Background:  Survival of HIV-1-infected infants into adulthood has become increasingly common with the availability of combination ART. We previously reported that these long-term survivors generally have CD4⁺ T cell counts, thymus volume, and T cell receptor recombination excision circle (TREC) values that are similar to uninfected young adults, even though most developed significant immunodeficiency prior to the availability of ART. However, these subjects displayed surprisingly vigorous persisting cellular immune responses against HIV-1 in the absence of detectable HIV RNA, suggesting substantial ongoing HIV-1 replication.

Methods:  We examined 20 adolescent and adult survivors of HIV-1 infection acquired perinatally (n = 18) or by neonatal transfusion (n = 2) for evidence of ongoing viral replication:  16 had prior CDC class B or C disease. All were receiving ART with viremia <400 copies/mL for at least 1 year. Thymic size was determined with volumetric computed tomography scans. TREC and HIV-1 DNA levels were quantified by real-time polymerase chain reaction (PCR), CD4⁺, CD8⁺, HLA-DR⁺/CD38⁺/CD8⁺, and CD45RA⁺/CD27⁺/CD4⁺ T cells by flow cytometry, and plasma interleukin-7 (IL-7) levels by ELISA. HIV seronegative subjects (18) served as controls.

Results:  The adolescent and adult survivors (n = 20) were slightly younger than the controls (mean 17.6 vs 20.6 years), but had similar thymus volume (20.2 vs 15.4 mL, p >0.05). CD4⁺ T cell percentages were higher in the control group than the adolescent and adult survivors (37.1% vs 25.3%, p =0.0007), but mean total and naïve CD4⁺ T cells and TREC were indistinguishable. The adolescent and adult survivors had a higher percentage of activated CD8⁺ T cells than controls, and high mean HIV-1 DNA viral load (3.7 logs/million CD4⁺ T cells). There was an inverse correlation between plasma IL-7 levels and total (r = –0.52, p = 0.02) and naive (r = –0.47, p = 0.037) peripheral blood CD4⁺ T cell concentrations in the adolescent and adult survivors group, suggesting limitations in IL-7 and T cell regeneration in these subjects under the stress of ongoing HIV replication. In contrast, IL-7 levels were unrelated to T cell numbers in the control group. Lymphocyte proliferation responses to phytohemagglutinin stimulation and candida and tetanus antigens were significantly lower in the adolescent and adult survivors compared to controls (p = 0.05, 0.01, 0.04).

Conclusions:  IL-7-mediated homeostatic mechanisms may be involved in the maintenance of thymopoiesis and T cell populations in adolescent and adult survivors; intensified ART may be needed to optimize their immunological function.