Long-term combination antiretroviral therapy often results in toxicity/tolerability problems, which are one of the main reasons for switching treatment. Despite the favorable profile of raltegravir ...(RAL), data on its combination with abacavir/lamivudine (ABC/3TC) are scarce. Based on clinical data, we evaluated this regimen as a switching strategy.
Multicenter, non-controlled, retrospective study including all virologically suppressed HIV-1-infected patients who had switched to RAL+ABC/3TC.
We evaluated effectiveness (defined as maintenance of HIV-1-RNA <50 copies/mL at 48 weeks) safety, tolerability, laboratory data, and CD4+ count at week 48 of this switching strategy.
The study population comprised 467 patients. Median age was 49 years (IQR: 45-53). Males accounted for 75.4%. Median CD4+ count at baseline was 580 cells/μL (IQR, 409). The main reasons for switching were toxicity/tolerability problems (197; 42.2%) and physician's criteria (133; 28.5%). At week 48, HIV-1 RNA remained at <50 copies/mL in 371/380 (97.6%; 95%CI: 96.4-99.0) when non-virological failure was censured. Virological failure was recorded in 1.9% patients and treatment failure in 20.5% of patients (96/467 95%CI, 16.9-24.2). The main reasons for treatment failure included switch to fixed-dose combination regimens (31; 6.6%), toxicity/poor tolerability (27; 5.8%), and physician's decision (17; 3.6%). A total of 73 adverse events were detected in 64 patients (13.7%). These resolved in 43 patients (67.2%). Of the 33 cases related or likely related to treatment, 30 were Grade-1 (90.9%). CD4+ count and renal, hepatic, and lipid profiles remained clinically stable over the 48 weeks.
Our findings suggest that RAL+ABC/3TC could be an effective, safe/tolerable, and low-toxicity option for virologically suppressed HIV-1-infected patients.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Based on data from clinical practice, we evaluated the effectiveness and safety of switching to abacavir/lamivudine plus rilpivirine (ABC/3TC+RPV) treatment in virologically suppressed HIV-1-infected ...patients.
We performed a multicenter, non-controlled, retrospective study of HIV-1-infected patients who switched treatment to ABC/3TC+RPV. Patients had an HIV-RNA <50 copies/mL for at least 24 weeks prior to changing treatments. The primary objective was HIV-1 RNA <50 copies/mL at week 48. Effectiveness was analyzed by intention-to-treat (ITT), missing = failure and on-treatment (OT) analyses. The secondary objectives analyzed were adverse effects changes in renal, hepatic or lipid profiles, changes in CD4+ cell count and treatment discontinuations.
Of the 205 patients included, 75.6% were men and the median age was 49. At baseline, before switching to ABC/3TC+RPV, median time since HIV diagnosis was 13.1 years, median time with undetectable HIV-1 RNA was 6.2 years and median time of previous antiretroviral regimen was 3.1 years (48.3% patients were taking efavirenz and ABC/3TC was the most frequent backbone coformulation in 69.7% of patients). The main reasons for switching were drug toxicity/poor tolerability (60.5%) and simplification (20%). At week 48, the primary objective was achieved by 187 out of 205 (91.2%) patients by ITT analysis, and 187 out of 192 (97.4%) patients by OT analysis. The CD4+ lymphocyte count and CD4+ percentage increased significantly from baseline to week 48 by a median of 48 cells/μL (-50 to 189) and 1.2% (-1.3% to 4.1%), respectively, P<0.001. Thirty-eight adverse events (AE) were detected in 32 patients. Of these, 25 had no clear association with treatment. Three patients interrupted therapy due to AE. We observed a decrease in all lipid parameters, P<0.001, and a slight improvement in the glomerular filtration rate, P<0.01. Therapy was considered to have failed in 18 patients owing to virological failure (5 2.4%), toxicity/poor tolerability (4 2%), clinical decision (3 1.5%), loss to follow-up (3 1.5%), death (1 0.5%), and no clinical data (2 1%).
The results of this study confirms that ABC/3TC+RPV is an effective, safe, and cost-effective option for the treatment of patients with virologically stable HIV-1 infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Background
Few women have been included in darunavir/cobicistat clinical development studies, and hardly any of them were antiretroviral experienced or treated with anything other than ...triple-based therapies.
Objectives
Our aim was to increase our knowledge about women living with HIV undergoing darunavir/cobicistat-based regimens.
Methods
A multicentre (21 hospitals), retrospective study including a centrally selected random sample of HIV-1 patients starting a darunavir/cobicistat-based regimen from June 2014 to March 2017 was planned. Baseline characteristics, 24 and 48 week viral load response (<50 copies/mL), CD4+ lymphocyte count increase, time to change darunavir/cobicistat and adverse event occurrence were all compared by sex. The study was approved by each of the 21 ethics committees, and patients signed informed consent.
Results
Out of 761 participants, 193 were women. Similar characteristics were found for both sexes, except that the women had a longer duration of HIV infection (P = 0.001), and were less frequently pre-treated with darunavir/cobicistat in their previous regimen (P = 0.02). The main reason for using a darunavir/cobicistat-based regimen was simplification, without differences by sex, while monotherapy seems to be more frequently prescribed in women than in men (P = 0.067). The main outcomes, HIV viral load response, CD4+ lymphocyte count increase at 24 or 48 weeks, occurrence of adverse events, main reasons for changing and time to the modify darunavir/cobicistat regimen, did not show differences between the sexes.
Conclusions
No sex disparities were found in the main study outcomes. These results support the use of a darunavir/cobicistat-based regimen in long-term pre-treated women. Clinical Trial.gov No. NCT03042390.
People in their fifties with HIV are considered older adults, but they appear not to be a homogeneous group.
To evaluate the differences among older adults with HIV according to their chronological ...age and the year of HIV diagnosis.
Cross-sectional study of the FUNCFRAIL cohort. Patients 50 or over with HIV were included and were stratified by both chronological age and the year of HIV diagnosis: before 1996 (long-term HIV survivors LTHS) and after 1996. We recorded sociodemographic data, HIV-related factors, comorbidities, frailty, physical function, other geriatric syndromes, and quality of life (QOL).
We evaluated 801 patients. Of these, 24.7% were women, 47.0% were LTHS, and 14.7% were 65 or over. Of the 65 or over patients, 73% were diagnosed after 1996. Higher rates of comorbidities among LTHS were found, being the more prevalent: COPD, history of cancer, osteoarthritis, depression, and other psychiatric disorders while the more prevalent among the 65 or over patients were: hypertension, diabetes, dyslipidemia, cancer, and osteoarthritis. LTHS showed a significantly worse QOL. There were no differences by the year of HIV diagnosis regarding frailty and functional impairment (SPPB <10) but they were more than twice as prevalent in the 65 or over patients compared to the other chronological age groups.
A LTHS and a 65 or over person are both "older adults with HIV," but their characteristics and requirements differ markedly. It is mandatory to design specific approaches focused on the real needs of the different profiles.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Background & Aims
Hepatitis C virus (HCV), human immunodeficiency virus (HIV) and cirrhosis induce metabolic disorders. Here, we aimed to evaluate the association of plasma metabolites with ...Child‐Turcotte‐Pugh (CTP) score and hepatic decompensation in HIV/HCV‐coinfected and HCV‐monoinfected patients with advanced cirrhosis.
Methods
A cross‐sectional study was carried out in 62 HIV/HCV‐coinfected and 28 HCV‐monoinfected patients. Metabolomics analysis was performed by gas chromatography‐mass spectrometry (GC‐MS) and liquid chromatography‐mass spectrometry (LC‐MS). The statistical association analysis was performed by partial least squares discriminant analysis (PLS‐DA) and generalized linear model (GLM) with binomial distribution (to analyse HIV coinfection, high alcohol intake, treatment with statins, previous HCV therapy failure and decompensation) and ordinal logistic regression (OLR) models to analyse different stages of cirrhosis (CTP score).
Results
The statistical analysis identified plasma metabolites associated with HIV coinfection, high alcohol intake, CTP score and hepatic decompensation. Overall, fatty acids, bile acids, aromatic and sulphur amino acids, butyrate derivatives, oxidized phospholipids, energy‐related metabolites and bacterial fermentation‐related metabolites were increased in more advanced cirrhosis stages; while lysophosphatidylcholines and lysophosphatidylethanolamines, branched‐chain amino acids (BCAA) and metabolites of tricarboxylic acid cycle, among others, were decreased in more advanced cirrhosis. Most of the significant metabolites displayed a similar trend after stratifying for HIV/HCV‐ and HCV‐infected patients. Glycolic acid, LPC (16:0) and taurocholic acid had high accuracy for discriminating patients according to decompensated cirrhosis (CTP ≥ 7).
Conclusion
Altered plasma metabolomic profile was associated with advanced stages of cirrhosis in HIV/HCV‐coinfected and HCV‐monoinfected patients.
Abstract
Background
Cobicistat, dolutegravir and rilpivirine are all modest inhibitors of proximal tubular creatinine secretion (IPTCrS) and hence a moderate and early non-progressive creatinine ...estimated glomerular filtration rate (Cr-eGFR) reduction has been observed in clinical trials. Data regarding the impact of combination of those drugs on Cr-eGFR, in the clinical practice, are scarcely known.
Methods
Changes in Cr-eGFR after starting darunavir/cobicistat alone or in combination with dolutegravir and/or rilpivirine were studied in a nationwide retrospective cohort study of consecutive HIV-infected patients initiating darunavir/cobicistat. The relationship between Cr-eGFR changes over time and the use of darunavir/cobicistat alone or darunavir/cobicistat plus dolutegravir and/or rilpivirine adjusted by different HIV patient’s characteristics, socio-demographics, HIV severity and use of tenofovir concomitant medication other than antiretrovirals was explored through univariate and multivariate analyses.
Results
The analysis included 725 patients. At 48 weeks, the combination of two or more IPTCrS (darunavir/cobicistat with rilpivirine and/or dolutegravir) was associated with higher decreases in Cr-eGFR adjusted median difference (±SD) –3.5 ± 1.6 (95% CI –6.6 to –0.3), P = 0.047, and a decrease up to or higher than 15 mL/min/1.73 m2 was more frequent adjusted OR 3.233 (95% CI 1.343–7.782), P = 0.009, with respect to darunavir/cobicistat alone. The Cr-eGFR changes between darunavir/cobicistat and darunavir/cobicistat with rilpivirine and/or dolutegravir showed more significant decreases in patients taking two or more IPTCrS at 12, 24 and 48 weeks. (ClinicalTrials.gov: NCT03042390).
Conclusions
Concomitant use of darunavir/cobicistat plus IPTCrS dolutegravir, rilpivirine, or both produced an additive effect in the expected Cr-eGFR decrease.
Lung cancer (LC) screening detects tumors early. The prospective GESIDA 8815 study was designed to assess the usefulness of this strategy in HIV + people (PLHIV) by performing a low-radiation ...computed tomography (CT) scan.
371 heavy smokers patients were included (>20 packs/year), >45 years old and with a CD4+<200mm3 nadir. One visit and CT scan were performed at baseline and 4 for follow-up time annually.
329 patients underwent the baseline visit and CT (CT0) and 206 completed the study (CT1 = 285; CT2 = 259; CT3 = 232; CT4 = 206). All were receiving ART. A total > 8 mm lung nodules were detected, and 9 early-stage PCs were diagnosed (4 on CT1, 2 on CT2, 1 on CT3 and 2 on CT4). There were no differences between those who developed LC and those who did not in sex, age, CD4+ nadir, previous lung disease, family history, or amount of packets/year. At each visit, other pathologies were diagnosed, mainly COPD, calcified coronary artery and residual tuberculosis lesions. At the end of the study, 38 patients quit smoking and 75 reduced their consumption. Two patients died from LC and 16 from other causes (p = 0.025)
The design of the present study did not allow us to define the real usefulness of the strategy. Adherence to the test progressively decreased over time. The diagnosis of other thoracic pathologies is very frequent. Including smokers in an early diagnosis protocol for LC could help to quit smoking.
El cribado de cáncer de pulmón (CP) detecta tumores precozmente. El estudio prospectivo GESIDA 8815 se diseñó para valorar la utilidad de esta estrategia en personas VIH+ (PVVIH) mediante la realización de una tomografía computarizada (TC) de baja radiación.
Se incluyeron 371 pacientes grandes fumadores (>20 paquetes-año), >45 años y con nadir de CD4+<200mm3. Se realizó una visita y TC basal y 4 de seguimiento anualmente.
Realizaron la visita y TC basal (TC0) 329 pacientes y completaron el estudio 206 (TC1 = 285; TC2 = 259; TC3 = 232; TC4 = 206). Todos recibían TAR. Se detectaron 35 nódulos pulmonares > 8 mm y se diagnosticaron 9 CP en estadio precoz (4 en TC1, 2 en TC2, 1 en TC3 y 2 en TC4). No existieron diferencias entre los que desarrollaron CP y los que no en sexo, edad, nadir CD4+, patología pulmonar previa, antecedentes familiares ni número de paquetes/año. En cada visita se diagnosticaron otras patologías fundamentalmente EPOC, coronarias calcificadas y lesiones residuales de tuberculosis. Al finalizar el estudio 38 pacientes dejaron de fumar y 75 redujeron el consumo. Fallecieron 2 pacientes por CP y 16 por otras causas (p = 0,025)
El diseño del presente estudio no permitió definir la utilidad real de la estrategia. La adherencia a la prueba disminuyó progresivamente a lo largo del tiempo. Es muy frecuente el diagnóstico de otras patologías torácicas. Incluir a pacientes fumadores en un protocolo de diagnóstico precoz de CP podría ayudar a dejar de fumar.
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