.
In the interim, staying in care is vital to staying well. The health of an HIV positive patient depends on receiving care from a multidisciplinary team of nurses, doctors, pharmacists, mental health specialists and financial counselors.
“If you’re blessed to get with somebody you shows compassion, explains things to do, and makes you feel good about yourself” Annie said. “If you hook up with a health care system where they show compassion and care, like you are their best friend, that means a lot. You need somebody to talk to and you need to talk to somebody who has knowledge. I didn’t get here by myself.”
UNC’s clinic is notable because many of the infectious disease specialists have seen the same patients regularly since their diagnosis – some, like those who attended the Sept. 12 celebration, for more than 20 years.
What is also unique is the relationship between the state and the UNC Hospitals Infectious Diseases Clinic.
“Between the state’s services and UNC’s clinic,” said Foust, “we can provide wraparound services that help us to keep up with the 36,000 people living with HIV in North Carolina.”
It’s a vastly different world now for a patient diagnosed in 1994 compared to one diagnosed in 2014.Dr. Cynthia Gay, an Assistant Professor of Medicine in the School of Medicine, tells her patients recently diagnosed with HIV: “’Whatever dreams or plans you had before you got that call, before someone sat you down and told you had HIV, these do not need to change. If you can do two things you're going to do well. The two things are: stay in care, which means you have to come see some kind of a provider regularly. And then when it's time … to take treatment, you take it everyday.’”
HIV infection is a manageable disease. That’s the information the state of North Carolina is trying to get out to citizens, as well. “Our message is: Get Real. Get Tested. Get Care. We are not going to leave anyone behind,” said Foust.
As evidenced by the 349 clinic patients who have survived the infection for two decades or more and were invited to the Sept. 12 event.
"I love my life. I don’t get sick. I feel good,'' Annie said.
“We all have to die, but we don’t have to die from this.”
1981UNC Hospitals admits its first AIDS patient in 1981 (a man with hemophilia).
1985UNC Health Care responds to the epidemic and establishes a specialized ward for infectious disease.
Responding to the epidemic
Since the virus was not identified until 1984 (an effort helped, in part, by samples taken at UNC), it is not immediately clear who should care for the many patients who are dying, and patient management becomes a real crisis.
Once established, the infectious disease service takes care of all HIV patients and opens a five-day-a-week clinic and walk-in clinic to relieve the burden on the emergency room. The fear and stigma surrounding AIDS in the 1980s cannot be overstated, and the very dedicated group of UNC physicians, nurses, and other health care professionals form a tight bond.
1986A team of researchers led by UNC’s Gil White, MD, publish in the journal Lancet the seminal finding that heating concentrated factor VIII, which people with hemophilia need to survive, could effectively kill HIV and thus make safe the blood supply for hemophilia patients.
1987The University begins offering “AIDS: Principles, Practices, and Politics,” a one hour credit course which looks at AIDS as a paradigm for the relationship between disease, society and public policy.
AIDS: Principles, Practices, and Politics
Each year, about 500 undergraduate, graduate and professional students enroll in the course, which consists of lectures from top leaders in the field, patient panel discussions, documentary screenings and interactive classroom activity.
1990Two UNC researchers are awarded a grant to assist the small, sub-Saharan African country of Malawi develop a strategy for the treatment and prevention of HIV.
HIV prevention in Malawi
Today, UNC Project-Malawi is a leading international research, care and training center for HIV and other infectious diseases. Since UNC began working in Malawi, that country’s HIV rates have fallen from nearly 30 percent to about 12 percent.
1994Researchers in the schools of medicine and public health begin to address HIV among the inmate population in North Carolina’s prisons.
HIV in North Carolina’s prisons
A number of important publications will come out of these efforts, including a study showing that as many as 61 percent of HIV cases in prisons go undetected.
November 1995The Food and Drug Administration approves a new drug, 3TC, for use in combination with AZT.
The drug is manufactured by Research Triangle-based Glaxo Wellcome and clinical trials are conducted at UNC and Duke. Study results showing that combination therapy is more effective than either drug alone are published in the Dec. 21, 1995, issue of the New England Journal of Medicine.
1996Led by Sue Fiscus, PhD, researchers found the drug AZT reduced the rates of HIV transmission from mother to child by two-thirds. The paper, published in the Journal of the American Medical Association, was cited as one of the most important developments in HIV research this year.
February 1997Researchers, including Joe Eron, MD, report in the NEJM that a 3-drug cocktail of indinavir, zidovudine, and lamivudine lowered the levels of HIV RNA to less than 500 viral copies per milliliter for as long as one year.
Lowering HIV RNA levels
All drugs were generally well tolerated. The study found the life-saving benefits of the drug combination were so strong that health officials decided to end the research more than a year early.
June 1997UNC research shows that treating other STDs reduces the infectiousness of HIV.
Treating other STDs
Conducted by UNC faculty working in Malawi, a study finds that men infected with HIV shed eight to 10 times as much virus in their semen if they also have other sexually transmitted diseases. The study suggests that widespread STD screening and therapy could help curtail the HIV/AIDS epidemic.
October 1998As treatment options for HIV advance, so do concerns over drug resistance.
UNC researchers find drug-resistant HIV in semen
A study led by UNC confirms the presence of mutated, drug-resistant HIV in the semen of men taking antiviral medications.
November 1998UNC establishes the Center for AIDS Research (CFAR).
One of 17 NIH-sponsored centers, the UNC CFAR provides infrastructure to support investigation of the HIV/AIDS epidemic using clinical research, behavioral research, research into HIV biology and pathogenesis at the molecular level, and educational outreach.
December 1998UNC establishes the UNC Fogarty AIDS International Training Research Program, the UNC Center for AIDS research, and publishes important an important paper about drug-resistant HIV.
UNC Fogarty AIDS International Training Research Program
UNC establishes the UNC Fogarty AIDS International Training Research Program to train investigators from Malawi, China, and Cameroon to conduct HIV-related research.
June 2000UNC researchers sign the Durban Declaration.
UNC researchers sign the Durban Declaration
UNC AIDS researchers play an instrumental role in the Durban Declaration, a statement signed by more than 5,000 prominent AIDS experts, other doctors and scientists around the world and released during the XIII International AIDS Conference in Durban, South Africa. The declaration, which states unequivocally that HIV causes AIDS, is an attempt to end once and for all any debate on the issue.
March 2002The UNC School of Pharmacy receives NIH funding to acquire a cutting-edge technology for AIDS pharmacology research.
The triple quadropole mass spectrophotometer is capable of measuring very low drug concentrations in small samples, which is crucial to AIDS drug research.
UNC researchers create and pilot an RNA-based strategy for real-time identification of acute HIV infection. UNC transferred the technology to the State Health Lab. This RNA testing strategy eventually becomes a state-funded project, which is duplicated in more than 25 municipalities across the country. The method became instrumental to the UNC Project in Malawi in 2007.
2004UNC receives CDC funding to study the safety and effectiveness of antiviral regimens in reducing infant HIV infection during breastfeeding.
UNC receives CDC funding
The BAN study in Malawi continued through 2008.
May 2005UNC joins the international effort to develop an AIDS vaccine.
UNC joins the international effort to develop an AIDS vaccine.
Through the NIH-funded “virtual research center” - the Center for HIV/AIDS Vaccine Immunology (CHAVI) – UNC AIDS researchers begin to study the biology of HIV infection during its earliest days, what is known as acute HIV infection. Understanding the early immune response, how the human body responds to the virus and how the virus behaves, is essential for the development of an effective vaccine.\
August 2005Research shows that a new combination therapy may attack dormant HIV viruses where it hides latent reservoirs of HIV may be attacked by drug therapy.
Attacking dormant HIV viruses
Using a drug known for its anti-seizure and antidepressant uses, the study findings suggest a new and practical approach to eliminate HIV and raise hope for a cure.
May 2008UNC researcher Adaora Adimora, MD, testified before a U.S. Congressional committee that AIDS in black men represents a national emergency.
Black men account for more than half of all AIDS deaths, and about 45 percent of new diagnoses.
December 2008The UNC AIDS International Training and Research Program marks its 10th year.
Marking 10 years
The AITRP provides HIV/AIDS research training for scientists in resource-constrained countries. After training, they return to work in their home countries. One success story from this program is Sam Phiri. A native Malawian, Sam now directs one of the largest HIV clinics in Malawi, providing antiretroviral therapy and clinical care to nearly 10,000 patients.
May 2009A vaginal microbicide gel trial, known as CAPRISA 004, shows that the gel reduces a woman’s risk of HIV by almost 40 percent.
The Clinical Pharmacology and Analytical Chemistry Core of the UNC CFAR handles the pharmacology for the trial. Soon after, UNC researchers reproduce the CAPRISA study with a humanized mouse model and obtain similar results. Their study further validates the use of humanized BLT mice in research to block HIV transmission.
August 2009Researchers in the UNC Department of Chemistry decode the structure of an entire HIV genome.
Decoding the HIV genome
The results have widespread implications for understanding the strategies that the virus uses to infect humans. The research is the cover story in the August 6 issue of the journal Nature.
June 2010The largest study to date of methods to prevent HIV infection among breastfeeding infants demonstrate that giving antiretroviral drugs to HIV-infected breastfeeding or their babies are both effective.
HIV and breastfeeding
The results of the UNC-led study are published in the June 17, 2010 issue of the New England Journal of Medicine.
2010Researchers for the BAN study in Malawi report that their intervention of combination therapies on HIV positive mothers effectively reduced HIV transmission to nursing babies.
May 2011A UNC-led study convincingly demonstrates that treatment as prevention works.
Demonstrating that treatment as prevention works
Results from HPTN 052 are released early after study data shows that treating people with antiretrovirals while their immune systems are still relatively healthy is 96% effective at preventing transmission to their partners. The news is covered around the world.
July 2011UNC researchers awarded a $32 million, five-year federal grant to develop ways to cure people with HIV by purging the virus hiding in the immune systems of patients taking antiretroviral therapy.
Purging the Virus
A new study confirmed the existence of a “trial effect” in clinical for treatment of HIV and also that the “trial effects” seen in studies between 1996 and 1999 were diminished in the period 2000-06. The trial effect refers to the benefit experienced by clinical study participants simply by virtue of their participating in the trial.
UNC scientists awarded a $3-million federal grant to develop and test a new generation of treatments aimed at preventing sexual transmission of HIV to uninfected individuals. This remains the most common cause of HIV infection worldwide.
October 2011A research team led by UNC investigators discovers that some people diagnosed with HIV-associated dementia have two genetically distinct HIV types in their cerebrospinal fluid – the clear liquid found in the spaces around and inside the brain and spinal cord.
Into the central nervous system
These viral variants are not detected in the HIV load that circulates in the blood, and one of the variants could be present years before the onset of dementia. This is evidence that HIV is growing in the central nervous system.
November 2011UNC School of Medicine selected as the new home of the North Carolina AIDS Training and Education Center.
The North Carolina AIDS Training and Education Center
December 2011The HIV Prevention Trials Network 052 study, led by UNC’s Myron Cohen, selected as the 2011 Breakthrough of the Year by the journal Science.
Breakthrough of the Year
The HIV Prevention Trials Network 052 study, led by UNC’s Myron Cohen, selected as the 2011 Breakthrough of the Year by the journal Science.
March 2012UNC researchers successfully flush latent HIV infection from hiding, in lab experiments, with a drug used to treat certain types of lymphoma.
Successfully flushing HIV infection from hiding
Tackling latent HIV in the immune system is critical to finding a cure for AIDS. While current antiretroviral therapies can very effectively control virus levels, they can never fully eliminate the virus from the cells and tissues it has infected.
April 2012UNC researchers find that early weaning – stopping breastfeeding before six months –offers little or no protective value against HIV transmission. Nor is it safe for infant survival.
May 2012A team of investigators led by UNC researchers demonstrate that HIV latency develops soon after a person is infected but the rate of latency slows when antiretroviral therapy is given.
Getting under control
While current therapies are effective at controlling HIV, some virus remains hidden in certain CD4+ T cells, specialized immune system cells that the virus uses to replicate. This latent infection remains a significant challenge to curing HIV.
UNC research helps clarify why some people infected with HIV are better able to control the virus. It may also pinpoint a target for treatment during early HIV infection aimed at increasing the supply of certain immune cells in the gut.
UNC School of Medicine researchers use a humanized mouse model to show that breast milk has a strong virus-killing effect and protects against oral transmission of HIV.
July 2012UNC researchers publish pioneering research in Nature showing that a drug used to treat certain types of lymphoma can dislodge hidden virus in patients receiving treatment for HIV.
January 2013UNC was awarded funding to establish a new Southern site for the Women’s Interagency HIV Study (WIHS), a longitudinal observational study of HIV infection among women.
March 2013UNC researchers show that deleting a specific gene inside the HIV virus, in mice, allows for immune system cells to kill the virus, suggesting a promising new target for HIV drugs.
June 2013Launching ONE CALL
Launching ONE CALL
The Division of Infectious Diseases at UNC School of Medicine has partnered with the Communicable Disease Branch of North Carolina’s Division of Public Health to launch ONE CALL, a toll-free HIV call center staffed by specially trained nurses who provide patients and non-specialist providers with referral to HIV care and support services across the state.
November 2013A study of 2,519 Kenyan men conducted by UNC researchers reveals that infection with the human papillomavirus (HPV) was associated with a higher subsequent risk of infection with HIV
January 2014Researchers at the UNC School of Medicine deploy a potential new weapon against HIV – a combination therapy that targets HIV-infected cells that standard therapies cannot kill.
A potential new weapon
Using mouse models composed of human immune systems, the researchers found that an antibody combined with a bacterial toxin can penetrate HIV-infected cells and kill them even though standard antiretroviral therapy had no effect.
February 2014UNC receives a seven-year, more than $40-million award from the NIH for a clinical trials unit that will implement the scientific agendas of five NIH networks devoted to HIV/AIDS treatment, prevention, and cure research.
April 2014UNC infectious diseases researchers awarded $7-million to develop treatments that target HIV reservoirs.
$7-million to develop treatments that target HIV reservoirs
Despite powerful and life-saving drug treatments, HIV continues to replicate at low levels in the body, and once treatment stops, the virus quickly rebounds. Called the “residual active viral reservoir” or “persistent reservoir,” these cells represent the single most important obstacle to eradicating HIV from the body.