Important note: Information in this article was accurate in January 1999. The state of the art may have changed since the publication date.AIDSWEEKLY Plus; Monday, January 11, 1999
Daniel J. DeNoon, Senior Editor
Vaccination or immune therapy appears to be a needed adjunct to highly active antiretroviral therapy (HAART).
Longitudinal studies of eight patients on successful HAART show that HIV specific cytotoxic T-lymphocyte (CTL) responses decay rapidly after treatment. Decay of immune control of HIV may be an important factor in the emergence of drug-resistant virus and treatment failure.
"An implication of this study is that boosting of HIV specific CTLe [effector CTL] by posttreatment vaccination or immunotherapy with cytokines may be an important adjunct to antiretroviral therapy," suggested Oxford University researcher G.S. Ogg and colleagues. "Such strategies could provide a means to maintain effective immunological control of potentially resistant virus."
Ogg et al. reported their findings in the Journal of Virology ("Decay Kinetics of Human Immunodeficiency Virus-Specific Effector Cytotoxic T Lymphocytes after Combination Antiretroviral Therapy," J Virol, 1999; 73(1):797-800).
The U.K./U.S. research team followed eight patients with human leukocyte antigen (HLA) phenotypes A*0201 or B*3501. They used synthetic HLA A*0201 or B*3501 tetramers with immunodominant HIV peptides to test for HIV specific CTL.
The patients had all been infected within 120 days of infection. All received HAART with zidovudine (AZT), lamivudine (3TC), and a protease inhibitor (ritonavir, nelfinavir, or indinavir). None were treated prior to seroconversion; five were treated while still asymptomatic.
All eight patients had a drop in viral load to undetectable levels which was maintained throughout the study (<500 copies/mL).
Soon after beginning HAART the patients exhibited rapid fluctuations in their HIV specific CTL responses. These fluctuations lasted for 1 to 2 weeks and were followed by an exponential decay with a median half-life of 45 days. Twenty-month follow-up of one patient, who prior to treatment had very high levels of HIV specific CTL, confirmed that this decay half-life remained constant.
"Given the prolonged decay time course, the CTLe fall is unlikely to be explained by redistribution from peripheral blood but instead is more consistent with a real loss of such activated effector CTL," Ogg et al. wrote.
The researchers noted that patients treated with HAART after HIV infection but prior to seroconversion maintain HIV specific T-cell responses. They suggested that the failure of patients treated during chronic infection to maintain such responses offers at least a partial explanation of why virus levels rise so rapidly upon emergence of drug-resistant strains.
This work was supported by grants from the NIH and the General Clinical Research Center and by the Wellcome Trust.
The corresponding author for this study is A.J. McMichael, Institute of Molecular Medicine, Nuffield Department of Medicine, Oxford OX3 9DS, United Kingdom. Phone: 44 1865 222336. Fax: 44 1865 222502. Email: <andrew.mcmichael@ndm.ox.ac.uk>.
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