scholarly journals Safety and Efficacy of Enfuvirtide in Combination with Darunavir-Ritonavir and an Optimized Background Regimen in Treatment-Experienced Human Immunodeficiency Virus-Infected Patients: the Below the Level of Quantification Study

2008 ◽  
Vol 52 (12) ◽  
pp. 4315-4319 ◽  
Author(s):  
Edwin DeJesus ◽  
Michael S. Gottlieb ◽  
Joseph C. Gathe ◽  
Michael L. Greenberg ◽  
Carol Jean Guittari ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Baseline Viral Load ◽  
Open Label ◽  
Coreceptor Tropism ◽  
Viral Loads ◽  
Immunological Responses ◽  
Hiv Rna ◽  
Background Regimen ◽  
Immunodeficiency Virus

ABSTRACT Enfuvirtide is the first fusion and entry inhibitor approved for use for the treatment of human immunodeficiency virus (HIV) type 1 infection and as such represents a novel class of agents. For the population of patients experienced with three antiretroviral classes, enfuvirtide provides an additional option for treatment. This prospective, open-label, 24-week, single-arm trial assessed the efficacy and safety of enfuvirtide (90 mg injected subcutaneously twice daily) in combination with darunavir-ritonavir (600/100 mg administered orally twice daily) in triple-antiretroviral-class-experienced adults failing their current regimen. The primary efficacy endpoint was the proportion of participants with plasma HIV RNA loads of <50 copies/ml. Other virological and immunological measures were also evaluated, as were the effects of the baseline viral coreceptor tropism and darunavir phenotype sensitivity scores on the outcomes. At week 24, 60.3%, 72.5%, and 84.0% of 131 participants achieved viral loads of <50 copies/ml and <400 copies/ml and a change from the baseline load of ≥1 log10 copies/ml, respectively. A baseline viral load of ≤5 log10 copies/ml was a significant predictor of achieving a viral load of <50 copies/ml at 24 weeks; however, neither background genotype sensitivity nor darunavir phenotype sensitivity was a significant predictor of the achievement of viral loads of <50 copies/ml. Although these findings are limited by the relatively small numbers of participants with darunavir susceptibility changes of ≥10-fold, they suggest that combining enfuvirtide and darunavir-ritonavir with an optimized background regimen in triple-class experienced participants naïve to these agents can result in positive virological and immunological responses regardless of most baseline parameters.

scholarly journals Cryptococcal Antigenemia in Human Immunodeficiency Virus Antiretroviral Therapy–Experienced Ugandans With Virologic Failure

2019 ◽  
Vol 71 (7) ◽  
pp. 1726-1731 ◽  
Author(s):  
Edward Mpoza ◽  
Radha Rajasingham ◽  
Lillian Tugume ◽  
Joshua Rhein ◽  
Maria Sarah Nabaggala ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Antiretroviral Therapy ◽  
Cryptococcal Meningitis ◽  
Virologic Failure ◽  
Cost Effective ◽  
World Health ◽  
Load Testing ◽  
Viral Loads ◽  
Immunodeficiency Virus

Abstract Background Detectable serum or plasma cryptococcal antigen (CrAg) precedes symptomatic cryptococcal meningitis. The World Health Organization recommends CrAg screening for human immunodeficiency virus–positive persons with CD4 count &lt;100 cells/μL initiating antiretroviral therapy (ART). However, an increasing proportion of patients with cryptococcosis are now ART experienced. Whether CrAg screening is cost-effective in those with virologic failure is unknown. Methods We retrospectively performed nationwide plasma CrAg testing among ART-experienced Ugandan adults with virologic failure (≥1000 copies/mL) using leftover plasma after viral load testing during September 2017–January 2018. For those who were CrAg positive, we obtained ART history, meningitis occurrence, and 6-month survival via medical records review. Results Among 1186 subjects with virologic failure, 35 (3.0%) were CrAg positive with median ART duration of 41 months (interquartile range, 10–84 months). Among 25 subjects with 6-month outcomes, 16 (64%) survived, 7 (28%) died, and 2 (8%) were lost. One survivor had suffered cryptococcal meningitis 2 years prior. Two others developed cryptococcal meningitis and survived. Five survivors were known to have received fluconazole. Thus, meningitis-free survival at 6 months was 61% (14/23). Overall, 91% (32/35) of CrAg-positive persons had viral load ≥5000 copies/mL compared with 64% (735/1151) of CrAg-negative persons (odds ratio, 6.0 [95% confidence interval, 1.8–19.8]; P = .001). CrAg prevalence was 4.2% (32/768) among those with viral loads ≥5000 copies/mL and 0.7% (3/419) among those with viral loads &lt;5000 copies/mL. Conclusions In addition to the CD4 threshold of &lt;100 cells/μL, reflexive CrAg screening should be considered in persons failing ART in Uganda with viral loads ≥5000 copies/mL.

Atherosclerotic Cardiovascular Events in Patients Infected With Human Immunodeficiency Virus and Hepatitis C Virus

2020 ◽  
Author(s):  
Boun Kim Tan ◽  
Mathieu Chalouni ◽  
Dominique Salmon Ceron ◽  
Alexandre Cinaud ◽  
Laure Esterle ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Hepatitis C Virus ◽  
Cardiovascular Risk ◽  
Viral Load ◽  
Hepatitis C ◽  
Baseline Viral Load ◽  
Hiv Viral Load ◽  
Factors Associated ◽  
Increased Risk ◽  
Immunodeficiency Virus

Abstract Background An increased risk of cardiovascular disease (CVD) was reported in patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV), without identifying factors associated with atherosclerotic CVD (ASCVD) events. Methods HIV–HCV coinfected patients were enrolled in the ANRS CO13 HEPAVIH nationwide cohort. Primary outcome was total ASCVD events. Secondary outcomes were coronary and/or cerebral ASCVD events, and peripheral artery disease (PAD) ASCVD events. Incidences were estimated using the Aalen-Johansen method. Factors associated with ASCVD were identified using cause-specific Cox proportional hazards models. Results At baseline, median age of the study population (n=1213) was 45.4 (interquartile range [IQR] 42.1−49.0) years and 70.3% were men. After a median follow-up of 5.1 (IQR 3.9−7.0) years, the incidence was 6.98 (95% confidence interval [CI] 5.19−9.38) per 1000 person-years for total ASCVD events, 4.01 (2.78−6.00) for coronary and/or cerebral events, and 3.17 (2.05−4.92) for PAD ASCVD events. Aging (hazard ratio [HR] 1.06, 95% CI 1.01−1.12), prior CVD (HR 8.48, 95% CI 3.14−22.91), high total cholesterol (HR 1.43, 95% CI 1.11−1.83), high-density lipoprotein cholesterol (HR 0.22, 95% CI 0.08−0.63), statin use (HR 3.31, 95% CI 1.31−8.38), and high alcohol intake (HR 3.18, 95% CI 1.35−7.52) were independently associated with total ASCVD events, while undetectable baseline viral load (HR 0.41, 95%CI 0.18−0.96) with coronary and/or cerebral events. Conclusion HIV–HCV coinfected patients experienced a high incidence of ASCVD events. Some traditional cardiovascular risk factors were the main determinants of ASCVD. Controlling cholesterol abnormalities and maintaining undetectable HIV viral load are essential to control cardiovascular risk.

scholarly journals Discrepancies between Protease Inhibitor Concentrations and Viral Load in Reservoirs and Sanctuary Sites in Human Immunodeficiency Virus-Infected Patients

2003 ◽  
Vol 47 (1) ◽  
pp. 238-243 ◽  
Author(s):  
Caroline Solas ◽  
Alain Lafeuillade ◽  
Philippe Halfon ◽  
Stéphane Chadapaud ◽  
Gilles Hittinger ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Lymph Node ◽  
Viral Load ◽  
Lymphoid Tissue ◽  
Drug Penetration ◽  
Hiv Rna ◽  
Drug Concentrations ◽  
Immunodeficiency Virus ◽  
Rna Levels

ABSTRACT The variable penetration of antiretroviral drugs into sanctuary sites may contribute to the differential evolution of human immunodeficiency virus (HIV) and the emergence of drug resistance. We evaluated the penetration of indinavir, nelfinavir, and lopinavir-ritonavir (lopinavir/r) in the central nervous system, genital tract, and lymphoid tissue and assessed the correlation with residual viral replication. Plasma, cerebrospinal fluid (CSF), semen, and lymph node biopsy samples were collected from 41 HIV-infected patients on stable highly active antiretroviral therapy regimens to determine drug concentrations and HIV RNA levels. When HIV RNA was detectable, sequencing of the reverse transcriptase and protease genes was performed. Ratios of the concentration in semen/concentration in plasma were 1.9 for indinavir, 0.08 for nelfinavir, and 0.07 for lopinavir. Only indinavir was detectable in CSF, with a concentration in CSF/concentration in plasma ratio of 0.17. Differential penetration into lymphoid tissue was observed, with concentration in lymph node tissue/concentration in plasma ratios of 2.07, 0.58, and 0.21 for indinavir, nelfinavir, and lopinavir, respectively. HIV RNA levels were <50 copies/ml in all CSF samples of patients in whom HIV RNA was not detectable in plasma. HIV RNA was detectable in the semen of three patients (two patients receiving nelfinavir and one patient receiving lopinavir/r), and its detection was associated with multiple resistance mutations, while the viral load in plasma was undetectable. HIV RNA was detectable in all lymph node tissue samples. Differential drug penetration was observed among the three protease inhibitors in the sanctuary sites, but there was no correlation between drug levels and HIV RNA levels, suggesting that multiple factors are involved in the persistence of viral reservoirs. Further studies are required to clarify the role and clinical relevance of drug penetration in sanctuaries in terms of long-term efficacy and drug resistance.

scholarly journals A High Viral Burden Predicts the Loss of CD8 T-Cell Responses Specific for Subdominant Gag Epitopes during Chronic Human Immunodeficiency Virus Infection

2007 ◽  
Vol 81 (24) ◽  
pp. 13809-13815 ◽  
Author(s):  
Christof Geldmacher ◽  
Clive Gray ◽  
Martha Nason ◽  
Jeffrey R. Currier ◽  
Antelmo Haule ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
T Cell ◽  
T Cell Responses ◽  
Cd8 T Cell ◽  
T Cell Response ◽  
Baseline Viral Load ◽  
Viral Control ◽  
Cell Responses ◽  
Immunodeficiency Virus

ABSTRACT Human immunodeficiency virus (HIV)-specific CD8 T-cell responses targeting products encoded within the Gag open reading frame have frequently been associated with better viral control and disease outcome during the chronic phase of HIV infection. To further clarify this relationship, we have studied the dynamics of Gag-specific CD8 T-cell responses in relation to plasma viral load and time since infection in 33 chronically infected subjects over a 9-month period. High baseline viral loads were associated with a net loss of breadth (P < 0.001) and a decrease in the total magnitude of the Gag-specific T-cell response in general (P = 0.03). Most importantly, the baseline viral load predicted the subsequent change in the breadth of Gag recognition over time (P < 0.0001, r 2 = 0.41). Compared to maintained responses, lost responses were low in magnitude (P < 0.0001) and subdominant in the hierarchy of Gag-specific responses. The present study indicates that chronic exposure of the human immune system to high levels of HIV viremia is a determinant of virus-specific CD8 T-cell loss.

scholarly journals Viral Dynamics during Structured Treatment Interruptions of Chronic Human Immunodeficiency Virus Type 1 Infection

2002 ◽  
Vol 76 (3) ◽  
pp. 968-979 ◽  
Author(s):  
Simon D. W. Frost ◽  
Javier Martinez-Picado ◽  
Lidia Ruiz ◽  
Bonaventura Clotet ◽  
Andrew J. Leigh Brown
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Immune Responses ◽  
Treatment Interruption ◽  
Viral Rebound ◽  
Viral Dynamics ◽  
Viral Loads ◽  
Treatment Interruptions ◽  
Immunodeficiency Virus

ABSTRACT Although antiviral agents which block human immunodeficiency virus (HIV) replication can result in long-term suppression of viral loads to undetectable levels in plasma, long-term therapy fails to eradicate virus, which generally rebounds after a single treatment interruption. Multiple structured treatment interruptions (STIs) have been suggested as a possible strategy that may boost HIV-specific immune responses and control viral replication. We analyze viral dynamics during four consecutive STI cycles in 12 chronically infected patients with a history (>2 years) of viral suppression under highly active antiretroviral therapy. We fitted a simple model of viral rebound to the viral load data from each patient by using a novel statistical approach that allows us to overcome problems of estimating viral dynamics parameters when there are many viral load measurements below the limit of detection. There is an approximate halving of the average viral growth rate between the first and fourth STI cycles, yet the average time between treatment interruption and detection of viral loads in the plasma is approximately the same in the first and fourth interruptions. We hypothesize that reseeding of viral reservoirs during treatment interruptions can account for this discrepancy, although factors such as stochastic effects and the strength of HIV-specific immune responses may also affect the time to viral rebound. We also demonstrate spontaneous drops in viral load in later STIs, which reflect fluctuations in the rates of viral production and/or clearance that may be caused by a complex interaction between virus and target cells and/or immune responses.

scholarly journals Emergence of CXCR4-Using Human Immunodeficiency Virus Type 1 (HIV-1) Variants in a Minority of HIV-1-Infected Patients following Treatment with the CCR5 Antagonist Maraviroc Is from a Pretreatment CXCR4-Using Virus Reservoir

2006 ◽  
Vol 80 (10) ◽  
pp. 4909-4920 ◽  
Author(s):  
Mike Westby ◽  
Marilyn Lewis ◽  
Jeannette Whitcomb ◽  
Mike Youle ◽  
Anton L. Pozniak ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Phylogenetic Analysis ◽  
Viral Load ◽  
Human Immunodeficiency Virus Type ◽  
Virus Type ◽  
Response To Treatment ◽  
Coreceptor Tropism ◽  
Immunodeficiency Virus ◽  
Hiv 1

ABSTRACT Antagonists of the human immunodeficiency virus type 1 (HIV-1) coreceptor, CCR5, are being developed as the first anti-HIV agents acting on a host cell target. We monitored the coreceptor tropism of circulating virus, screened at baseline for coreceptor tropism, in 64 HIV-1-infected patients who received maraviroc (MVC, UK-427,857) as monotherapy for 10 days. Sixty-two patients harbored CCR5-tropic virus at baseline and had a posttreatment phenotype result. Circulating virus remained CCR5 tropic in 60/62 patients, 51 of whom experienced an HIV RNA reduction from baseline of >1 log10 copies/ml, indicating that CXCR4-using variants were not rapidly selected despite CCR5-specific drug pressure. In two patients, viral load declined during treatment and CXCR4-using virus was detected at day 11. No pretreatment factor predicted the emergence of CXCR4-tropic virus during maraviroc therapy in these two patients. Phylogenetic analysis of envelope (Env) clones from pre- and posttreatment time points indicated that the CXCR4-using variants probably emerged by outgrowth of a pretreatment CXCR4-using reservoir, rather than via coreceptor switch of a CCR5-tropic clone under selection pressure from maraviroc. Phylogenetic analysis was also performed on Env clones from a third patient harboring CXCR4-using virus prior to treatment. This patient was enrolled due to a sample labeling error. Although this patient experienced no overall reduction in viral load in response to treatment, the CCR5-tropic components of the circulating virus did appear to be suppressed while receiving maraviroc as monotherapy. Importantly, in all three patients, circulating virus reverted to predominantly CCR5 tropic following cessation of maraviroc.

scholarly journals Safety, Pharmacokinetics, and Efficacy of (+/−)-β-2′,3′-Dideoxy-5-Fluoro-3′-Thiacytidine with Efavirenz and Stavudine in Antiretroviral-Naïve Human Immunodeficiency Virus-Infected Patients

2005 ◽  
Vol 49 (7) ◽  
pp. 2828-2833 ◽  
Author(s):  
C. Herzmann ◽  
K. Arastèh ◽  
R. L. Murphy ◽  
H. Schulbin ◽  
P. Kreckel ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Racemic Mixture ◽  
Pharmacokinetic Parameters ◽  
Viral Loads ◽  
Hiv Rna ◽  
Immunodeficiency Virus ◽  
Additional Therapy ◽  
Hiv 1 ◽  
Rna Levels

ABSTRACT Racivir [RCV; (+/−)-β-2′,3′-dideoxy-5-fluoro-3′-thiacytidine], a 50:50 racemic mixture of the two β nucleoside enantiomers, is currently in development for the treatment of human immunodeficiency virus type 1 (HIV-1) infections. RCV was administered once a day orally for 14 days at doses of 200, 400, or 600 mg in combination with stavudine and efavirenz to HIV-1-infected treatment-naïve male volunteers in a phase Ib/IIa study. Six volunteers at each dose were monitored for a total of 35 days for tolerance, pharmacokinetics, and plasma HIV RNA levels. RCV in combination with stavudine and efavirenz was well tolerated at all doses tested. Pharmacokinetic parameters were dose proportional, and the maximum concentration of drug in serum at all doses exceeded the 90% effective concentration for wild-type HIV-1. Viral loads dropped as expected in all dosage groups, with mean reductions from 1.13 to 1.42 log10 by day 4 and 2.02 to 2.43 log10 by day 14. HIV RNA levels remained suppressed for more than 2 weeks in the absence of any additional therapy, with mean viral loads ranging from 2.1 to 2.6 log10 below baseline through day 28. By day 35, HIV RNA levels began to increase but still remained >1 log10 below baseline levels.

Effect of a single bout of acute exercise on plasma human immunodeficiency virus RNA levels

1999 ◽  
Vol 86 (4) ◽  
pp. 1197-1201 ◽  
Author(s):  
Ronenn Roubenoff ◽  
Paul R. Skolnik ◽  
Abby Shevitz ◽  
Laura Snydman ◽  
Alicia Wang ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Acute Phase Response ◽  
Acute Exercise ◽  
Creatine Phosphokinase ◽  
Hiv Replication ◽  
Viral Loads ◽  
Hiv Rna ◽  
Serum Creatine Phosphokinase ◽  
Immunodeficiency Virus ◽  
Rna Levels

Acute exercise is known to activate the immune system and thus could lead to increased human immunodeficiency virus (HIV) replication. We sought to determine whether a single acute bout of exercise, similar to what people experience when starting an intensive exercise program, has a detrimental effect on plasma HIV RNA levels. Twenty-five patients with HIV infection performed one 15-min bout of acute exercise. Absolute neutrophil counts, serum creatine phosphokinase, and 72-h urinary 3-methylhistidine (a marker of muscle protein breakdown) were measured before and after the exercise, along with plasma HIV RNA levels. There were increases in neutrophil counts ( P < 0.06), serum creatine phosphokinase ( P < 0.01), and urinary 3-methylhistidine ( P < 0.01) in response to exercise, indicating a mild acute-phase response with muscle proteolysis. However, mean HIV RNA, which was elevated at baseline in 22 of the 25 subjects (mean of 4 × 105 ± 0.7 × 105 copies/ml), did not increase during the week after exercise ( P = 0.12). Small changes in RNA were seen in the three subjects with initially undetectable HIV RNA, but the significance of these changes is unclear. Acute exercise does not have a deleterious effect on HIV replication in adults with high viral loads. Because regular exercise training has not been shown to activate the acute-phase response, the lack of increased viral loads in response to an acute exercise intervention suggests that exercise training is safe in people with HIV infection.

scholarly journals Development and Characterization of a Novel Single-Cycle Recombinant-Virus Assay To Determine Human Immunodeficiency Virus Type 1 Coreceptor Tropism

2006 ◽  
Vol 51 (2) ◽  
pp. 566-575 ◽  
Author(s):  
Jeannette M. Whitcomb ◽  
Wei Huang ◽  
Signe Fransen ◽  
Kay Limoli ◽  
Jonathan Toma ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Viral Load ◽  
Human Immunodeficiency Virus Type ◽  
Plasma Viral Load ◽  
Coreceptor Tropism ◽  
Immunodeficiency Virus ◽  
U87 Cells ◽  
Hiv 1

ABSTRACT Most human immunodeficiency virus type 1 (HIV-1) strains require either the CXCR4 or CCR5 chemokine receptor to efficiently enter cells. Blocking viral binding to these coreceptors is an attractive therapeutic target. Currently, several coreceptor antagonists are being evaluated in clinical trials that require characterization of coreceptor tropism for enrollment. In this report, we describe the development of an automated and accurate procedure for determining HIV-1 coreceptor tropism (Trofile) and its validation for routine laboratory testing. HIV-1 pseudoviruses are generated using full-length env genes derived from patient virus populations. Coreceptor tropism is determined by measuring the abilities of these pseudovirus populations to efficiently infect CD4+/U87 cells expressing either the CXCR4 or CCR5 coreceptor. Viruses exclusively and efficiently infecting CXCR4+/CD4+/U87 cells are designated X4-tropic. Conversely, viruses exclusively and efficiently infecting CCR5+/CD4+/U87 cells are designated R5-tropic. Viruses capable of infecting both CXCR4+/CD4+/U87 and CCR5+/CD4+/U87 cells are designated dual/mixed-tropic. Assay accuracy and reproducibility were established by evaluating the tropisms of well-characterized viruses and the variability among replicate results from samples tested repeatedly. The viral subtype, hepatitis B virus or hepatitis C virus coinfection, and the plasma viral load did not affect assay performance. Minority subpopulations with alternate tropisms were reliably detected when present at 5 to 10%. The plasma viral load above which samples can be amplified efficiently in the Trofile assay is 1,000 copies per ml of plasma. Trofile has been automated for high-throughput use; it can be used to identify patients most likely to benefit from treatment regimens that include a coreceptor inhibitor and to monitor patients on treatment for the emergence of resistant virus populations that switch coreceptor tropism.

Sign in / Sign up

Export Citation Format

Share Document