Suchergebnisse

Background and purpose of the studyThe advent of antiretroviral therapy (ARV) resulted in a significant decrease in opportunistic infections; however these diseases still represent an important cause of morbidity and mortality. ARV also changed the spectrum of cancers presented by HIV patients as a result of immune recovery and increased life expectancy. We intend to describe the variety of infections and cancers, AIDS or non‐AIDS related, identified in our patients in the new era of ARV and also identify possible risk factors related to this conditions.MethodsAssessment and registry of infectious and neoplastic conditions occurring after initiation of ARV in a cohort of HIV‐infected patients who started ARV between January 2007 and December 2011. We included records of these conditions until March 2012. Epidemiological, clinical and laboratory data were analyzed and compared with a control group of HIV‐infected patients that started ARV in the same period but did not experience those comorbidities. Patients lost to follow‐up were excluded. Statistical significance of the differences encountered was evaluated with T‐student test and chi‐square; differences were considered statistically significant when p<0.05.Results497 patients were included (71.0% were men) with a mean age of 43.4±12.5 years and average follow‐up of 30.9±16.8 months. In the analyzed period there were 112 events in 91 patients: 85 infections and 27 cancers. The most common infectious condition was tuberculosis (n=13) and the most common cancer was non‐Hodgkin's lymphoma (n=8). The interval between the introduction of ARV and the onset of these conditions was 15.1 months (min: 0.03, max: 57.40). We identified 22 deaths: 11 were result of infection and 11 from cancer. Statistically significant differences between the groups compared were identified in the following variables: risk factor for HIV infection, co‐infection with hepatitis B, clinical stage, viral load and CD4 T lymphocyte count before the beginning of ARV.ConclusionsWe identified a substantial number of infections and cancers in our cohort, with tuberculosis and lymphomas continuing to be particularly noteworthy. Patients who had these conditions initiated ART with more severe immunosuppression and higher viral load which reinforces the importance to establish a prompt diagnosis which enables an efficient treatment and low morbidity associated with infections and cancers, particularly those related to AIDS.

BackgroundWith the availability of the 2nd‐generation non‐nucleoside reverse transcriptase inhibitor (NNRTI) etravirine (ETR), it is possible to obtain undetectable plasma viral load in HIV‐1‐infected treatment experienced patients with resistance mutations to NNRTIs. The purpose of this study is to determine the proportion of patients with prior exposure to NNRTIs who may benefit from a therapeutic regimen including ETR.Patients and methodsAnalysis of the genotypic resistance tests of patients having failed efavirenz (EFV) or nevirapine (NVP) antiretroviral‐based regimens, in a 5‐year period (2007–2011). Susceptibility to ETR was assessed using four different algorithms: HIVdb Stanford University HIV Drug Resistance Database, ANRS score, REGA score and Tibotec weighted genotypic score.ResultsOf 170 patients with a history of failure or abandonment of regimens containing EFV or NVP, 68 (40%) had mutations conferring resistance to these NNRTIs (RAMs). Resistance tests were carried out from seven months before to 3 years after (X=48±207 days) the NNRTIs discontinuation. Of the HIV‐1 subtypes identified (n=67), most were were subtype B (53.7%) and G (34.3%) RAMs found in the 68 samples successfuly genotyped: V90I (n=2), A98G (n=1), L100I (n=7), K101E (n=5), K103N (n=38), K103S (n=2), V106A (n=1), V106M (n=1), V108I (n=4), V179D (n=4), Y181C (n=18), Y188C (n=1), Y188H (n=1), G190A (n=11), G190E (n=1), G190S (n=1), H221Y (n=6), P225H (n=1), F227L (n=3) and K238T (n=2). In 27 (39.7%) patients only one RAM was detected, 30 (44.1%) had 2, 6 had three mutations and 5 other patients had more than three RAMs to NNRTIs. Susceptibility to ETR varied depending on the used algorithm:









Susceptible
Intermediate resistance
Resistant




ANRS
60 (88.2%)
3 (4.4%)
5 (7.4%)


HIVdb
49 (72.0%)
17 (25.0%)
2 (3.0%)


REGA
40 (58.8%)
27 (39.7%)
1 (1.5%)


Tibotec
44 (64.7%)
23 (33.8%)
1 (1.5%)




ConclusionIn this population with resistant virus to EFV and NVP, we found a low frequency of mutations conditioning severely impacting on susceptibility to ETR. Based on these results, ETR could be a useful component of effective treatment regimens for the majority of these patients with prior exposure to 1st‐generation NNRTIs.

Purpose of the studyGuidelines are based on clinical trial data as well as expert opinion and do not reflect economic considerations. Cost‐efficacy analysis of recommended regimens allows for a ranking which takes into account both clinical and economic considerations. The aim of the present analysis was thus complement the information provided by the EACS (v6) guidelines regarding recommended initial treatment for HIV‐1 infection.MethodsThe methodology used was that described in Blasco et al. 2011 [1], but applied to Portugal in terms of (i) resource prices, (ii) resource utilization upon ART initiation, regimen switch and treatment of adverse events, and (iii) subsequent regimen selection according to the initial regimen and the reason for switch. Regarding costs, the payer (National Healthcare Service) perspective was considered taking into account only differential direct costs. The time horizon was 48 weeks.Summary of resultsIn this analysis, efficacy ranged from 66% with ABC/3TC+LPV/r to 86% for TDF/FTC+RAL. TDF/FTC+NVP was the least expensive regimen both in terms of the 48 weeks' cost of the initial regimen and in terms of the total 48 weeks' costs (i.e., including sequential therapy and other direct medical costs) (7,592€). Nonetheless, once cost and efficacy are considered simultaneously, TDF/FTC+NVP ranks third (11,419€), ABC/3TC+EFV ranks second (11,073€) and TDF/FTC+EFV (also available, in a single tablet regimen) ranks first (10,888€) indicating that this is the regimen yielding the lowest cost per suppressed patient. Among regimens containing boosted protease inhibitors, TDF/FTC+DRV/r was the regimen with the lowest cost/efficacy ratio (13,020€) and TDF/FTC+ATV/r had the highest ratio (15,102€).ConclusionsViral suppression is a relevant efficacy outcome not only due to individual benefits but also from a public health perspective. In this analysis, TDF/FTC+EFV was the initial ART regimen with the lowest cost per suppressed patient at 48 weeks.

ObjectiveEvaluate the effectiveness and safety of simplification of tenofovir/emtricitabine/efavirenz (TDF/FTC/EFV) in selected treatment‐experienced HIV‐1‐infected patients who have been virologically suppressed for>3 months on their current regimen.MethodsWe selected patients who started the simplified regimen between December 1st 2008 and March 31st 2012. Exclusion criteria: prior therapeutic failure, presence of resistance mutations to any component of TDF/FTC/EFV and patients previously observed in other centers. Efficacy and safety assessments were performed at baseline, 4 weeks after switch and then every 12–24 weeks. Statistical analysis was performed with SPSS version 20.0.Results384 patients were evaluated; 302 (79%) male; mean age 47 (SD=10) years; median CD4 cells count was 504 cells/mm3 (367–710). Baseline median glomerular filtration rate (eGFR; Cockcroft‐Gault equation) was 100 mL/min (86–116) and median ALT was 33 U/L (21–47). Median total cholesterol (TC) was 205 mg/dL (176‐236), high‐density lipoproteins (HDL) 45 mg/dL (38–54); low‐density lipoproteins (LDL) 130 mg/dL (108–151); triglycerides (TG) 125 mg/dL (84–176). Prior NNRTI‐based regimen in 327 (85%) patients (TDF/FTC and EFV in 76%); protease inhibitor in 52 (14%) and integrase inhibitor in 5 (1%). Discontinuation of treatment occurred in 49 patients (13%) after a mean time of 1.1 years (SD=1.1) of follow‐up: nervous system symptoms (n=11), decreased eGFR (n=5), virological failure (n=5), pregnancy (n=5), gastrointestinal symptoms (n=3), rash (n=1), other reasons (n=2); 12 patients dropped out the treatment and 5 died. Occurrence of blips (transient increase in VL ≤200 copies/mL) was documented in 98 (26%) patients; in 70, VL decreased to <20 copies/mL after the blips and in 28 VL is not yet available. 317 patients (83%) achieved≥48 weeks of follow‐up after simplification. Compared with baseline, significantly higher levels of CD4 cells count, HDL and eGFR were found and lower levels of TC, LDL and TG.















CD4
AST
ALT
TC
HDL
LDL
TG
eGFR




Baseline










Median
501
27
32
203
46
130
123
100


Percentiles 25
358
22
22
174
39
108
84
85


Percentiles 75
712
36
45
236
54
151
179
113


Follow‐up










Median
541
28
32
196
49
123
115
111


Percentiles 25
397
22
22
174
41
101
80
96


Percentiles 75
734
36
46
223
57
141
155
133


p‐value
<0.001
0.395
0.513
<0.001
<0.001
<0.001
<0.001
<0.001




ConclusionSimplification to TDF/FTC/EFV was shown to be an efficient and safe option in virologically suppressed patients and without a previous virological failure.

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK

IntroductionCurrent guidelines recommend the start of antiretroviral therapy before advanced immunosuppression, which is not always possible. The purpose of this study is to evaluate factors associated with the degree of immunosuppression at the diagnosis of HIV infection.MethodsWe evaluated demographic and epidemiological data of HIV‐infected patients observed at the Department of Infectious Diseases diagnosed between 2006–2011, and analyzed the relationship between these data and the immune status at diagnosis. Statistical analysis was performed using SPSS version 20.0 for Windows.ResultsData from 600 new patients were analyzed. 584 (97.3%) infected by HIV‐1. 426 (71%) male. Mean age=42 years (SD=14). Risk factor for HIV infection: sexual in 548 patients (91.3%) (22.8% homo/bisexual). 153 (25.5%) patients had AIDS ‐defining illness. Origin of patients: general practitioner ‐ 153 (25.5%), hospitalization in the Department of Infectious Diseases ‐ 110 (18.3%), diagnostic screening after partner's diagnosis ‐ 69 (11.5%), hospital consultation ‐ 68 (11 3%), emergency room ‐ 61 (10.2%), anonymous diagnostic testing center ‐ 46 (7.7%), other hospital inpatient services ‐ 31 (5.2%), hospitalization in another hospital ‐ 30 (5%), attempted blood donation ‐ 15 (2.5%), drug addiction treatment center ‐ 8 (1.3%), pregnancy screening ‐ 3 (0.5%) and patient's own initiative ‐ 6 (1%). The mean CD4+ cell count was 319 cells/cmm (SD=274; range: 2–1416). Women were diagnosed at significantly higher CD4+ cell count levels (p=0.005), as well as younger patients (p<0.001). Homo/bisexual patients had CD4+ cell counts significantly higher than the other groups (p<0.001). There were differences in CD4+ cell count depending on the origin of the patients (p<0.001): patients diagnosed at anonymous diagnostic center, drug addiction treatment center, blood donors, pregnant women and coming on their own initiative, had higher CD4+ cell count levels (p<0.001). Patients admitted in the Department of Infectious Diseases were those with the lower CD4+ cell counts. No relationship was found between CD4+ cell count level and year of diagnosis.ConclusionThese results indicate the importance of early HIV screening even in individuals without a perceived risk of acquisition of this infection, so they can benefit from antiretroviral treatment before having advanced immunosuppression.