[Show abstract][Hide abstract] ABSTRACT: Rates of first antiretroviral therapy (cART) modifications are high in most observational studies. The age-related differences in treatment duration and characteristics of first cART modifications remain underinvestigated. With increasing proportion of older patients in HIV population it is important to better understand age-related treatment effects.
Patients were included into this analysis, if being cART naïve at the first visit at the clinic. Follow-up time was measured from the first visit date until first cART modification or 28 February 2013. First cART modification was defined as any change in the third drug component i.e. protease inhibitor (PI), non-nucleoside reverse transcriptase inhibitor (NNRTI), integrase inhibitor or fusion inhibitor. Cox proportional hazard models were used to identify factors related to first cART modification in three age groups: <30, 30–50 and >50.
In total 2027 patients with 14,965 person-years of follow-up (PYFU) were included. The oldest group included 136 patients with 1901, middle group 1202 with 8416 PYFU and youngest group consisted of 689 patients with 4648 PYFU. Median follow-up time was 5.8 (IQR 3.4–9.4) years, median time on first cART was 4.4 (IQR 2.1–8.5) years. 72.4 % of patients started PI-based and 26.1 % NNRTI-based regimen. In total 1268 (62.5 %) patients had cART modification (non-adherence 30.8 %, toxicity 29.6 %). Durability of first cART was the best in patients over 50 y.o. (log-rank test, p = 0.001). Factors associated with discontinuation in this group were late presentation (HR 0.45, [95 % CI 0.23–0.90], p = 0.02) and PI use (HR 2.17, [95 % CI 1.18–4.0], p = 0.01).
Rates of first cART modifications or discontinuation were comparable in all groups; however older patients were significantly longer on first cART regimen.
Full-text · Article · Dec 2016 · AIDS Research and Therapy
[Show abstract][Hide abstract] ABSTRACT: Background:
Numerous studies have shown that baseline drug resistance patterns may influence the outcome of antiretroviral therapy. Therefore guidelines recommend drug resistance testing to guide the choice of initial regimen. In addition to optimizing individual patient management, these baseline resistance data enable transmitted drug resistance (TDR) to be surveyed for public health purposes. The SPREAD-program systematically collects data to gain insight into TDR occurring in Europe since 2001.
Demographic, clinical and virological data from 4,140 antiretroviral-naive HIV-infected individuals from 26 countries who were newly diagnosed between 2008 and 2010 were analyzed. Evidence of TDR was defined using the WHO list for surveillance of drug resistance mutations. Prevalence of TDR was assessed over time by comparing the results to SPREAD data from 2002-2007. Baseline susceptibility to antiretroviral drugs was predicted using Stanford HIVdb v7.0.
The overall prevalence of TDR did not change significantly over time and was 8.3% (95%CI 7.2-9.5) in 2008-2010. The most frequent indicators of TDR were NRTI-mutations (4.5%), followed by NNRTI-mutations (2.9%) and PI-mutations (2.0%). Baseline mutations were most predictive of reduced susceptibility to initial NNRTI-based regimens: 4.5% and 6.5% of patient isolates were predicted to have resistance to regimens containing efavirenz or rilpivirine respectively, independent of current NRTI backbones.
Although TDR was highest for NRTIs, the impact of baseline drug resistance patterns on susceptibility was largest for NNRTIs. The prevalence of TDR assessed by epidemiological surveys does not clearly indicate to what degree susceptibility to different drug classes is affected.
Full-text · Article · Nov 2015 · Clinical Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: The aim of the study was to evaluate the spectrum of AIDS-defining malignancies (ADMs) and non-AIDS-defining malignancies (NADMs) in HIV-infected patients in Poland.
Material and methods: A retrospective observational study was conducted among HIV-infected adult patients who developed a malignancy between 1995 and 2012 in a Polish cohort. Malignancies were divided into ADMs and NADMs. Non-AIDS-defining malignancies were further categorised as virus-related (NADMs-VR) and unrelated (NADMs-VUR). Epidemiological data was analysed according to demographic data, medical history, and HIV-related information. Results were analysed by OR, EPITools package parameters and Fisher’s exact test.
Results: In this study 288 malignancies were discovered. The mean age at diagnosis was 41.25 years (IQR20-81); for ADMs 38.05 years, and for NADMs-VURs 46.42 years; 72.22% were male, 40.28% were co-infected with HCV. The risk behaviours were: 37.85% IDU, 33.33% MSM, and 24.31% heterosexual. Mean CD4+ at the diagnosis was 282 cells/mmł (for ADMs 232 and for NADMs-VUR 395). Average duration of HIV infection at diagnosis was 5.69 years. There were 159 (55.2%) ADMs and 129 (44.8%) NADMs, among whom 58 (44.96%) NADMs-VR and 71 (55.04%) NADMs-VUR. The most frequent malignancies were: NHL (n = 76; 26.39%), KS (n = 49; 17.01%), ICC (n = 34; 11.81%), HD (n = 23; 7.99%), lung cancer (n = 18; 6.25%) and HCC (n = 14; 4.86%). The amount of NADMs, NADMs-VURs in particular, is increasing at present. Male gender (OR = 1.889; 95% CI: 1.104–3.233; p = 0.024), advanced age: 50–60 years (OR = 3.022; 95% CI: 1.359–6.720; p = 0.01) and ≥ 60 years (OR = 15.111; 95% CI: 3.122–73.151; p < 0.001), longer duration of HIV-infection and successful HAART (OR = 2.769; 95% CI: 1.675–4.577; p = 0) were independent predictors of NADMs overall, respectively.
Conclusions: In a Polish cohort NHL was the most frequent malignancy among ADMs, whereas HD was the most frequent among NADMs. Increased incidence of NADMs appearing in elderly men with longer duration of HIV-infection and with better virological and immunological control was confirmed. As HIV-infected individuals live longer, better screening strategies, especially for NADMs-VUR, are needed. The spectrum of cancer diagnoses in Poland currently does not appear dissimilar to that observed in other European populations.
HIV, AIDS-defining malig- nancies, non-AIDS-defining malignancies, PLHIV, cART, cancer
Full-text · Article · Nov 2015 · Contemporary oncology
[Show abstract][Hide abstract] ABSTRACT: Objectives:
The objective of the 1st European AIDS Clinical Society meeting on Standard of Care in Europe was to raise awareness of the European scenario and come to an agreement on actions that could be taken in the future.
Data-driven presentations were given on specific topics followed by interactive panel discussions.
In Eastern European countries, the epidemic is largely driven by injecting drug use, in contrast with Western Europe where the infection mainly occurs through heterosexual contact. A high proportion of people living with HIV remain unaware of their infection. Substantial differences exist in Eastern Europe and Central Asia with respect to treatment coverage, regimen availability and continuity of drug supply. In 2012, tuberculosis case notification rates were 5-10 times higher in Eastern Europe compared with Western Europe, with an alarming proportion of newly diagnosed multi-drug-resistant cases. Hepatitis C is widespread in selected geographical areas and risk groups.
The key conclusion from the meeting was that a high-priority group of actions could be identified, including: increasing HIV awareness and testing, improving training for health care providers, ensuring equitable patient access to treatments and diagnostics for HIV and comorbidities, and implementing best practices in infection control and treatment of HIV-infected patients coinfected with tuberculosis and hepatitis C virus, for whom direct acting antiviral treatment. should be considered.
[Show abstract][Hide abstract] ABSTRACT: Objectives
INSIGHT (ClinicalTrials.gov NCT01513941) evaluated the efficacy, safety and pharmacokinetics of telaprevir-based therapy and specific antiretroviral agents in hepatitis C virus genotype 1 (HCV-1)/HIV-1-coinfected patients.
Patients and methods
Open-label, Phase IIIb, multicentre study of telaprevir with pegylated-IFN (Peg-IFN) α2a and ribavirin in treatment-naive or -experienced HCV-1/HIV-1-coinfected patients on stable HIV HAART comprising efavirenz, atazanavir/ritonavir, darunavir/ritonavir, raltegravir, etravirine or rilpivirine with two nucleos(t)ide analogues. Patients received 750 mg telaprevir (1125 mg, if on efavirenz) every 8 h plus 180 μg/week Peg-IFNα2a and 800 mg/day ribavirin for 12 weeks, followed by Peg-IFNα2a and ribavirin alone for 12 weeks (HCV treatment naive and relapsers without cirrhosis, with extended rapid virological response) or 36 weeks (all others).
Overall, 162 patients (median age of 46 years, 78% male, 92% Caucasian and mean CD4 count of 687 cells/mm3) were treated; 13% had cirrhosis. One-hundred-and-thirty-two patients (81%) completed telaprevir; 14 (9%) discontinued due to an adverse event (AE). Sustained virological response (SVR) 12 rates (
No preview · Article · Oct 2015 · Journal of Antimicrobial Chemotherapy
[Show abstract][Hide abstract] ABSTRACT: We investigated the safety, efficacy, and impact of ribavirin and peginterferon dose reduction on complete early virologic response and sustained virologic response (SVR) to triple therapy with telaprevir in treatment-experienced patients with advanced liver fibrosis.
Treatment was initiated for 211 patients who failed treatment with peginterferon and ribavirin, with bridging fibrosis (F3, n = 68) or cirrhosis (F4, n = 143), including 103 (49%) null-responders (NR), 30 (14%) partial responders (PR), and 78 (37%) relapsers (REL). Impaired liver function (ILF) platelets <100,000/mm3 or albumin <35 g/L were present in 40 patients. The distribution of hepatitis C virus subtypes was: 1a, 1b, or 1, with undetermined subtype for 10 (5%), 187 (89%), and 14 (6%) patients, respectively. Treatment was started with peginterferon alpha-2a or alpha-2b, ribavirin, and telaprevir at standard doses.
The overall SVR24 rate was 56% and was lower in cirrhotic patients (NR: 35%, PR: 40%, and REL: 63%, respectively) than in patients with bridging fibrosis (NR: 50%, PR: 75%, and REL: 75%, respectively). The lowest probability of SVR24 was in NRs with ILF (26%). The SVR24 rate significantly decreased in NRs receiving <60% vs >60% of the total ribavirin dose (23% vs 44%, respectively) or <80% vs >80% of the total ribavirin dose (33% vs 48%, respectively). A significant SVR24 decrease was noted subsequent to a total peginterferon dose reduction, both when comparing patients who received <60% vs >60% of the total dose (NR: 0% vs 44%; REL: 33% vs 68%) and patients who received <80% vs >80% of the total dose (NR: 17% vs 50%; REL: 46% vs 71%).
Serious adverse events were observed in 31 patients (15%). Deaths occurred in 4 patients. All of the deceased subjects were cirrhotic members of the ILF (baseline serum albumin level <35 g/L and/or platelet count <100,000/mm3) group.
Ribavirin dose reduction did not affect efficacy in REL but did in NR. Peginterferon dose reduction decreased the SVR24 rate for all groups, particularly in prior NR. ILF increased the risk of fatal complications with a low probability to achieve SVR24. One solution might be to provide wide and early access to novel, efficient, and safe interferon-free combinations to treatment-experienced patients, particularly those with liver cirrhosis.
[Show abstract][Hide abstract] ABSTRACT: Background:
In previous studies in virologically suppressed patients, protease inhibitor monotherapy has shown trends for more low-level elevations in HIV-1 RNA compared with triple therapy, but no increase in the risk of drug resistance.
A total of 273 patients with HIV-1 RNA less than 50 copies/ml on first-line antiretrovirals switched to darunavir/ritonavir (DRV/r) 800/100 mg once daily, either as monotherapy (n = 137) or as triple therapy with two nucleoside analogues (n = 136). Treatment failure was defined as HIV-1 RNA levels 50 copies/ml or above, or discontinuation of study treatment by week 48 (FDA Snapshot algorithm).
Patients were 83% male and 88% white, with mean age 42 years. In the primary efficacy analysis, HIV-1 RNA less than 50 copies/ml by week 48 [intention-to-treat (ITT)] was 118 of 137 (86%) in the DRV/r monotherapy arm versus 129 of 136 (95%) in the triple therapy arm (difference = -8.7%, 95% confidence interval -15.50, -1.80). In a post-hoc analysis, for patients with nadir CD4 cell count 200 cells/μl or above, rates of HIV-1 RNA suppression were 91 of 96 (95%) in the DRV/r monotherapy arm and 100 of 106 (94%) in the triple therapy arm. There was no difference in neurocognitive function or the risk of neuropsychiatric adverse events between DRV/r monotherapy and triple therapy. Two patients in the monotherapy arm with CD4 nadir less than 200 cells/μl developed viraemia in both cerebrospinal fluid (CSF) and plasma, with one symptomatic case.
In this study for patients with HIV-1 RNA less than 50 copies/ml at baseline, switching to DRV/r monotherapy showed lower efficacy versus triple therapy at week 48 in the primary ITT switch equals failure analysis, with two cases of viraemia in the CSF in the protease inhibitor monotherapy arm.
No preview · Article · Sep 2015 · AIDS (London, England)
[Show abstract][Hide abstract] ABSTRACT: Background
Syphilis is an infection frequently seen with HIV, and European guidelines on the management of syphilis suggest that HIV-infected patients may have an increased risk of early neurological involvement, sometimes asymptomatic. Recent study shows a relationship between neurosyphilis and cerebrospinal fluid (CSF) HIV viral load (VL), which in turn may be associated with subsequent neurocognitive decline.Objectives and methodsThe aim of the study was estimation of the frequency of neurosyphilis among HIV-positive patients with early syphilis. The study included all patients diagnosed with early syphilis who had lumbar puncture performed in the years 2008–2012. Analysis included CSF parameters (serology, mononuclear cells, protein, glucose, chloride and lactate levels), CD4 count, serum VL and highly active antiretroviral therapy (HAART). Diagnosis of neurosyphilis was confirmed by CSF serology [positive fluorescent treponemal antibody and/or Venereal Disease Research Laboratory (VDRL) test(s)] and increased number of mononuclear cells. Statistical analysis included χ2 tests with an accepted significance level of P < 0.05.ResultsLumbar puncture was performed in 72 patients, all men, with median age 33 (interquartile range 11) years. Neurosyphilis was confirmed in 65 (90.28%) of the patients. No statistically significant association between CSF parameters and CD4 count was found. However, statistically significant associations were found only between pleocytosis and serum VL > 1000 HIV-1 RNA copies/mL (P = 0.0451), as well as HAART treatment (P = 0.0328). The proportion of confirmed neurosyphilis cases, also in patients with low serum VDRL titres, was very high.Conclusions
Considering the high proportion of patients who objected to having LP performed in the absence of neurological symptoms and the risk associated with this procedure, it may be preferable to use treatments with good CNS penetration in all HIV-positive patients with early syphilis.
[Show abstract][Hide abstract] ABSTRACT: Association between hepatitis C virus (HCV) quasispecies and treatment outcome among patients with chronic hepatitis C has been the subject of many studies. However, these studies focused mainly on viral variable regions (E1 and E2) and usually did not include human immunodeficiency virus (HIV)-positive patients. The aim of the present study was to analyze heterogeneity of the 5′untranslated region (5′UTR) in HCV/HIV coinfected patients treated with interferon and ribavirin. The HCV 5′UTR was amplified from serum and peripheral blood mononuclear cells (PBMC) samples in 37 HCV/HIV coinfected patients treated for chronic hepatitis C. Samples were collected right before treatment, and at 2, 4, 6, 8, 12, 20, 24, 36, 44, 48, 60, and 72 weeks. Heterogeneity of the 5′UTR was analyzed by single strand conformational polymorphism (SSCP), cloning and sequencing. Sustained virological response (SVR) was achieved in 46% of analyzed HCV/HIV co-infected patients. Stable SSCP band pattern was observed in 22 patients (62.9%) and SVR rate among these patients was 23%. Decline in the number of bands and/or shift in band positions were found in 6 patients (17.1%), 5 (83%) of whom achieved SVR (p=0.009). A novel viral genotype was identified in all but one of these patients. In 5 of these 6 patients a new genotype was dominant. 5′UTR heterogeneity may correlate with interferon and ribavirin treatment outcome. In the analyzed group of HCV/HIV coinfected patients, viral quasispecies stability during treatment favored viral persistence, whereas decrease in the number of variants and/or emergence of new variants was associated with SVR. Among injection drug users (IDU) patients, a new genotype may become dominant during treatment, probably due to the presence of mixed infections with various strains, which have different susceptibility to treatment.
[Show abstract][Hide abstract] ABSTRACT: Syphilis recognition in HIV-positive patients has important implications. Initial data from this study, established in June 2012 to better understand the natural history of syphilis and treatment response, examine the characteristics of patients including sexual behaviour, rates of concurrent sexually transmitted infections (STI) and type of treatment given.
Patients were recruited from Ireland, Poland and Germany. Data gathered included demographics, method of syphilis acquisition, stage of syphilis infection, HIV status, nadir and current CD4 counts and HIV viral suppression rates. Data were then subanalysed into HIV-positive and HIV-negative groups.
Of 175 patients recruited, 68% were HIV-positive and 86.3% were men who have sex with men. Most HIV-positive patients presented with secondary syphilis (55.7% vs 13.2%) (p=0.0001) while the majority of HIV-negative patients had primary syphilis noted at the time of recruitment (47.2% vs18.9%, p=0.0002). Approximately half of all patients had a HIV RNA viral load <40 copies/mL (55%). Previous syphilis infection occurred more frequently in HIV-positive than HIV-negative patients (p=0.0001). Concurrent STIs at the time of syphilis diagnosis were found in 26.8%, of whom 31 (25.4%) were HIV-positive (p=0.64). HIV-positive patients received doxycycline more frequently than their HIV-negative counterparts (33.6% vs 1.9%, p=0.0001) while HIV-negative patients were treated with long-acting penicillin in 88.7% of cases vs 58% of HIV-positive patients (p=0.0002).
A 40% rate of unsuppressed viraemia, high levels of STIs and varying treatment regimens represent a public health risk for Europe, suggesting the model of sexual healthcare delivery in HIV-positive patients requires further evaluation.
Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Full-text · Article · Mar 2015 · Sexually Transmitted Infections
[Show abstract][Hide abstract] ABSTRACT: Abstract Aim To investigate epidemiology and characteristics of chronic pain in HIV-1 positive persons. Background Chronic pain is vital but still understudied problem in HIV clinical practice; therefore we have designed a study to analyse the prevalence and attributes of pain symptoms in the group of HIV-positive patients in the Out-Patient HIV Clinic in Warsaw. Materials and methods During their routine visit patients were asked to fill in a general information form and the Alcohol Use Disorders Identification Test Consumption (AUDIT-C) form. All patients reporting any pain were additionally asked to fill in the Brief Pain Inventory (BPI) form and were subject to a brief examination performed by a physician who afterwards completed a DN4 (Douleur Neuropathique en 4 Questions) form. Logistic regression models were used to identify factors associated with chronic pain occurrence. Results Forty nine patients completed the questionnaires. Nineteen patients (37.2%) reported chronic pain, occurring once daily in 39.4%, and in 42.9% lasting several hours. In univariate logistic regression analyses factors increasing the odds of chronic pain were age at the time of evaluation (OR = 1.07; 95% CI 1.02-1.08, p = 0.01), starting antiretroviral treatment with didanosine, zalcitabine and stavudine (OR = 6.75; 1.18-38.4, p = 0.03) and last CD4+ lymphocyte count (OR = 0.99; 0.99-1.00, p = 0.07). After adjusting for the three above only age at the evaluation time remained significant factor increasing the odds of experiencing chronic pain (OR = 1.07 [1.01-1.13]; p = 0.03). Conclusion Almost 40% of respondents reported chronic pain. We have found a strong correlation between age and chronic pain in the HIV infected population with the 7% increase in the odds of experiencing pain with each year of age.
No preview · Article · Mar 2015 · HIV and AIDS Review
[Show abstract][Hide abstract] ABSTRACT: Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice.
[Show abstract][Hide abstract] ABSTRACT: Aim Assessment of long-term safety and effectiveness of atazanavir in the first cART regimen. Background Achievement of longer life span in recent years increased HIV-positive patients' risk of experiencing conditions resulting from long term cART therapy including drug-induced toxicities like metabolic, hepatic or renal disorders. Materials and methods The study is a retrospective analysis of data collected in POLCA cohort. Safety analyses included changes in selected parameters: hepatic (ALT, AST, GGT, bilirubin, INR), metabolic (glucose, cholesterol, triglycerides) and renal (creatinine, urea). Effectiveness analyses included CD4 count on treatment vs. baseline and proportion of patients with durable VL suppression. Results After 12 and 24 months from starting treatment VL below 40 copies/mL had 60% and 56% of patients, respectively. VL below 200 copies/mL after 12 and 24 months had 80% and 76% of patients, respectively. The median CD4 count increased from baseline at all time points, and at 24 months was equal in late presents (baseline CD4 <350) and the whole group. Proportion of patients with normal levels of liver function parameters did not change significantly between baseline and treatment with exception of significant decrease for bilirubin. Differences in lipids and glucose levels did not change significantly between baseline and treatment with exception of significant increase for HDL at 24 months. Renal function parameters remained unchanged between baseline and treatment. Conclusion In POLCA cohort long term treatment with ATV was safe and effective, and observed drug-induced toxicities were similar or smaller than reported in literature.
No preview · Article · Feb 2015 · HIV and AIDS Review
[Show abstract][Hide abstract] ABSTRACT: Background:
Human immunodeficiency virus type 1 (HIV-1) subtype CRF01_AE originated in Africa and then passed to Thailand, where it established a major epidemic. Despite the global presence of CRF01_AE, little is known about its subsequent dispersal pattern.
We assembled a global data set of 2736 CRF01_AE sequences by pooling sequences from public databases and patient-cohort studies. We estimated viral dispersal patterns, using statistical phylogeographic analysis run over bootstrap trees estimated by the maximum likelihood method.
We show that Thailand has been the source of viral dispersal to most areas worldwide, including 17 of 20 sampled countries in Europe. Japan, Singapore, Vietnam, and other Asian countries have played a secondary role in the viral dissemination. In contrast, China and Taiwan have mainly imported strains from neighboring Asian countries, North America, and Africa without any significant viral exportation.
The central role of Thailand in the global spread of CRF01_AE can be probably explained by the popularity of Thailand as a vacation destination characterized by sex tourism and by Thai emigration to the Western world. Our study highlights the unique case of CRF01_AE, the only globally distributed non-B clade whose global dispersal did not originate in Africa.
Full-text · Article · Dec 2014 · The Journal of Infectious Diseases
[Show abstract][Hide abstract] ABSTRACT: Introduction
We report the SVR12 final analysis of a phase 3 study of telaprevir in combination with peginterferon (P)/ribavirin (R) in HCV-genotype 1, treatment-naïve and -experienced patients with HCV/HIV co-infection (INSIGHT).
Materials and Methods
Patients receiving stable, suppressive HIV antiretroviral (ARV) therapy, containing atazanavir/ritonavir, efavirenz, darunavir/ritonavir, raltegravir, etravirine or rilpivirine, received telaprevir 750 mg q8h (1125 mg q8h if on efavirenz) plus P (180 µg once-weekly) and R (800 mg/day) for 12 weeks, followed by an additional 12 weeks (non-cirrhotic HCV treatment-naïve and relapse patients with extended rapid viral response [eRVR]) or 36 weeks (all others) of PR alone. Analysis was performed when all patients had completed the follow-up visit of 12 weeks after last planned dose.
One hundred sixty-two patients were enrolled and treated (65 efavirenz, 59 atazanavir/ritonavir, 17 darunavir/ritonavir, 17 raltegravir, 4 etravirine). Mean age was 45 years, 78% were male, 92% were Caucasian; mean CD4 count was 687 cells/mm3. Sixty four patients (40%) were HCV treatment-naïve and 98 (60%) were treatment experienced (29 relapsers, 18 partial responders and 51 null responders). 64% were subtype 1a. 30% had bridging fibrosis (17%) or cirrhosis (13%). 19% of patients discontinued telaprevir, including 9% due to an adverse event (AE), 8% reaching a virologic endpoint and 2% for other reasons (non compliance or not defined). Treatment responses are shown in Table 1. There were no HIV RNA breakthroughs. Most frequently reported (≥20% patients) AEs were pruritus 43%; fatigue 27%; rash 34%, anorectal events 30% and influenza-like illness (25%). Anemia was reported in 15% of patients; grade ≥3 haemoglobin decrease occurred in 2.5% of patients. 6% of patients experienced serious AEs.
In this phase 3 study of HIV-infected, HCV treatment-naïve and -experienced patients, 49% achieved eRVR and 57% reached SVR12. In patients with an eRVR, SVR12 rates were >80%, irrespective of prior treatment history.
Full-text · Article · Nov 2014 · Journal of the International AIDS Society
[Show abstract][Hide abstract] ABSTRACT: Introduction
With increased usage of antiretroviral drugs (ARVs) in HIV uninfected persons proper reporting on suspected unexpected serious adverse reactions (SUSARs) and continued insight into serious adverse events (SAEs) is needed for adequate information on ARVs safety in such populations.
We have evaluated medical documentation of persons receiving ARVs after non-occupationally HIV exposure (nPEP) during five concomitant years (2009–2013). SAEs and SUSARs were evaluated by two HIV physicians and defined according to international standards. In statistical methods, Kaplan Meier survival analysis was used to estimate the probability of SAE and Cox proportional hazard models to identify independent predictors of developing SAE. Only the first SAE was included in these analyses.
In total, 375 persons received nPEP. The most common reason was needle stick (43%), followed by unprotected sexual intercourse (17%), rape (10%) and first aid (10%). In 84 (22%) cases, the source patient was either known to be HIV positive or within a high risk group (active injecting drug user). In total, 170 SAEs were reported, 139 persons had only one SAE and majority developed it within first two weeks. The most frequent first SAEs were gastrointestinal disorders (22%), followed by general symptoms (9%), hypersensitivity reactions (1.6%) and CNS symptoms (1.3%). The remaining events were laboratory abnormalities of liver and kidney function, haematological disorders, other and unknown, each contributing to less than 1% of all patients. 8 (2.1%) patients have developed a SUSAR (bradycardia, vivid dreams, lymphadenopathy of the neck, increased platelet count, swelling and pain of large joints, swelling of lower limbs, peripheral oedema and loss of concentration). 22 (5.9%) persons discontinued nPEP due to adverse event and 19 (5.1%) required a paid sick leave from work. In multivariate analyzes, only age was independent predictor of developing SAE (HR 1.17; [95% CI 1.03–1.34]; p=0.02).
In our observation, SAEs in reaction to nPEP were frequent yet usually mild events, mostly occurring in first two weeks and rarely causing discontinuation. The only significant factor increasing the risk of SAE was age. SUSARs were rare and moderately significant. More insight into this important area is required in order to ascertain proper pharmacovigilance of ARVs usage in HIV uninfected persons.
Full-text · Article · Nov 2014 · Journal of the International AIDS Society
[Show abstract][Hide abstract] ABSTRACT: Since the introduction of highly active antiretroviral treatment significant decrease of HIV related morbidity and mortality has been noted. Ritonavir boosted saquinavir is an alternatively recommended protease inhibitor. Therefore we evaluated log term efficacy and safety of saquinavir/r (SQV/r) containing initial antiretroviral regimen on the basis of Polish Observational Cohort of HIV/AIDS Patients (POLCA).Materials and Methods The analysed data were prospectively collected in routine clinical practice and included ART naive patients starting SQV/r regiment as their first ART.
No preview · Article · Nov 2014 · HIV and AIDS Review
[Show abstract][Hide abstract] ABSTRACT: Alisporivir (ALV) is an oral, investigational host-targeting agent, with pangenotypic activity against hepatitis C virus (HCV). This randomized, double-blind, placebo-controlled, Phase II study explored the efficacy and safety of ALV with peginterferon-α2a/ribavirin (PR) in patients with chronic HCV genotype 1 infection in whom prior PR had failed (43% relapsers, 34% null responders and 23% partial responders). Four-hundred-and-fifty-nine patients were randomized (1:1:1:1) to ALV 600 mg once daily (QD), ALV 800 mg QD, ALV 400 twice daily (BID) or placebo plus PR for 48 weeks. When the global ALV trial programme was put on clinical hold, all patients in this study had received ≥31 weeks of randomized treatment; patients completed 48 weeks on PR alone. All ALV groups demonstrated superior rates of complete early virologic response (cEVR; primary endpoint) vs PR alone (P ≤ 0.0131), with highest cEVR rate seen with ALV 400 mg BID (74% vs 36% with PR alone; P < 0.0001). Respective SVR12 rates (key secondary endpoint) were 65% vs 26% in prior relapsers, 63% vs 5% in partial responders and 68% vs 3% in null responders. In patients who received >40 weeks of randomized treatment, the SVR12 rate was 89% for ALV 400 mg BID vs 30% for PR alone (P = 0.0053). Rates of viral breakthrough and relapse were lowest with ALV 400 mg BID. One case of pancreatitis (fully recovered) occurred with ALV/PR. Common AEs were headache, fatigue, anaemia, neutropenia and nausea. Hypertension was infrequent, but more common with ALV. ALV merits further investigation in interferon-free regimens in combination with direct-acting antiviral agents.
Full-text · Article · Nov 2014 · Journal of Viral Hepatitis