AIDS treatment in an out of gender

aids treat part one

A dendritic cell


Although the decrease is not sufficient, the first therapeutic AIDS vaccine, designed from the dendritic cells of the actual patients by the Hospital Clinic of Barcelona-IDIBAPS in the framework of the HIVACAT, the Catalan programme for the development of therapeutic vaccines and prevention against the Human Immunodeficiency Virus (HIV), has achieved a significant response in the majority of patients.

The trial I results of the study (three more will come), which counted on an international collaboration with teams from France, the Hôpital Pitié-Salpêtriére and the Université Pierre et Marie Curie in Paris/INSERM,  and the USA, the National Institute of Cancer in Maryland, have been just published in the International Journal of Infectious Diseases.

The final aim of the therapeutic vaccine is to minimize the use and to avoid a life long treatment with antiretroviral drugs that, because of their expensive and a life long administration, bring about a great economic burden. Besides, there is no experience over the long term and it is not known if the treatments could bring about resistance, which they happen to do if not well taken, while some of them have proved to bring about side effects (for instance cardiovascular diseases.

“AIDS is unique among the infectious diseases since it is the only one that we cannot cure in spite of having very good drugs”, says Teresa Gallart, immunologist at the Hospital Clinic and one of the 17 authors of the study (9 women and 8 men).

The antiretroviral therapy suppresses the virus but if one stops taking it, in one week it can go back up with the same or even more strength then before.

“Nevertheless we know there is an immune response because some people, whom we call controllers, are in fact able to control the disease without taking antiretroviral treatments but only through their immune system, which means it is possible to do it. If we were able to increase sick people’s immune response we could also have them controlling the virus and not having to take so many drugs. So they could hopefully rest at least for some years from antiretroviral drugs”, she says.

That is why they decided to use the patients’ dendritics, immune cells already used to increase the immune response against cancer because of their role as patrollers of the body’s borders in search of pathogens and then starters of the response.

“This virus is so smart that it uses this function of the dendritic cells so that, when they get to the TCD4 cells, the main virus target, they pass the virus to them and there it starts replicating, making TCD4 drop until there is almost none left and any infection can therefore take place”.

The vaccine, personalized, was made from the dendritic cells of each patient sensitized in the laboratory against an inactive form of their own virus.

A total of 24 patients, none of whom received antiretroviral treatment, participated in this double blind clinical trial. Half of them formed the control group and did not receive the vaccine.  The great majority of the patients (83%) were men and the median age was 40. In 67% of patients, the risk factor of HIV infection was men who had sex with men.

On the low representation of women both Gatell and Felipe García from the Infectious Diseases Unit of IDIBAPS – Hospital Clinic, co-author of the study, say that “those who entered the study were those wanting to participate and who satisfied the criteria” (not taking antiretroviral drugs and to maintain a good T lymphatic blood load (>450 per mm3). “In a pilot study such as this”. García adds in his email, “patients are few and this might mean they won’t be representative of the population”. Gatell underlines that the research group has not thought of considering sex and gender as a relevant element to take into account in this study. “This gives a hint on how masculinized we are…But actually I think that women would need to be taken more into account in a preventive rather than in a therapeutic vaccine, especially one as this where one’s own cells are used”.

The reason why a vaccine might need to take into account both men and women is that evidence shows that after a HIV infection women present a lower viral load but a faster progression toward AIDS and worse outcomes than male seroconverters (Padian, 1997; Farzadegan, 1998; Moore, 2003;…). Moreover differences in the immune functions among male and female have also been shown. Finally physiological and morphological variations among male and female have proven to bring to different pharmacokinetics and pharmacodynamics, with women twice as more likely to present adverse drug reactions then men (see When sex matters for references on this issue).

Nevertheless more recent studies (I will dedicate a specific post to them) suggest that despite the fact that women present higher CD4+ cell counts and lower viral loads after a HIV infection, their subsequently experiencing significantly more combined HIV-related and AIDS defining events cannot be explained through biology.

According to the 2010 UNAIDS report in Spain there around 130 thousand people living with HIV, 25% of whom are women.

One year after receiving three dosages of the vaccine -with an interval of two weeks between each one- the majority of the patients showed an increase in their immune defences while in the whole population there had been a three times average reduction in the viral load. In no case did the virus become undetectable.  However, no therapeutic vaccine before had achieved the same level of response as in this study. The authors of the study estimate the vaccine could cost between 2 and 3 thousand euros while antiretroviral therapy costs between 8 and 9 thousand per year.

The results of the phase II trial (involving patients who do take antiretroviral treatments and stop after taking the vaccine) will be published at the end of the year when the ongoing observation period will come to an end.

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