30 years of progress on HIV research

Three veteran researchers reflect on how human immunodeficiency virus research has changed over their careers.

joerg schuepbachJörg Schüpbach, MD
Retired
Swiss National Center for Retroviruses
HIV/AIDS researcher since 1983

ResearchGate: What was the state of progress in fighting HIV when you started researching the disease? 

Jörg Schüpbach: Luc Montagnier's group had for the first time isolated a new retrovirus from a homosexual man with lymphadenopathy. This virus was called lymphadenopathy-associated virus, LAV. At that time, it was still unproven that LAV was indeed the cause of AIDS, and before one could think of eradicating AIDS one had to truly identify its cause. I was part of a group of researchers in the group of Robert Gallo at NIH who showed in May 1984 in four simultaneous Science publications (i) that a virus, HTLV-III (later shown to be the same as Montagnier’s LAV and subsequently named HIV) could be isolated from most patients with AIDS or at risk for AIDS, and (ii) that virtually all patients with AIDS or lymphadenopathy had specific antibodies to this virus, as detected by ELISA and Western blot. Mika Popovic from our group also developed the H9 cell line that permitted unlimited large-scale production of HIV. This work permitted industrial production of the first HIV screening and confirmation tests. These were instrumental to free the blood supply from HIV contamination and to reliably diagnose or exclude HIV infection in humans.

RG: What were your expectations when you first started your career in HIV research?

Schüpbach: I hoped of course that I would be able to contribute to the identification of the AIDS virus. Thinking back now, I wonder why the virus was not detected even earlier. Everything needed for HIV detection was already available: the possibility to culture T lymphocytes with the help of T-cell growth factor (IL-2), detection of retroviruses by reverse transcriptase tests, and electron microscopy. No test or procedure had to first be developed; if one had access to patient samples it should have been a matter of weeks or a few months to check whether a retrovirus was present in such cultures. That this did not happen was probably due to a lack of cooperation, or too much competition: everybody wanted to be the first and get the Nobel Prize – alone.

RG: What have (personal) breakthroughs in your research been since then?

Schüpbach: My colleagues at the Swiss National Center for Retroviruses and I developed methods (PERT assay, particle-associated retroviral RNA amplification) that permitted the detection and identification of unknown retroviruses present even at low concentration. The idea was to see whether further human diseases (tumors, autoimmune disorders etc.) would be caused by retroviruses. This was not the case. We also developed ultrasensitive PCR methods for detection of known viruses (MEGA-PCR). Furthermore, we developed the ultrasensitive p24 antigen assay that has the potential of rivaling PCR-based tests for diagnosing and monitoring HIV at low costs. This approach still holds promise for the future when huge technical advances in the detection of proteins will be routine.

RG: What are you working on now, and what contribution do you hope this work will have?

Schüpbach:  I am retired now, but will observe further developments with interest. I hope that research may benefit from a new spirit of collaboration.




Reuben Granich, MD/MPHReuben Granich
PEPFAR Office of the Global AIDS Coordinator
International Association of Providers of AIDS Care (IAPAC)
HIV/AIDS researcher since 1987

ResearchGate: What was the state of progress in fighting HIV when you started researching the disease?

Reuben Granich: I was a medical student at Stanford in 1987. HIV was relatively new. Fear was the dominant emotion since there were no treatments, it was clearly an infectious pathogen with 100 percent mortality, and young people and others were dying horrible deaths. At that time the HIV test had just been developed and tremendous scientific progress was being made on describing the virus and working on developing potential therapies. There was still quite a bit of fear regarding hospital-acquired infection and some confusion about how to treat people living with the virus. It was a time of moral crisis and many health care professionals were publically opting out of providing care to people living with HIV.  Some of my colleagues refused to work with people living with HIV. There was heavy stigma and discrimination with some politicians calling for drastic measures.  There were a few medical students in my class who recognized the threat of HIV. We felt that as medical students in training that it was important to step up and publically engage. There was no hope for eradication at that time. We were just hoping to be an example of how students and the medical profession writ large could take a strong position to provide care and address this major public health problem. Many other students were engaged on other social issues but for a few of us HIV was the priority.

RG: What were your expectations when you first started your career in HIV research?

Granich: I actually do not think that I am a researcher. I see myself as someone who had the opportunity to have the training needed to ask questions and then implement ways to stop the virus.  I had no expectations. I just knew that if we did not confront HIV the epidemic would continue to devastate our friends and communities and that if I did not engage then I would wonder in the future why I did not step up. It was a time of moral decision making, and my background translated into the strong feeling that I needed to make a commitment to work to help people and stop HIV. There was definitely a political connotation – in my mind confronting HIV was similar to confronting fascism in the 1930s. My sense was that if we did not collectively stand up early then the problem would become even more of a catastrophe. Leading from the front was the driving motivation behind my small contributions at that time.

RG: What have (personal) breakthroughs in your research been since then?

Granich: Public health is a team sport. I guess for me there have been a few breakthroughs. Our work on integrating HIV and TB response was not particularly sexy, but together we were able to shift the strategy to consider both diseases together – this is ongoing of course – early work in that area included collective work on the WHO’s TB/HIV collaborative activities. It was also a breakthrough when we conceptualized the Three I’s for HIV/TB (IPT, ICF, and IC) and early initiation of antiretroviral (ART) strategy while at WHO. Another breakthrough that comes to mind is our team’s work on treatment as prevention and the publication of a Lancet modeling paper on using Voluntary HIV testing and immediate treatment. The paper introduced the concept of HIV elimination and the potential power of “test and treat” to have a major impact on the epidemic in South Africa and by implication elsewhere. It directly challenged the dominant WHO led treatment paradigm, which was “test and wait” and status quo focus on a sustained broad response without an articulated end game. The paper was met with harsh criticism, but over time the concept of testing and offering immediate treatment as prevention has emerged as a fundamental element of the HIV response.

RG: What are your expectations now? How long do you think will it take to eradicate the disease?  

Granich: The new frontier is the “how” of implementation: using the resources that we have to get the job done. I am now focusing on addressing barriers to expansion and working with others trying to answer the major question of how can we use the existing resources, within a short time frame to reach the UN’s “90-90-90” targets for addressing the AIDS epidemic over the next five years.  We are also focused on providing support to cities that are moving towards 90-90-90 as part of the Fast Track Cities Initiative. I am optimistic that we have the tools and resources to control HIV in many settings. We also have built a significant global response that is highly motivated to confront HIV. Eradication is a long way off. However, we can consider elimination in the future in some geographic settings while also remembering that our goal is to provide health and near normal lifespan for at least 37 million people living with HIV. This translates into decades of future efforts to keep people alive on treatment while scientists work on new breakthroughs such as a cure. Keeping people alive and ending the epidemic now go hand in hand.

RG: What are you working on now, and what contribution do you hope this work will have?

Granich: My goal is to provide the evidence and arguments to support our efforts to expand access to testing and treatment. HIV is personal for me, and I will continue to do my utmost to stop HIV from spreading and killing people. My work with PEPFAR, the International Association of Providers of AIDS Care and the Fast Track Cities Initiative provides me with many opportunities to make a contribution to our collective efforts to end HIV.




Sharon Ruth Lewin, PhD/MDSharon Lewin
Doherty Institute
University of Melbourne
HIV/AIDS researcher since 1991

ResearchGate: What was the state of progress in fighting HIV when you started researching the disease?


Sharon Lewin: It was pretty bleak at that time with no effective treatments and young people dying at the peak of their lives. There was still a lot of fear, stigma, and discrimination. After my PhD, I went to New York to work at Rockefeller University in 1997 with David Ho at the Aaron Diamond AIDS Research Center. This was only a year after the beginning of antiviral therapy and there was tremendous excitement about the impact ART was having on people’s lives. We very quickly learned that ART was not going to cure HIV and that HIV was able to become dormant and hide in a person’s DNA. This was going to be a very difficult part of the virus to tackle. Back then everyone thought a cure was never going to be possible. Most felt it wasn’t worth even trying. I think that view has changed dramatically in recent years.

RG: What were your expectations when you first started your career in HIV research?

Lewin: When I started in HIV research there were so many unknowns, but the science was changing rapidly and there was always a sense of excitement, optimism, and passion from everyone that worked in the field. I don’t think I would have ever imagined that 20 years later we would now have highly effective treatment, that over 15 million people can now access treatment in low and middle income settings and that we have multiple highly effective ways to prevent HIV with treatment as prevention and Pre-Exposure Prophylaxis (PREP), a drug that protects HIV negative people at risk of contracting the virus. It’s been a very exciting shift in medicine and I feel privileged to have been part of it

RG: What have (personal) breakthroughs in your research been since then?

My own research has largely focused on the dormant form of HIV, which is called HIV latency, and why we can’t cure HIV. I am proud of the work my group has done on setting up multiple models to study HIV latency in the laboratory. These have made a major contribution as it is very difficult to study HIV latency in patient cells, as these dormant forms of the virus are so rare and hard to find in people. I am also really proud of the work we have done in clinical trials of drugs that aim to reverse latency and eliminate dormant forms of HIV. These clinical trials were done at a time when we knew little about the risks or benefits of latency reversal and the multiple participants in these studies were very brave and altruistic. These studies taught us a lot about how to tackle latency. The studies of course didn’t lead to a cure but they gave us many new ideas of what next steps are needed to eliminate latency.

RG: What are your expectations now? How long do you think will it take to eradicate the disease?

Lewin: I am optimistic that with widespread uptake of antivirals to treat and prevent infection, through PREP, we will continue to see increased life expectancy, declines in AIDS related deaths and declines in new infections. I really do think that achieving the UNAIDS targets of 90-90-90 is possible and this will have a profound impact on ending AIDS. I think ending HIV in children is a real possibility too. I am less optimistic about eradicating the virus from the 37 million people currently living with HIV. That’s going to take a lot more investment in science and a lot more hard work!

RG: What are you working on now, and what contribution do you hope this work will have?

Lewin: I am still working on understanding HIV latency – how it is established, maintained and reversed at a very basic fundamental level. We are also very interested in understanding how to reverse latency and whether we can find more potent and safer drugs to do this. I am also convinced that we need to not just focus on the virus but boost the immune system to allow patients to safely stop ART. To do this, we are looking closely at new drugs that boost immune function and make better killer T cells. These drugs are called immune check point blockers and are revolutionizing cancer treatment. I am hoping they will have a similar dramatic impact on an HIV cure!

Featured image courtesy of NAID.