HIV and AIDS tremble but stand firm

Inserm has seen the AIDS story unfold from its beginnings in 1981, when the first cases were reported and the alarm raised over this new epidemic. Although triple therapy now makes it possible to control the infection, transmission has barely declined, and patients remain infected for life. The efforts thus continue, especially at Inserm and the French National Agency for Research on AIDS and Viral Hepatitis (ANRS), to try to cure patients and stem the epidemic. Dominique Costagliola, an Inserm research director who was awarded an Inserm Research prize in 2013 for her work on HIV, looks back on this story, and reviews the current situation.

Virus du SIDA : Cellule massivement infectée par le VIH, montrant le bourgeonnement des particules virales sur toute la surface cellulaire (microscopie électronique à balayage) - © Inserm, P. Roingeard

1981: American physicians are intrigued by a young patient with Kaposi’s sarcoma, a type of skin tumour usually observed in elderly patients. Another presents with an atypical pneumocystis pneumonia. The observation of at least three other very unusual cases in the cities of Los Angeles, San Francisco and New York cause the American Centres for Disease Control to issue an alert on these profiles, which are preferentially affecting members of the homosexual community. This warning letter marks the starting point of the big crusade against AIDS, or acquired immune deficiency syndrome.

“This disease did not emerge violently in 1981. It has probably been endemic from the beginning of the 20th century in Africa, the breeding ground for the virus, which is derived from a monkey virus. But the flawed health systems and infrastructures in these countries prevent its detection,” recalls Dominique Costagliola. Reports of the first cases in “wealthy” countries therefore come as a shock, and soon reverberate internationally, with the identification of many other cases in homosexuals and haemophiliacs, including in France. 

A French team

This spread of the disease soon mobilises the scientific community, which suspects a virus, given the mode of transmission by blood and semen. A handful of French people gathered in a viral oncology laboratory at the Institut Pasteur-CNRS-Inserm soon prove that this is the case: the human immunodeficiency retrovirus is isolated from the lymph nodes of patients, and described in 1983. A discovery which will earn the Nobel Prize for Medicine for Luc Montagnier and Françoise Barré-Sinoussi in 2008. “These results were obtained very rapidly. It is hard to imagine the amount of work these researchers did to get on the right track, develop the right techniques and ultimately publish so quickly. A feat which might be explained by the desire of the French to get one over on the famous Robert Gallo, who discovered the first retrovirus, and was equally involved in this mad race in the United States,” explains Dominique Costagliola.

Rapid advances

© Inserm, M. Depardieu

This discovery enables rapid progress, with the development of the first tests for serological diagnosis from 1985, the first drug, AZT, an inhibitor of the key enzyme of the virus, reverse transcriptase, already developed in oncology in 1987, followed by other more HIV-specific drugs, such as the protease inhibitors, from 1995, which drastically reduce the quantity of virus in patients. At this time, the physicians try to block transmission of the virus from mother to child, which is wreaking havoc, especially in southern countries. A trial carried out in 1992 shows that taking AZT in the final weeks of pregnancy reduces the risk of transmission by two-thirds. “One of the biggest victories in the fight against HIV,” according to Dominique Costagliola.

But the physicians encounter an important problem. Antiretroviral drugs exert a pressure on the virus, which can mutate and become resistant to the treatment. This is the case for many patients, who then experience treatment failure and develop complications. A major turning point is therefore the arrival of dual therapies, followed by triple therapies, which involve combining several different drugs. The virus is thus overwhelmed and “lays down its arms.” It persists in cells, but in a latent state. The systematic use of triple therapies from 1996 marks a turning point in the management of the infection. The risk of AIDS occurring in patients infected with HIV collapses, going from 20% within a year to 2-3% after this date. Furthermore, the implementation of these treatments early in an infection reduces the viral load and hence the risk of transmitting the infection to anyone else, a key element in the attempt to stem the epidemic.

Southern countries access treatments

© Inserm, P. Latron

There remains the thorny problem of the southern countries, which do not have the means to pay for a lifetime of these drugs, which cost nearly €100 per month. However, 70% of these patients are concentrated in Sub-Saharan Africa. The flagrant inequality between the rich and the poor is no longer tolerable, and forces the international authorities to act. “The International AIDS Conference held in Durban, South Africa in 2000 is decisive. It was really there that the future of these populations was decided,” recalls Dominique Costagliola. This conference, followed by the Special Session of the United Nations General Assembly on HIV/AIDS in 2001, allows publication of new recommendations for management, and guarantees facilitated access to treatment for at least three million people living in countries with limited resources from now until 2005. “At the time, this seemed unrealistic. Today, 16 million people are receiving dual therapy in the southern countries!

 

Inadequate screening

“Since those years, treatments have not ceased to improve, thanks to more specific and better tolerated drugs. Thus, a patient diagnosed and treated early has the same life expectancy as a person not infected with HIV,” adds Dominique Costagliola. Unfortunately, detection is often delayed, and often follows the appearance of a first illness typical of AIDS. At that point the immune system is strongly depressed and it is much more difficult for these patients to regain their health, and there is an increased risk of dying in the next four years.”

In France, thousands of people continue to be infected each year, and over 150,000 people were living with HIV in 2010. Over half of these were diagnosed at an advanced stage, with a low level of CD4 T lymphocytes. Moreover, the incidence is increasing for some populations, particularly the homosexual community. “People have heard such wonderful things about triple therapies that they do not necessarily know that they have a reduced chance of survival if they are diagnosed late. They have the impression that it is a treatable disease,” according to the researcher. For her, screening absolutely needs to be intensified on a large scale, as the most frequent mode of transmission today is the heterosexual route. “It is the only means of rapid treatment that provides individual and collective benefit by reducing the risk of transmission,” judges the researcher.

Will the epidemic be ended by intensified screening and care? There are several emerging possibilities for a real cure for patients: reinvigorating their immune system for sustainable control of the infection without treatment, or eradicating the virus reservoirs. This is our best hope, since the possibility of preventive vaccination remains hypothetical despite the financial and human resources. Several candidate vaccines have been tested, but to no effect so far.

Further information 
To find out more about HIV/AIDS, consult our information file and the ANRS website 
Read the biographies of Françoise Barré-Sinoussi, Dominique Costagliola, France Lert and Jean-Paul Lévy

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