Viral Load In Individuals Research Articles

Meta-analysis of randomized trials on the association of prophylactic acyclovir and HIV-1 viral load in individuals coinfected with herpes simplex virus-2

To summarize the randomized evidence regarding the association between acyclovir use and HIV-1 replication as measured by plasma HIV-1 RNA viral load among individuals coinfected with herpes simplex virus (HSV)-2. Meta-analysis of seven randomized trials conducted between 2000 and 2009. Inclusion criteria composed of acyclovir or valacyclovir use as prophylaxis among individuals coinfected with HIV-1 and HSV-2 who were ineligible for highly active antiretroviral therapy. HIV-1 viral load was the outcome. Random-effects summarization was used to combine treatment effect estimates. Stratified and meta-regression analyses were used to compare estimated treatment effects by characteristics of trials and participants. The summary treatment effect estimate was -0.33 (95% confidence interval: -0.56, -0.10, 95% population effects interval: -0.74, 0.08) log(10) copies, an approximate halving of plasma viral load. However, there was marked heterogeneity (P < 0.001). Older median age, valacyclovir, higher compliance, earlier publication, and shorter study length were associated with a larger decrease in viral load as compared with their counterparts. Current evidence suggests a range of favorable effects of acyclovir on plasma HIV-1 viral load among persons coinfected with HSV-2.

Fucoidan Therapy Decreases the Proviral Load in Patients with Human T-Lymphotropic Virus Type-1-Associated Neurological Disease

Human T-lymphotropic virus type-1 (HTLV-1) is a human retrovirus that causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukaemia (ATL). A higher viral load in individuals with HTLV-1 infection increases their risk of developing HAM/TSP and ATL. Moreover, the high proviral load is associated with the clinical progression of HAM/TSP. Reduction of the number of HTLV-1-infected cells is therefore crucial for preventing and treating HTLV-1-associated diseases. Recently, fucoidan, a complex sulphated polysaccharide derived from marine seaweed, has been demonstrated to exert inhibitory effects on HTLV-1 infection in vitro. In this study, we examined the in vivo effects of fucoidan on HTLV-1 infection. In this single-centre open-label trial, 13 patients with HAM/TSP were treated with 6 g fucoidan daily for 6-13 months. The HTLV-1 proviral DNA load and frequencies of HTLV-1-specific CD8(+) T-cells, natural killer cells, invariant natural killer T-cells and dendritic cells in the peripheral blood were analysed. Furthermore, the in vitro inhibitory effect of fucoidan on cell-to-cell HTLV-1 infection was examined by using luciferase reporter cell assays. Fucoidan inhibited the cell-to-cell transmission of HTLV-1 in vitro. Furthermore, fucoidan therapy resulted in a 42.4% decrease in the HTLV-1 proviral load without affecting the host immune cells. During the treatment, no exacerbation was observed. Four patients with HAM/TSP developed diarrhoea, which improved immediately after stopping fucoidan administration. Fucoidan is a new potential therapeutic agent for the prevention and treatment of HTLV-1-associated diseases.

Meta-analysis of randomized trials on the association of prophylactic acyclovir and HIV-1 viral load in individuals coinfected with herpes simplex virus-2

Meta-analysis of randomized trials on the association of prophylactic acyclovir and HIV-1 viral load in individuals coinfected with herpes simplex virus-2

T cell receptor diversity of CD8+ T lymphocytes and its association with viral load in individuals with HIV-1 infection

To determine the complementary determining region 3 (CDR3) length diversity of T cell receptor Vbeta repertoires of CD8+ T lymphocytes and to explore its association with viral load in individuals with HIV-1 infection. Separation of CD8+ T cells from peripheral blood mononuclear cells (PBMCs) was carried out by using immunomagnetic beads coated with anti-CD8 antibody. Total RNAs from the purified CD8+ T lymphocytes were isolated and used to perform polymerase chain reaction (PCR) amplifications in CDR3 of 22 T cell receptor (TCR) gene families. CDR3 diversity and its association with viral load in individuals with HIV-1 infection were analyzed. An average diversity for all CDR3 profiles in CD8+ T cells from 9 HIV-infected individuals was significantly different as compared to 7 age-matched healthy donors (P<0.05) with the HIV-infected individuals losing diversity in the CDR3 profiles. There was positive correlation between changes in TCR CDR3 diversity and viral load (r=0.771, P<0.05). The changes in CDR3 length diversity of Vbeta families in HIV-infected individuals, particular in Vbeta2, Vbeta4, Vbeta5, Vbeta17, Vbeta20, Vbeta21, Vbeta23, Vbeta24, were statistically different from the healthy controls. HIV-1 infection might induce the loss of TCR Vbeta repertoire diversity and disrupt the CDR3 distributions within CD8+ T cells. There should be positive correlation between changes in TCR CDR3 diversity and the viral load in HIV-1 infected patients.

Immunodominant HIV-1 Cd4+ T Cell Epitopes in Chronic Untreated Clade C HIV-1 Infection

BackgroundA dominance of Gag-specific CD8+ T cell responses is significantly associated with a lower viral load in individuals with chronic, untreated clade C human immunodeficiency virus type 1 (HIV-1) infection. This association has not been investigated in terms of Gag-specific CD4+ T cell responses, nor have clade C HIV-1–specific CD4+ T cell epitopes, likely a vital component of an effective global HIV-1 vaccine, been identified.Methodology/Principal FindingsIntracellular cytokine staining was conducted on 373 subjects with chronic, untreated clade C infection to assess interferon-gamma (IFN-γ) responses by CD4+ T cells to pooled Gag peptides and to determine their association with viral load and CD4 count. Gag-specific IFN-γ–producing CD4+ T cell responses were detected in 261/373 (70%) subjects, with the Gag responders having a significantly lower viral load and higher CD4 count than those with no detectable Gag response (p<0.0001 for both parameters). To identify individual peptides targeted by HIV-1–specific CD4+ T cells, separate ELISPOT screening was conducted on CD8-depleted PBMCs from 32 chronically infected untreated subjects, using pools of overlapping peptides that spanned the entire HIV-1 clade C consensus sequence, and reconfirmed by flow cytometry to be CD4+ mediated. The ELISPOT screening identified 33 CD4+ peptides targeted by 18/32 patients (56%), with 27 of the 33 peptides located in the Gag region. Although the breadth of the CD4+ responses correlated inversely with viral load (p = 0.015), the magnitude of the response was not significantly associated with viral load.Conclusions/SignificanceThese data indicate that in chronic untreated clade C HIV-1 infection, IFN-γ–secreting Gag-specific CD4+ T cell responses are immunodominant, directed at multiple distinct epitopes, and associated with viral control.

HIV vaccine trial no longer PAVEs the way

HIV vaccine trial no longer PAVEs the way

Outbreaks of Genital Herpes: Effects on Plasma HIV Type 1 Viral Loads in Individuals Receiving Highly Active Antiretroviral Therapy

Outbreaks of Genital Herpes: Effects on Plasma HIV Type 1 Viral Loads in Individuals Receiving Highly Active Antiretroviral Therapy

In vitro reactivation of human immunodeficiency virus-1 upon stimulation with scrub typhus rickettsial infection.

While a number of microbial infections induce a transient burst in viral load in individuals infected with human immunodeficiency virus-1 (HIV-1), a recent study has suggested that scrub typhus may suppress HIV-1 infection. We investigated the effects of Orientia tsutsugamushi on HIV-1 infection. In vitro HIV-1 infection experiments were conducted using peripheral blood mononuclear cells (PBMC) acutely infected with R5 and X4 HIV-1 or PBMC derived from patients receiving highly active antiretroviral therapy (HAART) whose plasma viral load was undetectable. Stimulation of PBMC with O. tsutsugamushi induced production of proinflammatory cytokines and beta-chemokines, and markedly down-regulated expression of CCR5. Although pretreatment with O. tsutsugamushi rendered PBMC resistant to R5 HIV-1, it otherwise enhanced HIV-1 replication. Stimulation by O. tsutsugamushi induced HIV-1 replication in PBMC from patients receiving HAART. These findings suggest that scrub typhus does not necessarily suppress HIV-1 infection and does have potential to enhance HIV-1 replication.

Factors associated with the evolution of the viral load in individuals with HIV infection

The temporal evolution of the viral load (VL) in a group of patients under clinical care and the identification of individual variables that determined this evolution was studied using a retrospective descriptive study of the VL determinations on 1336 patients between September 1996 and June 2000. During follow-up, patients’ VLs increasingly fell below the detection threshold. Those patients who had received antiretroviral treatment prior to the monitoring of the viraemia presented lower VLs at the start of their follow-up. Those patients who had been cared for on the same unit throughout their follow-up maintained lower VLs. Female patients uniformly presented lower VL results than the males. The immunological status at the beginning of follow-up and the basal VL determined the initial evolution of the patients’ VL, although it did not do so in the final stages of follow-up. The immunological and virological state at the onset of the follow-up determines the evolution of the patients’ VL.

Strategy for the maximization of clinically relevant information from hepatitis C virus, RT-PCR quantification.

The increasing clinical application of viral load assays for monitoring viral infections has been an incentive for the development of standardized tests for the hepatitis C virus. To develop a simple model for the prediction of baseline viral load in individuals infected with the hepatitis C virus. Viral load quantification of each patient's first sample was assessed by RT-PCR-ELISA using the Roche MONITOR assay in triplicate. Genotype of the infecting virus was identified by reverse line probe hybridization, using amplicons resulting from the qualitative HCV Roche AMPLICOR assay. Retrospective evaluation of first quantitative values suggested that 82.4% (n=168/204) of individuals had a viral load between 4.3 and 6.7 log(10) viral copies per ml. A few patients (3.4%; n=7/204) have a serum viremia less than the lower limit of the linear range of the RT-PCR assay. Subsequent, prospective evaluation of hepatitis C viral load of all new patients using a model based on the dynamic range of viral load in the retrospective group correctly predicted the dynamic range in 75.9% (n=33/54). The dynamic range of hepatitis C viremia extends beyond the linear range of the Roche MONITOR assay. Accurate determination of serum viremia is substantially improved by dilution of specimens prior to quantification.

RANTES production in HIV-1 antigen-stimulated whole blood culture: relationship with type 1 immune response and plasma viral load in individuals infected with HIV-1.

Host factors which control replication and clearance of human immunodeficiency virus (HIV) are poorly understood. RANTES (regulated on activation, normal T cell expressed and secreted) and other beta-chemokines may be HIV-1-suppressive factors but their role in the progression of HIV-1 infection is a subject of controversy. We investigated the relationship between production of RANTES and correlates of disease progression in 15 patients infected with HIV-1. We used whole blood culture to study the production of RANTES, interferon (IFN)-gamma, interleukin (IL)-4 and IL-13 in response to supernatant of T cells infected with HIV-1. A defect of RANTES production was associated with a predominant type 2 and decreased type 1 cytokine profile (IL-4 and/or IL- 13 > IFN-gamma). We obtained a positive correlation between RANTES and IFN-gamma (P = 0.004) and the ratio of type 1 and type 2 cytokines IFN-gamma/IL-4 (P = 0.04) and IFN-gamma/IL-13 (P = 0.003), and a negative correlation between RANTES production and HIV-1 RNA copy number in plasma (P = 0.01). The same pattern of correlation was observed between HIV-1 p24-stimulated production of RANTES and the plasma viral load (P = 0.02, n = 15). The measurement of RANTES produced by heparinized whole blood in response to HIV-1 antigens appears as a potentially valuable tool to assess the defect of type 1 immune response in individuals infected with HIV-1 and to define whether the absence of a RANTES response may play a role in the increased rate of HIV-1 replication.

Randomised trial of addition of lamivudine or lamivudine plus loviride to zidovudine-containing regimens for patients with HIV-1 infection: the CAESAR trial

Previous studies have shown that combination therapy with lamivudine plus zidovudine causes pronounced and sustained increases in CD4 counts and reductions in viral load in individuals infected with HIV-1. We assessed the clinical benefit of the addition of lamivudine to zidovudine-based regimens in patients infected with HIV-1 who had CD4 counts of 25-250/microL. Eligible patients receiving zidovudine monotherapy or zidovudine plus zalcitabine or didanosine combination therapy were assigned 52 weeks of treatment with the addition of placebo, lamivudine (150 mg twice a day), or lamivudine (150 mg twice a day) plus loviride (100 mg three times a day). Patients were unaware of type of treatment allocated. The primary endpoint was progression to a new protocol-defined AIDS event or death. The study was terminated following the second interim analysis because of a highly significant reduction in progression to AIDS or death in the patients treated with lamivudine rather than placebo. In the final analysis of 1840 patients, progression had occurred in 95 (20%) of 471 placebo-treated patients, 86 (9%) of 907 lamivudine-treated patients, and 42 (9%) of 462 patients who received lamivudine plus loviride (p < 0.0001, relative hazard 0.42 [95% CI 0.32-0.57]). A significant survival benefit was also seen (p = 0.0007, relative hazard 0.40 [0.23-0.69]). Significantly fewer patients in the lamivudine group than in the placebo group required hospital admission, unscheduled visits, or prescribed medications for HIV-related events. There were no differences in the frequency or severity of clinical or laboratory toxicities between the treatment groups. The addition of lamivudine to zidovudine-containing treatment regimens significantly slowed the progression of HIV disease and improved survival. However, it is unlikely that this combination alone would be sufficient to achieve long-term complete suppression of viral replication in all patients.