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CD4 Counts May Bounce Back, but Does Immunity?

AIDS Clinical Care, December 2003

By G. 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.

ORIGINAL ARTICLE- NATAP Review

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

<A HREF= " http://www.natap.org/2003/sept/093003_8.htm " >

http://www.natap.org/2003/sept/093003_8.htm</A>

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 numbersâ€.

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