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The mystery of the Visconti study

Researchers in France reviewed several databases and analysed medical records of HIV-positive participants and found 14 people who were treated very early in the course of their infection. These participants later interrupted ART and for the most part their subsequent viral loads were relatively low (less than 400 copies/ml), and they did not need to resume therapy. This French study is called Visconti and presents an interesting finding. However, at this time there is no firm evidence that in the future such an outcome would be likely with the vast majority of HIV-positive people given very early treatment. Certainly Visconti did not cure anyone. Instead, the Visconti results should be viewed as an important finding that raises many research questions that could form the basis for further experiments in the laboratory and perhaps in clinical trials of a robust statistical design.

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Study details

Researchers presented results from 14 people (10 men and four women) who had initiated ART very early in the course of their infection (called primary HIV infection) between 1996 and 2002.

Twelve of the 14 people had symptoms of primary HIV infection (these are similar to those of a flu-like illness). Primary HIV infection was generally estimated to have occurred between one and two months after exposure to the virus.

Participants were given the standard of care at the time they sought medical attention. We do not have information on the specific regimens used, but they were mostly a combination of two nukes (nucleoside analogues) and a protease inhibitor.

At the time of primary HIV infection, before starting ART, their average viral load was 100,000 copies/ml and average CD4+ counts were just over 500 cells.

Within a few months after starting ART, viral loads fell to less than 50 copies/ml and CD4+ counts rose to just over 900 cells.

Participants remained on ART for about three years before interrupting treatment for unknown reasons.

Following treatment interruption, eight of 14 participants maintained a very low viral load at subsequent tests; their viral loads in the blood ranged between 1 and 39 copies/ml.

In the case of the remaining six participants, viral loads in the blood ranged from less than 40 copies/ml to 400 copies/ml. In a few cases, on several occasions viral loads were greater than 400 copies/ml but usually returned to less than 400 copies/ml after some time.

The last available CD4+ counts generally were elevated, ranging from 441 cells in one participant to nearly 1,600 cells in another.

Extensive laboratory testing was done on blood samples from participants. Mostly this testing revealed unexpected results:

Genetics

Participants did not appear to carry genes that researchers associate with good virologic control of HIV. Moreover, several participants had genes associated with the rapid development of AIDS, so the fact that they were ultimately able to keep their viral loads suppressed without ART was remarkable.

CD8+ cells

These are important cells for controlling infections and are used by the body to destroy HIV-infected cells. However, the CD8+ cells taken from participants had, according to researchers, only a “poor” ability to suppress HIV.

Infected cells

In eight participants for whom the researchers had data, the proportion of HIV-infected cells in the blood remained more or less the same in two participants, increased in one and decreased in five others despite the absence of treatment. Overall, this suggests that among these five participants, the reservoir, or burden, of HIV-infected cells was “very small,” according to the research team.

It is noteworthy that none of the 14 people in the Visconti study had been cured. However, for the most part they have been able to keep their viral loads relatively low without having to reinitiate ART. The precise mechanism underpinning these remarkable results remains a mystery but French researchers are actively trying to find out.

Issues related to Visconti (and similar studies) appear in the next report.

—Sean R. Hosein

REFERENCES:

  1. Sáez-Cirión A, Bacchus C, Hocqueloux L, et al. Post-treatment HIV-1 controllers with a long-term virological remission after the interruption of early initiated antiretroviral therapy ANRS VISCONTI study. PloS Pathogens. 2013 Mar;9(3):e1003211.
  2. Hamimi C, Pancino G, Barré-Sinoussi F, et al. Will it be possible to live without antiretroviral therapy? Current Opinion in HIV/AIDS. 2013; in press.
  3. Sáez-Cirión A, Hamimi C, Bergamaschi A, et al. Restriction of HIV-1 replication in macrophages and CD4+ T cells from HIV controllers. Blood. 2011 Jul 28;118(4):955-64.
  4. Lamine A, Caumont-Sarcos A, Chaix ML, et al. Replication-competent HIV strains infect HIV controllers despite undetectable viremia (ANRS EP36 study). AIDS. 2007 May 11;21(8):1043-5.