Even the researchers admit any definitive conclusions must await more rigorous investigation. But on the eve of World AIDS Day the news of a possible novel, less onerous, and much more affordable approach to the treatment of HIV infection splashed across news sites worldwide. (Well, more in Africa, Asia and Europe than in the U.S. Three days into the weekend announcement, in fact, there was nary a word from the Gray Lady, the Washington Post or even the Wall Street Journal.)
An exciting if simplistic version of the story would go something like this: researchers in France announced that immunization of a small group of HIV-infected individuals with a personally tailored cellular therapy (sometimes called a therapeutic or treatment “vaccine”) resulted in CD4 cell rises and drops of plasma virus on the order of 80% which persisted for more than 3 months after only one series of immunizations. In close to half the study volunteers, levels of plasma virus dropped by over 90%, and these viral load reductions persisted for one year or more. Not only did CD4 cell counts “increase significantly” (although no numbers are apparent in published paper) and plasma HIV RNA levels fall, but so did cell-associated HIV DNA, the virus’ genetic code that hides inside infected cells and instructs them to pump out more virus.
The cell therapy preparation was tailor made for each of the 18 individual study participants — from his or her own immune system dendritic cells along with a chemically inactivated form of his or her host HIV.
A more sober take on the published results might point out the following: The number of people in the study was very small and, more importantly, there was no control (or comparator) group. To be eligible for the study, people had to be off all antiretroviral therapy — and virologically “stable” — for six months. So how exactly were these individuals identified and recruited? And how might they have fared even without the cell therapy?
Co-investigators Jean-Marie Andrieu and Louis Wei Lu note that while trial volunteers’ plasma viral loads had been stable prior to immunization, they lost an average of 100 CD4 cells over those six months. Once they got the vaccine treatment, CD4 cell counts “increased significantly” — at least until the totemic Day 112. Which begs an additional question: what happened at Day 112? According to the Nature Medicine paper, CD4 cell counts began to fall (and “returned progressively to baseline” values) and viral control flagged in several individuals. Was this simply an artifact of the study’s design? Or had it something to do with the actual response to the therapy?
The only reported side effect of the treatment was an increase in the size of peripheral (groin and armpit) lymph nodes, of 3- to 5-fold (from 0.33 cm at study entry to 1.50-1.70 cm days 28 to day 224 — and 1.0 cm at one year).
The so-called “Good Responders” in the study, presumably the 8 of 18 who appeared to control virus for an entire year after immunizations, had entry CD4 cell counts of 450 cells/ml or greater — and, as previously noted, were controlling virus off ARV therapy for a full six months prior to study entry. So just how representative of the average HIV+ person in need of treatment were they? Finally, since each person’s therapy was hand tailored to his or her own virus and cells, it is unclear how this type of treatment could be rolled out on a mass scale anytime soon — even if it were to prove effective in broader testing. (Although Andrieu writes that the treatment could be available for “routine use” before 2008.) Stay tuned.
- Nature Medicine online, 28 November 2004: “Therapeutic Dendritic-cell Vaccine for Chronic HIV-1 Infection”
- Le Monde, 29 November 2004: “Un espoir de vaccin thérapeutique pour les séropositifs”