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1.
HIV Med ; 24(2): 224-230, 2023 02.
Article in English | MEDLINE | ID: mdl-35934954

ABSTRACT

OBJECTIVES: Our objective was to determine whether antiretroviral drugs (ARVs) were used according to the European AIDS Clinical Society (EACS) guidelines for people with HIV/hepatitis C virus (HCV) coinfection treated with direct-acting antivirals (DAAs) between 30 November 2014 and 31 December 2019 in the pan-European EuroSIDA study. METHODS: At each publication date of the EACS guidelines, plus 3 and 6 months, we calculated the number of people receiving DAAs with potential and actual ARV contraindications ('red shading' in the EACS guidelines). We used logistic regression to investigate factors associated with using contraindicated ARVs. RESULTS: Among 1406 people starting DAAs, the median age was 51 years, 75% were male, 57% reported injected drug use as an HIV risk, and 76% were from western Europe. Of 1624 treatment episodes, 609 (37.5%) occurred while the patient was receiving ARVs with potential contraindications; among them, 38 (6.2%; 95% confidence interval [CI] 4.3-8.2) involved a contraindicated ARV (18 non-nucleoside reverse transcriptase inhibitors), 16 involved protease inhibitors, and four involved integrase strand transfer inhibitors. The adjusted odds of receiving a contraindicated ARV were higher (3.25; 95% CI 1.40-7.57) among participants from east/central east Europe (vs. south) and lower (0.22; 95% CI 0.08-0.65) for 2015-2018 guidelines (vs. 2014). In total, 29 of the 32 (90.6%) patients receiving a contraindicated ARV and 441 of the 461 (95.7%) with potential ARV contraindications experienced a sustained virological response ≥12 weeks after stopping treatment (SVR12; p = 0.55). CONCLUSION: In this large heterogenous European cohort, more than one-third of people with HIV/HCV coinfection received DAAs with potential ARV contraindications, but few received a contraindicated ARV. Use of contraindicated ARVs declined over time, corresponding to the increased availability of ARV therapy regimens without interactions with DAA across Europe. Participants who received a contraindicated DAA and ARV combination still had a high rate of SVR12.


Subject(s)
Acquired Immunodeficiency Syndrome , Coinfection , HIV Infections , Hepatitis C, Chronic , Hepatitis C , Humans , Male , Middle Aged , Female , Antiviral Agents/therapeutic use , Hepacivirus , HIV Infections/complications , HIV Infections/drug therapy , Coinfection/drug therapy , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Anti-Retroviral Agents/therapeutic use , Hepatitis C/complications , Hepatitis C/drug therapy , Acquired Immunodeficiency Syndrome/drug therapy
2.
J Antimicrob Chemother ; 74(3): 746-753, 2019 03 01.
Article in English | MEDLINE | ID: mdl-30544247

ABSTRACT

OBJECTIVES: In subjects with transmitted thymidine analogue mutations (TAMs), boosted PIs (PI/b) are often chosen to overcome possible resistance to the NRTI backbone. However, data to guide treatment selection are limited. Our aim was to obtain firmer guidance for clinical practice using real-world cohort data. METHODS: We analysed 1710 subjects who started a PI/b in combination with tenofovir or abacavir plus emtricitabine or lamivudine, and compared their virological outcomes with those of 4889 patients who started an NNRTI (predominantly efavirenz), according to the presence of ≥1 TAM as the sole form of transmitted drug resistance. RESULTS: Participants with ≥1 TAM comprised predominantly MSM (213 of 269, 79.2%), subjects of white ethnicity (206 of 269, 76.6%) and HIV-1 subtype B infections (234 of 269, 87.0%). Most (203 of 269, 75.5%) had singleton TAMs, commonly a revertant of T215Y or T215F (112 of 269, 41.6%). Over a median of 2.5 years of follow-up, 834 of 6599 (12.6%) subjects experienced viraemia (HIV-1 RNA >50 copies/mL). The adjusted HR for viraemia was 2.17 with PI/b versus NNRTI-based therapy (95% CI 1.88-2.51; P < 0.001). Other independent predictors of viraemia included injecting drug use, black ethnicity, higher viral load and lower CD4 cell count at baseline, and receiving abacavir instead of tenofovir. Resistance showed no overall impact (adjusted HR 0.77 with ≥1 TAM versus no resistance; 95% CI 0.54-1.10; P = 0.15). CONCLUSIONS: In this cohort, patients harbouring ≥1 TAM as the sole form of transmitted drug resistance gained no apparent virological advantage from starting first-line ART with a PI/b.


Subject(s)
Anti-HIV Agents/therapeutic use , Drug Resistance, Viral , HIV Infections/drug therapy , HIV Infections/virology , HIV-1/drug effects , HIV-1/genetics , Mutation , Protease Inhibitors/therapeutic use , Adult , Alleles , Amino Acid Substitution , Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active , Female , Genotype , Humans , Kaplan-Meier Estimate , Male , Prognosis , Protease Inhibitors/administration & dosage , RNA, Viral , Treatment Outcome , Viral Load
3.
Clin Infect Dis ; 64(10): 1413-1421, 2017 May 15.
Article in English | MEDLINE | ID: mdl-28329090

ABSTRACT

BACKGROUND: Antiretrovirals (ARVs) affect bone density and turnover, but their effect on risk of fractures and osteonecrosis of the femoral head is less understood. We investigated if exposure to ARVs increases the risk of both bone outcomes. METHODS: EuroSIDA participants were followed to assess fractures and osteonecrosis. Poisson regression identified clinical, laboratory and demographic predictors of either bone outcome. Ever, current, and cumulative exposures to ARVs were assessed. RESULTS: During 86118 PYFU among 11820 included persons (median age 41y, 75% male, median baseline CD4 440/mm3, 70.4% virologically suppressed), there were 619 fractures (incidence/1000 PYFU 7.2; 95% CI 6.6-7.7) and 89 osteonecrosis (1.0; 0.8-1.3). Older age, white race, lower BMI, IV drug use, lower baseline CD4, HCV coinfection, prior osteonecrosis, prior fracture, cardiovascular disease, and recent non-AIDS cancer (last 12 months) were associated with fractures. After adjustment, persons who had ever used tenofovir disoproxil fumarate (TDF) (1.40; 1.15-1.70) or who were currently on TDF (1.25; 1.05-1.49) had higher incidence of fractures. There was no association between cumulative exposure to TDF and fractures (1.08/5 y exposure; 0.94-1.25). No other ARV was associated with fractures (all P > .1). Risk of osteonecrosis was associated with white race, lower nadir CD4, prior osteonecrosis, prior fracture, and prior AIDS. After mutual adjustment, no ARV was associated with osteonecrosis. CONCLUSIONS: In human immunodeficiency virus (HIV) infection, host factors, HIV-specific variables, and comorbidities contribute to risk of fractures and osteonecrosis. Exposure to TDF, but not other ARVs, was an independent risk factor for fractures.


Subject(s)
Anti-HIV Agents/adverse effects , Fractures, Bone/etiology , HIV Infections/complications , Osteonecrosis/etiology , Adult , Anti-HIV Agents/administration & dosage , Anti-HIV Agents/therapeutic use , Bone Density/drug effects , CD4 Lymphocyte Count , Cohort Studies , Coinfection/epidemiology , Data Collection , Europe/epidemiology , Female , Femoral Fractures/epidemiology , Femoral Fractures/etiology , Femoral Fractures/virology , Fractures, Bone/epidemiology , Fractures, Bone/ethnology , Fractures, Bone/virology , HIV Infections/drug therapy , HIV Infections/epidemiology , HIV Infections/virology , Humans , Male , Middle Aged , Osteonecrosis/epidemiology , Osteonecrosis/virology , Regression Analysis , Risk Factors , Tenofovir/adverse effects , Tenofovir/therapeutic use
5.
Infection ; 45(2): 215-220, 2017 Apr.
Article in English | MEDLINE | ID: mdl-28054251

ABSTRACT

This study assessed the likelihood of referral for liver transplantation assessment in a prospective cohort of patients co-infected with HIV and hepatitis B or C with complications of cirrhosis. There were 141 co-infected patients from 11 UK centres with at least one complication of cirrhosis recorded (either decompensation or hepatocellular carcinoma) out of 772 identified with cirrhosis and/or HCC. Only 23 of these 141 (16.3%) were referred for liver transplantation assessment, even though referral is recommended for co-infected patients after the first decompensation episode.


Subject(s)
Coinfection/complications , HIV Infections/complications , Hepatitis B, Chronic/complications , Hepatitis C, Chronic/complications , Liver Cirrhosis/epidemiology , Liver Cirrhosis/surgery , Liver Transplantation , Adult , Female , Humans , Male , Middle Aged , Prospective Studies , United Kingdom
6.
J Neurovirol ; 22(6): 852-860, 2016 12.
Article in English | MEDLINE | ID: mdl-27194435

ABSTRACT

The central nervous system has been proposed as a sanctuary site where HIV can escape antiretroviral control and develop drug resistance. HIV-1 RNA can be at higher levels in CSF than plasma, termed CSF/plasma discordance. We aimed to examine whether discordance in CSF is associated with low level viraemia (LLV) in blood. In this MRC-funded multicentre study, we prospectively recruited patients with LLV, defined as one or more episode of unexplained plasma HIV-1 RNA within 12 months, and undertook CSF examination. Separately, we prospectively collected CSF from patients undergoing lumbar puncture for a clinical indication. Patients with durable suppression of viraemia and no evidence of CNS infection were identified as controls from this group. Factors associated with CSF/plasma HIV-1 discordance overall were examined. One hundred fifty-three patients were recruited across 13 sites; 40 with LLV and 113 undergoing clinical lumbar puncture. Seven of the 40 (18 %) patients with LLV had CSF/plasma discordance, which was significantly more than 0/43 (0 %) with durable suppression in blood from the clinical group (p = 0.005). Resistance associated mutations were shown in six CSF samples from discordant patients with LLV (one had insufficient sample for testing), which affected antiretroviral therapy at sampling in five. Overall discordance was present in 20/153 (13 %) and was associated with nadir CD4 but not antiretroviral concentrations in plasma or CSF. CSF/plasma discordance is observed in patients with LLV and is associated with antiretroviral resistance associated mutations in CSF. The implications for clinical practice require further investigation.


Subject(s)
HIV Infections/diagnosis , RNA, Viral/blood , RNA, Viral/cerebrospinal fluid , Viremia/diagnosis , Adult , Anti-HIV Agents/therapeutic use , CD4 Lymphocyte Count , Central Nervous System/drug effects , Central Nervous System/metabolism , Central Nervous System/pathology , Central Nervous System/virology , Drug Resistance, Viral/genetics , Female , HIV Infections/blood , HIV Infections/cerebrospinal fluid , HIV Infections/drug therapy , HIV-1/drug effects , HIV-1/genetics , HIV-1/growth & development , Humans , Male , Middle Aged , Neuropsychological Tests , Prospective Studies , RNA, Viral/antagonists & inhibitors , Viremia/blood , Viremia/cerebrospinal fluid , Viremia/drug therapy
7.
Cytokine ; 83: 139-146, 2016 07.
Article in English | MEDLINE | ID: mdl-27131579

ABSTRACT

INTRODUCTION: HIV-1 RNA can be found at higher levels in cerebrospinal fluid (CSF) than in plasma, termed CSF/plasma discordance. The clinical significance of CSF/plasma discordance is not known and the degree of discordance considered important varies. We aimed to determine whether a panel of CSF cytokines, chemokines and associated mediators were raised in patients with CSF/plasma discordance at different levels. METHODS: A nested case-control study of 40 CSF samples from the PARTITION study. We used a cytometric bead array to measure CSF mediator concentrations in 19 discordant and 21 non-discordant samples matched for plasma HIV-1 RNA. Discordant samples were subdivided into 'high discordance' (>1log10) and 'low discordance' (0.5-1log10, or ultrasensitive discordance). CSF mediators significant in univariate analysis went forward to two-way unsupervised hierarchical clustering based on the patterns of relative mediator concentrations. RESULTS: In univariate analysis 19 of 21 CSF mediators were significantly higher in discordant than non-discordant samples. There were no significant differences between samples with high versus low discordance. The samples grouped into two clusters which corresponded to CSF/plasma discordance (p<0.0001). In cluster one all mediators had relatively high abundance; this included 18 discordant samples and three non-discordant samples. In cluster two all mediators had relatively low abundance; this included 18 non-discordant samples and one non-discordant sample with ultrasensitive discordance only. CONCLUSIONS: CSF/plasma discordance is associated with potentially damaging neuroinflammatory process. Patients with discordance at lower levels (ie. 0.5-1log10) should also be investigated as mediator profiles were similar to those with discordance >1log10. Sensitive testing may have a role to determine whether ultrasensitive discordance is present in those with low level CSF escape.


Subject(s)
HIV Infections , HIV-1 , Inflammation Mediators , RNA, Viral , Adult , Female , HIV Infections/blood , HIV Infections/cerebrospinal fluid , Humans , Inflammation Mediators/blood , Inflammation Mediators/cerebrospinal fluid , Male , Middle Aged , Prospective Studies , RNA, Viral/biosynthesis , RNA, Viral/cerebrospinal fluid
8.
J Infect Dis ; 210(3): 363-73, 2014 Aug 01.
Article in English | MEDLINE | ID: mdl-24585896

ABSTRACT

BACKGROUND: Tenofovir disoproxil fumarate (TDF) has been linked to renal impairment, but the extent to which this impairment is reversible is unclear. We aimed to investigate the reversibility of renal decline during TDF therapy. METHODS: Cox proportional hazards models assessed factors associated with discontinuing TDF in those with an exposure duration of >6 months. In those who discontinued TDF therapy, linear piecewise regression models estimated glomerular filtration rate (eGFR) slopes before initiation of, during, and after discontinuation of TDF therapy. Factors associated with not achieving eGFR recovery 6 months after discontinuing TDF were assessed using multivariable logistic regression. RESULTS: We observed declines in the eGFR during TDF exposure (mean slopes, -15.7 mL/minute/1.73 m(2)/year [95% confidence interval {CI}, -20.5 to -10.9] during the first 3 months and -3.1 mL/minute/1.73 m(2)/year [95% CI, -4.6 to -1.7] thereafter) and evidence of eGFR increases following discontinuation of TDF therapy (mean slopes, 12.5 mL/minute/1.73 m(2)/year [95% CI, 8.9-16.1] during the first 3 months and 0.8 mL/minute/1.73 m(2)/year [95% CI, .1-1.5] thereafter). Following TDF discontinuation, 38.6% of patients with a decline in the eGFR did not experience recovery. A higher eGFR at baseline, a lower eGFR after discontinuation of TDF therapy, and more-prolonged exposure to TDF were associated with an increased risk of incomplete recovery 6 months after discontinuation of TDF therapy. CONCLUSIONS: This study shows that a decline in the eGFR during TDF therapy was not fully reversible in one third of patients and suggests that prolonged TDF exposure at a low eGFR should be avoided.


Subject(s)
Adenine/analogs & derivatives , Anti-HIV Agents/adverse effects , Glomerular Filtration Rate/drug effects , HIV Infections/drug therapy , Kidney Diseases/chemically induced , Organophosphonates/adverse effects , Adenine/adverse effects , Adenine/therapeutic use , Adult , Anti-HIV Agents/therapeutic use , Cohort Studies , Drug Administration Schedule , Female , Humans , Male , Middle Aged , Organophosphonates/therapeutic use , Proportional Hazards Models , Tenofovir , Viral Load
9.
J Infect Dis ; 210(2): 234-43, 2014 Jul 15.
Article in English | MEDLINE | ID: mdl-24493824

ABSTRACT

BACKGROUND: Low 25-hydroxyvitamin D (25(OH)D) has been associated with inflammation, human immunodeficiency virus (HIV) disease progression, and death. We aimed to identify the prognostic value of 25(OH)D for AIDS, non-AIDS-defining events and death, and its association with immunological/inflammatory markers. METHODS: Prospective 1-1 case-control study nested within the EuroSIDA cohort. Matched cases and controls for AIDS (n = 50 matched pairs), non-AIDS-defining (n = 63) events and death (n = 41), with plasma samples during follow-up were selected. Conditional logistic regression models investigated associations between 25(OH)D levels and annual 25(OH)D change and the probability of events. Mixed models investigated relationships between 25(OH)D levels and immunological/inflammatory markers. RESULTS: In sum, 250 patients were included. Median time between first and last sample and last sample and event was 44.6(interquartile range [IQR]: 22.7-72.3) and 3.1(IQR: 1.4-6.4) months. Odds of death decreased by 46.0%(95% confidence interval [CI], 2.0-70.0, P = .04) for a 2-fold increase in latest 25(OH)D level. There was no association between 25(OH)D and the occurrence of AIDS or non-AIDS-defining events (P > .05). In patients with current 25(OH)D <10 ng/mL, hsIL-6 concentration increased by 4.7%(95% CI, .2,9.4, P = .04) annually after adjustment for immunological/inflammatory markers, and no change in hsCRP rate was observed (P = .76). CONCLUSIONS: Low Vitamin D predicts short term mortality in HIV-positive persons. Effectiveness of vitamin D supplementation on inflammation and patient outcomes should be investigated.


Subject(s)
Biomarkers/blood , HIV Infections/immunology , HIV Infections/mortality , Vitamin D/blood , Adult , Cohort Studies , Disease Progression , Female , HIV Infections/diagnosis , HIV Infections/pathology , Humans , Male , Middle Aged , Prognosis , Prospective Studies , Survival Analysis
11.
J Antimicrob Chemother ; 68(6): 1354-9, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23435690

ABSTRACT

OBJECTIVES: The pharmacokinetic and pharmacodynamic effects of antiretroviral therapy may differ in older compared with younger subjects with HIV infection. We aimed to assess factors associated with plasma antiretroviral drug exposure, including age, within a large HIV-infected cohort undergoing therapeutic drug monitoring (TDM). METHODS: Data from the Liverpool TDM Registry were linked with the UK Collaborative HIV Cohort (CHIC) Study. All TDM of protease inhibitors (PIs) and non-nucleoside reverse transcriptase inhibitors (NNRTIs) was included and in order to account for different antiretroviral drugs the plasma concentrations were standardized by group measurements according to drug, dosing and timing of TDM. Regression modelling was used to evaluate associations of drug exposure with age and clinical parameters, including hepatic transaminase results and time to antiretroviral treatment modification. RESULTS: Data from 3589 TDM samples were available from 2447 subjects. The greatest numbers of plasma concentrations were assessed for lopinavir (22.4%), efavirenz (18.5%), atazanavir (17.0%) and saquinavir (11.6%). As age increased, median standardized NNRTI concentrations remained constant, whereas PI concentrations increased (correlation coefficient 0.04, P = 0.033). In a regression analysis stratified by antiretroviral drug class, standardized plasma concentrations were significantly associated with age for PIs (0.05 increase in standard deviation of drug concentration with each 10 year increase in age, P = 0.044), but not for NNRTIs or other clinical parameters, including hepatic transaminase results or time to antiretroviral treatment modification. CONCLUSIONS: With increasing age, statistically significant rises in plasma PI exposure, but not NNRTI exposure, were observed. The clinical relevance of this observation merits further investigation.


Subject(s)
Aging/metabolism , Anti-HIV Agents/blood , Antiretroviral Therapy, Highly Active , HIV Infections/blood , Adult , Aged , Anti-HIV Agents/adverse effects , Anti-HIV Agents/pharmacokinetics , Antiretroviral Therapy, Highly Active/adverse effects , Chromatography, High Pressure Liquid , Cohort Studies , Drug Monitoring , Female , HIV Infections/complications , HIV Infections/drug therapy , Hepatitis C/complications , Humans , Liver Function Tests , Male , Mass Spectrometry , Middle Aged , Reverse Transcriptase Inhibitors/blood , Reverse Transcriptase Inhibitors/pharmacokinetics , United Kingdom , Viral Load
12.
J Infect Dis ; 205(4): 540-7, 2012 Feb 15.
Article in English | MEDLINE | ID: mdl-22279171

ABSTRACT

INTRODUCTION: The CD4 count and CD4 percentage (CD4%) are both strong predictors of clinical disease progression in human immunodeficiency virus (HIV). Although individuals may show discordancy between their CD4 count and CD4%, the clinical relevance of this is unclear. METHODS: Discordancy was defined where the CD4% was ≤10th percentile for a selected CD4 count range (referred to as low discordancy), within the central 80% range (concordant), or ≥90th percentile (high discordancy). Regression methods identified factors associated with low and high discordancy in untreated individuals and assessed the impact of discordancy on treatment responses to highly active antiretroviral therapy (HAART). RESULTS: High discordancy was associated with female sex, low viral load, and white ethnicity; low discordancy was associated with black or nonwhite ethnicity, older age, and injection drug use. Clinical event rates were higher in individuals with high discordancy starting HAART, but there was no association with subsequent HIV progression by 6 months after starting HAART. CD4 count increases remained lower, by 20 cells/mm(3), in individuals with low discordancy, and higher, by 27 cells/mm(3), in those with high discordancy. CONCLUSIONS: Overall discrepancies between the CD4/CD4% are small, confirming the use of absolute CD4 counts as a monitoring tool.


Subject(s)
Anti-HIV Agents/administration & dosage , Antiretroviral Therapy, Highly Active , Drug Monitoring/methods , HIV Infections/drug therapy , HIV Infections/immunology , Adult , CD4 Lymphocyte Count , Female , Humans , Male , Middle Aged , Treatment Outcome
13.
HIV Med ; 13 Suppl 2: 1-85, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22830364

ABSTRACT

The overall purpose of these guidelines is to provide guidance on best clinical practice in the treatment and management of adults with HIV infection with antiretroviral therapy (ART). The scope includes: (i) guidance on the initiation of ART in those previously naïve to therapy; (ii)support of patients on treatment; (iii) management of patients experiencing virological failure; and (iv) recommendations in specific patient populations where other factors need to be taken into consideration. The guidelines are aimed at clinical professionals directly involved with and responsible for the care of adults with HIV infection and at community advocates responsible for promoting the best interests and care of HIV-positive adults. They should be read in conjunction with other published BHIVA guidelines.


Subject(s)
Anti-HIV Agents/therapeutic use , HIV Infections/drug therapy , HIV-1/drug effects , Adult , Anti-Retroviral Agents/therapeutic use , Humans , Societies, Medical , United Kingdom
14.
Postgrad Med J ; 88(1036): 59-65, 2012 Feb.
Article in English | MEDLINE | ID: mdl-22173691

ABSTRACT

INTRODUCTION: 26% of people living with HIV in the UK remain undiagnosed and over 50% of adults with HIV are significantly immunocompromised at the time of diagnosis. Current guidelines recommend routine testing in all patients presenting with a range of conditions in low prevalence areas (< 2/1000). METHODS: The authors conducted an online survey of the knowledge, attitudes and practice of non-HIV specialist physicians with regard to HIV testing in two areas of the UK with a lower prevalence of HIV. Key outcomes included recognition of recommended clinical indications for HIV testing and perceived barriers to performing HIV tests more routinely. All responses were collected in July 2009. RESULTS: Recommended indications for HIV testing were identified by 0-43.7% of 119 respondents. 47.9% cited a low prevalence of HIV as a barrier to routine testing. 88% of 60 consultant physicians were unaware of current guidelines on testing for HIV. CONCLUSION: The authors found a low awareness of current guidance on testing for HIV and a high level of perceived barriers to testing. Reducing the high number of late diagnoses is a clinical and public health priority. To achieve this, the authors recommend improved policy dispersal coupled with education that targets perceived barriers to testing.


Subject(s)
Diagnostic Tests, Routine/statistics & numerical data , HIV Infections/diagnosis , Health Knowledge, Attitudes, Practice , Physicians/psychology , AIDS Serodiagnosis , Data Collection , Delayed Diagnosis , HIV Infections/epidemiology , Health Status Indicators , Humans , Online Systems
16.
Eur J Neurol ; 18(3): 527-34, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21159073

ABSTRACT

BACKGROUND AND PURPOSE: Data describing the incidence and survival of HIV-related central nervous system diseases (CNS-D) in recent years are sparse. METHODS: Between 1996 and 2007, adult subjects without previous CNS-D within a large UK cohort were included (n=30,954). CNS-D were HIV encephalopathy (HIVe), progressive multifocal leucoencephalopathy (PML), cerebral toxoplasmosis (TOXO) and cryptococcal meningitis (CRYP). Associations between demographic, clinical and laboratory parameters with incidence and survival of CNS-D were evaluated using Poisson regression analysis and Kaplan-Meier techniques. RESULTS: Six hundred and thirteen new CNS-D occurred in 574 subjects (HIVe:187, PML:113, TOXO:184, CRYP:129). Incidence of all CNS-D declined from 13.1 per 1000 PY in 1996/1997 to 1.0 per 1000 PY in 2006/2007 (P=0.0001). Current CD4+ cell count below 200 cells/ul and plasma HIV RNA above 100,000 copies/ml were independently associated with the development of CNS-D. Calendar year 1996/1997, older age, prior AIDS diagnosis and PML diagnosis were significantly associated with shorter survival. CONCLUSIONS: An ongoing decline in the incidence of CNS-D has been observed in very recent years. Mortality following such a diagnosis remains high.


Subject(s)
AIDS Dementia Complex/epidemiology , AIDS-Related Opportunistic Infections/epidemiology , Antiretroviral Therapy, Highly Active , HIV Infections/complications , HIV Infections/drug therapy , Cohort Studies , Humans , Incidence , Kaplan-Meier Estimate , Leukoencephalopathy, Progressive Multifocal/epidemiology , Leukoencephalopathy, Progressive Multifocal/etiology , Meningitis, Cryptococcal/epidemiology , Meningitis, Cryptococcal/etiology , Toxoplasmosis, Cerebral/epidemiology , Toxoplasmosis, Cerebral/etiology
18.
J Acquir Immune Defic Syndr ; 86(2): 248-257, 2021 02 01.
Article in English | MEDLINE | ID: mdl-33079903

ABSTRACT

OBJECTIVES: To investigate the effectiveness, safety, and reasons for premature discontinuation of direct-acting antivirals (DAAs) in a diverse population of HIV/hepatitis C virus (HCV) coinfected individuals in Europe. METHODS: All HIV/HCV coinfected individuals in the EuroSIDA study that started interferon free DAA treatment between January 6, 2014, and January 3, 2018, with ≥12 weeks of follow-up after treatment stop were included in this analysis. Sustained virological response (SVR) was defined as a negative HCV-RNA result ≥12 weeks after stopping treatment (SVR12). Logistic regression was used to explore factors associated with SVR12. RESULTS: 1042 individuals started interferon-free DAA treatment after 1/6/2014 and were included, 862 (82.2%) had a known response to treatment, and 789 [91.5%, 95% confidence interval (CI): 89.7 to 93.4] of which achieved SVR12. There were no differences in SVR12 across regions of Europe (P = 0.84). After adjustment, the odds of achieving SVR12 was lower in individuals that received sofosbuvir/simeprevir ± ribavirin (RBV) [adjusted odds ratio 0.21 (95% CI: 0.08 to 0.53)] or ombitasvir/paritaprevir/dasabuvir ± RBV [adjusted odds ratio 0.46 (95% CI: 0.22 to 1.00)] compared with sofosbuvir/ledipasvir ± RBV. Forty-three (4.6%) individuals had one or more components of their HCV regimen stopped early, most commonly because of toxicity (n = 14); of these 14, 11 were treated with ribavirin. Increased bilirubin was the most common grade 3 or 4 laboratory adverse event (n = 15.3%) and was related to treatment with atazanavir and ribavirin. CONCLUSIONS: Our findings from real-world data on HIV/HCV coinfected individuals across Europe show DAA treatment is well tolerated and that high rates of SVR12 can be achieved in all regions of Europe.


Subject(s)
Antiviral Agents/therapeutic use , Coinfection/drug therapy , HIV Infections/drug therapy , Hepatitis C/drug therapy , Interferons/therapeutic use , Anilides , Antiviral Agents/administration & dosage , Benzimidazoles , Cyclopropanes , Female , Fluorenes , Hepacivirus , Hepatitis C/complications , Hepatitis C, Chronic/drug therapy , Humans , Interferons/administration & dosage , Lactams, Macrocyclic , Male , Middle Aged , Proline/analogs & derivatives , Ribavirin/administration & dosage , Ribavirin/therapeutic use , Simeprevir/administration & dosage , Simeprevir/therapeutic use , Sofosbuvir/administration & dosage , Sofosbuvir/therapeutic use , Sulfonamides , Sustained Virologic Response , Valine
19.
J Antimicrob Chemother ; 65(1): 129-37, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19897506

ABSTRACT

BACKGROUND: The protease inhibitors lopinavir and atazanavir are both recommended for treatment of HIV-infected patients. Considerable inter-individual variability in plasma concentration has been observed for both drugs. The aim of this study was to evaluate which demographic factors and concomitant drugs are associated with lopinavir and atazanavir plasma concentration. METHODS: Data from the Liverpool TDM (therapeutic drug monitoring) Registry were linked with the UK Collaborative HIV Cohort (CHIC) study. For each patient, the first measurement of lopinavir (twice daily) or atazanavir [once daily, ritonavir boosted (/r) or unboosted] plasma concentration was included. Linear regression was used to evaluate the association of dose, gender, age, weight, ethnicity and concomitant antiretroviral drugs or rifabutin with log-transformed drug concentration, adjusted for time since last intake. RESULTS: Data from 439 patients on lopinavir (69% 400 mg/r, 31% 533 mg/r; 3% concomitant rifabutin) and 313 on atazanavir (60% 300 mg/r, 32% 400 mg/r, 8% 400 mg) were included. Multivariable models revealed the following predictors for lopinavir concentration: weight (11% decrease per additional 10 kg; P = 0.001); dose (25% increase for 533 mg/r; P = 0.024); and rifabutin (116% increase; P < 0.001). For atazanavir the predictors were dose (compared with 300 mg/r: 40% increase for 400 mg/r, 67% decrease for 400 mg; overall P < 0.001) and efavirenz (32% decrease; P = 0.016) but not tenofovir (P = 0.54). CONCLUSIONS: This analysis confirms that efavirenz decreases atazanavir concentrations, and there was a negative association of weight and lopinavir concentrations. The strong impact of rifabutin on lopinavir concentration should be studied further.


Subject(s)
Anti-HIV Agents/blood , Anti-HIV Agents/pharmacokinetics , Oligopeptides/blood , Oligopeptides/pharmacokinetics , Plasma/chemistry , Pyridines/blood , Pyridines/pharmacokinetics , Pyrimidinones/blood , Pyrimidinones/pharmacokinetics , Adult , Alkynes , Atazanavir Sulfate , Benzoxazines/blood , Benzoxazines/pharmacokinetics , Body Weight , Cyclopropanes , Female , HIV Infections/drug therapy , Humans , Lopinavir , Male , Middle Aged , Rifabutin/blood , Rifabutin/pharmacokinetics , United Kingdom
20.
AIDS ; 34(10): 1485-1495, 2020 08 01.
Article in English | MEDLINE | ID: mdl-32675562

ABSTRACT

BACKGROUND: Hepatitis C virus (HCV) infection has been associated with increased risk of chronic kidney disease (CKD). We investigated the impact of HCV cure on CKD in HIV-positive persons in the EuroSIDA study. METHODS: HIV-positive persons with known HCV status and at least three serum creatinine measurements after 1/1/2004 were compared based on time-updated HCV-RNA and HCV treatment: anti-HCV-negative, spontaneously cleared HCV, chronic untreated HCV, successfully treated HCV, and HCV-RNA positive after HCV treatment. Poisson regression compared incidence rates of CKD [confirmed (>3 months apart) eGFR <60 ml/min per 1.73 m] between HCV strata. RESULTS: Fourteen thousand, seven hundred and fifty-four persons were included; at baseline 9273 (62.9%) were HCV-Ab negative, 696 (4.7%) spontaneous clearers, 3021 (20.5%) chronically infected, 922 (6.2%) successfully treated and 842 (5.7%) HCV-RNA positive after treatment. During 115 335 person-years of follow-up (PYFU), 1128 (7.6%) developed CKD; crude incidence 9.8/1000 PYFU (95% CI 9.2-10.4). After adjustment, persons anti-HCV negative [adjusted incidence rate ratio (aIRR) 0.59; 95% CI 0.46-0.75] and spontaneous clearers (aIRR 0.67; 95% CI 0.47-0.97) had significantly lower rates of CKD compared with those cured whereas persons chronically infected (aIRR 0.85; 95% CI 0.65-1.12) and HCV-RNA positive after treatment (aIRR 0.71; 95% CI 0.49-1.04) had similar rates. Analysis in those without F3/F4 liver fibrosis using a more rigorous definition of CKD showed similar results. CONCLUSION: This large study found no evidence that successful HCV treatment reduced CKD incidence. Confounding by indication, where those with highest risk of CKD were prioritized for HCV treatment in the DAA era, may contribute to these findings.


Subject(s)
Antiviral Agents , Coinfection , HIV Infections , Hepatitis C, Chronic , Renal Insufficiency, Chronic , Antiviral Agents/therapeutic use , Coinfection/drug therapy , HIV Infections/complications , HIV Infections/drug therapy , Hepacivirus , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/drug therapy , Humans , Prospective Studies , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/epidemiology
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