HIV / Aids

One of the very first photographs of the AIDS virus (HIV-1), taken on February 4, 1983. Partial view of a cross-section of a T lymphocyte infected by the virus isolated in a patient - © Institut Pasteur

Forty years after Institut Pasteur scientists discovered the HIV-1 virus (a discovery that was recognized by the 2008 Nobel Prize in Medicine), AIDS remains an unacceptable scourge. Indeed, the HIV epidemic is still ongoing. AIDS is now one of the leading causes of death in the world for teenagers and women of childbearing age. The number of new infections has been increasing in Eastern Europe and there are about 6,000 new cases in France each year*. There still is a gap between the time of infection and diagnosis of HIV infection (median time in France is 3 years).

It is estimated that some 38 million people are currently infected, all around the world

6,000 new cases in France each year

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Cause

HIV stands for human immunodeficiency virus. It is contracted by sexual contact, contaminated blood, and mother-to-child transmission. In the latter case, transmission of the virus from mother to child can take place:

during the last trimester of pregnancy, by HIV passage through the placental barrier during blood exchange between the mother and the fetus;
during childbirth.
while breastfeeding.

Taking antiretroviral therapy during pregnancy can bring the rate of transmission to less than 1%.It targets T lymphocytes, cells that are vital for a healthy immune system. Without treatment, HIV gradually weakens the immune system, and sufferers develop serious diseases over the long term, known as “opportunistic diseases” as they are caused by microorganisms that are harmless for those with a healthy immune system.

Acquired immunodeficiency syndrome (AIDS) is the final stage of HIV infection, when those infected develop one or more opportunistic diseases. During the first years, there are generally no clinical symptoms. However, CD4+ T cells are already progressively declining before the symptoms arise. In the absence of treatment, the disease occurs after several years of infection (median time is 7 years after infection but this time span varies among the individuals and can be shorter or longer).

Symptoms

The clinical symptoms of HIV vary according to the different stages of the disease. The first stage is known as primary infection, when those infected may have no symptoms or may develop flu-like symptoms after an incubation period of one to several weeks (high fever, muscle pain, headaches, diarrhea).

After the primary infection stage comes an asymptomatic stage that can last for several years. During this period, the virus is still present and those infected remain contagious. HIV gradually weakens the immune system, leading to other symptoms such as weight loss, fever, skin infections, diarrhea, and cough.

If left untreated, the disease develops into Acquired Immunodeficiency Syndrome, or AIDS, the final stage of HIV infection. This stage is characterized by the emergence of “opportunistic” diseases, which take advantage of the weakened immune system. AIDS sufferers may contract any number of bacterial, fungal, and parasitic infections, as well as some cancers.

Treatment

There is currently no treatment that can completely eliminate HIV from the body. Treatments have been developed to stop HIV spreading in seropositive patients, allowing them to maintain a functional immune system. These treatments are known as triple therapies, since they combine several antiretroviral molecules. Research and clinical trials are ongoing to study if in individuals where HIV is efficiently suppressed, the therapy can be simplified, by using for example two instead of three drugs, or by being able to take vacation of treatment or by testing long-lasting drugs that are injected only monthly or even less.

The first generation of antiretroviral drugs often caused side effects, including nausea, vomiting, tiredness, loss of appetite, fever, diarrhea, and skin reactions. The hope is that the new generation of drugs if taken early on after infection allow a normal life. Long-term side effects, such as gain of weight or inflammation, are though not excluded.

It is recommended to initiate treatment as soon as possible after infection. This helps to keep the immune system as intact as possible, to reduce the chronic inflammation induced by the infection and also to reduce the risk of HIV transmission. Unfortunately, most HIV infections are only detected after many years of infection, and only 60% of people infected with HIV worldwide have access to treatment.

Strong control of the virus in rare cases

A tiny percentage of people living with HIV (less than 1%) spontaneously control HIV infection. This means that they are infected, but the virus is present in only very low levels in the body and often below detection level in the blood. This spontaneous control is often associated with a particular genetic background, corresponding to specific HLA genes that allow very strong anti-HIV CD8 + T cell responses.

There are also some individuals who control the virus after receiving a treatment. These individuals most often initiated the treatment very early, i.e. only a couple of weeks after HIV infection. Between 5% and 10% of early treated Caucasians might display such post-treatment control. They are in a state of HIV remission.

Other very rare people are even resistant to the infection. This resistance is generally caused by a mutation in the “CCR5” chemokine receptor gene, which is a co-receptor for the virus.

Cases of “paradoxical couples” (that is to say, "serodiscordant" couples) have been described where one observes, without being able to explain it, that the seronegative partner is not infected by the HIV-positive partner). Sex workers that do not use preventive methods or children born to infected mothers have a risk of HIV exposure but remain seronegative in some cases. The reasons for that are not fully elucidated.

Prevention

There still does not exist an efficient vaccine against HIV. However, multiple methods of prevention can be used as tools to reduce the risk of transmission.

Treatment as prevention (TasP) is an efficient way to reduce transmission. Efficient anti-retroviral treatment leads to undetectable virus in blood reducing considerably the risk of transmission.

Pre-exposure prophylaxis (or PrEP) is medicine taken to prevent getting HIV. PrEP is highly effective for preventing HIV when taken as prescribed. PrEP reduces the risk of getting HIV from sex by about 99%. PrEP reduces the risk of getting HIV from injection drug use by at least 74%.

Epidemiology

Emergence in the 1980s

AIDS was first described in 1981, but retrospective studies on serum specimens from Zaire (now Congo) indicate that the virus has existed since 1959. Other studies have shown that HIV has been circulating in humans for longer than that, probably since the end of the 19th century.

HIVs have an animal reservoir. At least forty African monkey species (including chimpanzees, gorillas, green monkeys, mangabeys, and mandrills) are naturally infected by retroviruses closely related to HIV known as simian immunodeficiency viruses (SIVs). The infection does not result in AIDS in some of these species. The viruses circulating in some of these African non human primate species have been transmitted to humans and gave rise to HIV type 1 and type 2. There must have been at least 12 events of transmissions to humans.

It is possible that HIV was originally contained within an isolated population before spreading as a result of increasing urbanization and population movements at the beginning of the 20^th century. Some of the HIV variants are more efficient than others in spreading. This is the case in particular for variants of the HIV-1 group M, which are responsible for most cases of HIV infection in the world.

The animal reservoir of HIV-1 are chimpanzees and gorillas in West-Central Africa. It is possible that hunters got exposed to the SIV present in chimpanzees and gorillas. The other human virus, HIV-2, is closely related to the SIV that infects mangabey monkeys living in West Africa. It is possible that humans may have been contaminated after being bitten by these monkeys.

Rapid spread

Since 1981, when the HIV epidemic was discovered, the virus has spread from Africa to North America and subsequently to Europe. Men having sex with men were the first to be reported in the United States. The epidemic was then observed in blood transfusion patients, hemophiliacs, and drug addicts, emphasizing the risks of blood-borne transmission. In Asia, the disease only emerged around 1986-87, firstly in Thailand and then in other Southeast Asian countries. Sex working and intravenous drug use were major factors in the spread of HIV in these countries. Intravenous drug use were also major factors for spreading in some regions in Europe and North America. HIV also continues to spread among men having sex with men and from mother to child. Of note, the most common mode of HIV transmission worldwide is heterosexual intercourse. It is estimated that some 38 million people are currently infected (see AIDS in figures).

At the Institut Pasteur

Among the study and fight against infectious diseases, including Covid-19, the research on HIV/AIDS continues to be a major target of the Institut Pasteur in Paris and the Institut Pasteur International Network, in the countries that are most affected by the epidemic.

The work of the research teams covers most of the current priority research areas:

the mechanisms by which HIV replicates in human cells
the mechanisms responsible for chronic inflammation and immunodeficiency
the research on the immune responses controlling the virus
the mechanisms of the virus persistence despite effective treatment
the role of the microbiome and metabolic changes
the effects of the treatments on the virus and immune responses
the factors leading to HIV remission
the development of vaccine candidates and therapeutic strategies toward HIV cure.

This research is carried out in close partnership with the French National Agency for Research on AIDS and emerging infectious diseases (ANRS-MIE), and the Vaccine Research Institute (VRI).

AIDS research at the Institut Pasteur

Read our Press document

Video (in French) - HIV: towards new treatments

Françoise Barré-Sinoussi, Professor at the Institut Pasteur, Nobel Prize for Medicine 2008

Almost 35 years after the discovery of HIV-1, AIDS remains an unacceptable scourge, particularly affecting the poorest countries and populations: 37 million people are living with HIV / AIDS in the world and, in France, another 6000 new infections per year. Antiretrovirals now provide good control of the disease but not a cure. Françoise Barré-Sinoussi, Nobel Prize for Medicine for the discovery of HIV, explains the current challenges of research on this virus, including new ways that could lead to a cure. (in French).