Background:  HIV protease inhibitors (PI) may have immunomodulatory effects independent of their anti-HIV viral activity. We have recently observed that, healthy HIV-negative health care workers increased thymic-derived naïve T cells as seen by an increase in T-cell receptor (TCR) excision circles (TREC) from the peripheral blood after receiving nelfinavir (NFV), zidovudine (ZVD), and lamivudine (3TC) HAART for 28 days for post-HIV-exposure prophylaxis (PEP). With increasing evidence that HIV PI  have intrinsic anti-apoptotic properties, we postulated that NFV-induced reductions in thymic T-cell apoptosis might contribute to the increases in TREC numbers in HIV-negative patients who receive HAART. Consequently, we sought to determine whether HIV PI treatment alone in HIV-negative adults would increase naïve T-cell number as measured by peripheral blood TREC levels.

Methods:  Thymic-derived naïve T-cell levels were determined by TREC in peripheral blood from HIV-negative subjects aged 22 to 95 years. Additionally, TREC analysis was performed at baseline, during and after 21 days of NFV therapy (1250 mg twice daily) in 15 subjects.

Results:  Thymic-derived naïve T cells decreased with increasing subject age with mean baseline TREC levels (TREC copies/copies CCR5 in peripheral blood mononuclear cells) for subjects 39 years or younger, 40 to 65, and 66 years or older were 3.8 x 10³, 1.19 x 10³, and 0.18 x 10³, respectively. TREC copies/copies CCR5 increased following NFV monotherapy in 8 patients (p <0.02), and did not change in 7 patients (p = NS). The subjects who responded were younger than those who did not (p <0.03), and the increase in TREC was most pronounced in patients younger than 40 years old (p <0.01).

Conclusions:  Baseline naïve T-cell numbers from the peripheral blood decrease with increasing age. NFV therapy for 21 days results in a significant increase in thymic-derived naïve T cells in HIV-negative adults.