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PubMed1995

Prospective study of antigenemia, plasma viremia and lymphocytic viremia in HIV-infected hemophiliacs.

A total of 186 blood samples from 24 HIV-1 seropositive hemophiliac patients, monitored every four months for 29 months, were investigated for the presence of viral antigen in plasma. In addition, peripheral blood mononuclear cells (PBMC) were cultured for HIV-1, using normal PBMC as a target for replication. Antigenemia was detected in 51% of the patients and from PBMC in 87.5% of the patients. The incidence of HIV isolation in asymptomatic patients (42.8%) was similar to that found in symptomatic patients (51.4%). Patients with opportunistic infections had a higher incidence of lymphocytic viremia (p < 0.05). Plasma viremia was closely associated (p < 0.05) with low CD4+ counts and infection progression. The persistence of antigenemia was also a marker of a poor clinical course. In treated patients, plasma viremia was the marker that better correlated with the clinical course, and it did not appear during the first nine months of therapy. Zidovudine doses of > 500 mg/day significantly lowered the appearance of antigenemia and lymphocytic viremia (p < 0.05).

Adolescent↗
PubMed2004

A period of transient viremia and occult infection precedes persistent viremia and antiviral immune responses during multiple low-dose intravaginal simian immunodeficiency virus inoculations.

In rhesus macaques, classic systemic infection, characterized by persistent viremia and seroconversion, occurred after multiple low-dose (10(3) 50% tissue culture infective doses) intravaginal (IVAG) inoculations with simian immunodeficiency virus (SIV) strain SIVmac251. Monkeys developed classic SIV infections after a variable number of low-dose IVAG exposures to SIVmac251. Once established, the systemic infection was identical to SIV infection following high-dose IVAG SIV inoculation. However, occult systemic infection characterized by transient cell-associated or cell-free viremia consistently occurred early in the series of multiple vaginal SIV exposures. Further, antiviral cellular immune responses were present prior to the establishment of a classic systemic infection in the low-dose vaginal SIV transmission model.

Administration, Intravaginal↗
PubMedDate not supplied

Prevalence of viremia in human immunodeficiency virus-infected patients with renal disease.

BACKGROUND: The prevalence of viremia and its relationship to the pathogenesis of nephropathy in human immunodeficiency virus (HIV)-infected patients with renal disease is unknown. To assess the prevalence of plasma viremia in HIV-infected patients with chronic renal disease, we performed a cohort study in two urban university medical centers. METHODS: Samples of blood from 11 HIV-infected patients with renal failure who were treated with hemodialysis were analyzed concurrently with control samples from three non-HIV-positive patients receiving hemodialysis treatment. Samples from four HIV-infected patients with chronic renal insufficiency were evaluated concurrently. Thirty-three HIV-infected patients with serum creatinine levels of less than 132 mumol/L (1.5 mg/dL), and trace or absent dipstick proteinuria served as controls for the population with renal disease. The patients infected with HIV were staged by CD4 cell counts and the presence of opportunistic infections. Blood samples were analyzed for plasma HIV p24 antigenemia by antigen capture enzyme-linked immunosorbent assay. Blood samples were analyzed for the presence of viremia by infection of normal stimulated peripheral blood mononuclear cell cultures with plasma samples and detection of HIV p24 antigen in culture supernatants. RESULTS: Two of the 11 patients treated with hemodialysis had evidence of HIV p24 antigenemia, while seven of the 11 had evidence of plasma viremia. The proportion of hemodialysis patients with detectable antigenemia and viremia was similar to that in patients with chronic renal insufficiency. A significantly greater proportion of HIV-infected patients with renal disease had plasma viremia and antigenemia, compared with HIV-infected patients without renal disease. In logistic regression analysis, race, CD4 cell count (either on a continuous scale or dichotomized at 0.2 x 10(9)/L), and treatment with zidovudine were not significantly associated with the presence of plasma viremia, but patient age and the presence of renal disease were factors independently associated with viremia. CONCLUSIONS: The similar proportions of HIV-infected patients with viremia in groups of patients with chronic renal insufficiency and with renal disease treated with hemodialysis suggest that dialysis treatment does not increase the prevalence of plasma viremia in HIV-infected patients with renal disease. The similar proportions of HIV-infected hemodialyzed patients and patients with chronic renal insufficiency with plasma viremia, and the greater prevalence of viremia in patients with renal disease compared with HIV-infected patients without clinical renal disease suggest that plasma viremia and renal dysfunction are related. Whether this represents a cause and effect relationship is unknown. The greater prevalence of viremia in HIV-infected patients with renal disease has implications for the pathogenesis of HIV-related renal diseases and for caregivers in clinical settings and dialysis units.

Adult↗
PubMed2001

Prevalence and predictive value of intermittent viremia with combination hiv therapy.

CONTEXT: In HIV-infected patients having virologic suppression (plasma HIV RNA <50 copies/mL) with antiretroviral therapy, intermittent episodes of low-level viremia have been correlated with slower decay rates of latently infected cells and increased levels of viral evolution, but the clinical significance of these episodes is unknown. OBJECTIVE: To determine if HIV-infected patients with intermittent viremia have a higher risk of virologic failure (confirmed HIV RNA >200 copies/mL). DESIGN AND SETTING: Retrospective analysis of subjects in well-characterized cohorts, the AIDS Clinical Trials Group (ACTG) 343 trial of induction-maintenance therapy (August 1997 to November 1998) and the Merck 035 trial (ongoing since March 1995). PATIENTS: Two hundred forty-one ACTG 343 patients, of whom 101 received triple-drug therapy throughout the study, and a small group of 13 patients from Merck 035 having virologic suppression after 6 months of indinavir-zidovudine-lamivudine. MAIN OUTCOME MEASURES: Association of intermittent viremia (plasma HIV RNA >50 copies/mL with a subsequent measure <50 copies/mL) with virologic failure (2 consecutive plasma HIV RNA measures >200 copies/mL) in both study groups; evidence of drug resistance in 7 patients from the small (n = 13) study group with long-term follow-up. RESULTS: Intermittent viremia occurred in 96 (40%) of the 241 ACTG 343 patients of whom 32 (13%) had 2 consecutive HIV RNA values >50 copies/mL during the median 84 weeks of observation (median duration of observation after first intermittent viremia episode was 46 weeks). Of the 101 individuals receiving triple-drug therapy throughout, 29% had intermittent viremia; the proportion of episodes occurring during the maintenance period was 64% for the entire cohort and 68% for the group not receiving triple-drug therapy throughout vs 55% for those who did (P =.25). Intermittent viremia did not predict virologic failure: 10 (10.4%) of 96 patients with and 20 (13.8%) of 145 patients without intermittent viremia had virologic failure (relative risk, 0.76; 95% confidence interval [CI], 0.29-1.72). In a Cox proportional hazards model, the risk for virologic failure was not significantly greater in the ACTG 343 patients with intermittent viremia (hazard ratio, 1.28; 95% CI, 0.59-2.79). Median viral load in 10 ACTG 343 patients assessed between 24 and 60 weeks of therapy using an ultrasensitive 2.5-copies/mL detection level assay was 23 copies/mL in those with intermittent viremia vs <2.5 copies/mL in those without (P =.15). Intermittent viremia occurred in 6 of 13 patients from the small study group assessed after 76 to 260 weeks of therapy (using the 2.5-copies/mL detection level assay) and was associated with a higher steady state of viral replication (P =.03), but not virologic failure over 4.5 years of observation. Viral DNA sequences from 7 patients did not show evolution of drug resistance. CONCLUSIONS: Intermittent viremia occurred frequently and was associated with higher levels of replication (Merck 035), but was not associated with virologic failure in patients receiving initial combination therapy of indinavir-zidovudine-lamivudine (ACTG 343 and Merck 035). In this population, treatment changes may not be necessary to maintain long-term virologic suppression with low-level or intermittent viremia.

Anti-HIV Agents↗
PubMed2002

Prevalence and clinical correlates of HIV viremia ('blips') in patients with previous suppression below the limits of quantification.

OBJECTIVE: To examine the prevalence and clinical correlates of subsequently measurable viremia in HIV-infected patients who have achieved viral suppression below the limits of quantification (< 50 copies/ml). DESIGN: Non-randomized dynamic cohort study of ambulatory HIV patients in nine HIV clinics in eight cities. PATIENTS: Patients had two consecutive HIV-1 RNA levels < 50 copies/ml (minimum, 2 months apart) that were followed by at least two more viral level determinations while remaining on the same antiretroviral therapy (ART) between January 1997 and June 2000 (median 485 days). Transiently viremic patients were defined having a subsequently measurable viremia but again achieved suppression < 50 copies/ml. RESULTS: Of the 448 patients, 122 (27.2%) had transient viremia, 19 (4.2%) had lasting low-level viremia and 33 (7.4%) had lasting high-level viremia (defined as 50-400 and > 400 copies/ml, respectively). Only 16 (13.1%) of those who had transient viremia later had persistent viremia > 50 copies/ml. The occurrence of transient viremia did not vary with whether the patient was ART-naive or experienced (P = 0.31), or currently taking protease inhibitors or not (P = 0.08). On consistent ART, the median percentage increase in CD4 cell count was statistically different between subgroups of our cohort (Kruskal-Wallis, P = 0.002). CONCLUSIONS: Transiently detectable viremia, usually 50-400 copies/ml, was frequent among patients who had two consecutive HIV-1 RNA levels below the limits of quantification. In this analysis, such viremia did not appear to affect the risk of developing lasting viremia. Caution is warranted before considering a regimen as 'failing' and changing medications.

Anti-HIV Agents↗
PubMed2004

Immunologic and virologic evolution during periods of intermittent and persistent low-level viremia.

BACKGROUND: HIV replication, HIV-specific T-cell responses and T-cell activation each contributes to disease outcome during untreated HIV infection. The interaction of these factors is not well understood, particularly in the setting of antiretroviral therapy. METHODS: This is a longitudinal study of antiretroviral-treated patients with plasma HIV RNA levels < 1000 copies/ml. Patients were divided into three groups: suppressed viremia, intermittent viremia ('blips') and persistent low-level viremia. HIV-specific immunity was measured using interferon-gamma ELISPOT. T-cell activation was defined by CD38 and HLA-DR co-expression. Drug resistance was quantified using a phenotypic susceptibility assay. RESULTS: The breadth and the magnitude of the HIV-specific CD8 T-cell response was greater in patients with either intermittent or persistent viremia compared to patients with suppressed viremia. In contrast, T-cell activation was significantly elevated only in those patients with persistent viremia. Patients with persistent low-level viremia had moderate levels of phenotypic antiretroviral drug resistance that increased over time. Virologic failure (confirmed increase in viral load > 1000 HIV RNA copies/ml) was primarily observed in the persistently viremic group. CONCLUSIONS: Antiretroviral-treated individuals with intermittent viremia appear to mount an effective HIV-specific T-cell response while not experiencing increases in the level of immune activation. This may limit viral evolution and emergence of drug resistance. In contrast, antiretroviral-treated individuals with persistent low-level viremia exhibit significant increases in overall immune activation and a substantial risk of subsequent treatment failure. It is likely that higher viremia and stronger immune activation act synergistically to accelerate the development of systemic drug resistance.

Anti-HIV Agents↗
PubMed1997

[Quantification of viremia in patients infected with human immunodeficiency virus with different degrees of immunosuppression].

BACKGROUND: Many of the therapeutical decisions related to patients infected with human immunodeficiency virus (HIV) are taken considering the CD4+ lymphocyte count. The recent availability of procedures which quantitate the number of viral particles in peripheral blood has disclosed that viremia degree is the best predictor of HIV disease progression. Nevertheless, the proportion of subjects who despite a normal CD4+ lymphocyte count, have a high viremia and a high risk of short term progression to AIDS is not well known. PATIENTS AND METHODS: Plasma viremia was investigated in 120 adults subjects with a known time of HIV infection. Fifty-two patients had a CD4+ lymphocyte count > 500 x 10(6)/l (CDC group 1), 42 had a number of CD4+ lymphocytes ranging from 200 and 500 x 10(6)/l (CDC group 2), and 26 had a count < 200 x 10(6)/l (CDC group 3). None of the patients was receiving antiretroviral treatment or had intercurrent infections at the time of the study. RESULTS: Mean values of viremia showed an inverse significant relationship with the CD4+ lymphocyte count. In CDC group 1 subjects the distribution of viremia was as follows: low (< 3,000 copies of HIV RNA/ml) in 16 (30.8%), intermediate in 20 (38.4%), and high (> 30,000 copies of HIV RNA/ml) in 16 (30.8%). In eight subjects from CDC group 1, the duration of HIV infection was less than 5 years. In contrast, in patients from CDC group 3, viremia was high in 17 (65.4%), intermediate in 9 (34.6%), and none of them had a low degree viremia. In CDC group 2 patients, viremia was high in 14 (33.3%), intermediate in 20 (47.6%), and low in 8 (19.1%). CONCLUSION: There is an inverse correlation between the viremia degree and the CD4+ lymphocyte count among HIV-positive patients. Nevertheless, there can be a high viremia in absence of low CD4+ lymphocyte count, particularly among subjects with HIV infection for less than 5 years, in whom an early therapeutical intervention might be warranted.

Adult↗
PubMed1971

Effect of an immunosuppressive agent, cyclophosphamide, on chronic lactic dehydrogenase virus viremia of mice.

The immunosuppressive drug cyclophosphamide was used to study the effect of immunosuppression on the degree of chronic lactic dehydrogenase virus (LDV) viremia in mice. Weekly injections of cyclophosphamide caused an increase of LDV viremia of ca. 2.5 log(10) 50% infectious doses per ml as compared to the viremia in the nontreated mice. This increase occurred at about the same time that the formation of antibody with a neutralization index of 2 to 3 log(10) per ml could be demonstrated in the serum of control mice, whereas both neutralizing antibody and sensitized (antibody-bound but infectious) virus were absent in the immunosuppressed mice. In one experiment, antibody did not reappear 28 weeks after a 24-week course of cyclophosphamide treatment. In another experiment in which the drug was given for 12 weeks, antibody appeared again in the treated mice 14 weeks after cessation of drug administration and was accompanied by a decrease in viremia. The normal decrease of early viremia during the first 2 weeks of infection in immunosuppressed mice suggests that the immune response is not the cause of this initial decrease in LDV viremia but that interferon and perhaps other nonimmune factors may be involved here. The increased viremia in the immunosuppressed mice during the later stages of infection indicates that the immune response plays an important role in partial control of chronic viremia. The quantitative correlation between the decrease in neutralizing antibody and the increase in viremia in immunosuppressed mice suggests that antibody rather than cellular immunity may be the more important immune factor in the control of chronic viremia.

Animals↗
PubMedDate not supplied

Studies of turkey herpesvirus viremia in two strains of vaccinated chickens strain difference and effects of vaccine dose.

Turkey herpesvirus (HVT) viremia was studied at 3-week intervals through 21 weeks of age in individual chickens of experimental (WSU-VS) and commercial strains (C-WL) of White Leghorns vaccinated with graded doses of HVT. HVT viremia was consistently detectable in all WSU-VS birds through 21 weeks postvaccination (PV) regardless of vaccine dose employed, whereas the viremia could not be detected in some of the C-WL birds 9 to 15 weeks PV and thereafter. C-WL birds that lost detectable viremia remained so up to 21 weeks PV, or returned to low levels of viremia which was followed in some birds again by no detectable viremia. Viremia titers were significantly lower in the C-WL than in the WSU-VS birds despite the same vaccination. Both strains of chickens exhibited significantly lower viremia titers when vaccinated with 240 plaqueforming units (PFU) than with 1,480 or 6,600 PFU of HVT, and other C-WL birds lost detectable viremia earlier and more frequently with smaller vaccine doses. This observation indicated a possible genetic difference between the two strains of chickens in susceptibility and viremic response to HVT as well as dose-dependence of HVT viremia.

Animals↗
PubMed2000

Usefulness of pp65 antigenemia and viremia in the follow-up of renal transplant recipients with cytomegalovirus disease treated with ganciclovir.

We prospectively evaluated the usefulness of the pp65 antigenemia assay (AGA) and viremia (isolation) in the follow-up of 15 renal transplant recipients with a cytomegalovirus disease treated with ganciclovir. The AGA was performed with the extraction of PMNL with saline dextran, and the viremia detected by the inoculation of them in the MRC-5 cell line (shell-vial). Sixty-nine blood samples were studied, and 55 (79.7%) positive AGA and 42 (60.8%) positive viremia detected. The AGA needed a median of 9 days to negativize, and the viremia only 4 days. In eight patients (53%) the AGA and viremia were negative simultaneously. In seven patients (47%) the viremia was negative before the AGA (median 10.7 days). In this group, three patients (43%) presented a paradoxal rising of the AGA values after the negativization of the viremia. For the follow-up of renal transplant recipients treated with ganciclovir, the viremia was the most useful method of control. The viremia was negative before the AGA in many patients, demonstrating the therapeutic efficacy of ganciclovir.

Antiviral Agents↗
PubMed1990

Role of primary and secondary maternal viremia in transplacental guinea pig cytomegalovirus transfer.

The modulation of the outcome of intrauterine guinea pig cytomegalovirus (GPCMV) infection by maternal viremia was investigated in the guinea pig model. Virus assay and in situ hybridization were used to study GPCMV infection of maternal blood, placentas, and fetuses following inoculation of pregnant guinea pigs by the subcutaneous, intracardiac, or intranasal route. Animals were inoculated in early gestation and were evaluated every 7 to 10 days throughout pregnancy. Although placental and fetal infections occurred in all groups examined, transfer of GPCMV to placentas and fetuses was most efficient in mothers inoculated subcutaneously. Primary viremia was followed by virus clearance from blood and by an episode of secondary viremia in the three groups of mothers examined. Placental and fetal infections in animals infected subcutaneously or intracardially were first detected at the time of primary viremia, persisted throughout gestation, and increased during secondary viremia. In contrast, placental and fetal infections in animals inoculated intranasally were demonstrated primarily during secondary viremia. Fetal infection was detected in all mothers with detectable primary and secondary viremia but in only 33% of mothers that experienced only primary viremia. These results suggest that secondary maternal viremia is associated with increased placental and fetal GPCMV infections.

Abortion, Spontaneous↗
PubMedDate not supplied

Changes in hepatitis C viral response after initiation of highly active antiretroviral therapy and control of HIV viremia in chronically co-infected individuals.

BACKGROUND: HIV seropositive individuals co-infected with hepatitis C virus (HCV) have an increased risk for liver cirrhosis. We examined the long-term effect of controlling HIV infection with highly active antiretroviral therapy (HAART) on HCV viremia among co-infected patients. METHOD: HIV/HCV co-infected patients who initiated HAART and were able to control HIV viremia to <500 copies/mL were evaluated. HIV and HCV viremia were measured at each time point from frozen plasma samples by using bDNA methodology. Liver function tests and CD4+ and CD8+ T cell counts of all patients were obtained at each time point. RESULTS: Seventeen co-infected patients met criteria for study from a cohort of 156 patients. Median time to achieve an HIV viral load (VL) <500 copies/mL after initiation of HAART was 28 weeks (range, 5-225 weeks). Thirteen of 17 patients had increases in HCV VL. Slope analysis of HCV VL vs. HIV VL was -0.14 (p=.0496), demonstrating a 0.14 log increase in HCV VL concomitant with control of HIV viremia. HCV viremia returned toward baseline levels in the 16 patients who maintained HIV suppression for 6 months. None cleared HCV after initiation of HAART during this time. Alkaline phosphatase, ALT, and AST levels were not significantly changed from baseline nor correlated with change in HCV VL (p>.05). CONCLUSION: Control of HIV viremia may result in an early increase in HCV viremia. In this study, for every 1 log decrease of HIV VL there was a 0.14 log increase of HCV VL. The exact mechanism of this flare seen with control of HIV viremia is unknown. However, HAART alone was not able to eliminate or significantly reduce the HCV viremia in this cohort of co-infected patients.

Adult↗
PubMed1997

Determination of the number of blood samples needed for optimal detection of cytomegalovirus viremia in immunocompromised patients using a shell-vial assay.

To establish the number of blood samples necessary for the diagnosis of viremic episodes caused by cytomegalovirus (CMV), a prospective analysis was conducted of 238 patients (38 renal transplant recipients and 200 HIV-infected patients) who developed CMV viremia. The usefulness of samples and the volume of blood required to demonstrate the presence of viremia by CMV was also studied. The first blood sample was diagnostic for CMV viremia in 53.3% of the viremic patients; the second sample documented an additional 22.2% of cases of viremia (75.5% of infected patients); and the third sample demonstrated viremia in the remaining 24.5%. Thus, a diagnosis of CMV viremia was established in every patient (100% of episodes of viremia). In this study, the use of three 3 ml blood samples collected at 24 h intervals was sufficient to detect all episodes of CMV viremia in patients clinically suspected to have disseminated disease.

Cytomegalovirus Infections↗
PubMed2004

The utility of indirect predictors of hepatitis C viremia.

OBJECTIVE: Although the majority of injection drug users (IDUs) have been exposed to hepatitis C (HCV), only 60-85% remain chronically viremic and at risk for HCV-induced progressive liver damage or transmitting HCV to others. Access to direct viral testing to establish the presence or absence of viremia is limited due to its expense. This study of 500 current and former IDUs examines the utility of demographic and biochemical features as a means of indirectly predicting HCV viremia. METHODS: Retrospective chart and laboratory review. RESULTS: Overall, 409 (81.8%) were viremic at the time of presentation. HCV viremia did not correlate with the presence of active drug or alcohol use, drug of abuse, duration of drug use, or length of injecting career, but was more common in males and African-Americans. An elevated ALT, found in 36% of patients, was the best biochemical predictor: 95.6% of these patients were viremic. Other predictors of viremia included thrombocytopenia, hypoalbuminemia, elevated GGT, and total bilirubin level, with a stepwise increase in viremia seen as the number of abnormal biochemical predictors increased. The absence of HCV viremia was more difficult to predict. Viremia was found in 66.3% of those lacking all biochemical predictors and even in 43.8% of those in the lowest 10th percentile of ALT. CONCLUSION: Although indirect demographic and laboratory parameters may be used to help predict viremia in 40% of HCV-exposed IDUs, they are inadequate substitutes for direct viral testing and instead should be used only as an adjunct to education and referrals in high-risk patients.

Adult↗
PubMed2005

Detection and quantification of proviral HIV-1 184 M/V in circulating CD4(+) T cells of patients on HAART with a viremia less than 1,000 copies/ml.

BACKGROUND: Highly active anti-retroviral therapy (HAART) effectively reduces HIV replication but does not completely hinder it. Sub-optimal therapy leads to HIV resistance to the drugs administered. However, the role of low-level viremia (viral-load less than 1,000 copies/ml) on mutation genesis and incorporation of resistant forms in the long-lived CD4(+) T cellular DNA compartment is not clear. OBJECTIVE: To investigate the relationship between lamivudine associated mutant-type 184 V and the wild-type 184 M proviral forms in the circulating CD4(+) T cells of patients and low-level viremia. STUDY DESIGN: Cross-sectional study of 50 patients on long-term HAART, with a viremia of less than 1 000 copies/ml. Patients were stratified into three groups; on lamivudine, group I (viral load <20 copies/ml), group II (viral load 20-1000 copies/ml) and as lamivudine experienced, group III (viral load <1000 copies/ml). 184 M and 184 V proviral HIV-1 was detected and quantified by a specific and sensitive assay combining a TaqMan real-time PCR analysis with the amplification-refractory mutation system (ARMS) principle. RESULTS: Fifty-six percent of patients with low-level viremia had 184 V in the CD4(+) T cellular DNA compartment as compared to only 8% in those with undetectable viremia. The presence of 184 V was significantly associated with a higher viral load (P=0.001). Patients with low-level viremia without 184 V in the CD4(+) T cellular DNA compartment, had a median plasma viral load of 135 copies/ml, while patients harbouring 184 V had a median viral load of 498 copies/ml (P=0.006). No significant differences between the groups were observed in proviral HIV-1 DNA load. CONCLUSIONS: The frequency of the 184 V mutation was significantly lower, in the CD4(+) T cellular compartment of patients with a viral load of less than 20 copies/ml as compared to patients with a viremia of 20-1,000 copies/ml. Viremia, sustained below 20 copies/ml may prevent the appearance of 184 V mutation in this reservoir and therefore should be the objective of treatment.

Adult↗
PubMed2005

Randomized, placebo-controlled trial of nonpegylated and pegylated forms of recombinant human alpha interferon 2a for suppression of dengue virus viremia in rhesus monkeys.

Dengue fever and dengue hemorrhagic fever are caused by infection with any one of the four dengue viruses (DVs) and are significant public health burdens throughout the tropics. Higher viremia levels are associated with greater dengue disease severity. A therapeutic intervention to suppress viremia early in DV infection could potentially ameliorate severe disease. Recombinant alpha interferon 2a (rIFN-alpha-2a, Roferon-A) suppressed DV replication in human peripheral blood mononuclear cells in vitro. We therefore examined the effects of rIFN-alpha-2a and pegylated recombinant IFN-alpha-2a (PEG-rIFN-alpha-2a, PEGASYS) on DV serotype 2 (DV-2) viremia in rhesus monkeys. Flavivirus-naïve monkeys were inoculated with DV-2 and randomized to receive a single dose of rIFN-alpha-2a (10 million international units/m2) versus placebo or PEG-rIFN-alpha-2a (6 microg/kg) versus placebo 1 day after the onset of viremia. Serial daily viremia levels were measured, and convalescent-phase DV-2 neutralizing antibody titers were determined. Compared to placebo, a single injection of rIFN-alpha-2a temporarily suppressed DV-2 replication and delayed the time to peak viremia by a median of 3 days. However, measures of total viral burden were not different between the two groups. A single injection of PEG-rIFN-alpha-2a significantly lowered daily viremia levels and improved virus clearance, starting 48 h after administration. There were no significant differences in DV-2 neutralizing antibody titers between the treatment and placebo groups at 30 and 90 days postinfection. Based on their individual effects, future studies should investigate a combination of rIFN-alpha-2a and PEG-rIFN-alpha-2a for suppression of dengue virus viremia and as a potential therapeutic intervention.

Animals↗