NATAP: CTL Activity & HIV Progression

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Effector CTL activity an ominous sign in long-term HIV nonprogressors

By Rauscher

NEW YORK (Reuters Health) - Effector cytotoxic T-lymphocyte (CTLe) activity

may be an early warning sign of progression in individuals with long-term

asymptomatic HIV infection, according to new data from the Australian Long-Term

Nonprogressor cohort.

Dr. Keoshkerian from Sydney Children's Hospital and colleagues

investigated CTLe activity in 27 long-term nonprogressors (LTNPs) - individuals

with HIV who have stable high CD4 counts (>500 cells per microliter) and who

remain asymptomatic for more than 8 years.

" LTNPs are an important group to study as they control infection without

intervention and thus provide valuable information on disease progression and

how

it is influenced by immunological, virological, and genetic factors, " Dr.

Keoshkerian said.

Nineteen of the 27 LTNPs had no detectable effector CTL activity, the

investigators report in the December Journal of Medical Virology.

The eight patients with detectable CTLe activity had " broadly directed

activity that was not specific for any particular region of the HIV genome, " Dr.

Keoshkerian told Reuters Health.

CTLe activity was associated with higher plasma levels of HIV-1 RNA (p =

0.014), p24 antigen (p = 0.006), and beta2-microglobulin (p = 0.009).

Of note, " CTLe activity and viral load were associated with an increased risk

of disease progression (i.e., loss of LTNP status) within 4 years of study

entry, " Dr. Keoshkerian said.

She and colleagues believe this is the first study of LTNPs to show a link

between CTLe activity, viral replication, and loss of LTNP status.

Dr. Keoshkerian suggested that " detection of CTLe activity and increasing

viral load may be used as a predictive marker for disease progression in LTNPs, "

although longitudinal studies are needed.

J Med Virol 2003;71:483-491.

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