Neil Canavan

July 10, 2013

KUALA LUMPUR, Malaysia — Total viral suppression and complete immunologic reconstitution has been achieved in patients with chronic HIV, report the VISCONTI investigators.

Their latest data demonstrate that the effect is durable after treatment suspension.

"Our group has recently shown that obtaining a functional cure in some patients is an achievable goal," said Laurent Hocqueloux, MD, from the Centre Hospitalier Régional in Orléans, France, referring to the headline-grabbing VISCONTI study.

"These patients, whom we call post-treatment controllers, are, at the time of treatment interruption, characterized by a weak viral reservoir and a high immune reconstitution. Indeed, the median CD4 count for these patients is around 900 cells/mm³," he explained.

However, the VISCONTI study was not powered to make conclusions about the early treatment of patients in the chronic phase of infection. Dr. Hocqueloux presented these results here at the 7th International AIDS Society Conference on HIV Pathogenesis, Treatment and Prevention.

The researchers conducted a single-center study of 309 people. All patients were treated with combination antiretroviral therapy in the early chronic stage of their infections and had sustained viral loads below 50 copies/mL.

They assessed CD4 and CD8 cell counts, cell-associated HIV DNA levels in peripheral blood mononuclear cells, and HLA B activation markers at multiple time points. For 77 patients (25%), HIV DNA was determined prior to treatment initiation.

The study's primary composite end point was a normal CD4 cell count (≥900 cells/mm³), a CD4/CD8 ratio of 1, and a low HIV DNA level (<2.3 log copies/10¶ peripheral blood mononuclear cells).

At study entry, investigators stratified patients by CD4 count.

Table. Patients Stratified by CD4 Count at Study Entry

Cohort CD4 Count (cells/mm³) Patients (n)
Highest ≥500 30
Middle 200–499 155
Lowest <200 124

 

Participants in the highest cohort were younger (P < .047), had fewer AIDS-related illnesses (P < .001), and had lower viral loads at baseline (P < .004) than those in the middle and lowest cohorts.

Participants in the highest cohort were also significantly more likely to achieve a normal CD4 cell count than those in the middle and lowest cohorts (30% vs 3% vs 0%; P < .001).

Treatment initiation when the CD4 count was at least 500 cells/mm³ was the only statistically significant predictor of achieving a normal CD4 count (P < .001).

Overall, there was a negative correlation between HIV DNA level and CD4 count during suppressive combination therapy (P value not reported), which was strongest when the CD4 count was at least 500 cells/mm³ (P = .003).

"Our results support the paradigm of early treatment," said Dr. Hocqueloux. "Fully one third of the high-CD4 cohort achieved a normal T-cell count and CD4/CD8 ratio."

The presentation was met with no small amount of enthusiasm and a number of pointed questions.

Generating Excitement

Session chair Robert Murphy, MD, professor of infectious diseases at Northwestern University in Chicago, questioned whether these data will have an impact on guidelines, "especially the guidelines in developing countries right now, because the data seem to support it." He noted that the findings might warrant a change in the way patients are followed, and added that perhaps DNA monitoring should become the order of the day.

One audience member asked which regimen, if any, was more likely to lead to a normal CD4 count. Dr. Hocqueloux explained that given the timeframe and the common practice of switching therapies, these data could not answer that question.

Other listeners wanted to know more about the correlation between HIV DNA levels and immune activation, but Dr. Hocqueloux explained that the study was not designed to elicit such data.

Dr. Hocqueloux and Dr. Murphy have disclosed no relevant financial relationships.

7th International AIDS Society (IAS) Conference on HIV Pathogenesis, Treatment and Prevention: Abstract WEAB0102. Presented July 3, 2013.

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