Suchergebnisse

Purpose of the studySince X4/DM HIV‐1 tropism is associated with poorer prognosis and worse response to treatment, the aim of this study was to assess whether X4/DM HIV‐1 tropism is also related with a higher accumulation of resistance in patients experiencing treatment failure.MethodsHIV protease (PR) and reverse transcriptase (RT) resistance mutations and tropism test results were extracted from a national database. Viral tropism data included enhanced sensitivity Trofile assay (ESTA) and geno2pheno results at 10% false positive rate. Historical resistance mutations (HRM) for PI, NRTI and NNRTI, detected in all genotypic tests performed during patient treatment history, were selected according to IAS‐USA indications.Summary of resultsOverall, 1280 patients were included: males 65%, median age 45 years (IQR: 40–50), median CD4 nadir 116 (IQR: 34–272), median past regimens 7 (IQR: 3–12), median previous NRTI used 5 (IQR: 4–7), median previous NNRTI used 1 (IQR 1–2) and median previous PI used 3 (IQR 1–5). HIV tropism was assessed by ESTA in 271 patients (21.2%) and by geno2pheno in 1009 patients (78.8%). Four hundred and fifteen patients (32.4%) carried X4/DM virus and 321 (25.1%) had ≥1 HRM for each antiretroviral class. The mean number of HRM was higher in patients harboring X4/DM virus than in patients harboring R5 virus (5.1±6.4 vs. 4.3±5.9, p = 0.02 at ANOVA test). X4/DM strains also harbored a higher mean number of PI‐related HRM (1.8±2.8 vs. 1.5±2.6, p = 0.003) and NNRTI‐related HRM (1.2±1.6 vs. 0.9±1.4, p = 0.001), but not of NRTI‐related HRM (2.2±2.6 vs. 2.0±2.6). At logistic regression, patients with HRM for all the 3 classes had a significant higher risk of also harboring X4/DM virus (OR: 1.6, 95% CI: 1.0–2.4, p = 0.04). Moreover, X4/DM virus was found to be associated with previous use of NNRTI‐containing regimens (OR: 1.4, 95% CI: 1.1–1–9, p = 0.03) and lower CD4 nadir (OR: 0.9, 95% CI: 0.9–1.0, p = 0.001, per 50‐CD4 increase). The analysis was adjusted by number of genotypic tests, number of treatment lines, age and HV subtype. Single mutations significantly associated with X4/DM tropism were: for PI, V32I and L76V; for NRTI: M41L, K70R, L74V and T215Y and for NNRTI: E138G and V179T.ConclusionsOur data suggest that X4/DM tropism is associated with accumulation of resistance mutations during treatment history. X4/DM tropism is also confirmed to be a marker of a more compromised clinical and immune‐virological condition.

Purpose of the studyPerinatal transmission of HIV has fallen dramatically in countries where access to antiretrovirals is available, placing the focus of research on safety. The aim of this study is to assess whether in naïve or pretreated HIV‐1 women, a dual, zidovudine sparing regimen (3TC+ PI) initiated during pregnancy can control maternal viral load while preventing maternal and infant toxicities related to in utero exposure to zidovudine.MethodsWe performed a retrospective, descriptive study between January 2006 and 2012. Seventeen naïve and 28 pretreated women who received dual therapy (3TC + PI) during pregnancy were included in the studied group and compared to 49 women on standard triple therapy (3TC/ ZDV+ PI), who delivered in the same time interval, at the same hospital. The primary endpoint was the% of women with viral loads (VL) ≤ 50 cp/ml at delivery. Secondary endpoints included% of women with VL ≤ 400 cp/ml after one month of dual therapy and of women who remained under dual therapy until delivery and achieved a VL ≤ 50 cp/ml at delivery. We also compared safety outcomes during pregnancy and until 18 months in children.Summary of resultsGroups had indistinguishable median VL at day zero (200 vs. 1680, p = 0.29) and gestational ages at initiation of therapy (19.6 vs 18 weeks, p = 0.18). At initiation of dual therapy (in 80% of cases: 3TC + LPV/r; ATV/r or ATV), the median VL was 21,692 cp/ml (6589 to 31,269) for naïve women and 43 cp/ml (20 to 200) for pretreated women. In intent‐to‐treat analysis of the dual therapy group, 41/45 women (91.11%, 95% CI 78.7 to 97.5%) achieved their primary endpoint. The table presents proportions of viral success at primary and secondary endpoints in the dual (N = 45) and control (N = 49) groups. Groups had similar proportions of cesarean section (28.8% vs 34.7%, p = 0.65) and of prematurity and changes in ART due to intolerance. There was one case of MTCT for the controls and none in the dual therapy group. Newborns with prenatal ZDV exposure had higher proportions of clinical syndromes at birth (50% vs 25%, p = 0.02) and SAE in the first 18 months of life (90.3% vs 68.2%, p = 0.05) and worse haematological values at birth, with lower levels of haemoglobin (15.6 vs 17.5 g/dl, p = 0.05).









ITT
3TC+PI
3TC/ZDV+PI

p





VL at delivery


<50
91.1%
88.5%
0.72


VL at M1


<400
91.1%
73.4%
0.03


Virological success and maintained therapy p



VL at delivery


<50
82.2%
85.7%
0.76




ConclusionsThe 3TC+ PI dual therapy strategy in naïve or pretreated women achieved a satisfactory virologic effectiveness and resulted in less SAE in the first 18 months of life and better haematological parameters at birth for children.

HIV‐1 subtype A infection predominates in Russia; however, little experience of response to maraviroc in this subtype exists and population genotyping in this setting requires further exploration. One hundred and twenty‐one treatment‐naïve HIV‐1‐infected individuals from seven centres in Russia were screened using V3 loop population genotyping with a false‐positive rate of 10% (geno2pheno); 75% of patients were confirmed to have CCR5 (R5)‐tropic HIV‐1, 21% of patients had non‐R5 HIV‐1, and 4% of tests were non‐reportable. Seventy‐seven patients met the inclusion criteria and were treated with maraviroc 300 mg twice daily (BID) in combination with lamivudine/zidovudine. Virologic and immunologic responses were assessed in this 24‐week planned interim analysis. Fifty‐one male (66.2%) and 26 (33.8%) female patients were enrolled. In total, 76.3% of patients had subtype A infection, and 28.6% were co‐infected with hepatitis C virus. At baseline, the mean (± standard deviation [SD]) CD4 count was 404±122 cells/mm3, and the mean viral load was 4.77±0.74 log10 copies/mL, with 38% of patients having viral loads ≥100,000 copies/mL. At Week 24, 80.5% of patients had viral loads <50 copies/mL and the mean (±SD) CD4 cell count was 411±124 cells/mm3. No treatment‐emergent adverse events were attributed to maraviroc, and three patients experienced Grade 4 anaemia associated with lamivudine/zidovudine. Seven patients discontinued from the study, but only one of these discontinuations was due to an insufficient clinical response. Two patients had 3TC resistance at the time of discontinuation. Virologic responses to a maraviroc‐based regimen in patients infected with R5‐tropic HIV‐1 subtype A, determined using population genotyping, were confirmed.

Cardiovascular (CV) [1] and cerebrovascular [2] events threaten HIV+ subjects, affecting them earlier as compared to the general population and the current algorithms seem inadequate to estimate the CV risk, in particular concerning the weight of drugs, immunity and virus‐related inflammation as risk factors. We analysed three Italian HIV cohorts from January 2005 to August 2011, extracting cases of acute myocardial infarction (AMI) or stroke. We analysed at the time of the event the subjects' age, the risk factors, the Framingham score, the antiviral regimen and the time spent on each drug, the CDC stage, the nadir CD4+ T cells and the outcome. Out of 4893 patients 92 experienced major CV events (76 AMI and 19 stroke, 2 subjects having both) and 10 died, at a median age of 50 years (range 33–77). Classical risk factors were widely represented, mainly smoke (72.8%) and dyslipidemia (53.3%). Three young subjects had no risk factors and dramatic coronary patterns, leading in one case to transplantation. No one ever had pathological bone fractures, and only 4/81 had GFR <60 mL/min (range 33.6–57.4). The median 10 years' Framingham score was 10.5 (range 1–31). Abacavir had been taken by 19 subjects, equal to tenofovir and less than zidovudine (n=55), and lopinavir/ritonavir by 20, and no single drug emerged as risk. The median time spent on abacavir and/or on lopinavir/ritonavir was 48 weeks (range 1–552) and 106 weeks (range 8–256), respectively. One patient was antiretroviral–naïve. The CD4 nadir was 183/mm3 and 41.3% were CDC stage C. Although infrequent (1.8%), major CV events affect HIV people at younger age. Classical risk factors are common, while no drug effect emerged clearly. HIV infection was managed late in most of the patients. Early initiation of HAART [3] and reduction of risk factors seem the key points for preventing the occurrence of CV disease.

Purpose of the studyHIV‐1‐infected patients have elevated levels of immune activation and systemic inflammatory markers which are partially strong predictors of disease progression or are associated with increased cardiovascular risk. The dependency of anti‐retroviral treatment (ART), the usage of NNRTI or PI‐based and the application of non‐nuc regimens is analysed here on the basis of a dataset (Chronic Inflammation Dependency on TREatment: CIDRE cohort) from 1500 patients in Berlin.MethodsIn a retrospective analysis we compared relative CD4+ cell counts, viral load, relative CD8+CD38+DR‐and CD3+DR+cells, concentration of high‐sensitivity C‐reactive protein (hsCRP) and interleukin‐6 (IL‐6) in therapy‐naïve or treated patients dependent on usage or non‐usage of NUCs, PI or NNRTI. Statistics were performed with R (R Core Team; 2012; R: A language and environment for statistical computing) using Wilcoxon rank sum test in two‐sided analysis.Summary of resultsAs to expect, ART‐naïve patients (n=190) had significantly higher viral loads and lower CD4+cell counts (p: both<0.05) and showed higher activation levels than treated patient (CD8+CD38+DR‐ and CD3+DR+both<0.05). But no significant difference was calculated for hsCRP or IL‐6. Nuc‐sparing regimen (n=46) did not show any distinction compared to nuc‐containing therapies (n=1249) for the analysed parameters. Significant differences were detected for PI‐regimen (n=711) with lower CD4+ cell counts and higher activation (CD8+38+DR‐, CD3+DR+) and IL‐6 (p: all<0.05) but not for hsCRP (p=0.39). The opposite was true for NNRTI‐based therapies (n=445) with higher CD4+ cell percentages and lower activation and inflammation markers (p: all<0.05) and as well no difference in hsCRP (p=0.97) compared with all other treated patients.ConclusionsThe lack of differences between therapy‐naïve patients and patients on ART for inflammation markers may be due to the relative good immunological state of the first group, which could be one of the reasons why they are not treated so far. The number of nuc‐sparing regimen is perhaps too low and too undifferentiated to find diverse inflammation states. Although the differences in activation status can be attributed to different treatment strata, there is no clear explanation for this outcome. A possible reason could be a pre‐selection bias either for NNRTI‐based or PI‐based regimens. Additional data is acquired to perform longitudinal analysis to gain further insight.

BackgroundHIV‐infected postmenopausal women have higher rates of bone loss than HIV negative women. We aimed to identify predictors of body mass density (BMD) in HIV infected women entering menopause and to evaluate the pre‐ and post‐menopausal BMD change, with regard to tenofovir (TDF) use.MethodsWomen with at least one DEXA measurement were enrolled. The observation period was divided into: "Reproductive period", "Menopause transition period", "Early menopause period", "Late menopause period". BMD of the lumbar spine (L1‐4) and femur neck were measured by DEXA. Lowess smoothing curves were drawn to analyze impact of menopause and TDF on BMD. Three different longitudinal linear regression models with random effects were built. Longitudinal regression analysis fits cross sectional time series regression models and allows to analyze repeated measures for each patient.ResultsFifty‐five women were included. Median age at enrollment was 46 years (IQ range 44–49). Median observation period was 16 months (IQ range 8; 23) and 33 months (IQ range 23; 72) for pre‐ and post‐menopausal respectively. At enrollment mean CD4 cell count was 553 cell/mL (±269.62) and HIV‐VL was undetectable in 77.5% of patients: 6 women were not undergoing ART. Most common backbone TDF/FTC (46.9%) and ABC/3TC (20.4%). At the time of inclusion in the cohort osteopenia and ostoeporosis were present in 60% and 3.64%, respectively. At the time of last DEXA evaluation osteopenia and osteoporosis were present in 78.18% and 36.36%, respectively. The impact of menopause on lumbar BMD was depicted (fig. 1) using a lowess smoothing analysis according to current TDF exposure (as treated model). Lumbar BMD change predictors were years from menopause and TDF current exposure in the "Early menopause period" and years from menopause, Baseline lumbar BMD, BMI and vitD supplementation in the "Late menopause period".DiscussionThis is the first study analyzing BMD across menopause. BMD was stable in the pre‐menopause period while BMD loss characterized the post‐menopause period. Traditional risk factors contributed to BMD change in the post ‐menopause period. Current TDF exposure was independently associated with BMD change in the "Early menopause period" only, but not confirmed in the "Late menopause period", suggesting a compensating mechanism occurring after the second year post‐menopause.
image
















Transitional period
Early menopause
Late menopause



β
95% CI
p‐value
β
95% CI
p‐value
β
95% CI
p‐value




Years to (from*) menopause
−0.1
−0.03; 0.01
0.407
−0.01
−0.02; − 0.01
<0.001
−0.1
−0.2; − 0.003
0.009


Baseline lumbar BMD
0.0002
−0.001; 0.003
0.078
0.0002
−0.0001; 0.0004
0.074
0.9
0.70−1.09
<0.001


PTH
−0.0005
−0.001; 0.0004
0.280
0.0001
−0.0004; 0.0002
0.535
−0.0001
−0.0002; 0.0002
0.800


BMI
0.003
−0.005; 0.010
0.489
0.004
−0.001; 0.010
0.142
0.008
0.002; 0.014
0.010


VitD supplementation
−0.003
−0.05; 0.04
0.865
0.008
−0.010; 0.026
0.392
0.03
0.001; 0.054
0.038


TDF current exposure
−0.03
−0.07; 0.01
0.125
−0.03
−0.05; −0.01
0.012
−0.04
−0.09; 0.01
0.129

Purpose of studyOnce‐daily ritonavir‐boosted darunavir (DRV/RTV) is a preferred antiretroviral regimen for treatment‐naïve patients. Population pharmacokinetic modelling of the interaction between DRV and RTV allows evaluation of alternative dosing strategies, particularly lower RTV doses (e.g. 800/50 mg once daily) and assessment of factors that may influence DRV/RTV PK.MethodsData were pooled from 3 DRV/RTV PK studies. Fifty‐one HIV‐infected patients (7 female) stable on DRV/RTV (800/100 mg or 900/100 mg once daily; n=32 and 19, respectively) were included. Median age, weight and baseline CD4 cell count were 39 yr (21–63), 74 kg (57–105) and 500 cells/mm3 (227–1129), respectively; 49 had undetectable viral load. Nonlinear mixed effects modelling (Monolix v.4.1.2) was applied simultaneously to DRV and RTV to determine PK parameters, interindividual variability and residual error. Covariates evaluated included: age, weight, sex and study. The model was validated by simulation and visual predictive check. DRV/RTV 800/50 mg once daily was simulated.Summary of resultsRTV and DRV were described by a 1 and 2‐compartment model, respectively with first‐order absorption and lag‐time. A maximum effect model, in which RTV inhibited DRV clearance (CL/F), best described the relationship between the two drugs. A RTV concentration of 0.33 mg/L was associated with 50% maximum inhibition of DRV CL/F with the maximum inhibitory effect fixed at 1. The population CL/F of DRV in the absence of RTV was 13.7L/h. Inclusion of weight on RTV CL/F and volume and age on DRV CL/F and study on DRV CL/F, volume and absorption improved the fit. Based on visual predictive check 93% and 91% of observed RTV and DRV concentrations were within the 95% prediction interval, indicative of an adequate model. Of 1000 simulated DRV troughs, 10% and 0% were below the MEC for treatment‐experienced (<0.55 mg/L) and naïve patients (<0.055 mg/L), respectively. For DRV/RTV 800/50 mg once daily this corresponded to 14% and 0%. Median area under the curve was 17% lower with 50 mg compared to 100 mg RTV (53.5 mg.h/L vs. 64.2 mg.h/L), which is consistent with previous data [1].ConclusionsA population model describing the PK of once‐daily DRV/RTV has been developed and validated and included the influence of RTV concentration on DRV CL/F. The model allowed simulation of DRV/RTV 800/50 mg once daily; concentrations were lower but trough concentrations remained within the therapeutic range for treatment‐naïve patients.

Antiretroviral treatment simplification with darunavir/ritonavir or lopinavir/ritonavir monotherapy maintains sustained HIV viremia suppression in clinical trials. However, data about the efficacy of this strategy in routine clinical practice is still limited, and no direct comparison between darunavir/ritonavir and lopinavir/ritonavir has been performed to date. We retrospectively studied all HIV‐1‐infected subjects who initiated monotherapy with darunavir/ritonavir or lopinavir/ritonavir while having plasma VL<50 c/mL, and had at least 1 subsequent follow‐up visit in our clinic. When two consecutive PI‐monotherapy regimens were used, each regimen was considered separately. The primary endpoint was the percentage of patients who maintained virological suppression (HIV‐1 VL <50 c/mL) through follow‐up. Virological failure was defined as at least two consecutive HIV‐1 VL >50 c/mL. We also evaluated other reasons for treatment discontinuation. Analyses were performed considering all regimens (full dataset analysis) either as "on treatment" or as "treatment switch equals failure". Five hundred and seventy‐three PI‐monotherapy regimens corresponding to 520 subjects were included, 262 with darunavir/ritonavir and 311 with lopinavir/ritonavir. Medians (IQR) follow‐up were 50 (26.3–107.6) and 85.6 (36.9–179.1) weeks for subjects on darunavir/ritonavir and lopinavir/ritonavir, respectively (p<0.001). Overall, 67 (11.7%) subjects experienced virological failure, 23 (8.7%) were on darunavir/ritonavir and 42 (13.5%) were on lopinavir/ritonavir (p=0.796). Two hundred and three (77.5%) patients on darunavir/ritonavir and 154 (49.5%) on lopinavir/ritonavir maintained virological suppression in the "treatment switch equals failure" (p=0.002). Other reasons for treatment discontinuation were gastrointestinal toxicity and dyslipidemia in 7.2% and 5.9% of cases, respectively. Gastrointestinal toxicities and dyslipidemia leading to treatment discontinuation were more frequent in patients on lopinavir/ritonavir (10.6% and 10.3%, respectively) than in patients on darunavir/ritonavir (3.1% and 0.8%, respectively). Monotherapy with darunavir/ritonavir or lopinavir/ritonavir as simplification strategy appears to be effective and safe in subjects with virological suppression in clinical practice. Virological efficacy seems to be similar between regimens. However, rates of discontinuation due to toxicities were higher in subjects on lopinavir/ritonavir than darunavir/ritonavir.

Purpose of the studyHCV is one of the most relevant co‐morbidities seen in HIV‐infected individuals as evidenced by the negative impact that HIV exerts on the course of HCV infection. Despite remarkable results on HIV infection alone, the impact of highly active antiretroviral therapy (HAART) on liver disease in co‐infection remains unknown. We sought to explore the impact of raltegravir (RAL) on amino transferase (ALT) in HIV/HCV co‐infected individuals.MethodsHIV‐infected individuals co‐infected with HCV within the last 5 years receiving non‐integrase inhibitor containing HAART with a subsequent switch to RAL‐containing HAART were identified from a retrospectively maintained outpatient database. Patient demographics were extracted. Biochemical, virological and immunological parameters were collated and individuals received pegylated interferon with ribavirin were excluded. ALT levels at switch and post switch were compared using Kruskal‐Wallis test. Spearman's Rank correlation was used to assess the relationship between ALT and HCV‐RNA.Summary of resultsTwenty‐seven HIV‐HCV co‐infected individuals were identified between January 2007 and January 2012 and seven individuals were excluded. Median age was 44 years (range: 31–68). Five had acute and fifteen had chronic HCV infection during the switch. Twenty (100%) had HIV‐RNA‐1<40 copies/mL at time of RAL switch. In chronic HCV infected individuals, median ALT levels at the time of switch were 465 IU/L, decreased significantly to 179 IU/L 1 month following switch (p=0.0261) and to 140 IU/L 6 months later (p=0.0225). On the other hand, in acute HCV infected individuals median ALT levels were 1005 IU/L at time of switch but decreased significantly to 220 IU/L 1 month later (p=0.0034) and to 35 IU/L 6 month later (p=0.0026). Sustained improvement in ALT levels from baseline to 1 month and up to 24 weeks after switch to RAL was observed in both groups but the reduction in ALT levels was statistically more significant in acutely infected individuals. ALT and HCV‐RNA levels showed a positive correlation at 6 months pre, post and at time of switch both in acute and chronic HCV‐infected individuals (Spearman's Rank correlation).ConclusionIn our study, RAL had a favourable effect on the liver up to 24 weeks after switch in HIV/HCV infected individuals.image

Patients' acceptability of HAART is a subjective variable that may deeply influence therapeutic outcome. The feeling of the patient may alter adherence and lead to virologic failure. Acceptability may depend on various variables often difficulty evaluated by the care‐giver. In a clinical setting the evaluation of acceptability is difficult, too, as patients may feel a judgement and be less sincere. Aim of this study was to asses adherence and acceptability of HAART. To limit reporting biases, the study was performed in five different non‐clinic settings covering North and Central Italy. A total of 230 patients on stable HAART were asked to complete a semi‐structured, anonymous questionnaire reporting their attitude toward HAART, their adherence and the acceptability of their regimen. In these notes we focus on this last patient‐oriented outcome. Most of the subjects were males (66%) with a mean age of 46 years, with higher education level (72%) and a long history of HIV infection (mean 13.6 years). Consequently only 17% of patients were on a first‐line regimen. Patients reporting a high or very high acceptability of HAART were 60% compared to a 31% reporting a fair grade of satisfaction and a 9% indicating low or null acceptability. However the type of the regimen significantly influenced patients' acceptability. Single‐tablet regimens (STRs), OD regimens with more than one tablet/day or BID regimens were scored as highly acceptable in 84%; 61%; and 53% of cases, respectively (P < 0.0001) (Figure). Statistical significance was retained when the dosing schedule was entered in a multivariate logistic model. When the analysis was restricted to experienced patients 62% of them were currently on a regimen based on a reduced number of pills compared to the previous one. Patients scored the previous regimen as more difficult to comply with in 72% of cases; as difficult in 22% and less difficult in 6%. The eventuality of AEs (40%); respect of timing of pill intake (39%) and number of pills (27%) were the major reasons of patients' low acceptability of HAART. High acceptability is one of the winning characteristics of a regimen, favoring long‐term adherence, durability and efficacy. Although highly subjective, acceptability may be positively influenced by characteristics of the HAART regimen such as simplicity. According to our results, STRs show a higher acceptability compared to more complex regimens.Patient reported acceptability for thier current HAART regimen.image

This study compared adherence (persistence and execution) during pregnancy and postpartum in HIV‐positive women having taken part in the adherence‐enhancing program of the Community Pharmacy of the Department of Ambulatory Care and Community Medicine in Lausanne between 2004 and 2012. This interdisciplinary program combined electronic drug monitoring and semi‐structured, repeated motivational interviews. This was a retrospective, observational study. Observation period spread over from first adherence visit after last menstruation until 6 months after childbirth. Medication‐taking was recorded by electronic drug monitoring. Socio‐demographic and delivery data were collected from Swiss HIV Cohort database. Adherence data, barriers and facilitators were collected from pharmacy database. Electronic data were reconciled with pill‐count and interview notes in order to include reported pocket‐doses. Execution was analyzed over 3‐day periods by a mixed effect logistic model, separating time before and after childbirth. This model allowed us to estimate different time slopes for both periods and to show a sudden fall associated with childbirth. Twenty‐five pregnant women were included. Median age was 29 (IQR: 26.5, 32.0), women were in majority black (n = 17,68%) and took a cART combining protease and nucleoside reverse transcriptase inhibitors (n = 24,96%). Eleven women (44%) were ART‐naïve at the beginning of pregnancy. Twenty women (80%) were included in the program because of pregnancy. Women were included at all stages of pregnancy. Six women (24%) stopped the program during pregnancy, 3 (12%) at delivery, 4 (16%) during postpartum and 12 (48%) stayed in program at the end of observation time. Median number of visits was 4 (3.0, 6.3) during pregnancy and 3 (0.8, 6.0) during postpartum. Execution was continuously high during pregnancy, low at beginning of postpartum and increased gradually during the 6 months of postpartum.imageMajor barriers to adherence were medication adverse events and difficulties in daily routine. Facilitators were motivation for promoting child‐health and social support. The dramatic drop and very slow increase in cART adherence during postpartum might result in viral rebound and drug resistance. Although much attention is devoted to pregnant women, interdisciplinary care should also be provided to women in the community during first trimester of postpartum to support them in sustaining cART adherence.

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.

BackgroundWith the expansion of HIV‐2 epidemic beyond African countries, co‐infection with HIV‐1 becomes a global challenge. We have recently identified an HIV‐1/2 dual infection with both viruses bearing multiclass drug resistance in an untreated patient [1]. We now present the patient's combined antiretroviral treatment (cART) outcome after 6 months follow‐up.Patient and MethodsClinical samples were obtained upon informed consent from a 23‐year‐old man living in Guinea‐Bissau until March 2011 when he moved to Switzerland. As previously reported [1], HIV‐1/2 co‐infection was confirmed by HIV‐1 PCR (21.000 copies/ml) and total HIV‐1/2 viremia (4.351 nU/ml) by product‐enhanced reverse transcriptase (PERT) assay. The patient denied previous HIV testing or exposure to antiretroviral drugs. Dual infection consisted of HIV‐1 CRF02_AG bearing resistance mutations M184V/V90I and HIV‐2 clade A, harboring K65R/D67N mutations as amplified from proviral‐DNA. Baseline CD4 + T‐cell count was 408 cell/mm3. We initiated cART in accordance to drug resistance mutations (see below). Treatment compliance was assessed with an electronic pillbox device and drug‐plasma concentrations. Clinical and laboratory follow up were done at weeks 2, 4, 9, 12 and 24.ResultscART was initiated with tenofovir/emtricitabine (TDF/FTC), boosted‐darunavir (DRV/r) and raltegravir(RAL). Treatment compliance was fluctuant during the first 3 months after which it remained stable with an average monthly intake of 92%. Antiretroviral drug‐plasma concentrations were traced at percentile 25th. HIV‐1 viremia became undetectable at week 12. Additionally, HIV‐2 viremia was retrospectively assessed by real‐time RT‐PCR at two independent laboratories showing undetectable values across the study period including baseline. Thus, baseline viremia, as assessed by the PERT test for particle‐associated reverse transcriptase activity was due to HIV‐1 alone. CD4 + T‐cell count was 559 cell/mm3 at week 24. Laboratory assessments showed a neutrophile drop to 0.96 at week 4, fully restored at week 9.ConclusionThis case of HIV‐1/2 dual infection underscores the importance of assessing genotypic analysis of both viruses ahead to treatment choice. It also highlights viral load platforms constraints when it comes to clinical monitoring of HIV‐1/2 co‐infection in western settings. Overall, first‐line salvage treatment was well tolerated and suppressed HIV‐1 resistant clade allowing recovery of CD4+ T‐cell count.

Complexity of antiretroviral treatment (ART) is a reason for non‐adherence and may impact treatment outcome. The association between daily dosing and pill burden and chance of virological success (VS) of first ART has been rarely assessed. 3,674 naïve patients who started treatment after January 2000 were identified from the ICoNA cohort. Number of daily doses and pills were estimated on the basis of the drugs used to rank first ART complexity: 1–2 daily pills once a day (low‐pills QD [lpQD]); 3–6 daily pills QD (high‐pills QD [hpQD]); 2–5 daily pills BID (low‐pills BID [lpBID]); >6 daily pills BID (high‐pills BID [hpBID]). VS was the date of first HIV RNA <50 cp/ml. Follow‐up was censored at the date of VS or last available HIV RNA. Kaplan‐Meier curves estimated probability of achieving VS according to ART complexity. Univariable and multivariable Cox regression stratified by clinical site was used to identify variables associated with VS. ITT principle was applied, using competing risk approach for death. Population: male 75%; median age 37 y (IQR, 32–44); HIV transmission heterosexual 43%, homosexual 33%, drug use 16%; Italian origin 86%; CDC group C 17%; median pre‐ART CD4 and log HIV‐RNA were 271/mm3 (range, 0–1672) and 4.84 cp/ml (1.70–6.38), respectively. Regimens were started in '00–'02 24%,'03–'05 17%,'06–'08 17%,'09–'12 42% and based on NNRTI in 40%, PI/r 43%, PI 8%, other ART 10%. Frequencies in complexity ranks were: 19% lpQD, 23% hpQD, 32% lpBID, 26% hpBID. VS was achieved by 85% of patients with an overall median time to VS of 5.6 months (95% CI: 5.4–5.8). Median months to VS were shorter with decreasing complexity: hpBID 6.5; lpBID 6.0; hpQD 5.3, lpQD 4.5. Kaplan‐Meier curves are shown (Figure).imageAfter stratifying for clinical site and adjusting for age, gender, origin, transmission route, CDC group C, HCV/HBV infection, years of HIV, pre‐cART CD4 and HIV‐RNA, type of regimen a significantly reduced likelihood of achieving VS was found for ART complexity (hpQD: HR 0.76 95% CI 60–0.96; lpBID: 0.74, 0.59–0.94) when compared with lpQD. The chance of VS was higher in people starting ART more recently (RH 1.28 [95% CI 1.09–1.51] for '03–'05; RH 1.64 [1.27–2.10] for '09–'12; vs. '00–'02) and was lower in people with previous AIDS (RH 0.85 [0.73–0.98]). Once‐a‐day dosing of ART, especially when combined with low daily pill burden, seems to be one of main factors contributing to the higher rate of success of ART in recent years.

BackgroundThe peculiarity of Romanian HIV epidemic is the high number of long‐time survivors, nosocomially infected with F subtype during early childhood. Although ART is provided for free, patients from certain regions are difficult to attain viral load (VL) and HIV resistance tests.ObjectivesTo assess the durability of first‐line antiretroviral therapy (1st ART) in Romanian HIV patients.MethodsRetrospective assessment of new HIV diagnosed patients during 2005–2010, monitored every 24 weeks (wk) in HIV clinic from Galati ‐ Romania, considering demographic data, HIV transmission pattern, immunity, HIV‐RNA blood levels, co‐morbidities, 1st ART regimen and adherence according to the national protocol. The endpoint was term on loss to follow‐up, death or 96 wk of ART.Results100 new diagnosed HIV patients since 2005 received 1st ART. Characteristics of naïve patients: median age on HIV diagnostic=22.5 years old; sex ratio M/F=53/47; living area rural/urban=55/45; low literacy 26%; HIV infection pattern paediatric/ sexual/ unknown=29/61/10; advanced late presenters 51%; TB as HIV indicator 22%; VHB co‐infection 22%; baseline av. CD4Ly=171/mm3. Experience of 1st ART: 2 NRTI+EFV 38% or LPV 27% or other protease inhibitor 35%. The reasons for 58% interrupting 1st ART: 9% dead, 17% abandoned, 18% failed, 12% developed adverse events and 2% drug‐drug interactions. While 53% patients were adherent previous to endpoint, no more than 42% kept on 1st ART>96 wk and recovered immunity with av. CD4Ly=213/mm3. Poor recovery of CD4Ly<100/mm3 was acquired by 13/48 patients with available HIV‐RNA<50 c/ml in 48 wk. The main risks below 24 weeks of 1st ART are the death (p=0.005; OR=36) and the adverse events (p=0.018; OR=24). Abandon rate (p=0.016; OR=5.14) is higher over 48 weeks. Regardless of 1st ARV regimen, adherence behaviour, immunologic benefits and ART durability were comparable. Viral failure is related to non‐adherence (p=0.03; OR=4.5) and low literacy situation (p<0.001; OR=7.5). Mortality is 4.6 times higher in TB and 2 times in HBV co‐morbidities.ConclusionsOver a half of naïve HIV patients continued 1st ART less than 96 wk. 26% patients with low literacy are a vulnerable group and require individualised educational and adherence programmes. To improve the sustainability of the 1st ART in HIV patients from Galati needs to intensify the support for earlier HIV diagnostic and current virology follow‐up.