CSF LPV concentrations and viral load in viral suppressed patients on LPV/r monotherapy given once daily

Introduction: Plasma trough concentrations of lopinavir (LPV) given as LPV/r 800/200 mg once daily (OD) are reduced in comparison with 400/100 mg twice daily (BID). While OD dosage of LPV/r is sufficient to achieve viral suppression in plasma, data about drug penetration and viral suppression in central nervous system (CNS) is needed, mainly if LPVr is used as maintenance monotherapy strategy in selected patients. The objective of this study was to evaluate CSF HIV‐1 RNA and CSF LPV concentrations in patients receiving LPV/r monotherapy OD (LPVrMOD). Material and Methods: This is a cross‐sectional sub‐study within a prospective, open‐label pilot simplification study to evaluate the efficacy and safety of LPV/rMOD in virologically suppressed patients previously receiving a BID LPV/r monotherapy regimen (LPV/rMBID), the “Kmon study” (NCT01581853). To assess LPV concentrations and HIV‐1 RNA in CSF, a lumbar puncture (LP) was performed in a subgroup of patients after at least one month of LPVrMOD treatment. Plasma‐paired samples of all patients were also obtained. HIV‐1 RNA was determined by real‐time PCR (limit of detection 40 copies/mL). Liquid chromatography‐tandem mass spectrometry (Tandem labs, NJ) was used to determine CSF and blood plasma LPV concentrations. Results: Nine patients were included. Median (range) age was 48 (34–56) years, median CD4 cell count 672 (252–1,408) cells/mL, median nadir CD4 count 125 (35–537) cells/mL and 40% of subjects were HCV‐positive. Before starting LPV/rMOD median time on a LPV/r‐containing regimen and on LPV/rMBID were 9 (4–11) years and 15 (7–24) months respectively, median time with undetectable HIV viral load was 5 (3–12) years and 2 patients had a previous documented blip. LP was performed a median of 24 (8–36) weeks after starting LPV/rMOD and 24 (11–28) hours after the last LPV/rMOD dose CSF and plasma HIV RNA was 40 copies/mL in all patients. Median LPV CSF concentration was 9.78 (1.93–78.3) ng/mL, median LPV plasma concentration 1,103 (377–16,700) ng/mL and median LPV CSF/plasma ratio 0.3% (0.1–1.2). Conclusions: No CSF viral escape was detected and LPV concentrations were above the IC50 for wtHIV‐1 (1.9 ng/mL). However, as concentrations were close to IC50 in some patients, a careful clinical follow up of patients receiving this regimen would be advisable. Larger longitudinal studies will be helpful for a better understanding of the CNS antiviral activity of LPVr monotherapy

Long-term fat redistribution in ARV-naïve HIV+ patients initiating a non-thymidine containing regimen in clinical practice

Lipodystrophy is still a matter of concern in HIV patients receiving ART. However, long-term fat change in patients taking non-thymidine regimens is not well known

HIV-1-RNA Decay and Dolutegravir Concentrations in Semen of Patients Starting a First Antiretroviral Regimen

Background. The objective of this study was to quantify human immunodeficiency virus (HIV) type 1 RNA decay and dolutegravir (DTG) concentrations in the semen of HIV-infected patients receiving DTG-based first-line therapy

ACTG-HIV symptoms changes in patients switched to RPV/FTC/TDF due to previous intolerance to CART. Interim analysis of the PROSTR study

Introduction: Tolerability and convenience are crucial aspects for the long-term success of combined antiretroviral therapy (cART). The aim of this study was to investigate the impact in routine clinical practice of switching to the single tablet regimen (STR) RPV/FTC/TDF in patients with intolerance to previous cART, in terms of patients’ well-being, assessed by several validated measures. Methods: Prospective, multicenter study. Adult HIV-infected patients with viral load under 1.000 copies/mL while receiving a stable ART for at least the last three months and switched to RPV/FTC/TDF due to intolerance of previous regimen, were included. Analyses were performed by ITT. Presence/magnitude of symptoms (ACTG-HIV Symptom Index), quality of life (EQ-5D, EUROQoL & MOS-HIV), adherence (SMAQ), preference of treatment and perceived ease of medication (ESTAR) through 48 weeks were performed. Results: Interim analysis of 125 patients with 16 weeks of follow up was performed. 100 (80%) were male, mean age 46 years. Mean CD4 at baseline was 629.59307.29 and 123 (98.4%) had viral load B50 copies/mL; 15% were HCV co-infected. Ninety two (73.6%) patients switched from a NNRTI (84.8% from EFV/FTC/TDF) and 33 (26.4%) from a PI/r. The most frequent reasons for switching were psychiatric disorders (51.2%), CNS adverse events (40.8%), gastrointestinal (19.2%) and metabolic disorders (19.2%). At the time of this analysis (week 16), four patients (3.2%) discontinued treatment: one due to adverse events, two virologic failures and one with no data. A total of 104 patients (83.2%) were virologically suppressed (B50 copies/mL). The average degree of discomfort in the ACTG-HIV Symptom Index significantly decreased from baseline (21915.55) to week 4 (10.89912.36) & week 16 (10.81912.62), pB0.001. In all the patients, quality of life tools showed a significant benefit in wellbeing of the patients (Table 1). Adherence to therapy significantly and progressively increased (SMAQ) from baseline (54.4%) to week 4 (68%), pB0.001 and to week 16 (72.0%), pB0.001. Conclusions: Switching to RPV/FTC/TDF from another ARV regimen due to toxicity, significantly improved the quality of life of HIV-infected patients, both in mental and physical components, and improved adherence to therapy while maintaining a good immune and virological response

Effectiveness and tolerability of abacavir-lamivudine-nevirapine (ABC/3TC/NVP) in a multicentre cohort of HIV-infected, ARV-naïve patients

PURPOSE: Very scarce information has been published to date with the combination of ABC/3TC/NVP but it is currently being used in clinical practice in Spain and Portugal. Our aim was to present the clinical experience with this regimen in a cohort of adult HIV-infected antiretroviral (ARV)-naïve patients. METHODS: Retrospective, multicentre, cohort study. Consecutive adult HIV-infected ARV-naïve HLA-B*5701-negative patients, who started ABC/3TC/NVP between 2005-2013, with at least one follow-up visit, were included. Demographic, clinical and laboratory variables were assessed at baseline, month 1, and every three-four months thereafter. The primary end point was HIV-1 viral load (VL)<40 c/mL at 48 weeks. Data were analyzed by intent-to-treat (ITT) (switch=failure, and missing=failure) and on treatment (OT) analyses. RESULTS: 78 patients were included. Median follow up was 26 (0.1-84) months. 86% were male, median age 41 (23-69) years, 9% had AIDS, 8% were HCV+, baseline CD4 was 275 (10-724) cells/µL and median VL 4.58 (3.02-6.92) log. After 48 weeks, VL was<40 c/mL in 89.8% (OT), 79.7% (M=F) and 65.4% (S=F) and at 96 weeks in 88.5%, 78.9% and 61.6%, respectively. CD4 increased +246 (p<0.001) and +292 (p<0.001) cells/uL after 48 and 96 weeks, respectively. One or more drugs of the regimen were discontinued in 33 (42.3%) patients. In 15 (19.2%) patients (13 NVP, 2 ABC/3TC) therapy was stopped due to toxicity after a median of one month (in only two cases after six months of follow up): 80% of them had rash/liver toxicity. Six (7.7%) patients discontinued ART due to virologic failure, five (6.4%) because of other reasons and seven (9%) were lost to follow-up. ALT but not AST significantly increased (+0.07 ukat/L at 96 weeks, p=0.033). A significant increase of 25%, 26% and 42% in total cholesterol, LDLc and HDLc, respectively, and a significant decrease in TC/HDL ratio (6%, p=0.008) was observed after 96 weeks. CONCLUSIONS: Despite a considerable proportion of patients had to stop therapy due to toxicity (most associated with NVP), those initially tolerating this regimen presented a high virologic and immunologic response after 96 weeks, as well as a favourable lipid profile. ABC/3TC/NVP may be a suitable alternative first regimen, mainly in countries with economic constraints

CSF LPV concentrations and viral load in viral suppressed patients on LPV/r monotherapy given once daily

Introduction: Plasma trough concentrations of lopinavir (LPV) given as LPV/r 800/200 mg once daily (OD) are reduced in comparison with 400/100 mg twice daily (BID). While OD dosage of LPV/r is sufficient to achieve viral suppression in plasma, data about drug penetration and viral suppression in central nervous system (CNS) is needed, mainly if LPVr is used as maintenance monotherapy strategy in selected patients. The objective of this study was to evaluate CSF HIV‐1 RNA and CSF LPV concentrations in patients receiving LPV/r monotherapy OD (LPVrMOD). Material and Methods: This is a cross‐sectional sub‐study within a prospective, open‐label pilot simplification study to evaluate the efficacy and safety of LPV/rMOD in virologically suppressed patients previously receiving a BID LPV/r monotherapy regimen (LPV/rMBID), the “Kmon study” (NCT01581853). To assess LPV concentrations and HIV‐1 RNA in CSF, a lumbar puncture (LP) was performed in a subgroup of patients after at least one month of LPVrMOD treatment. Plasma‐paired samples of all patients were also obtained. HIV‐1 RNA was determined by real‐time PCR (limit of detection 40 copies/mL). Liquid chromatography‐tandem mass spectrometry (Tandem labs, NJ) was used to determine CSF and blood plasma LPV concentrations. Results: Nine patients were included. Median (range) age was 48 (34–56) years, median CD4 cell count 672 (252–1,408) cells/mL, median nadir CD4 count 125 (35–537) cells/mL and 40% of subjects were HCV‐positive. Before starting LPV/rMOD median time on a LPV/r‐containing regimen and on LPV/rMBID were 9 (4–11) years and 15 (7–24) months respectively, median time with undetectable HIV viral load was 5 (3–12) years and 2 patients had a previous documented blip. LP was performed a median of 24 (8–36) weeks after starting LPV/rMOD and 24 (11–28) hours after the last LPV/rMOD dose CSF and plasma HIV RNA was 40 copies/mL in all patients. Median LPV CSF concentration was 9.78 (1.93–78.3) ng/mL, median LPV plasma concentration 1,103 (377–16,700) ng/mL and median LPV CSF/plasma ratio 0.3% (0.1–1.2). Conclusions: No CSF viral escape was detected and LPV concentrations were above the IC50 for wtHIV‐1 (1.9 ng/mL). However, as concentrations were close to IC50 in some patients, a careful clinical follow up of patients receiving this regimen would be advisable. Larger longitudinal studies will be helpful for a better understanding of the CNS antiviral activity of LPVr monotherapy

Cerebrospinal fluid and plasma lopinavir concentrations and viral response in virologically suppressed patients switching to lopinavir/ritonavir monotherapy once daily.

BACKGROUND: Lopinavir/ritonavir (LPV/r) monotherapy is used in selected virologically suppressed HIV-infected patients. Some would prefer a once-daily (OD) dose instead of the usual twice-daily dose to favour adherence. However, trough concentrations of the drug in blood and particularly in cerebrospinal fluid (CSF) may not be adequate to maintain viral suppression. METHODS: Prospective, open-label pilot study to evaluate the efficacy and safety of LPV/r monotherapy OD. HIV-1-infected patients, virologically suppressed for at least 6 months were enrolled. HIV viral load (VL) was determined at baseline and at weeks 4, 8, 12, 16, 24, 36 and 48. Lumbar puncture was performed in a subgroup of patients to evaluate CSF VL and CSF LPV concentrations. RESULTS: A total of 21 patients were included. At week 48, 85.7% (n=18) showed viral suppression (VL<40 copies/ml). Two patients had viral failure (9.5%) and a third was withdrawn from the study because of gastrointestinal symptoms. Nine patients were enrolled in the substudy. CSF VL was <40 copies/ml in all cases. Median (range) LPV concentration was 9.78 ng/ml (1.93-78.3) in CSF and 1,970 (154-16,700) ng/ml in plasma; the CSF/plasma ratio was 0.004 (0.001-0.186). CONCLUSIONS: In this small pilot study, LPV/r monotherapy OD maintained plasma HIV RNA suppression at 48 weeks in most patients, with no cases of CSF viral escape. However, CSF LPV concentrations were close to the 50% inhibitory concentration threshold in several patients; hence, this intervention should be avoided in patients with advanced immune suppression and/or those individuals presenting with significant comorbidities such as hepatitis C coinfection.This study was partially funded by the RD12/0017/0013 project, a part of the Plan Nacional 223 R+D+I, and was cofinanced by the ISCIII, Subdirección General de Evaluación y el 224 Fondo Europeo de Desarrollo Regional (FEDER)

Long-term fat redistribution in ARV-naïve HIV+ patients initiating a non-thymidine containing regimen in clinical practice

Lipodystrophy is still a matter of concern in HIV patients receiving ART. However, long-term fat change in patients taking non-thymidine regimens is not well known