scholarly journals Population Pharmacokinetics and Pharmacodynamic Modeling of Abacavir (1592U89) from a Dose-Ranging, Double-Blind, Randomized Monotherapy Trial with Human Immunodeficiency Virus-Infected Subjects

2000 ◽  
Vol 44 (8) ◽  
pp. 2052-2060 ◽  
Author(s):  
Stephen Weller ◽  
Kristine M. Radomski ◽  
Yu Lou ◽  
Daniel S. Stein
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Count ◽  
Population Pharmacokinetics ◽  
Pharmacodynamic Modeling ◽  
Population Pharmacokinetic ◽  
Parameter Estimates ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Rna Levels

ABSTRACT Abacavir (formerly 1592U89) is a carbocyclic nucleoside analog with potent anti-human immunodeficiency virus (anti-HIV) activity when administered alone or in combination with other antiretroviral agents. The population pharmacokinetics and pharmacodynamics of abacavir were investigated in 41 HIV type 1 (HIV-1)-infected, antiretroviral naive adults with baseline CD4+ cell counts of ≥100/mm3 and plasma HIV-1 RNA levels of >30,000 copies/ml. Data for analysis were obtained from patients who received randomized, blinded monotherapy with abacavir at 100, 300, or 600 mg twice-daily (BID) for up to 12 weeks. Plasma abacavir concentrations from sparse sampling were analyzed by standard population pharmacokinetic methods, and the effects of dose, combination therapy, gender, weight, and age on parameter estimates were investigated. Bayesian pharmacokinetic parameter estimates were calculated to determine the peak concentration of abacavir in plasma (C max) and the area under the concentration-time curve from time zero to infinity (AUC0–∞) for individual subjects. The pharmacokinetics of abacavir were dose proportional over the 100- to 600-mg dose range and were unaffected by any covariates. No significant correlations were observed between the incidence of the five most common adverse events (headache, nausea, diarrhea, vomiting, and malaise or fatigue) and AUC0–∞. A significant correlation was observed betweenC max and nausea by categorical analysis (P = 0.019), but this was of borderline significance by logistic regression (odds ratio, 1.45; 95% confidence interval, 0.95 to 2.32). The log10 time-averaged AUC0–∞ minus baseline (AAUCMB) values for HIV-1 RNA and CD4+ cell count correlated significantly withC max and AUC0–∞, but with better model fits for AUC0–∞. The increase in AAUCMB values for CD4+ cell count plateaued early for drug exposures that were associated with little change in AAUCMB values for plasma HIV-1 RNA. There was less than a 0.4 log10 difference over 12 weeks in the HIV-1 RNA levels with the doubling of the abacavir AUC0–∞ from 300 to 600 mg BID dosing. In conclusion, pharmacodynamic modeling supports the selection of abacavir 300 mg twice-daily dosing.

scholarly journals Frequency of Cytomegalovirus Viral Load in Iranian Human Immunodeficiency Virus-1-Infected Patients with CD4+ Counts <100 Cells/mm3

Intervirology ◽  
2021 ◽  
pp. 1-5
Author(s):  
Mohammad Reza Jabbari ◽  
Hoorieh Soleimanjahi ◽  
Somayeh Shatizadeh Malekshahi ◽  
Mohammad Gholami ◽  
Leila Sadeghi ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Cell Count ◽  
Previous History ◽  
Cd4 Count ◽  
Cd4 Cell Count ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Cd4 Cell ◽  
Hiv 1

<b><i>Objectives:</i></b> The aim of present work was to assess cytomegalovirus (CMV) viremia in Iranian human immunodeficiency virus (HIV)-1-infected patients with a CD4+ count &#x3c;100 cells/mm<sup>3</sup> and to explore whether CMV DNA loads correlate with CD4+ cell counts or associated retinitis. <b><i>Methods:</i></b> This study was conducted at the AIDS research center in Iran on HIV-1-infected patients with CD4+ count &#x3c;100 cells/mm<sup>3</sup>, antiretroviral therapy-naive, aged ≥18 years with no previous history of CMV end-organ disease (CMV-EOD). <b><i>Results:</i></b> Thirty-nine of 82 patients (47.56%) had detectable CMV viral load ranging from 66 to 485,500 IU/mL. CMV viral load in patients with retinitis ranges from 352 to 2,720 IU/mL, and it was undetectable in 2 patients. No significant associations between CMV viremia and CD4+ cell count was found (<i>p</i> value = 0.31), whereas significant association of CMV viremia in HIV-infected patients with retinitis was found (<i>p</i> &#x3c; 0.02). <b><i>Conclusions:</i></b> We estimated the frequency of CMV viral load infection in Iranian HIV-1-infected patients with a CD4+ cell count &#x3c;100 mm<sup>3</sup>/mL in the largest national referral center for HIV-1 infection in Iran. Further research is required on the relevance of CMV viral load in diagnostic and prognostic value of CMV-EOD.

scholarly journals Plasma Profiles of Inflammatory Markers Associated With Active Tuberculosis in Antiretroviral Therapy-Naive Human Immunodeficiency Virus-Positive Individuals

2019 ◽  
Vol 6 (2) ◽  
Author(s):  
Oskar Olsson ◽  
Per Björkman ◽  
Marianne Jansson ◽  
Taye Tolera Balcha ◽  
Daba Mulleta ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Cell Count ◽  
Inflammatory Markers ◽  
Area Under The Curve ◽  
Hiv Positive ◽  
Cd4 Cell Count ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Cd4 Cell ◽  
Rna Levels

Abstract Background Diagnosis of tuberculosis (TB) in human immunodeficiency virus (HIV)-coinfected individuals is challenging. We hypothesized that combinations of inflammatory markers could facilitate identification of active TB in HIV-positive individuals. Methods Participants were HIV-positive, treatment-naive adults systematically investigated for TB at Ethiopian health centers. Plasma samples from 130 subjects with TB (HIV+/TB+) and 130 subjects without TB (HIV+/TB−) were tested for concentration of the following markers: CCL5, C-reactive protein (CRP), interleukin (IL)-6, IL12-p70, IL-18, IL-27, interferon-γ-induced protein-10 (IP-10), procalcitonin (PCT), and soluble urokinase-type plasminogen activator receptor (suPAR). Analyzed markers were then assessed, either individually or in combination, with regard to infection status, CD4 cell count, and HIV ribonucleic acid (RNA) levels. Results The HIV+/TB+ subjects had higher levels of all markers, except IL12p70, compared with HIV+/TB− subjects. The CRP showed the best performance for TB identification (median 27.9 vs 1.8 mg/L for HIV+/TB+ and HIV+/TB−, respectively; area under the curve [AUC]: 0.80). Performance was increased when CRP was combined with suPAR analysis (AUC, 0.83 [0.93 for subjects with CD4 cell count &lt;200 cells/mm3]). Irrespective of TB status, IP-10 concentrations correlated with HIV RNA levels, and both IP-10 and IL-18 were inversely correlated to CD4 cell counts. Conclusions Although CRP showed the best single marker discriminatory potential, combining CRP and suPAR analyses increased performance for TB identification.

scholarly journals Comparison of NucliSens and Amplicor Monitor Assays for Quantification of Human Immunodeficiency Virus Type 1 (HIV-1) RNA in Plasma of Persons with HIV-1 Subtype A Infection in Abidjan, Côte d’Ivoire

1998 ◽  
Vol 36 (9) ◽  
pp. 2495-2498 ◽  
Author(s):  
John N. Nkengasong ◽  
Mirielle Kalou ◽  
Chantal Maurice ◽  
Celestin Bile ◽  
Marie-Yolande Borget ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Plasma Samples ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Subtype A ◽  
Hiv 1 ◽  
Rna Levels

We compared the sensitivity and accuracy of the NucliSens assay and those of both the standard and modified (addition of a new primer set, primer mix 1, supplied by Roche) Amplicor HIV Monitor assays to quantify human immunodeficiency virus type 1 (HIV-1) RNA in persons infected with HIV-1 subtype A in Abidjan, Côte d’Ivoire. Seventy-one plasma samples from HIV-1-seropositive persons at different stages of HIV infection and 15 samples from HIV antibody-negative persons were analyzed. The HIV-1 genetic subtype was determined either by DNA sequencing or by a restriction fragment length polymorphism assay. Of the 71 samples, 70 (98%) were subtype A and 1 was subtype G. Of the 70 subtype A samples, the proportion of RNA-positive plasma samples and mean HIV-1 RNA levels were significantly higher by the modified HIV Monitor assay (n = 67 [96%]; mean RNA levels, 5.2 log10 HIV-1 RNA copies/ml) than the NucliSens assay (n = 56 [80%]; 4.3 log10 HIV-1 RNA copies/ml) or the standard HIV Monitor assay (n = 44 [63%]; mean RNA levels, 3.8 log10 HIV-1 RNA copies/ml) (all P values were <0.05). The HIV-1 RNA levels by the modified HIV Monitor assay correlated significantly with those by the NucliSens assay (r = 0.76; P< 0.001) and the standard HIV Monitor assay (r = 0.57; P < 0.001), as did the RNA levels by the NucliSens and the standard HIV Monitor assays (r = 0.60; P < 0.001). Lower CD4 cell counts were significantly correlated with higher HIV-1 RNA levels by all three assays (r = −0.47 for the NucliSens assay, −0.45 for the standard HIV Monitor assay, and −0.62 for the modified HIV Monitor assay). These results indicate that the modified HIV Monitor assay has the highest sensitivity and efficiency at quantifying the levels of RNA in persons infected with HIV-1 subtype A and thus constitutes a valuable tool for the monitoring of RNA levels in areas of Africa were HIV-1 subtype A is predominant.

scholarly journals Efficacy of Zidovudine Compared to Stavudine, Both in Combination with Lamivudine and Indinavir, in Human Immunodeficiency Virus-Infected Nucleoside-Experienced Patients with No Prior Exposure to Lamivudine, Stavudine, or Protease Inhibitors (Novavir Trial)

2002 ◽  
Vol 46 (6) ◽  
pp. 1906-1913 ◽  
Author(s):  
Véronique Joly ◽  
Philippe Flandre ◽  
Vincent Meiffredy ◽  
Françoise Brun-Vezinet ◽  
Jean-Albert Gastaut ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Adverse Events ◽  
Protease Inhibitors ◽  
Primary Endpoint ◽  
Virological Failure ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Cd4 Cell ◽  
Hiv 1 ◽  
Rna Levels

ABSTRACT We compared the efficacy and the toxicity of zidovudine (AZT) versus stavudine (d4T), in combination with lamivudine (3TC) and indinavir, in AZT-, dideoxyinosine (ddI)-, and/or dideoxycytosine (ddC)-experienced patients in a randomized comparative multicenter trial. One hundred seventy human immunodeficiency virus type 1 (HIV-1)-infected patients, who had received AZT, ddI, and/or ddC for at least 6 months but were naive for d4T, 3TC, and protease inhibitors, were randomized to AZT at 250 to 300 mg twice daily, 3TC at 150 mg twice daily, and indinavir at 800 mg every 8 h or to d4T at 40 mg twice daily, 3TC at 150 mg twice daily, and indinavir at 800 mg every 8 h. The primary endpoint was time to virological failure, defined as plasma HIV-1 RNA levels of >5,000 copies/ml after at least 8 weeks of antiretroviral therapy. Additional endpoints were change from baseline in CD4 cell counts, AIDS-defining events and adverse events, and proportion of patients with HIV-1 RNA levels of <500 copies/ml and HIV-1 RNA levels of <50 copies/ml. At week 80, 15 patients in the AZT arm and 14 patients in the d4T arm had reached the primary endpoint, and time to virological failure did not differ between the two arms (P = 0.98). In the d4T and in the AZT arms, 67 and 73% of patients, respectively, had HIV-1 RNA levels of <500 copies/ml (P = 0.50). The median change from baseline in CD4 cell count was 195 × 106 and 175 × 106/liter for the d4T- and AZT-containing arms, respectively. The proportions of patients with HIV-1 RNA levels of <50 copies/ml at weeks 8, 16, and 24 were similar in the two arms. The occurrence of serious adverse events was not significantly different between arms. In conclusion, in these patients heavily pretreated with AZT, switching from AZT to d4T when initiating indinavir and 3TC did not bring any additional benefit compared to maintaining AZT.

scholarly journals Immunological Responses and Long-Term Treatment Interruption after Human Immunodeficiency Virus Type 1 (HIV-1) Lipopeptide Immunization of HIV-1-Infected Patients: the LIPTHERA Study

2008 ◽  
Vol 15 (3) ◽  
pp. 562-568 ◽  
Author(s):  
Gilles Pialoux ◽  
Romina P. Quercia ◽  
Hanne Gahery ◽  
Nathalie Daniel ◽  
Laurence Slama ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Antiretroviral Therapy ◽  
Cell Count ◽  
Human Immunodeficiency Virus Type ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Haart Interruption ◽  
Hiv 1

ABSTRACT We studied the time course of immunological and virological markers after highly active antiretroviral therapy (HAART) interruption in chronically human immunodeficiency virus type 1 (HIV-1)-infected patients immunized with an HIV lipopeptide preparation. In a prospective open pilot study, 24 HIV-1-infected HAART-treated patients with undetectable plasma viral loads (pVLs) and CD4+ T-cell counts above 350/mm3 were immunized at weeks 0, 3, and 6 with a candidate vaccine consisting of six HIV lipopeptides. At week 24, patients with pVLs of <1.7 log10 copies/ml were invited to stop taking HAART. Antiretroviral therapy was resumed if the pVL rose above 4.47 log10 copies/ml and/or if the CD4+ cell count fell below 250/mm3. Immunological and virologic parameters were studied before and after HAART interruption. The median baseline and nadir CD4+ cell counts were 482 (interquartile range [IQR], 195 to 826) and 313 (IQR, 1 to 481)/mm3, respectively. New specific CD8+ cell responses to HIV-1 epitopes were detected after immunization in 13 (57%) of 23 assessable patients. Twenty-one patients were evaluated 96 weeks after HAART interruption. The median time to pVL rebound was 4 weeks (IQR, 2 to 6), and the median peak pVL was 4.26 (IQR, 3 to 5) log10 copies/ml. Thirteen of these 21 patients resumed HAART a median of 60 weeks after immunization (IQR, 9.2 to 68.4 weeks), when the median pVL was 4.8 (IQR, 2.9 to 5.7) log10 copies/ml and the median CD4+ cell count was 551 (IQR, 156 to 778)/mm3. Eight patients were still off therapy at 96 weeks, with a median pVL of 4 (IQR, 1.7 to 4.6) log10 copies/ml and a median CD4+ cell count of 412 (IQR, 299 to 832)/mm3. No clinical disease progression had occurred. Despite the lack of a control arm, these findings warrant a randomized study of therapeutic vaccination with HIV lipopeptides followed by long-term HAART interruption in AIDS-free chronically infected patients.

scholarly journals Population Pharmacokinetics of Lamivudine in Adult Human Immunodeficiency Virus-Infected Patients Enrolled in Two Phase III Clinical Trials

1999 ◽  
Vol 43 (12) ◽  
pp. 3025-3029 ◽  
Author(s):  
Katy H. P. Moore ◽  
Geoffrey J. Yuen ◽  
Elizabeth K. Hussey ◽  
Gary E. Pakes ◽  
Joseph J. Eron ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Renal Function ◽  
Creatinine Clearance ◽  
Cell Count ◽  
Population Pharmacokinetics ◽  
Phase Iii ◽  
Pharmacokinetic Studies ◽  
Mixed Effect ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Lamivudine population pharmacokinetics were investigated by using nonlinear mixed-effect modelling (NONMEM) analysis of data from 394 human immunodeficiency virus (HIV)-infected patients treated with lamivudine (150 to 300 mg every 12 h) in two large, phase III clinical efficacy-safety trials, NUCA3001 and NUCA3002. Analyses of 1,477 serum lamivudine concentration determinations showed that population estimates for lamivudine oral clearance (CL/F; 25.1 liters/h) and volume of distribution (V/F; 128 liters) were similar to values previously reported for HIV-infected patients in phase I pharmacokinetic studies. Lamivudine CL/F was significantly influenced by the covariates creatinine clearance and weight and not affected by age, Centers for Disease Control and Prevention (CDC) classification, CD4+ cell count, HIV type 1 (HIV-1) RNA PCR, or gender and race when CL/F was corrected for differences in patient weight. The population estimate for lamivudine V/F was not significantly influenced by the covariates gender, race, age, weight, renal function, HIV-1 RNA PCR, or CDC classification and CD4+ cell count when creatinine clearance was included with CL/F in the model. Lamivudine disposition was significantly influenced by renal function. However, as only three patients had an estimated creatinine clearance of <60 ml/min, dosage adjustments for patients with impaired renal function should not be determined based on the population parameters derived in this analysis.

scholarly journals Purifying selection of CCR5-tropic human immunodeficiency virus type 1 variants in AIDS subjects that have developed syncytium-inducing, CXCR4-tropic viruses

2006 ◽  
Vol 87 (5) ◽  
pp. 1285-1294 ◽  
Author(s):  
Guerau Fernàndez ◽  
Anuska Llano ◽  
Miriam Esgleas ◽  
Bonaventura Clotet ◽  
José A. Esté ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
T Cell ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Purifying Selection ◽  
Selective Pressures ◽  
Cell Counts ◽  
Immunodeficiency Virus ◽  
Hiv 1

Human immunodeficiency virus type 1 (HIV-1) infection is established by virus variants that use the CCR5 co-receptor for entry (CCR5-tropic or R5 variants), whereas viruses that use CXCR4 as co-receptor (CXCR4-tropic or X4 variants) emerge during disease progression in approximately 50 % of infected subjects. X4 variants may have a higher fitness ex vivo and their detection is usually accompanied by faster T-cell depletion and the onset of AIDS in HIV-1-positive individuals. Here, the relationship between the sequence variation of the HIV-1 env V3–V5 region and positive selective pressure on R5 and X4 variants from infected subjects with CD4 T cell counts below 200 cells μl−1 was studied. A correlation was found between genetic distance and CD4+ cell count at late stages of the disease. R5 variants that co-existed with X4 variants were significantly less heterogeneous than R5 variants from subjects without X4 variants (P<0·0001). Similarly, X4 variants had a significantly higher diversity than R5 variants (P<0·0001), although residues under positive selection had a similar distribution pattern in both variants. Therefore, both X4 and R5 variants were subjected to high selective pressures from the host. Furthermore, the interaction between X4 and R5 variants within the same subject resulted in a purifying selection on R5 variants, which only survived as a homogeneous virus population. These results indicate that R5 variants from X4 phenotype samples were highly homogeneous and under weakly positive selective pressures. In contrast, R5 variants from R5 phenotype samples were highly heterogeneous and subject to positive selective pressures.

scholarly journals Safety, tolerance, and efficacy of atevirdine in asymptomatic human immunodeficiency virus-infected individuals.

1996 ◽  
Vol 40 (11) ◽  
pp. 2664-2668 ◽  
Author(s):  
A M Been-Tiktak ◽  
I Williams ◽  
H M Vrehen ◽  
J Richens ◽  
D Aldam ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Transcriptase Inhibitor ◽  
Viral Loads ◽  
Nonnucleoside Reverse Transcriptase Inhibitor ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Immunodeficiency Virus ◽  
Reverse Transcriptase Inhibitor ◽  
Cd4 Cell ◽  
Hiv 1

Atevirdine is a nonnucleoside reverse transcriptase inhibitor of human immunodeficiency virus type 1 (HIV-1). In this study we investigated the effect of atevirdine in asymptomatic antiretroviral naive HIV-infected patients with CD4+ cell counts of between 200 and 750 cells per mm3. Patients were randomized to receive 600 mg of atevirdine (n = 15) or a placebo (n = 15) three times a day for 12 weeks. There was no statistically significant effect of atevirdine on viral loads (HIV p24 antigen and HIV-1 RNA levels by PCR) or CD4+ cell counts. The data do not support the use of atevirdine as a monotherapy in the treatment of HIV-infected patients.

Changes in human immunodeficiency virus type 1 virus load during mobilization and harvesting of hemopoietic progenitor cells

Blood ◽  
2000 ◽  
Vol 95 (1) ◽  
pp. 48-55
Author(s):  
Thomas B. Campbell ◽  
Anne Sevin ◽  
Robert W. Coombs ◽  
Gregory C. Peterson ◽  
Mary Rosandich ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Progenitor Cells ◽  
Mononuclear Cells ◽  
Ex Vivo ◽  
Hemopoietic Stem Cell ◽  
Immunodeficiency Virus ◽  
Hiv 1 ◽  
Hemopoietic Progenitor ◽  
Hemopoietic Progenitor Cells ◽  
Rna Levels

Genetic modification of hemopoietic progenitor cells ex vivo, followed by the infusion of the genetically modified cells into the human immunodeficiency virus-1 (HIV-1) infected donor, has been proposed as a treatment for HIV-1 infection. The current study was undertaken to evaluate the effect of hemopoietic stem cell mobilization and harvesting on HIV-1 replication in persons with HIV-1 infection. Eighteen HIV-1–infected persons received recombinant granulocyte colony-stimulating factor (G-CSF; Filgrastim) 10 μg/kg per day, for 7 days. On days 4 and 5, peripheral blood mononuclear cells were harvested by leukapheresis. The CD4+ lymphocyte count at entry was >500/μL for 6 subjects, 200 to 500/μL for 6 subjects, and <200/μL for 6 subjects. For 9 of 18 subjects, plasma HIV-1 RNA levels increased 4- to 100-fold (>0.6 log10) above baseline between days 4 and 7 and returned to baseline by day 27. Significant increases of plasma HIV-1 RNA levels occurred in 5 subjects despite 3-drug antiretroviral therapy. Changes in CD4+ and CD34+ cells during mobilization and harvesting were similar in all subjects whether they had or did not have increased plasma HIV-1 RNA levels. Thus, mobilization and harvesting of bone marrow progenitor cells from persons infected with HIV-1 induced a transient increase in viral replication in some patients but was not associated with adverse effects. (Blood. 2000;95: 48-55)

Sign in / Sign up

Export Citation Format

Share Document