Slower CD4 cell decline following cessation of a 3 month course of HAART in primary HIV infection: Findings from an observational cohort

Imperial College, St Mary's Hospital, London, UK.
AIDS (Impact Factor: 5.55). 07/2007; 21(10):1283-91. DOI: 10.1097/QAD.0b013e3280b07b5b
Source: PubMed


To investigate the effect of a short course of HAART during primary HIV infection (PHI) on rate of CD4 cell and viral load change.
Data following HAART cessation from 89 individuals (seroconverting 1999-2003) who chose to take a 3 month course of HAART at PHI were compared with 179 untreated controls in CASCADE, using linear and nonlinear random effects models. Participants were non-randomized but frequency matched for age, sex, risk factor, year of seroconversion and presentation within the first 6 months of seroconversion. Time to CD4 cell count < 350 cells/microl and initiation of clinically indicated antiretroviral therapy (ART) were also compared as competing risks.
The rate of CD4 cell decline following therapy cessation appeared significantly slower among treated participants than untreated controls: losses of 51 cells/microl [95% confidence interval (CI), 32-69] and 77 cells/microl (95% CI, 65-89), respectively, 3 years after seroconversion (P = 0.011). Based on extrapolated data, viral loads also differed significantly at this point (4.09 and 4.53 copies/ml, respectively). At 2 years, there was no significant difference in mean viral load levels: 4.31 copies/ml (95% CI, 4.14-4.48) and 4.47 copies/ml (95% CI, 4.28-4.66), respectively. CASCADE seroconverters were more likely to reach CD4 cell count < 350 cells/microl or initiate clinically indicated ART (hazard ratio, 1.45; 95% CI, 1.02-2.05; P = 0.039).
A short course of ART at PHI may delay CD4 cell decline. Confirmation of this requires a randomized clinical trial powered to address definitively the role of ART intervention in PHI (currently underway through SPARTAC).

Download full-text


Available from: Sarah Fidler, Apr 11, 2014

  • [Show abstract] [Hide abstract]
    ABSTRACT: HIV-1 elicits vigorous humoral and cell-mediated responses: these fail to clear the infection but contain viral replication for several years, at the expense of ongoing immune activation and CD4+ T cell loss. Over the past 25 years, several mechanisms by which HIV-1 and other AIDS viruses evade host immune responses have been elucidated. Genetic variability, rapid establishment of a reservoir of latently-infected long-lived CD4+ T cells and resistance to neutralization by antibodies are formidable obstacles to the development of a preventive vaccine. This has been highlighted by the disappointing results of recent efficacy trials. However, this remains an urgent priority, as available prevention strategies have been insufficient to stop the global epidemic. Rare individuals who show no signs of progression after one or two decades of infection indicate that immune control of HIV-1 is possible and may inform vaccine design.
    Medicine 01/2001; 33(7-37):321-325. DOI:10.1016/j.mpmed.2009.03.008 · 4.35 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Treatment of primary HIV-1 infection may alter the natural history of HIV-1 infection and delay the need for chronic antiretroviral therapy; it may also be a public health measure. We discuss the results of therapeutic trials and cohort studies, the occurrence of transmitted drug resistance, and recent findings in terms of immunopathogenesis and decay of viral reservoirs. Events at the time of primary HIV-1 infection are understood to set the scene for persistence of immunologic damage and chronic immune activation, with a rapid viral onslaught primarily on memory CD4 T cells at mucosal effector sites. The initiation of antiretroviral therapy at primary HIV-1 infection has been associated with a high degree of undetectable viremia in compliant patients and substantial decay of reservoirs in peripheral blood. The degree of immune reconstitution at the gut mucosal level, however, does not appear to be comparable to that in peripheral blood. Recent insights into the long-term consequences of the early burst of HIV-1 replication - together with transmitted drug resistance, onward transmission, and the possibility of decay of viral reservoirs - are important steps in helping to design future therapeutic strategies in primary HIV-1 infection in an era of intense drug and vaccine development.
    Current opinion in HIV and AIDS 02/2008; 3(1):67-74. DOI:10.1097/COH.0b013e3282f31d4b · 4.68 Impact Factor
Show more