Might Treatment-On-Infection Allow For Treatment Interruption?

Study Questions Hypothesis That Early Intervention Provides Greater HIV Control

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In March 2013, French scientists with the on-going Visconti Study reported that 14 out of 70 patients in their study were able to maintain fully suppressed (undetectable) viral loads without treatment after having been prescribed antiretrovirals within ten weeks of infection. Of the 14 able to sustain viral control—some for up to seven years—CD4 counts were reported to have increased from an average of 500 cells/mL to 900 cells/mL.

The news seemed to support the hypothesis that treatment during the early (acute) stage of infection could provide a benefit in terms of greater viral control and immune stability—so much so, in fact, that the need for antiretrovirals might no longer be necessary.

Some had postulated that early intervention might prevent the establishment of so-called "latent reservoirs"—essentially cellular hiding places—where HIV can lie dormant for years, only to re-emerge (or "rebound") later when an opportunity presents itself. 

It was suggested that by preventing these reservoirs from taking hold, rebound as we know it might not occur simply because there are few "hidden" HIV to mount an attack should a treatment either fails or be stopped.

Testing the Early Intervention Hypothesis

In a 2014 study published in the medical journal AIDS, researchers from the French PRIMO cohort study decided to test the theory by retrospectively analyzing 727 patients, all of whom had a known date of infection.

Of those included in the investigation

  • 265 started treatment early and maintained uninterrupted adherence during the course of therapy;
     
  • 244 started treatment soon after infection but interrupted treatment either once (53%) or more than once (47%), and;
     
  • 218 deferred treatment of an average of 2.5 years but had no treatment interruptions during the course of therapy.

    Median time from infection ranged from 6.1 years for the deferred group to 9.5 years for those with treatment interruptions.

    Not surprisingly, the early starters who maintained adherence fared best, with current CD4 counts averaging a healthy 731 cells/mL.

    By contrast, neither of other two groups had significant difference in their immune status. While the deferred group did have a higher, average CD4 count at the time of diagnosis compared to early/intermittent group (554 versus 471), their current CD4 was practically the same (654 versus 645).

    Furthermore, the early starters on continuous therapy were seen to have far better CD4/CD8 ratios (the ratio of which measures the deterioration of the immune response as CD4 cells are depleted). Among this group, 64 percent were able to achieve a CD4/CD8 ratio over 1.0, considered within the "normal" range.

    Meanwhile, only 40 percent of those who deferred treatment and 36 percent who started early but interrupted therapy were able to achieve similar results.

    What Does This Actually Tell Us?

    While the study doesn't dispel the benefits of early treatment—both in terms of immune reconstitution and disease avoidance—it does seem to undermine the conceit that early intervention might afford some with lasting, if not permanent, viral control.

    It is important to note that the research did not evaluate the association between HIV viral load and early intervention. One such investigation, which analyzed data from the on-going Swiss HIV Cohort Study (SHCC), showed that individuals treated during acute infection, who then stopped treatment after 18 months, had only transient benefit in term of reduced viral loads. The investigators noted that, by 36 months, average viral loads had rebounded to more or less the same level as those who had not been treated.

    Sources:

    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 Pathology. March 14, 2013; 0(3):e1003211.

    Seng, R.; Goujard, C.; Krastinova, E.; et al. "Influence of lifelong cumulative HIV viremia on long-term recovery of CD4+ count and CD4+/CD8+ ratio among patients on combination antiretroviral therapy." AIDS. January 13, 2015; published ahead of print; DOI: 10.1097/QAD.0000000000000571.

    von Wyl, V.; Gianella, S.; Fischer, M.; et al. "Early antiretroviral therapy during primary HIV-1 infection results in a transient reduction of the viral setpoint upon treatment interruption." PLoS|One. November 15., 2011; 6(11):e27463.

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