We evaluated the impact of HIV risk practice on immune reconstitution in a prospective cohort of 288 patients (176 former injecting drug users) who maintained complete virus suppression for more than ...24 months. Significant differences in CD4 cell counts at 6 and 24 months were detected. Multivariate analysis showed that drug use was an independent predictor of poor immunological recovery. Injection drug abuse impairs short and long-term CD4 cell recovery in HIV-positive patients initiating successful highly active antiretroviral therapy.
Regimens with two nucleoside analogue reverse transcriptase inhibitors (NRTI) plus tenofovir DF have been associated with a high failure rate when administered as first line therapy. Little is known ...about patients with undetectable viral loads who are switched to these regimens.
A post-hoc review of the virological outcomes at 24 weeks of patients who switched from a successful (< 50 copies/ml) highly active antiretroviral therapy regimen to a tenofovir plus two NRTI combination.
Fifty-five patients started a two NRTI plus tenofovir regimen mostly because of previous toxicity/intolerance of the original drugs (74%). After 24 weeks, only 17 patients (31%) remained virologically suppressed. Patients with a regimen including a didanosine plus tenofovir-based regimen had significantly poorer outcomes than those on other combinations (success rate 5 versus 47.1%, P = 0.001). In contrast, patients on a regimen including zidovudine plus tenofovir showed a trend towards a better outcome (75 versus 27%, P = 0.083). Multivariate analysis confirmed the combination of didanosine plus tenofovir as the only variable associated with a higher rate of failure (odds ratio 17.7; 95% confidence interval 2.1-147; P = 0.007). Patients with previous reverse transcriptase mutations presented virological failure in all cases. At failure a new pattern, including the K65R mutation with M184V or thymidine analogue mutations, was observed.
Even in patients with suppressed viraemia, a two NRTI plus tenofovir regimen is associated with a high virological failure rate, but significant variations are found depending on the nucleosides included.
Introduction
Patient preference to antiretroviral therapy (ART) characteristics should be a key consideration in treatment decisions. ART options exist for people living with HIV (PLWH), however ...concerns remain related to PLWH satisfaction with current ARTs. The current study examines patient preferences and the strength of preferences for treatment characteristics associated with ART.
Materials and Methods
Patients’ preferences to ART were explored using a discrete choice experiment (DCE). Seven defined treatment characteristics (each with three categories) were identified from a literature review, input from experts, PLWH and physicians. A total of 1582 PLWH from France, Germany, Spain, Italy and the UK were recruited for the study. An adjusted odds ratio <1 signified lower odds of selecting a treatment with this characteristic category, compared to the reference category, independently of other characteristics.
Results
The patient preference analyses showed that participants preferred treatments with a rapid reduction in viral load (OR=0.78; 95% CI 0.74–0.81) and CD4 count (OR=0.86; 95% CI=0.82–0.89). Participants had a strong preference for avoiding diarrhoea (Odds ratio, OR=0.36 95% CI=0.33–0.38) and long term health problems (OR=0.30, 95% CI=0.28–0.32). Convenience related issues related to restrictions on taking drugs because of food or drug interactions were important to avoid (OR=0.80, 95% CI=0.76–0.83 and OR=0.72 95% CI=0.69–0.76 respectively). Participants also had a strong preference to avoid drugs which limited the effectiveness of future treatments (OR=0.70, 95% CI=0.67–0.73).
Conclusions
Avoidance of diarrhoea and long‐term complications were the most important drivers of patient choice. This study, from a large sample of European patients, demonstrates the importance to patients when different aspects of HIV treatment are considered simultaneously.
To assess the rate of long-term effectiveness and factors associated with response to protease inhibitor therapy in a cohort of HIV-infected patients.
Prospective, non-randomized study in a tertiary ...care centre.
A total of 400 HIV-infected patients who started on protease inhibitor therapy (saquinavir, 28%; ritonavir, 26%; indinavir, 46%) from March 1996 to March 1997.
Long-term virological and immunological effectiveness were defined as HIV RNA levels below 200 copies/ml and CD4+ cell count increase greater than 100 x 10(6)/l, respectively, after 12 months of therapy.
Fifty-seven per cent of patients had a prior AIDS-defining illness, and 91% had received nucleoside analogues for a median time of 28 months. Median CD4+ count was 86 x 10(6) cells/l and HIV RNA level was 4.46 log10 copies/ml. The global rate of virological and immunological effectiveness at 1 year was 45 and 59%, respectively. In a logistic regression analysis, treatment failure was associated with higher baseline HIV load relative risk (RR), 2.10; P<0.01, prior antiretroviral therapy (RR, 2.07; P<0.01), and use of saquinavir (RR, 1.55; P = 0.03), whereas a reduction of more than 1 log10 in HIV load within the first 3 months on therapy was strongly associated with response (RR, 0.65; P<0.01). There was no strict correlation between virological and immunological effectiveness (r = -0.35; P = 0.01).
Nearly half of the patients maintain undetectable HIV load after 1 year of therapy, although important immunological benefit can be obtained in a greater proportion of patients. These data suggest the use of the most potent antiretroviral therapy in pretreated patients with high HIV load, and the capacity of initial virological decline to predict the long-term outcome.
In the present update of the guidelines, a starting combination antiretroviral treatment (cART) is recommended in symptomatic patients, in pregnant women, in serodiscordant couples with a high risk ...of transmission, in patients co-infected with hepatitis B virus requiring treatment, and in patients with HIV-related nephropathy. Guidelines on cART are included in the event of a concurrent diagnosis of HIV infection with an AIDS-defining event. In asymptomatic naïve patients, cART is recommended if the CD4(+) lymphocyte count is <500cells/μL; if the CD4(+) lymphocyte count is >500cells/μL, cART can be delayed, although it may be considered in patients with liver cirrhosis, chronic infection due to hepatitis C virus, high cardiovascular risk, plasma viral load (PVL) >10(5)copies/mL, CD4(+) lymphocyte percentage <14%, cognitive impairment, and age >55 years. cART in naïve patients requires a combination of 3 drugs, and its aim is to achieve undetectable PVL. Treatment adherence plays a key role in sustaining a favorable response. cART can, and should be, changed if virological failure occurs, in order to return to undetectable PVL. Approaches to cART in acute HIV infection, in women, in pregnancy, in tuberculosis, and post-exposure prophylaxis are also examined.
Darunavir, previously known as TMC-114, is a new protease inhibitor (PI) with a high affinity for the HIV-1 protease and strong ability to inhibit its action, even in mutated forms. Consequently, ...this drug is considered to have great intrinsic potency and a high genetic barrier. At the time of writing, data on the tolerability and safety of darunavir come mainly from studies of late rescue therapy (POWER, DUET), which have included more than 1,600 patients. Recent data, relating to shorter time periods, are also available from studies in early treatment-experienced patients (TITAN) and in treatment-naïve patients (ARTEMIS), increasing experience to a further 600 patients. Lastly, more than 4,000 patients who have received darunavir through the Expanded Access Program have allowed the drug's generally good safety and tolerability profile to be defined. In the studies performed to date, darunavir has been well tolerated, with a better profile than that of the PIs used in control groups in terms of adverse effects such as diarrhea, gastrointestinal tolerability and lipid alterations. Moreover, to date, no unexpected severe adverse effects have been reported.
Resistance testing is useful in the management of virological failure patients, although the best method to be used in clinical practice has not been determined.
A prospective, randomized, ...double-blind, multicentre, controlled clinical trial was performed to compare the usefulness of drug resistance testing with a recombinant viral phenotype method or with a virtual phenotype, a genotyping interpretation system. Planned 300 HIV-infected adults failing their current antiretroviral therapy (HIV RNA > 1000 copies/ml) were centrally randomized 1:1 to resistance testing with a recombinant viral phenotype method or with a virtual phenotype, after stratifying according to previous drug exposure (one or two versus three drug classes). Percent of patients with HIV RNA suppression (% < 400 copies/ml) after 24 weeks was the primary outcome variable. Median HIV RNA concentration and change from baseline in HIV RNA concentration were also used to compare effectiveness. An extended analysis was performed at week 48.
Of the 300 patients enrolled, a total of 276 patients could be analysed; 139 patients were randomized to the phenotype group and 137 patients were randomized to the virtual phenotype group. After 24 weeks of follow-up, 46.8 and 56.2% of patients had HIV RNA < 400 copies/ml (P = 0.1) in the phenotype and virtual phenotype, respectively. Mean decrease from baseline in viral load was 1.0 and 1.3 log copies/ml in the phenotype and virtual phenotype groups, respectively (P = 0.017). In a multivariate linear regression analysis, after adjusting for baseline HIV RNA and adherence to treatment, the virtual phenotype was associated with a greater mean decrease in plasma HIV RNA (P = 0.0063). The results observed at week 48 were similar.
Virtual phenotype is at least as effective as phenotype when used to select an optimized treatment for patients who have failed one or more antiretroviral regimens.
Background
The advent of combined antiretroviral therapy (ART) in the past decade has led to HIV suppression in most cases. Virological failure was the main reason for ART switch a few years ago; ...however, toxicity and treatment simplification have now gained importance due to the availability of more effective and convenient drugs. This study assessed the reasons for ART switch in daily practice.
Material and Methods
Observational retrospective study that included patients whose ART was switched between January 2011 and July 2012. Patients with any other switch during the follow‐up period (until September 2013) were excluded.
Results
A total of 246 patients were included. Main reasons for ART switch were simplification (33%) and toxicity (31%), followed by clinical trial inclusion (13%), virological failure (6%), drug interaction (4%), patient decision (3%), lack of adherence (2%), pregnancy (1%) and other (8%). Eighty patients switched to a simpler regimen (median age 48 40–53, mean CD4 count 608±265 cells/cl, 89% <50 copies/ml, mean number of previous regimens 6±5, mean time on previous ART 3±2 years). In this case, previous ART mostly included 2NRTI+1PI/r (54%) (Figure 1). The simplification strategy mainly contained nuke‐sparing regimens (60%) based on PI (DRV/r 48%): monotherapy 46%, dual therapy 13% (PI/r+maraviroc 9%, PI/r+NNRTI 4%) and triple therapy 1% (PI/r+maraviroc+raltegravir). The second preferred simplification option was 2NRTI+1NNRTI (24%). Seventy‐seven patients switched due to toxicities (median age 47 43–53, mean CD4 count 606±350 cells/μl, <50 copies/ml 82%, mean number of previous regimens 4±3, mean time on previous ART 3±3 years). Renal (25%) and CNS (18%) toxicities were the main reasons for ART switch, followed by diarrhoea (16%), liver enzyme elevation (ALT 10%; AST 9%; bilirubin 7%), lipid elevation (cholesterol 5%; triglycerides 8%), nausea (7%) and other (=5%) (Figure 2). All patients with renal toxicity were under TDF and in most cases this drug was removed from the new regimen (with 3TC/ABC or nuke‐sparing). Among patients with CNS toxicity, 79% were taking EFV; the main new treatment was a second‐generation NNRTI (ETR)+2NRTI. Toxicities were completely resolved in 66% of patients, partially resolved in 22% and not resolved in only 12%; the median time from ART switch to toxicity resolution was 4 (2–8) months.
Conclusions
The main reasons for ART switch in daily practice are simplification and toxicities, renal and CNS toxicities being the most prevalent. The preferred simplification strategies are nuke‐sparing regimens, mainly DRV/r‐based monotherapy and dual therapy. ART switch leads to a complete resolution of toxicities in most cases in the short term.
Syncytial giant cell hepatitis (SGCH) among adult human immunodeficiency virus (HIV)–infected patients has been rarely described. Most cases have been reported in subjects coinfected with the ...hepatitis C virus (HCV), but its prevalence and outcome remain unknown. We performed a retrospective analysis of all cases of SGCH among 332 liver biopsies from HIV-infected patients seen at a tertiary center in Madrid, Spain, between 1984 and March 2004. Two hundred fifty specimens were obtained from HCV-coinfected patients. There were 2 cases of SGCH, leading to an observed overall prevalence of 0.6% (0.8% when considering only HCV-coinfected patients). In addition to histological changes secondary to chronic hepatitis C, the liver cords were replaced by syncytial giant cells with up to 30 nuclei. There was no histological evidence of measles (among paramyxoviruses) or herpes viruses group infections. In patient 1, there was a progressive clinical worsening after a 3-month course of prednisone, leading to liver failure and death. His postmortem liver biopsy showed more abundant giant hepatocytes accompanied with the development of a histologic pattern of severe fibrosing cholestatic hepatitis. The second patient received a prolonged course of pegylated interferon-
α-2b and ribavirin with clearance of syncytial giant hepatocytes despite HCV-RNA persistence. SGCH is a rare histological finding among HIV-infected patients with chronic hepatitis C. Specific treatment with pegylated interferon and ribavirin can lead to histological resolution and biochemical improvement, even in the absence of HCV-RNA clearance.
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