Viremia

About: Viremia is a research topic. Over the lifetime, 4216 publications have been published within this topic receiving 212531 citations. The topic is also known as: viraemia & Viremia.

CD8+ T-cell responses to different HIV proteins have discordant associations with viral load

Abstract: Selection of T-cell vaccine antigens for chronic persistent viral infections has been largely empirical. To define the relationship, at the population level, between the specificity of the cellular immune response and viral control for a relevant human pathogen, we performed a comprehensive analysis of the 160 dominant CD8(+) T-cell responses in 578 untreated HIV-infected individuals from KwaZulu-Natal, South Africa. Of the HIV proteins targeted, only Gag-specific responses were associated with lowering viremia. Env-specific and Accessory/Regulatory protein-specific responses were associated with higher viremia. Increasing breadth of Gag-specific responses was associated with decreasing viremia and increasing Env breadth with increasing viremia. Association of the specific CD8(+) T-cell response with low viremia was independent of HLA type and unrelated to epitope sequence conservation. These population-based data, suggesting the existence of both effective immune responses and responses lacking demonstrable biological impact in chronic HIV infection, are of relevance to HIV vaccine design and evaluation.

Viral dynamics in hepatitis B virus infection

Abstract: Treatment of chronic hepatitis B virus (HBV) infections with the reverse transcriptase inhibitor lamivudine leads to a rapid decline in plasma viremia and provides estimates for crucial kinetic constants of HBV replication We find that in persistently infected patients, HBV particles are cleared from the plasma with a half-life of approximately 10 day, which implies a 50% daily turnover of the free virus population Total viral release into the periphery is approximately 10(11) virus particles per day Although we have no direct measurement of the infected cell mass, we can estimate the turnover rate of these cells in two ways: (i) by comparing the rate of viral production before and after therapy or (ii) from the decline of hepatitis B antigen during treatment These two independent methods give equivalent results: we find a wide distribution of half-lives for virus-producing cells, ranging from 10 to 100 days in different patients, which may reflect differences in rates of lysis of infected cells by immune responses Our analysis provides a quantitative understanding of HBV replication dynamics in vivo and has implications for the optimal timing of drug treatment and immunotherapy in chronic HBV infection This study also represents a comparison for recent findings on the dynamics of human immunodeficiency virus (HIV) infection The total daily production of plasma virus is, on average, higher in chronic HBV carriers than in HIV-infected patients, but the half-life of virus-producing cells is much shorter in HIV Most strikingly, there is no indication of drug resistance in HBV-infected patients treated for up to 24 weeks

Transient high levels of viremia in patients with primary human immunodeficiency virus type 1 infection.

Abstract: Background. The rapidly evolving clinical picture of primary infection with the human immunodeficiency virus type 1 (HIV-1) suggests that a better understanding of the kinetics of viral replication in vivo during the short period before seroconversion may provide insight into the pathogenesis of the acquired immunodeficiency syndrome (AIDS). Methods and Results. Titers of infectious HIV-1 were determined by end-point-dilution culture in sequential samples of plasma and peripheral-blood mononuclear cells from four patients with primary infection, with peak titers of 1000 to 10,000 tissue-culture—infective doses per milliliter of plasma and 100 to 10,000 infective doses per 106 peripheral-blood mononuclear cells. The high viral burden in mononuclear cells was confirmed by quantitative studies using a polymerase-chain-reaction method. In as little as 10 days, the high HIV-1 load in both plasma and cells decreased spontaneously and precipitously, at least 100-fold, in all four patients. Conclusions. ...

Protection of Macaques against Pathogenic Simian/Human Immunodeficiency Virus 89.6PD by Passive Transfer of Neutralizing Antibodies

Abstract: The role of antibody in protection against human immunodeficiency virus (HIV-1) has been difficult to study in animal models because most primary HIV-1 strains do not infect nonhuman primates. Using a chimeric simian/human immunodeficiency virus (SHIV) based on the envelope of a primary isolate (HIV-89.6), we performed passive-transfer experiments in rhesus macaques to study the role of anti-envelope antibodies in protection. Based on prior in vitro data showing neutralization synergy by antibody combinations, we evaluated HIV immune globulin (HIVIG), and human monoclonal antibodies (MAbs) 2F5 and 2G12 given alone, compared with the double combination 2F5/2G12 and the triple combination HIVIG/2F5/2G12. Antibodies were administered 24 h prior to intravenous challenge with the pathogenic SHIV-89.6PD. Six control monkeys displayed high plasma viremia, rapid CD4(+)-cell decline, and clinical AIDS within 14 weeks. Of six animals given HIVIG/2F5/2G12, three were completely protected; the remaining three animals became SHIV infected but displayed reduced plasma viremia and near normal CD4(+)-cell counts. One of three monkeys given 2F5/2G12 exhibited only transient evidence of infection; the other two had marked reductions in viral load. All monkeys that received HIVIG, 2F5, or 2G12 alone became infected and developed high-level plasma viremia. However, compared to controls, monkeys that received HIVIG or MAb 2G12 displayed a less profound drop in CD4(+) T cells and a more benign clinical course. These data indicate a general correlation between in vitro neutralization and protection and suggest that a vaccine that elicits neutralizing antibody should have a protective effect against HIV-1 infection or disease.

Early establishment of a pool of latently infected, resting CD4+ T cells during primary HIV-1 infection

Abstract: The presence of latently infected, resting CD4+ T cells carrying replication-competent HIV-1 has been demonstrated in chronically infected individuals who are antiretroviral therapy naive as well as in those who are receiving highly active antiretroviral therapy (HAART). It is not clear, however, whether the establishment of a pool of latently infected CD4+ T cells can be blocked by early initiation of HAART after primary infection. The present study demonstrates that initiation of HAART in infected individuals as early as 10 days after the onset of symptoms of primary HIV-1 infection did not prevent generation of latently infected, resting CD4+ T cells carrying integrated HIV-1 DNA as well as infectious HIV-1 despite the successful control of plasma viremia shortly after institution of HAART. Furthermore, there was no correlation between either the duration of HAART at the time of study (range: 0.2–17 months) or the time of initiation of HAART after the onset of symptoms of primary HIV-1 infection (range: 0.3–4 months) and the frequencies of resting CD4+ T cells carrying either integrated HIV-1 DNA or infectious virus. These results underscore the rapidity with which latent reservoirs are established in primary HIV-1 infection and indicate that it is unlikely that early treatment during primary infection can prevent establishment of a pool of latently infected, resting CD4+ T cells as long as treatment is initiated after plasma viremia becomes evident.