HIV: 40 years of pandemic

The thir­ti­eth edi­tion of the CROI (Con­fer­ence on Retro­virus­es and Oppor­tunis­tic Infec­tions)¹, which brings togeth­er spe­cial­ists in Human Immun­od­e­fi­cien­cy Virus (HIV), was held last Feb­ru­ary. Let’s take it as an oppor­tu­ni­ty to take stock of the cur­rent sit­u­a­tion of HIV in the world!

This virus was iden­ti­fied and iso­lat­ed in 1983 by a team from the Pas­teur Insti­tute². Like oth­er sci­en­tists at the time, they were look­ing for the ori­gin of a weak­en­ing of the immune sys­tem, observed in a grow­ing num­ber of patients in the Unit­ed States since 1981 – the infa­mous acquired immun­od­e­fi­cien­cy syn­drome (or AIDS). HIV has the par­tic­u­lar­i­ty of infect­ing cells of the immune sys­tem, in par­tic­u­lar T lym­pho­cytes car­ry­ing the CD4 mark­er, often called T4 lym­pho­cytes. These cells are pro­gres­sive­ly killed by the virus and their dis­ap­pear­ance even­tu­al­ly pre­vents the body from defend­ing itself against oth­er infec­tions. There are dif­fer­ent types of HIV, derived from sev­er­al adap­ta­tions of mon­key virus­es to humans. The one at the ori­gin of the cur­rent pan­dem­ic, HIV‑1 type M, is thought to have emerged in the 1920s in Kin­shasa³.

HIV can be trans­mit­ted through three bod­i­ly flu­ids: blood, sex­u­al secre­tions, and breast milk. The devel­op­ment of AIDS fol­low­ing infec­tion takes place in three stages. Dur­ing the pri­ma­ry infec­tion, i.e. the encounter with the virus, it mul­ti­plies in the body and the CD4 cell count drops. Anti-HIV anti­bod­ies begin to be pro­duced and will remain detectable in the blood of patients, who thus become HIV-pos­i­tive. As such, the term “HIV-pos­i­tive” means “hav­ing anti­bod­ies” and is some­times used with­out spec­i­fy­ing the infec­tious agent involved when refer­ring to HIV.

The immune sys­tem takes over after a few weeks, keep­ing the virus under con­trol dur­ing an asymp­to­matic phase that can last up to ten years. This rep­re­sents a first dif­fi­cul­ty in the fight against HIV. Indeed, these patients who have no symp­toms and often do not know that they are infect­ed can still be con­ta­gious. It is both to enable treat­ment to be put in place and to avoid invol­un­tary con­t­a­m­i­na­tion dur­ing this asymp­to­matic phase that screen­ing is essential.

After a while, HIV weak­ens the immune sys­tem enough to mul­ti­ply again in the body. This is when AIDS begins: the body can no longer effec­tive­ly defend itself against oppor­tunis­tic infec­tions which, if left untreat­ed, will even­tu­al­ly lead to death.

HIV is a dead­ly retro­virus, but for­tu­nate­ly there are treat­ments that can keep it under con­trol. Anti­retro­vi­ral med­ica­tions gen­er­al­ly com­bine mol­e­cules tar­get­ing three dif­fer­ent stages of the virus’ mul­ti­pli­ca­tion cycle, hence the term “tri-ther­a­py”. This com­bi­na­tion of sev­er­al active ingre­di­ents is essen­tial to con­trol HIV because the virus mutates a lot, allow­ing it to devel­op resis­tance. The more we restrain it, the low­er the prob­a­bil­i­ty that it will suc­ceed in adapting.

The dif­fer­ent com­po­nents of tri-ther­a­py can now be com­bined in a sin­gle tablet to be tak­en dai­ly. They block the growth of the virus to the point where it is unde­tectable in the body, which has two enor­mous advan­tages. On the one hand, as the immune sys­tem is no longer under attack, it can once again play its pro­tec­tive role and pre­vent the devel­op­ment of AIDS. More­over, the ear­li­er the treat­ment is tak­en, the less the immune sys­tem has suf­fered before­hand and the more effec­tive it is. If a risk is iden­ti­fied, it is pos­si­ble to take emer­gency post-expo­sure treat­ment with­in 48 hours to try to pre­vent the virus from tak­ing hold. In addi­tion, many stud­ies have shown that when HIV is unde­tectable, it is not trans­mis­si­ble⁴. Treat­ment is there­fore also a pre­ven­tion tool.

The best way to fight an infec­tious agent is to avoid catch­ing it. This means iden­ti­fy­ing sit­u­a­tions where there is a risk of trans­mis­sion and tak­ing pre­cau­tions to avoid them (such as using con­doms dur­ing sex). How­ev­er, zero risk rarely exists and, for the past ten years, a new pre­ven­tive tool has been avail­able for peo­ple who do not feel suf­fi­cient­ly pro­tect­ed against HIV, what­ev­er the rea­son: pre-expo­sure pro­phy­lax­is, or PreP. This approach con­sists of tak­ing a com­bi­na­tion of anti­retro­vi­rals before risky sit­u­a­tions for unin­fect­ed peo­ple. Numer­ous tri­als have shown that this dras­ti­cal­ly reduces the risk of con­t­a­m­i­na­tion, and stud­ies are under­way to eval­u­ate dif­fer­ent meth­ods of admin­is­tra­tion (con­tin­u­ous or on-demand, oral or injectable, etc.), includ­ing one in the Paris region⁵. Despite its effec­tive­ness, PreP is still not well known to the gen­er­al pub­lic, but it is avail­able in France from the age of 15 and is reim­bursed by the French social secu­ri­ty system. 

An esti­mat­ed 190,000 peo­ple are liv­ing with HIV in France. This num­ber is con­stant­ly increas­ing, as there are more new diag­noses than deaths of peo­ple with the virus every year. While the effec­tive­ness of treat­ments is excel­lent news, the num­ber of new infec­tions has been rel­a­tive­ly sta­ble for the past ten years. It has decreased in 2020 and 2021, although it is not real­ly pos­si­ble to draw any con­clu­sions, as the SARS-CoV­‑2 health cri­sis has had com­plex reper­cus­sions on behav­iour and the health sys­tem. In any case, it is esti­mat­ed that around 5,000 peo­ple dis­cov­ered their HIV sta­tus in France in 2021, 51% of whom linked their infec­tion to het­ero­sex­u­al inter­course. Unfor­tu­nate­ly, about 30% of patients were already at an advanced stage of the dis­ease at the time of their diag­no­sis, a fig­ure that has also been sta­ble for the last ten years⁶.

Accord­ing to UNAIDS fig­ures⁷, glob­al­ly, about 1.5 mil­lion peo­ple were infect­ed with HIV in 2021 and 650,000 died of AIDS. An esti­mat­ed 40 mil­lion peo­ple have died since the pan­dem­ic began in the 1980s, rough­ly the same num­ber as are cur­rent­ly liv­ing with the virus. 15% of these peo­ple, or about 6 mil­lion, do not know they are infect­ed, and a quar­ter do not have access to anti­retro­vi­ral ther­a­py. But these fig­ures hide wide vari­a­tions across the world.

Out­side sub-Saha­ran Africa, 94% of new HIV infec­tions are among sex work­ers, men who have sex with men, inject­ing drug users, trans­gen­der women, or the sex­u­al part­ners of all of these. In sub-Saha­ran Africa, where the major­i­ty of HIV car­ri­ers live, only half of all new infec­tions are among these groups. And 63% of those infect­ed in 2021 were women or girls.

Inter­na­tion­al tar­gets are reg­u­lar­ly set to try to end the HIV pan­dem­ic. The 2020 tar­get has unfor­tu­nate­ly not been met⁸ and the 2030 tar­get can be sum­marised in three num­bers: 95–95-95. That 95% of peo­ple liv­ing with HIV know their sta­tus, that 95% of those who know their sta­tus are on treat­ment and that 95% of those on treat­ment have an unde­tectable viral load⁹. In 2021, these fig­ures were 85%, 88% and 92% respectively.

The fight against dis­crim­i­na­tion is also essen­tial, as peo­ple with HIV suf­fer from strong sero­pho­bia, both in the med­ical envi­ron­ment, at work and in their pri­vate lives¹⁰. In a sur­vey car­ried out in France in 2021, 36% of par­ents expressed dis­com­fort at the idea of an HIV-pos­i­tive per­son look­ing after their child¹¹, even though this sit­u­a­tion does not present any risk of con­t­a­m­i­na­tion (which is non-exis­tent in any case when treat­ment makes the virus unde­tectable). Edu­ca­tion is there­fore essen­tial on these subjects.

Progress in HIV treat­ment and pre­ven­tion approach­es is to be cel­e­brat­ed, but the road to erad­i­ca­tion is still long. Espe­cial­ly as we still have nei­ther an effec­tive vac­cine nor a treat­ment that can cure the virus once and for all (although a few excep­tion­al cas­es are known, to which we will devote a future arti­cle). Final­ly, let us salute the indis­pens­able work of the asso­ci­a­tions which, since the begin­ning of this pan­dem­ic forty years ago, have played a fun­da­men­tal role in pre­ven­tion, sup­port for patients and the fight against their stigmatisation.