- Pharmacokinetic Changes during Pregnancy According to Genetic Variants: A Prospective Study in HIV-infected Patients Receiving Atazanavir/Ritonavir. [Journal Article]
- AAAntimicrob Agents Chemother 2018 May 14
- Atazanavir/ritonavir concentrations change over pregnancy in HIV-positive patients; the impact of genetic variants is unknown. 20 patients were enrolled: antiretrovirals' plasma and intracellular con...
Atazanavir/ritonavir concentrations change over pregnancy in HIV-positive patients; the impact of genetic variants is unknown. 20 patients were enrolled: antiretrovirals' plasma and intracellular concentrations were measured in addition to single nucleotide polymorphisms in transport affecting genes. Linear logistic regression showed that genetic variants in organic-anion-transporter-1B1 and pregnane-X-receptor encoding genes affected third trimester atazanavir exposure. In this prospective study genetic variants partially explained the observed inter-patient variability in third-trimester antiretrovirals' exposure.
- HIV aspartyl protease inhibitors modify the percentage of activated leukocytes, as well as serum levels of IL-17A and NO during experimental leishmaniasis. [Journal Article]
- IIInt Immunopharmacol 2018 May 07; 60:179-188
- HIV aspartyl protease inhibitors are able to modulate multiple defense mechanisms. However, their influence on the immune response against Leishmania has rarely been investigated. The aim of our stud...
HIV aspartyl protease inhibitors are able to modulate multiple defense mechanisms. However, their influence on the immune response against Leishmania has rarely been investigated. The aim of our study was to investigate whether in vivo treatment with HIV aspartyl protease inhibitors is able to modulate the immune response during Leishmania infection. Using Leishmania (L.) amazonensis-infected mice, we analyzed the disease evolution and parasite load, immunophenotypic profiles of splenic T and B lymphocytes, numbers of lymphoid aggregates in the spleen, percentages of circulating atypical lymphocytes and reactive monocytes, and serum levels of cytokines and nitric oxide (NO) after 30 days of oral treatment with lopinavir/ritonavir (LPV/RTV) or atazanavir (ATV). We observed that LPV/RTV and ATV did not modify the disease evolution or parasite load. However, the antiretroviral treatment induced an increase in activated lymphocytes in the spleen and blood, as well as a decrease in CD69 expression in T and B lymphocytes in the spleen. The treatment also resulted in an increase in activated monocytes in the blood. In addition, antiretrovirals decreased levels of IL-17A and increased levels of NO in sera from Leishmania-infected mice. Thus, our results demonstrate for the first time that in vivo treatment with HIV aspartyl protease inhibitors modifies innate and adaptative immune responses during Leishmania infection and suggest that these drugs could change the clinical course of leishmaniasis in HIV infected-individuals.
- Subclinical cardiovascular disease in patients starting contemporary protease inhibitors. [Journal Article]
- HMHIV Med 2018 May 10
- CONCLUSIONS: CIMT was a more sensitive marker of subclinical vascular disease progression than arterial stiffness in antiretroviral-naïve patients starting antiretroviral therapy with contemporary protease inhibitors. Classical risk factors but not antiretroviral therapy were associated with faster CIMT progression.
- Cardiovascular disease and use of contemporary protease inhibitors: the D:A:D international prospective multicohort study. [Journal Article]
- LHLancet HIV 2018 May 03
- CONCLUSIONS: Cumulative use of ritonavir-boosted darunavir, but not of ritonavir-boosted atazanavir, is associated with progressively increasing risk of cardiovascular disease. Causal inference is limited by the observational nature of the D:A:D study. Our findings should prompt investigation into the possible underlying mechanisms of this finding.
- Long-term treatment with atazanavir (ATV) in real life in Belgium: a retrospective observational cohort of 2264 HIV patients. [Journal Article]
- ACActa Clin Belg 2018 May 02; :1-8
- Objectives This 5-year follow-up study aimed to assess clinical outcomes of HIV-1 infected adults treated with atazanavir (ATV) in clinical practice in Belgium, to describe patient profiles and chara...
Objectives This 5-year follow-up study aimed to assess clinical outcomes of HIV-1 infected adults treated with atazanavir (ATV) in clinical practice in Belgium, to describe patient profiles and characteristics, as well as treatment safety. Methods A multicenter, non-interventional, non-comparative, retrospective cohort study was performed in HIV-1 positive adult patients treated with ATV between 2006 and 2012. Data were collected from 8 AIDS reference centers' databases. All analyses were on-treatment. Sub-analyses were carried out in unboosted ATV treated patients and in females. The primary endpoint was defined as the time-to-treatment-discontinuation. Furthermore, virological suppression, immunological response, time to loss of virological response, reasons for ATV initiation, and discontinuation were also assessed. Results 2264 ARV-naive and ARV-experienced patients (median age: 41 years) were included. Females and non-Caucasians were broadly represented (40 and 45%, respectively). The probability to remain on treatment was 0.78 (CI: 0.76; 0.78) for the first and 0.69 (CI: 0.66; 0.71) for the second year and was similar between males and females. Overall, 771 patients (34.1%) discontinued ATV over time, the median (Q1-Q3) time to discontinuation being 0.8 (0.3-1.5) year. In unboosted ATV-treated patients, results were comparable to the overall ATV population, except for a higher rate of discontinuation-over-time (45.1%). Conclusions Clinical and safety data from this 5 year-cohort study show that the vast majority of patients remained on ATV treatment for the first and second years, overall as well as patients treated with unboosted ATV and females.
- Emerging resistance mutations in PI-naive patients failing an atazanavir-based regimen (ANRS multicentre observational study). [Journal Article]
- JAJ Antimicrob Chemother 2018 Apr 27
- CONCLUSIONS: Resistance to atazanavir is rare in patients failing the first line of an atazanavir-based regimen according to the ANRS. Emergent NRTI resistance-associated mutations were reported in 18% of patients.
- Monomorphic ventricular tachycardia due to protease inhibitor intoxication by atazanavir. [Journal Article]
- CEClin Exp Emerg Med 2018 Apr 30
- Atazanavir is a protease inhibitor approved for use in combination with other antiretroviral drugs for the treatment of human immunodeficiency virus infection. Atazanavir and other protease inhibitor...
Atazanavir is a protease inhibitor approved for use in combination with other antiretroviral drugs for the treatment of human immunodeficiency virus infection. Atazanavir and other protease inhibitors can sometimes induce corrected QT prolongation and ventricular arrhythmia. A 40-year-old man with no comorbidities, except human immunodeficiency virus 1 infection, presented with palpitations 3 days after an overdose of 150 caps of atazanavir, with suicidal intent. His initial electrocardiogram showed monomorphic ventricular tachycardia, and hyperbilirubinemia was observed in his initial blood test. Immediately after magnesium sulfate infusion, his ventricular tachycardia was converted into junctional bradycardia with prolonged corrected QT. After 3 days of close observation in the intensive care unit, the corrected QT prolongation and hyperbilirubinemia were normalized.
- Birth Outcomes for Pregnant Women with HIV Using Tenofovir-Emtricitabine. [Journal Article]
- NEJMN Engl J Med 2018 04 26; 378(17):1593-1603
- CONCLUSIONS: The risk of adverse birth outcomes was not higher with TDF-FTC-LPV/r than with ZDV-3TC-LPV/r or TDF-FTC-ATV/r among HIV-infected women and their infants in the United States, although power was limited for some comparisons. (Funded by the National Institutes of Health and others.).
- Coupling of an Acyl Migration Prodrug Strategy with Bio-activation To Improve Oral Delivery of the HIV-1 Protease Inhibitor Atazanavir. [Journal Article]
- JMJ Med Chem 2018 May 10; 61(9):4176-4188
- HIV-1 protease inhibitors (PIs), which include atazanavir (ATV, 1), remain important medicines to treat HIV-1 infection. However, they are characterized by poor oral bioavailability and a need for bo...
HIV-1 protease inhibitors (PIs), which include atazanavir (ATV, 1), remain important medicines to treat HIV-1 infection. However, they are characterized by poor oral bioavailability and a need for boosting with a pharmacokinetic enhancer, which results in additional drug-drug interactions that are sometimes difficult to manage. We investigated a chemo-activated, acyl migration-based prodrug design approach to improve the pharmacokinetic profile of 1 but failed to obtain improved oral bioavailability over dosing the parent drug in rats. This strategy was refined by conjugating the amine with a promoiety designed to undergo bio-activation, as a means of modulating the subsequent chemo-activation. This culminated in a lead prodrug that (1) yielded substantially better oral drug delivery of 1 when compared to the parent itself, the simple acyl migration-based prodrug, and the corresponding simple l-Val prodrug, (2) acted as a depot which resulted in a sustained release of the parent drug in vivo, and (3) offered the benefit of mitigating the pH-dependent absorption associated with 1, thereby potentially reducing the risk of decreased bioavailability with concurrent use of stomach-acid-reducing drugs.
New Search Next
- Incidence of symptomatic CSF viral escape in HIV infected patients receiving atazanavir/ritonavir (ATV/r)-containing ART: a tertiary care cohort in western India. [Journal Article]
- JNJ Neurovirol 2018 Apr 24
- This single-center study attempts to quantify the incidence of symptomatic CSF viral escape (CSFVE) in patients receiving atazanavir/r (ATV/r)-containing regimen. We performed a retrospective analysi...
This single-center study attempts to quantify the incidence of symptomatic CSF viral escape (CSFVE) in patients receiving atazanavir/r (ATV/r)-containing regimen. We performed a retrospective analysis of patients receiving ATV/r-containing ART who were diagnosed with symptomatic CSFVE from August 2012 to January 2017. Primary objective was to assess the incidence of symptomatic CSFVE in patients receiving ATV/r-containing ART in clinical practice. Incidence rates were calculated by dividing the number of patients who experienced CSFVE by the number of person-months at risk and summarized as per 10,000 (ten thousand) person-months at risk. Nine hundred thirty-three patients receiving ATV/r containing ART with a total of 36,068 person-months of follow-up were included. Incidence rate of symptomatic CSFVE was 4.4 per 10,000 person-months (95% CI 2.7 to 7.2). The incidence of CSFVE was 9.5 per 10,000 person-months (95% CI 5.7 to 15.7) when the nadir CD4 count was ≤ 200 compared to 0.49 (95% CI 0.07 to 3.5) with a nadir CD4 count > 200 (IRR 19.1 (95% CI 2.93 to 802.8), p < 0.0001). Nadir CD4 count ≤ 200 was associated with substantially increased risk of symptomatic CSFVE, further strengthening efforts to diagnose and treat patients early in disease.