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HIV-specific gag responses in early infancy correlate with clinical outcome and inversely with viral load.

ABSTRACT: Many HIV-infected infants progress to AIDS during the first year of life when antiretroviral therapy (ART) is not given. The immune determinants of progression to AIDS are not known. We hypothesized that distinct HIV-specific T cell responses correlate with viral load and survival over the first year of life. Whole blood of infants at 3, 6, 9, and 12 months of age was incubated with HIV antigens Gag and Env. The frequency of specific T cells producing interferon (IFN)-? was then measured by flow cytometry. Viral load and CD4% in HIV(+) infants were determined at each time point. ART was not available for this population at the time of sample collection. Those infants who survived to 12 months of age (n=12) had lower viral loads and higher Gag-specific CD8(+) T cell responses at 3 months, compared with infants who died (n=8). Furthermore, the frequency of Gag-specific CD4(+) T cells correlated inversely with viral load at 3 and 6 months of age. Together these data indicate that the early presence of quantitatively higher Gag-specific T cell responses in HIV-infected infants is associated with lower viral loads and decreased mortality in the first year of life. Our data support the design of a vaccine that preferentially elicits Gag responses, which may result in lower levels of viremia and possibly improve outcome.

SUBMITTER: Nqoko B

PROVIDER: S-EPMC3227240 | biostudies-literature | 2011 Dec

REPOSITORIES: biostudies-literature

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HIV-specific gag responses in early infancy correlate with clinical outcome and inversely with viral load.

Nqoko Bongeka B Day Cheryl L CL Mansoor Nazma N De Kock Marwou M Hughes E Jane EJ Hawkridge Tony T Kaplan Gilla G Boom W Henry WH Hussey Gregory D GD Hanekom Willem A WA

AIDS research and human retroviruses 20110512 12

Many HIV-infected infants progress to AIDS during the first year of life when antiretroviral therapy (ART) is not given. The immune determinants of progression to AIDS are not known. We hypothesized that distinct HIV-specific T cell responses correlate with viral load and survival over the first year of life. Whole blood of infants at 3, 6, 9, and 12 months of age was incubated with HIV antigens Gag and Env. The frequency of specific T cells producing interferon (IFN)-γ was then measured by flow ...[more]

PMID: 21476948

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Project description:UnlabelledEffector CD4 T cell responses have been shown to be critically involved in the containment and clearance of viral pathogens. However, their involvement in the pathogenesis of HIV infection is less clear, given their additional role as preferred viral targets. We previously demonstrated that the presence of HIV-specific CD4 T cell responses is somewhat associated with HIV control and that specific CD4 T cell functions, such as direct cytolytic activity, can contribute to control of HIV viremia. However, little is known about how the induction of HIV-specific CD4 T cell responses during acute HIV infection influences disease progression and whether responses induced during the early phase of infection are preferentially depleted. We therefore longitudinally assessed, in a cohort of 55 acutely HIV-infected individuals, HIV-specific CD4 T cell responses from acute to chronic infection. Interestingly, we found that the breadth, magnitude, and protein dominance of HIV-specific CD4 T cell responses remained remarkably stable over time. Moreover, we found that the epitopes targeted at a high frequency in acute HIV infection were recognized at the same frequency by HIV-specific CD4 T cells in chronic HIV infection. Interestingly the induction of Gag-specific CD4 T cell responses in acute HIV infection was significantly inversely correlated with viral set point in chronic HIV infection (R = -0.5; P = 0.03), while the cumulative contribution of Env-specific CD4 T cell responses showed the reverse effect. Moreover, individuals with HIV-specific CD4 T cell responses dominantly targeting Gag over Env in acute HIV infection remained off antiretroviral therapy significantly longer (P = 0.03; log rank). Thus, our data suggest that the induction of HIV-specific CD4 T cell responses during acute HIV infection is beneficial overall and does not fuel disease progression.ImportanceCD4 T cells are critical for the clearance and control of viral infections. However, HIV preferentially infects HIV-specific CD4 T cells. Thus, their contribution to the control of HIV viremia is uncertain. Here, we study HIV-specific CD4 T cell responses from acute to chronic HIV infection and show that the generation of certain CD4 responses is associated with control rather than disease progression.

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HIV-specific gag responses in early infancy correlate with clinical outcome and inversely with viral load.

Publications

HIV-specific gag responses in early infancy correlate with clinical outcome and inversely with viral load.

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