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CD4 Counts May Bounce Back, but Does Immunity?
  Internet Use and Early Syphilis Infection Among Men Who Have Sex with Men --- San Francisco, California, 1999--2003
AIDS Clinical Care, December 2003
By G. Sonia Nagy, MD
HIV-infected patients with good CD4-cell count responses to therapy had a poorer response to common immunizations compared with HIV-negative controls.

Whether the gains in CD4-cell counts that come with potent combination antiretroviral therapy are indicative of fully restored immunity remains unclear: Do reconstituted immune cells respond to antigenic challenge to the same extent as native immune cells? To address this question, researchers conducted an open-label, prospective, case-control study of response to immunizations in HIV-infected patients with good immunologic response to antiretroviral therapy.
Investigators at an urban HIV clinic enrolled 32 patients with CD4 counts >450 cells/mm3 and viral loads <400 copies/mL for the previous year while taking at least three antiretroviral drugs. Cases and 10 age-matched controls received diphtheria/tetanus toxoid (DT) intramuscularly and keyhole limpet hemocyanin (KLH) intradermally on days 3 and 31. Lymphocyte proliferation and serologic responses (tetanus, diphtheria, and KLH IgG antibodies) were measured twice before immunization and on days 17, 31 and 59. Delayed-type hypersensitivity (DTH) responses to Candida albicans antigens were measured 48 to 72 hours after intradermal administration. Researchers assessed immune responses and created one score of all immune responses from baseline, a second score that excluded the response to tetanus (because some patients may have had baseline immunity), and a third score that excluded all baseline scores, and divided all positive immune responses by all possible responses.
Overall, 28 cases completed the protocol. Although all cases and controls had protective levels of antibody to DT at baseline, cases had lower levels of antibody than controls by the last evaluation (day 59). No cases or controls had protective levels of KLH antibodies at baseline, and the response at day 59 was lower in cases than in controls. Response to DTH skin test was lower in cases than in controls at baseline, but was similar at day 59. By univariate analysis, CD4 nadir <250 cells/mm3and reduced presence of CD28-expressing CD4 cells were significantly asscocuiated with diminished responses to immunization for each of the 3 immune scores. There was no association between baseline CD4-cell count and any of the immune response scores.
These patients were carefully selected and had been successfully treated, with excellent immune reconstitution and virologic suppression. The findings are intriguing and suggest that immune recovery on antiretroviral therapy may be incomplete and that loss of native CD4 cells before initiating therapy may have lasting effects on immune function, even in the setting of successful therapy by current measures. Further studies are needed to determine whether there is an absolute CD4 nadir below which immune reconstitution may be permanently impaired. In addition, longer follow-up will be needed whether such "subclinical" immunodeficiency has any specific medical consequences.
Dr. Nagy is Assistant Professor of Medicine at Mt. Sinai Medical School.
Lange CG et al. Nadir CD4 + T-cell count and numbers of CD28+ CD4+ T-cells predict functional responses to immunizations in chronic HIV-1 infection. AIDS 2003; 17:2015-23.
Nadir Cd4 Count May Predict Immunity: Nadir CD4+ T-cell count and numbers of CD28+ CD4+ T-cells predict functional responses to immunizations in chronic HIV-1 infection.
The authors concluded: “Even among persons who controlled HIV replication and normalized CD4 T-cell counts with HAART, pretreatment CD4 T-cell count and numbers of circulating CD4+CD28+ T-cells at immunization, but not current CD4 T-cell count, predict the ability to respond to vaccination. Delaying the initiation of HAART in chronic HIV-1 infection results in impaired functional immune restoration despite normalization of circulating CD4 T-cell numbers”.
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