Highly active antiretroviral therapy restores in vitro mitogen and antigen-specific T-lymphocyte responses in HIV-1 perinatally infected children despite virological failure

Abstract

SUMMARY To analyse the effect of highly active antiretroviral therapy (HAART) on T-lymphocyte functions we selected seven HIV-1 perinatally infected children (CDC immunological category 1 or 2) who had neither a fall in their plasma HIV-1 RNA levels nor a significant rise in CD4+ lymphocyte counts while receiving HAART. Clinical signs and symptoms were monitored monthly. Plasma viral load, CD4+, CD8+, CD19+ lymphocyte counts and in vitro T-lymphocyte proliferative responses to mitogens (anti-CD3, phytohaemoagglutinin, concanavalin A and pokeweed mitogen) and recall antigens (Candida albicans and tetanus toxoid) were tested at baseline and after 1, 3, 6 and 12 months of HAART. Twenty-two healthy age-matched children were studied as controls. A gain in body weight, no worsening of the disease and no recurrence of opportunistic infections were observed. At baseline, the majority of the children had low responses to mitogens, and all of them had a defective in vitro antigen-specific T-lymphocyte response (<2 standard deviations below the mean result for controls). During HAART, a significant increase in the response to mitogens and antigens was observed in all the patients. The T-lymphocyte response was restored more consistently against antigens to which the immune system is constantly exposed (Candida albicans, baseline versus 12 months: P < 0·001) compared with a low-exposure antigen (tetanus toxoid, baseline versus 12 months: P < 0·01). HAART restores in vitro T-lymphocyte responses even in the absence of a significant viral load decrease and despite any significant increase in CD4+ lymphocyte counts. It implies that a direct mechanism might be involved in the overall immune recovery under HAART.

Programmed Death 1 Receptor ChangesEx Vivoin HIV-Infected Adults following Initiation of Highly Active Antiretroviral Therapy

“…This is consistent with previous reports (20,21) and may serve as evidence of early signs of immune recovery. We also observed a decrease in PHA-induced proliferation when expressed as net cpm; however, when expressed as SI, PHA induced proliferation was unchanged by HAART.…”

Immune Failure in the Absence of Profound CD4+T-Lymphocyte Depletion in Simian Immunodeficiency Virus-Infected Rapid Progressor Macaques

“…Levels of p24 proliferative responses positively correlate with Gag-specific CTL frequencies and negatively correlate with plasma viral load, suggesting a causal relationship between these parameters (21,22,32,34,40). Such patients also exhibit a reduced ability to respond to non-HIV antigens such as tetanus toxoid, and these responses are partially restored by antiviral therapy (38,48). A similar loss in proliferative capacity of CD4 ϩ T cells has been observed early in disease course in SIV-infected macaques (26), and proliferative responses inversely correlate with plasma viremia.…”

Two-Year Clinical and Immune Outcomes in Human Immunodeficiency Virus–Infected Children Who Reconstitute CD4 T Cells Without Control of Viral Replication After Combination Antiretroviral Therapy

“…7,9,10,12 Children who develop immune reconstitution despite viral rebound have clinical disease progression rates that are lower than those of historical control groups with similar viral levels. 9,10,12,13 We studied the longterm outcomes of growth, prevalence of HIV-associated illnesses, and immune function among children who display discordant immune and viral responses to combination antiretroviral therapy (viral failure/ immune success [VF/IS]) compared with children who have similar pretherapy viral burden and CD4 T-cell counts and have optimal viral and immune response to combination antiretroviral therapy (viral success/immune success [VS/IS]) as well as with those who failed therapy (viral failure/immune failure [VF/IF]).…”