Response to report from 11th CROI on treatment in primary infection

2 June 2004. Related: Correspondence.

Dr Sarah Fidler

Keith Henry, reporting from the 11th CROI conference, in HTB April 2004, claimed that there is little benefit from treating acute HIV infection. [1]

This conclusion was based upon data presented by Prof. Bruce Walker and his colleagues, who have reported little clinical advantage from antiretroviral intervention with structured treatment interruption (STI) with/without vaccine in small cohorts of treated seroconverters over the past 3-5 years [2]. However, none of these studies have been sufficiently powered to address definitively the role played by antiretroviral treatment in acute HIV infection and none have had a randomised untreated comparison arm. Primary HIV infection is very heterogeneous, and leads to a wide range of clinical outcomes. [3] For example, it is reasonably well established that symptomatic seroconversion carries a worse prognosis than asymptomatic seroconversion. HIV-specific CD4+ T-helper responses have been shown to correlate with good virological control in acute infection [4, 5], and several small studies support the hypothesis that preservation of these CD4+ T-helper responses with early ART may influence virological control. [6-9] However, more recent work has demonstrated limited longevity of these responses, although this remains controversial. [10]

The clinicians’ dilemma as to whether to offer ART intervention in patients presenting with acute HIV infection remains unanswered. The only way to address this is with a large-scale randomised clinical trial appropriately powered to definitively answer this question.

The Spartac trial, is a Welcome Trust funded 5-year multi-centred randomised study, which started in 2004 with sites in the UK, South Africa, Russia and Australia and will answer this question.

Clinicians and patients wishing to find more information about taking part in this study should contact Dr Sarah Fidler [s.fidler@imperial.ac.uk, Tel: +44 20 7594 3903]; or Dr Judy Fox [Tel: 20 7886 1466] or Mr Ken Legg [Tel: 20 7886 6790] at St Marys Hospital clinical trials unit Paddington, London.

References:

1. Henry K – Little benefit seen for treatment during acute infection. HTB May 2004.
2. Kaufman D, Lichterfeld, Altfeld M., et al. Limited durability of immune control following acute HIV infection. 11 CROI 2004 Oral abstract 24.
3. Berrey MM, Schacker T, Collier AC et al. Treatment of primary infection with potent antiretroviral therapy reduces frequency of progression to AIDS. J Infect Dis 2001 183 1466-1475.
4. Rosenberg E, Billingsley JM, Caliendo AM et al. Vigorous HIV-1 specific CD4+ T-cell responses associated with control of viraemia. Science 1997 278 1447-1450.
5. Gloster SE, Newton P, Cornforth D et al. Association of strong virus-specific CD4 T-cell responses with efficient natural control of primary HIV-1 infection. AIDS 2004 18 749-755.
6. Smith D, Walker B, Cooper, D et al. Is antiretroviral treatment of primary HIV infection clinically justified on the basis of current evidence? AIDS 2004 18 709-718.
7. Oxenius A, Price D, Easterbrook P, et al. Early highly active antiretroviral therapy for acute HIV-1 infection preserves immune function of CD4+ and CD8+ T-lymphocytes. PNAS 2000 97 3382-338.
8. Fidler S, Oxenius, A, Brady M et al. Virological and immunological effects of short course antiretroviral therapy in primary HIV infection. AIDS 2002 16 2049-2054.
9. Lillo FB, Ciuffreda D, Veglia F et al. Viral load and burden modification following early antiretroviral therapy of primary HIV-1 infection. AIDS 1999 13, 791-796.
10. Fox J, Scriba, et al. The longevity of HIV specific CD4+ T- helper responses following short course antiretroviral therapy in primary HIV infection. Abstract 211, Molecular mechanisms of HIV pathogenesis Keystone, April 2004.