HIV: New Treatments Are Effective but Diagnosis Is Still Too Late

Science

Using the French Hospital Database on HIV (FHDH ANRS CO4), an Inserm team has evaluated the immunologic efficacy of the new antiretroviral treatments. While satisfactory, the results remain linked to earliness of diagnosis. The team also emphasizes the importance of measuring the CD4/CD8 ratio, especially at treatment initiation.

"We manage a database* which pools information on people living with HIV and who are treated in the hospital setting. We use it to answer questions of clinical relevance" explains Dominique Costagliola, who leads the Clinical epidemiology of HIV infection: therapeutic strategies and comorbidities** team, in Paris. Since 2006, antiretroviral drugs have been developed which are more effective and better tolerated than the first generations. This raises the question of their efficacy and the parameters which influence patient response.

Bourgeonnement du virus du SIDA en surface d’une cellule. Crédits : Inserm/Philippe Roingeard
AIDS virus budding from the surface of a cell. Credits : Inserm/Philippe Roingeard

The human immunodeficiency virus (HIV), responsible for AIDS, attacks a specific category of immune cells, known as CD4 cells. This makes the plasma level of CD4 a good indicator of disease progression. In addition to the disappearance of the virus in the blood, it is also against this yardstick that we measure the efficacy of antiretrovirals: how fast do the CD4 cells recover a normal count (above 500 per mm3 of plasma)? It is of course the most-studied biological indicator since the beginning of the epidemic. But what about these new treatments?

Effective molecules

Using its wealth of data, Costagliola’s team conducted a study on a cohort of over 6,000 people living with HIV and who began antiretroviral treatment between 2006 and 2014. The result: around 70 % of those treated recovered a "normal" CD4 count after 6 years. In addition, with these new drugs the study confirms what we already knew with the other drugs: a high CD4 count at treatment initiation is a good prognosis for recovery. "This once again underlines the issue of late diagnosis: too many patients already have very low CD4 counts (below 200) when they discover the infection, bringing with it a reduced chance of recovery" emphasizes the researcher.

The team also took a closer look at two aspects which had hitherto received little attention. First of all, the new treatments include integrase inhibitors (INIs). These make it possible to obtain rapid control of viral load. In other words, with the INIs the amount of virus present in the plasma very quickly becomes undetectable. But does this rapid elimination represent a genuine benefit for CD4 recovery and patient clinical outcomes? The response is negative: while they shorten by several weeks the period during which the person is potentially infectious (a period often lasting several years prior to diagnosis…), the INIs bring no particular benefit in terms of recovering immune balance.

An important parameter

Another aspect which has often been overlooked until now is the ratio between the CD4 and CD8 counts. "CD8s are a population of lymphocytes implicated in activating immune defenses. A high CD8 count indicates a state of activation and inflammation" explains Costagliola. Yet this study shows that a CD4/CD8 ratio which is altered at the time of treatment initiation – therefore a situation cumulating immunosuppression and inflammation – is reflected by a lower probability of CD4 recovery: the patient will respond to the antiretroviral treatment more slowly. This result is in favor of systematic CD8 counts when patients are admitted to a hospital setting. "This does not incur any additional costs because we have it when we do the CD4 count. It simply needs to be taken into account" states the researcher.

This CD4/CD8 ratio is all the more important given that a consistently high CD8 count is not just linked to the risk of AIDS-related illnesses, such as myocardial infarction. This is what Costagliola’s team has already demonstrated. A young researcher in her laboratory is currently writing a Ph.D. on the prognostic role of the CD4/CD8 ratio, particularly in terms of cancer and other comorbidities…

Note:
* French Hospital Database on HIV FHDH ANRS CO4
** Unit 1136 Inserm/UPMC, Pierre Louis Institute of Epidemiology and Public Health, Clinical epidemiology of HIV infection: therapeutic strategies and comorbidities team, Paris

Source : H. Roul et coll., 2018, CD4 cell count recovery after combined antiretroviral therapy in the modern cART era, AIDS, DOI: 10.1097/QAD.0000000000002010