BACKGROUND: Although highly active antiretroviral therapy has significantly reduced morbidity and mortality in HIV-infected children, it often fails to completely suppress viral replication, thereby allowing the emergence of drug-resistant variants. Protease inhibitor (PI) based therapy has been hypothesized to depress cell-mediated immune responses by reducing antigen presentation. OBJECTIVES: To determine the effects of partial treatment interruption (PTI) of PI on HIV-specific cellular immune responses in children. METHODS: We conducted a retrospective longitudinal study of HIV-specific cellular immune responses in 13 children who were vertically infected with HIV. All had detectable plasma viremia and had undergone PTI for a median of 1.0 year (range, 0.41-3.35 years) while continuing nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor therapy. RESULTS: No significant changes in viral load were observed in the immediate time-point before and during PTI (P = 0.84) as well as in the overall period before and during PTI (P = 0.17). CD4 T-cell levels declined slowly immediately before and during PTI (P = 0.07) as well as during the overall PTI period (P = 0.0002), but the rate of CD4 T-cell decline was not significantly increased during PTI. Immediate to PTI, HIV-specific CD4 and CD8 T-cell responses increased by 70% (P < 0.0001) and 92% (P < 0.0001), respectively, and CD4 and CD8 T-cell activation levels (P = 0.6834 and P = 0.6081, respectively) remained unchanged. CONCLUSION: HIV-specific cellular immune responses are boosted in children who have interrupted PI-based therapy.
BACKGROUND: Although highly active antiretroviral therapy has significantly reduced morbidity and mortality in HIV-infectedchildren, it often fails to completely suppress viral replication, thereby allowing the emergence of drug-resistant variants. Protease inhibitor (PI) based therapy has been hypothesized to depress cell-mediated immune responses by reducing antigen presentation. OBJECTIVES: To determine the effects of partial treatment interruption (PTI) of PI on HIV-specific cellular immune responses in children. METHODS: We conducted a retrospective longitudinal study of HIV-specific cellular immune responses in 13 children who were vertically infected with HIV. All had detectable plasma viremia and had undergone PTI for a median of 1.0 year (range, 0.41-3.35 years) while continuing nucleoside reverse transcriptase inhibitor and non-nucleoside reverse transcriptase inhibitor therapy. RESULTS: No significant changes in viral load were observed in the immediate time-point before and during PTI (P = 0.84) as well as in the overall period before and during PTI (P = 0.17). CD4 T-cell levels declined slowly immediately before and during PTI (P = 0.07) as well as during the overall PTI period (P = 0.0002), but the rate of CD4 T-cell decline was not significantly increased during PTI. Immediate to PTI, HIV-specific CD4 and CD8 T-cell responses increased by 70% (P < 0.0001) and 92% (P < 0.0001), respectively, and CD4 and CD8 T-cell activation levels (P = 0.6834 and P = 0.6081, respectively) remained unchanged. CONCLUSION: HIV-specific cellular immune responses are boosted in children who have interrupted PI-based therapy.
Authors: Frances L Wong; Alice J Hsu; Paul A Pham; George K Siberry; Nancy Hutton; Allison L Agwu Journal: Pediatr Infect Dis J Date: 2012-12 Impact factor: 2.129
Authors: Ravi Tandon; Maria T M Giret; Devi Sengupta; Vanessa A York; Andrew A Wiznia; Michael G Rosenberg; Esper G Kallas; Lishomwa C Ndhlovu; Douglas F Nixon Journal: PLoS One Date: 2012-09-24 Impact factor: 3.240
Authors: Aaruni Khanolkar; William J Muller; Bridget M Simpson; Jillian Cerullo; Ruth Williams; Sun Bae Sowers; Kiana Matthews; Sara Mercader; Carole J Hickman; Richard T D'Aquila; Guorong Liu Journal: Commun Med (Lond) Date: 2022-03-04