scholarly journals Darunavir/cobicistat/emtricitabine/tenofovir alafenamide versus dolutegravir /abacavir/lamivudine in antiretroviral-naïve adults (SYMTRI): a multicenter randomized open-label study (PReEC/RIS-57)

2021 ◽  
Author(s):  
D Podzamczer ◽  
R Micán ◽  
J Tiraboschi ◽  
J Portilla ◽  
P Domingo ◽  
...  
Keyword(s):  
Combination Therapy ◽  
Virologic Failure ◽  
Drug Discontinuation ◽  
Weight Changes ◽  
Open Label ◽  
Cd4 Cell Count ◽  
Exposed Population ◽  
Tenofovir Alafenamide ◽  
Almost All ◽  
Cd4 Cell

Abstract Background D/C/F/TAF is the reference for combination therapy based on protease inhibitors due to its efficacy, tolerability, and convenience. Head-to-head randomized comparisons between D/C/F/TAF and combination therapy based on integrase inhibitors in antiretroviral-naïve patients are lacking. Methods Adult (>18 y) HIV-infected antiretroviral-naïve patients (HLA B5701– and HBV-negative), with VL ≥500 c/mL, were centrally randomized to initiate D/C/F/TAF or DTG/3TC/ABC after stratifying by viral load and CD4 count. Clinical and analytical assessments were performed at weeks 0, 4, 12, 24, and 48. The primary endpoint was VL <50 c/mL at week 48 in the ITT-exposed population (FDA snapshot analysis, 10% non-inferiority margin). Results Between September 2018 and 2019, 316 patients were randomized and 306 patients were included in the ITT-exposed analysis (151 D/C/F/TAF and 155 DTG/3TC/ABC). Almost all (94%) participants were male and their median age was 35 years. 40% had a baseline VL >100,000 copies/mL, and 13% had <200 CD4 cells/μL. Median weight was 73 kg and median BMI 24 kg/m 2. At 48 weeks, 79% (D/C/F/TAF) vs 82% (DTG/3TC/ABC) had VL <50 c/mL (difference –2.4%, 95%CI –11.3 to 6.6). 8% vs 4% experienced virologic failure but no RAMs emerged. 4% vs 6% had drug discontinuation due to adverse events. In the per protocol analysis, 94% vs 96% patients had VL <50 c/mL (difference –2%, 95%CI –8.1 to 3.5). There were no differences in CD4 cell count or weight changes. Conclusions We could not demonstrate the non-inferiority of D/C/F/TAF relative to DTG/ABC/3TC as initial ART, although both regimens were similarly well tolerated.

scholarly journals 2344. FDA Analysis of CD4+ Cell Count Declines Observed in HIV-Infected Children Treated With Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide

2018 ◽  
Vol 5 (suppl_1) ◽  
pp. S697-S697
Author(s):  
Tanvir Bell ◽  
Melisse Baylor ◽  
Sung Rhee ◽  
LaRee Tracy ◽  
Mario Sampson ◽  
...  
Keyword(s):  
Cell Count ◽  
Cd4 Cell Count ◽  
Tenofovir Alafenamide ◽  
Cd4 Cell

Pulmonary cryptosporidiosis in an AIDS patient: successful treatment with paromomycin plus azithromycin

2005 ◽  
Vol 16 (7) ◽  
pp. 515-517 ◽  
Author(s):  
F Palmieri ◽  
S Cicalini ◽  
N Froio ◽  
E B Rizzi ◽  
D Goletti ◽  
...  
Keyword(s):  
Antiretroviral Therapy ◽  
Combination Therapy ◽  
Respiratory Tract ◽  
Highly Active Antiretroviral Therapy ◽  
Favourable Outcome ◽  
Antimicrobial Treatment ◽  
Cd4 Cell Count ◽  
Highly Active ◽  
Intestinal Involvement ◽  
Cd4 Cell

Extra-intestinal cryptosporidiosis, especially of the biliary and respiratory tract, is likely in the course of an intestinal involvement, whereas it is rare without such a localization. We report a case of pulmonary cryptosporidiosis without apparent intestinal involvement in an AIDS patient, with favourable outcome after antimicrobial combination therapy with paromomycin plus azithromycin. The successful response to antimicrobial treatment was subsequently maintained by effective highly active antiretroviral therapy (HAART). We suggest that respiratory cryptosporidiosis should be investigated in HIV-infected patients with pulmonary symptoms and low CD4 cell count, and, if detected, treatment should include HAART plus the combination of paromomycin and azithromycin.

scholarly journals Switching to Tenofovir Alafenamide in Elvitegravir-Based Regimens: Pharmacokinetics and Antiviral Activity in Cerebrospinal Fluid

2019 ◽  
Vol 71 (4) ◽  
pp. 982-988 ◽  
Author(s):  
Qing Ma ◽  
Andrew J Ocque ◽  
Gene D Morse ◽  
Chelsea Sanders ◽  
Alina Burgi ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Antiviral Activity ◽  
Virologic Failure ◽  
Plasma Concentrations ◽  
Open Label ◽  
Assay Sensitivity ◽  
Once Daily ◽  
Hiv Rna ◽  
The Central Nervous System ◽  
Tenofovir Alafenamide

Abstract Background Tenofovir alafenamide fumarate (TAF) co-formulated with elvitegravir (EVG; E), cobicistat (C), and emtricitabine (F), a recommended antiretroviral regimen, was evaluated for distribution and antiviral activity in cerebrospinal fluid (CSF) as well as neurocognitive (NC) performance change in participants switching from E/C/F/tenofovir disoproxil fumarate (TDF) to E/C/F/TAF. Methods This was a 24-week, single-arm, open-label study in treatment-experienced adults living with human immunodeficiency virus (HIV). Nine participants switched from E/C/F/TDF (150/150/200/300 mg once daily) to E/C/F/TAF (150/150/200/10 mg once daily) at week 12. CSF and total plasma concentrations of EVG, TDF, TAF, tenofovir (TFV), and HIV RNA levels were measured at baseline and week 24. NC performance was estimated by the Montreal Cognitive Assessment. Results EVG concentrations in CSF and the CSF:plasma ratio remained stable (P = .203) over time. Following the switch, TFV concentrations in CSF and plasma declined (P = .004), although the TFV CSF:plasma ratio increased (P = .004). At week 24, median TAF plasma concentration was 11.05 ng/mL (range, 2.84–147.1 ng/mL) 2 hours postdose but was below assay sensitivity 6 hours after dosing. TAF was below assay sensitivity in all CSF specimens. HIV RNA was ≤40 copies/mL in all CSF and plasma specimens. Three participants (33%) had NC impairment at baseline and 2 (22%) remained impaired at week 24. Conclusions Switch to E/C/F/TAF was associated with reductions in TFV concentrations in CSF but stable EVG concentrations that exceeded the 50% inhibitory concentration for wild-type HIV, suggesting that EVG achieves therapeutic concentrations in the central nervous system. No virologic failure or significant NC changes were detected following the switch. Clinical Trials Registration NCT02251236.

scholarly journals Exposure-response relationships for saquinavir, zidovudine, and zalcitabine in combination therapy.

1997 ◽  
Vol 41 (11) ◽  
pp. 2433-2438 ◽  
Author(s):  
G F Vanhove ◽  
J M Gries ◽  
D Verotta ◽  
L B Sheiner ◽  
R Coombs ◽  
...  
Keyword(s):  
Cell Count ◽  
Drug Exposure ◽  
Randomized Study ◽  
Primary Study ◽  
Open Label ◽  
Maximum Increase ◽  
Cd4 Cell Count ◽  
Exposure Response ◽  
Cd4 Cell ◽  
Response Variables

The relationship of CD4+ cell response, level of RNA in plasma, and quantitative peripheral blood mononuclear cell (PBMC) titer to apparent drug exposure was investigated by using data from AIDS Clinical Trial Group protocol 229, a multicenter randomized study. Patients received either saquinavir, zalcitabine, or a combination of both, along with open-label zidovudine. Approximately 100 patients were enrolled in each arm, and the primary study duration was 24 weeks. Individual drug exposure, the area under the concentration-time curve, was estimated by using population-based pharmacokinetic methods. Response was defined as the maximum increase in CD4+ cell count or the maximum decrease in RNA in plasma or PBMC titer adjusted for baseline CD4+ cell count, RNA in plasma, and PBMC titer, respectively. Regression of responses on exposure demonstrated an exposure effect for saquinavir which was significant for the maximum increase in CD4+ cell count and the decrease in RNA in plasma. For the PBMC titer, no significant relationship could be demonstrated but the results suggested a trend similar to that of the other response variables. For all three response variables, the slope of the saquinavir exposure response was greater with the triple combination (saquinavir, zidovudine, and zalcitabine) than with the combination of saquinavir and zidovudine, suggesting possible synergism between saquinavir and zalcitabine.

The safety and efficacy of indinavir and ritonavir (400/400 mg BID) in HIV-1-infected individuals from an inner-city minority population: a pilot study

2003 ◽  
Vol 14 (11) ◽  
pp. 732-736 ◽  
Author(s):  
D T Jayaweera ◽  
E Scerpella ◽  
M Robinson ◽  
R Rode ◽  
R Campo ◽  
...  
Keyword(s):  
Cell Count ◽  
Minority Population ◽  
Open Label ◽  
Safety And Efficacy ◽  
Cd4 Cell Count ◽  
American Black ◽  
Intent To Treat ◽  
Cd4 Cell ◽  
Hiv 1 ◽  
Cell Count Increase

We evaluated the safety and efficacy of indinavir 400 mg and ritonavir 400 mg twice daily (RIT/IND 400/400) in HIV-1-infected individuals, using an open label, proof of concept study. All patients received indinavir 400 mg and ritonavir 400 mg twice daily. Patients were followed up to 48 weeks. Nineteen subjects were enrolled, 11 (58%) men and eight (42%) women. The majority were American Black (nine; 47%) or Haitian (eight; 42%). The median baseline plasma HIV-1 viral load (VL) was 5.13 log10 copies/mL and the median CD4 cell count was 112 cells/mm3. The proportion of compliant patients with VL <400 copies/mL at week 24 was 60% compared with 0% for non-compliant patients ( P=0.011 [intent-to-treat] or P=0.085 [on-treatment]). VL at week 4 predicted week 24 VL response. Compliant patients had a median average CD4 cell count increase of 83.2 cells/mm3 compared with 42.0 cells/mm3 for non-compliant patients (P=0.010). The median average changes in triglycerides and cholesterol were significantly higher in compliant patients. This is a potent, safe combination for the treatment of HIV-1. VL at week 4 is predictive of viral outcome at week 24. Fasting serum cholesterol and triglycerides were significantly elevated during the study.

scholarly journals Evaluation of glycoprotein B genotypes and load of CMV infecting blood leukocytes on prognosis of AIDS patients

2011 ◽  
Vol 53 (2) ◽  
pp. 82-88 ◽  
Author(s):  
Aldo Albuquerque Cunha ◽  
Vitor Hugo Aquino ◽  
Viviane Mariguela ◽  
Maurício Lacerda Nogueira ◽  
Luiz Tadeu Moraes Figueiredo
Keyword(s):  
Viral Load ◽  
Aids Patients ◽  
Blood Leukocytes ◽  
Cd4 Cell Count ◽  
Biologically Relevant ◽  
Cell Counts ◽  
Cd4 Cell Counts ◽  
Almost All ◽  
Cmv Disease ◽  
Cd4 Cell

BACKGROUND: Cytomegalovirus (CMV) remains an important pathogen to immunocompromised patients even in the era of HAART. The present study aimed at evaluating the influence of CMV viral load and its gB genotypes on AIDS patients' outcome. METHODS: Blood samples of 101 AIDS patients were collected and tested for HIV load, CD4 - cell count and opportunistic pathogens, including CMV. Semi-nested PCRs were run to detect CMV genome and in the positive samples, gB genotyping and CMV load were established using enzymatic restriction and real time PCR, respectively. All patients were clinically followed for four years. RESULTS: In thirty patients (31%) CMV was detected and all fatal cases (n = 5) occurred in this group of patients (p = 0.007), but only two patients had CMV disease (1.9%). However, viral load was not statistically associated with any analyzed parameter. The most frequently observed CMV genotype was gB2 (45.16%) followed by gB3 (35.48%). gB2 genotype was more frequently found in patients with CD4-cell counts under 200 cells/mm³ (p = 0.0017), and almost all fatal cases (80%) had gB2 genotype. CONCLUSIONS: Our study suggests that CMV and its polymorphisms in biologically relevant genes, such as the gB encoding ORF, may still influence the prognosis and outcome of AIDS patients. The gB2 genotype was associated to patient's bad outcome.

Drug–drug interaction between itraconazole capsule and efavirenz in adults with HIV for talaromycosis treatment

2020 ◽  
Author(s):  
Quanhathai Kaewpoowat ◽  
Romanee Chaiwarith ◽  
Saowaluck Yasri ◽  
Navaporn Worasilchai ◽  
Ariya Chindamporn ◽  
...  
Keyword(s):  
Drug Interaction ◽  
Geometric Mean ◽  
Compartmental Analysis ◽  
Concomitant Administration ◽  
Open Label ◽  
Capsule Formulation ◽  
Post Dose ◽  
Cd4 Cell Count ◽  
Drug Drug Interaction ◽  
Cd4 Cell

Abstract Objectives To assess the pharmacokinetic of itraconazole capsule formulation and its active metabolite, hydroxyitraconazole, in adults with HIV diagnosed with talaromycosis in an endemic area, and to evaluate the drug–drug interaction between itraconazole/hydroxyitraconazole (ITC/OH-ITC) and efavirenz. Methods Open-label, single arm, sequential pharmacokinetic study. Eligible subjects were adults with HIV, ≥18 years old, with confirmed talaromycosis, initiating itraconazole capsule as part of standard talaromycosis treatment, in whom efavirenz-based ART was anticipated. Steady-state pharmacokinetic assessments (pre-dose and at 1, 3, 4, 5, 6, 8 and 12 h post dose) were performed for itraconazole/hydroxyitraconazole without and with efavirenz use. Mid-dose efavirenz concentrations were also assessed. Pharmacokinetics parameters were calculated using non-compartmental analysis. Results Ten subjects (70% male) were enrolled. At entry, median (range) age was 29.5 years (22–64), and CD4 cell count was 18.0 (1–39) cells/mm3. Geometric mean (95% CI) of itraconazole and hydroxyitraconazole AUC0–12 without efavirenz were 9097 (6761–12 239) and 11 705 (8586-15 959) ng·h/mL, respectively, with a median metabolic ratio of OH-ITC : ITC of 1.3 (95% CI 0.9–1.9). Intra-subject comparison revealed that both itraconazole and hydroxyitraconazole exposures were significantly reduced with concomitant efavirenz use, with the mean AUC0–12 of itraconazole and hydroxyitraconazole being 86% (71%–94%) and 84% (64%–97%) lower, respectively. With efavirenz, itraconazole trough concentrations were also below the recommended therapeutic level (0.5 μg/mL). All subjects had mid-dose efavirenz concentrations &gt;1000 ng/mL. Conclusions Concomitant administration of itraconazole capsule with efavirenz significantly reduced itraconazole and hydroxyitraconazole exposures. The clinical impact of this drug–drug interaction on talaromycosis treatment or prophylaxis in the era of potent ART needs further evaluation.

Maintenance of virologic suppression and improvement in comorbidities after simplification to raltegravir plus boosted darunavir among treatment-experienced HIV-infected patients

2020 ◽  
Vol 31 (5) ◽  
pp. 467-473
Author(s):  
José L Casado ◽  
Pilar Vizcarra ◽  
José L Blanco ◽  
Rocío Montejano ◽  
Eugenia Negredo ◽  
...  
Keyword(s):  
Cell Count ◽  
Virologic Failure ◽  
Density Lipoprotein ◽  
People Living With Hiv ◽  
Virologic Suppression ◽  
Cd4 Cell Count ◽  
Cholesterol Ratio ◽  
Intention To Treat ◽  
Heavily Pretreated ◽  
Cd4 Cell

The use of two potent, well-tolerated, drugs could permit the maintenance of virologic suppression even in heavily pretreated people living with HIV. In this retrospective, multicenter, simplification study (NCT03348449), we included those patients with virologic suppression who switched to raltegravir (RAL) plus boosted darunavir (b/DRV). Overall, 345 patients (75 females, 25%) were included. Patients were largely pretreated (mean, 9.4 regimens), suppressed for a median of 41.1 months. Fifty patients had ≥1 mutation against DRV. At 96 weeks, the efficacy by intention-to-treat analysis (snapshot) was 73% (95%CI, 68.4–77.8%), but 97.1% (95%CI, 95.4–98.9) excluding changes due to non-virologic reasons, and virologic failure was rare (0.9%; 95%CI, 0.1–1.2%). Median CD4/CD8 ratio increased from 0.59 to 0.62 (p < 0.01), CD4+ cell count by +90 cells/µl (p < 0.01), and mean estimated glomerular filtration rate (eGFR) increased from 85.2 to 88.5 ml/min at 96 weeks, greater for patients receiving tenofovir disoproxil fumarate (eGFR, +3.6 ml/min, p = 0.04; serum phosphate +0.33 mg/dl; p < 0.01). There was a continued and significant improvement in the total cholesterol/high-density lipoprotein-cholesterol ratio. In conclusion, the simplification to a dual regimen with the combination of RAL and b/DRV is associated with maintenance of virologic suppression, even in largely pretreated patients, with improvements in CD4+ cell count, CD4/CD8 ratio, and in renal and lipid parameters.

Sign in / Sign up

Export Citation Format

Share Document