Impact of Therapeutic Immunization on HIV‐1 Viremia after Discontinuation of Antiretroviral Therapy Initiated during Acute Infection

Abstract

Treatment strategies that would induce durable virological control of human immunodeficiency virus (HIV)-1 in the absence of continued antiretroviral therapy (ART) are highly desirable.METHODS. We assessed, in a randomized, double-blind, placebo-controlled trial, whether the addition of therapeutic vaccines (ALVAC-HIV [vCP1452] or ALVAC-HIV and Remune) to ART initiated during acute infection could increase the probability of having a plasma viral load </=1000 HIV-1 RNA copies/mL 24 weeks after planned discontinuation of ART.RESULTS. All 79 randomized subjects completed the immunization schedule, and 78 discontinued ART with no major safety concerns. After immunization, subjects in the vaccine study arms had significantly increased HIV-1-specific CD4(+) and CD8(+) T cell responses, by interferon- gamma enzyme-linked immunospot assay, compared with those in the placebo study arm. Overall, 17.7% of subjects had </=1000 HIV-1 RNA copies/mL 24 weeks after discontinuation of ART, with no significant difference between the vaccine study arms and the placebo study arm (15.4% vs. 22.2%; difference, -6.8% [95% confidence interval, -26.8% to 10.0%]; P=.54).CONCLUSION. Therapeutic immunization and ART, compared with ART alone, generated HIV-1-specific cellular immunity but did not lead to better virological control of HIV-1 24 weeks after discontinuation of ART. Our trial design appears to be feasible and safe for testing future immune-boosting strategies.

Long-Lasting Decrease in Viremia in Macaques Chronically Infected with Simian Immunodeficiency Virus SIVmac251 after Therapeutic DNA Immunization

“…Early therapy was hypothesized to work by limiting the damage to the immune system. Despite evidence of immunogenicity of therapeutic vaccination, some studies did not show substantial virologic benefit (10,18). Therapeutic vaccination of persons treated with ART early after infection showed evidence of an induction of immune responses, but the magnitude and dynamics of virus rebound after therapy discontinuation was similar in both vaccinated and unvaccinated subjects (18).…”

NYVAC immunization induces polyfunctional HIV‐specific T‐cell responses in chronically‐infected, ART‐treated HIV patients

“…Along the same line, various vaccine strategies have been proposed to help restimulate HIV-specific immunity allowing HIV-infected patients to reduce time on antiretroviral therapy (ART) [7,8]. Various therapeutic vaccine candidates including peptide-, protein-, and viral vector-based vaccines have shown modest efficacy in experimental animal models [9,10] and patients [11][12][13][14][15][16][17][18]. Some candidate vaccines, such as ALVAC or Ad5, have induced potent increase in HIV-specific immune responses [19,20].…”

Influence of IFNγ Co-Expression on the Safety and Antiviral Efficacy of Recombinant Fowlpox Virus HIV Therapeutic Vaccines Following Interruption of Antiretroviral Therapy

“…25 Despite measurable immune responses being induced in both trials upon vaccination there was no correlation between immunogenicity and viral control during ATI. 11,25 Contrary to these results upon vaccination of chronically HIV-infected patients with the canarypox vector vCP1433 and the lipopeptides HIV-LIPO-6T followed by three cycles of IL-2 enhanced viral control of the vaccinated group was observed that correlated with the measured immune response. 26 In summary the FC was demonstrated to be safe and well tolerated in patients with HIV-1 infection.…”

“…There was no significant difference between placebo and active groups in their ability to control HIV viral replication in the ATI. 11 Comparable results were observed upon vaccination of a similar patient group with vCP1452 + gp160. 25 Despite measurable immune responses being induced in both trials upon vaccination there was no correlation between immunogenicity and viral control during ATI.…”

“…[10][11][12] Here we have examined the effect of vaccination Here we have examined the effect of vaccination with recombinant fowlpox virus vector vaccines expressing HIV-1 Gag/Pol with and without the Th1 cytokine human interferon-γ (IFNγ) gene 13 on viral control and immune responses during an analytical treatment interruption (ATI) in patients who commenced stable CART soon after primary infection. This study extends a previous safety and immunogenicity trial where the vaccines were shown to be safe and well tolerated without generating significant anti-HIV immune responses despite both constructs being immunogenic in macaques.…”