Little benefit seen for treatment during acute infection
Keith Henry, thebody.com
Bruce Walker walked across the hall from the immune response session (featuring four Walker-linked studies) to present an update on his highly visible and often-presented small study of patients treated during primary infection who subsequently underwent several sequential treatment interruptions (STIs).
The initial results from the study (3/8 maintained <5,000 copies HIV RNA after the first STI and 5/8 maintained <5,000 copies/mL after the second STI) suggested that very early antiretroviral therapy during primary infection, followed by a series of brief treatment interruptions, could lead to improved immune control of HIV off therapy. Those results have stimulated the practice of treating primary infection and spawned enthusiasm that immunologic interventions (such as therapeutic vaccination) could also be utilised in chronic infection.
Dr Walker then presented the longitudinal data for 14 patients (all had acute retroviral syndrome) followed for an average of 5.3 years including for up to three years after the last STI. Only 1/14 of the patients had maintained control of viraemia (defined as <5,000 copies RNA/mL). The second and third STI failed more quickly, with the fourth STI providing no observable benefit.
The rate of CD4 count loss when antiretroviral therapy was stopped was quite high and it was not much different from the CD4 loss observed when stopping antiretroviral therapy in the setting of chronic infection. Dr Walker then discussed what factors could be identified that could predict the control of viraemia. They had looked at HLA type, CCR5 status, GBV-C infection, time of treatment since onset of ARS symptoms, viral load at seroconversion, and anti-HIV immunity from CD4+ or CD8+ T-cells. None of those factors predicted control of viral rebound.
Particularly disappointing was the observation that, although anti-HIV immunity appeared to be enhanced with the STIs, this did not translate into observable clinical benefit. These results were interpreted to indicate that durable maintenance of low-level viraemia might be difficult to achieve. The CD4 declines were substantial with immune escape at even low viral loads sufficient to be a problem.
In a question to Dr Walker, Joe Eron made the comment that the window to perhaps protect anti-HIV immunity during primary infection may be vanishingly short. Another questioner pointed out that the definition of failure (confirmed viral load >5,000 copies/mL or one level >50,000) made it difficult to perhaps see some attenuation in the true magnitude of viral rebound. Although Dr Walker stated that randomised clinical trials of early treatment and immune interventions are needed, the enthusiasm about the potential for this to achieve much has waned.
In all, the different presentations on acute infection suggested that we could do much better in finding and preventing recent infections. Although discussed a lot, superinfections still seem to be relatively unusual but are a growing problem. And it’s still unclear how helpful treatment during acute infection is.
Kaufmann D, Lichterfeld M, Altfeld M et al. Limited durability of immune control following acute HIV infection. 11th CROI 2004, Oral abstract 24.