Suchergebnisse

IntroductionTransmission in serodiscordant couples (SDCs) accounts for approximately half of all new HIV infections, both in Kenya and the wider sub‐Saharan region [1]. With evidence to suggest inconsistent condom use within this population [2], the World Health Organization has recommended two new methods of HIV prevention for SDCs: Treatment as Prevention (TasP) and Pre‐Exposure Prophylaxis (PrEP). However, there has been little research about the attitudes of SDCs towards these strategies [3, 4]; knowledge that is paramount for successfully predicting the acceptability and efficacy of each method, as well as for informing decisions regarding HIV policy changes in Kenya.MethodsAn exploratory, qualitative study was conducted in the Muhoroni constituency of Nyando district, Kenya from January to March 2013. Purposive sampling was predominately used to recruit 21 HIV‐positive and 17 HIV‐negative individuals in a serodiscordant relationship from four hospitals and health centres. During face‐to‐face semi‐structured interviews, topic guides were used to elicit information about participants' attitudes and preferences towards TasP and PrEP. Collected data underwent framework analysis, allowing the development of overarching categories, sub‐themes and inductive interpretation.ResultsThe majority of participants, irrespective of gender and HIV status, found TasP more acceptable than PrEP. A key factor influencing this decision was HIV‐negative participants' limited motivation to take and adhere to antiretrovirals (ARVs), primarily due to a predominantly external health locus of control, a lack of cultural acceptance of prophylactic medication and concerns about side effects. In addition to this, the likely health improvements TasP offers HIV‐positive partners, as well as the attitude that the sick individual should be the first to receive HIV medication, also contributed to this conclusion. Issues of risk compensation were raised, with some HIV‐negative partners indicating a desire to stop using condoms if ARV‐based prevention methods were available.ConclusionsFindings from the study indicate that TasP may represent a more viable approach to HIV prevention in Kenya than PrEP. Couples' preferences, however, may differ depending on local attitudes towards prophylaxis and health locus of control.

IntroductionIn clinical trials, toxicity leading to discontinuation of tenofovir (TDF) is a rare occurrence (3% by two years)[1, 2]; however, in clinical practice it seems to be higher. Previous studies suggested that TDF toxicity is higher when it is co‐administered with ritonavir‐boosted protease inhibitors (PI/r)[3, 4]. The aim of this study is to assess the rate of TDF discontinuations in clinical practice and to explore associated factors.MethodsAll previously antiretroviral‐naïve patients initiating a TDF‐containing regimen were selected from the ICONA cohort, unless they were positive for hepatitis B. The primary outcome was TDF discontinuation (>30 days) regardless of the reason, the secondary was TDF discontinuation due to toxicity. All analyses were repeated for the isolated stop of TDF (no stop of associated drugs). The main reason for discontinuation as reported by the treating physicians was used to classify stops. Kaplan–Meier (KM) analysis and Cox proportional hazards model were used.ResultsA total of 3,303 naïve patients were enrolled: 674 (20.4%) were female, the median age was 38 years (32–45), 55% were on PI/r‐based regimen and 45% on NNRTI; 80% of calculated estimated glomerular filtration rates (eGFR) were >90 ml/min. The probability of discontinuation of TDF regardless of the reason was 10% (95% CI 8–11) at two years, 20% by eight years. The causes of discontinuation were: toxicity (33%), failure (10%), non‐adherence (21%), simplification (16%) and other/unknown causes (20%). The five‐year KM estimates in the PI/r vs. not PI/r groups were 23% vs. 10%, respectively (log‐rank p=0.0001), for the outcome of stopping regardless of the reason, and 8% vs. 4% (p=0.18) for discontinuation due to toxicity. In a multivariable Cox model, PI/r use and lower body weight were associated with increased risk of discontinuing TDF regardless of the reason; lower eGFR at baseline was associated with TDF discontinuation for toxicity and PI/r use was associated with isolated stop of TDF (Figure). No differences in rates of TDF discontinuations between PIs were found.ConclusionIn our cohort, the observed frequency of TDF discontinuations was low although higher than estimated in clinical trials (10% by two years). Co‐administration of TDF with PI/r was associated with an increased rate of TDF discontinuations. This finding should guide further investigations of the mechanism that may have led to discontinuation of TDF in patients using PI/r.

IntroductionNEAT001/ANRS143 was an open‐label, randomized, non‐inferiority study comparing raltegravir+darunavir/r(RGV+DRV/r) vs. tenofovir/emtricitabine+darunavir/r (TDF/FTC+DRV/r) in HIV‐infected antiretroviral naïve adults. Primary efficacy outcome was a composite of virological and clinical events by week 96.Materials and MethodsClinical trial units collected and translated supporting documentation (SD) related to the investigator‐reported events. A coordinator checked events and SD for consistency and completeness. The Endpoint Review Committee (ERC) determined if clinical events met pre‐defined diagnostic criteria in categories "confirmed" or "probable". The ERC of 12 experienced, independent clinicians served in groups of three conducting individual reviews in writing, blinded to treatment arm. Differences of opinion were adjudicated in a second review by direct dialogue between reviewers. "Confirmed" events required adequate SD like laboratory, radiographic or pathology diagnostic reports. "Probable" events were typically based on clinical criteria.ResultsOf the 164 serious and 3,964 adverse events reported in the study, 133 qualified for endpoint review, for a total of 153 adjudications:Sixty of 111 per protocol endpoints were confirmed (n=53) or probable (n=7), which equals an acceptance rate of 54%. In two confirmed cases, SD was partly adequate and evaluation uncertain. Of 51 rejected events, 13 had insufficient SD, two were recurrent events. The rate of rejected events was comparable between treatments with 41% rejected events in the RGV+DRV/r arm compared to 52% in the TDF/FTC+DRV/r arm. The IRIS acceptance rate was low (3 of 18), demonstrating the difference in perception of IRIS in daily patient management and the stricter protocol definition.ConclusionsBlinded endpoint review prevented unacceptably high false positive event rates documenting that real‐time ascertainment of clinical endpoints is crucial for appropriateness of the overall results. Non‐confirmed events jeopardize the statistical power in this and probably all kinds of clinical studies. The rejection rate was not indicative of poor study conduct – on the contrary over‐reporting prevented missing events, which would have adversely impacted the trial. Adequacy of SD and investigator training on possible differences in event criteria in daily pragmatic clinical management compared to protocol defined criteria is essential.

IntroductionCombination antiretroviral therapy (cART) containing rilpivirine plus 2 NRTIs are effective antiretroviral (ARV) regimens for ARV‐naive HIV‐infected patients who had baseline plasma HIV RNA load (PVL) <5 log10 copies/mL and as switch therapy for those with viral suppression. In this study, we aimed to assess the short‐term safety of rilpivirine‐containing regimens among HIV‐infected patients who initiated or switched to rilpivirine plus two NRTIs in Taiwan.Materials and MethodsBetween January and June 2014, medical records of all HIV‐infected patients who initiated or switched to rilpivirine plus two NRTIs, during the follow‐up were reviewed to assess the tolerance and adverse effects. Using a standardized data collection form, we recorded data of PVL and CD4 count, serologies for hepatitis B and C virus (HBV and HCV, respectively), haemogram, aminotransferases, bilirubin and serum creatinine before starting rilpivirine‐containing regimens at four weeks and every 12 weeks thereafter.ResultsDuring the study period, medical records of 246 patients initiated their first ARV therapy with rilpivirine‐containing regimens (n=90) or switched to rilpivirine‐containing regimen from other regimens (156). Of the 246 patients, 73.4% were men who have sex with men and 9.1% and 25.6% tested positive for HBsAg and anti‐HCV antibody, respectively. Baseline CD4 was 395 cells/mm3 (range, 2‐1581) and PVL, 2.76 log10 copies/mL (range, <1.3>7.0 log10 copies/mL). As of 10 July, 23 patients (9.3%) stopped rilpivirine‐containing regimens due to gastrointestinal upset (n=4), skin rash (2), depression (2), poor sleep (3), anaemia (4, all being with zidovudine/lamivudine), nail hyperpigmentation (1), presence of transmitted drug resistance (4), and elevated aminotransferase levels (1). The proportion of the patients with aminotransferases of fivefold or higher than the upper limit of normal (ULN) was 1.7% and 1.5% for AST and ALT, respectively, before starting rilpivirine‐containing regimens; the respective value was 1.4% and 2.4% after 12 weeks of cART.ConclusionsRilpivirine‐containing regimens were generally well tolerated and less than 10% of the patients had to stop rilpivirine due to various reasons. Despite a higher prevalence of chronic HBV or HCV infection, rilpivirine‐containing regimens did not cause significant changes of aminotransferases from baseline.

IntroductionIn the last years, we observed an alarming increase in the number of newly diagnosed HIV infected intravenous drug users (IDUs) co‐infected with hepatitis viruses or with severe bacterial infections. The aim of our study was to assess the incidence, the demographic and clinical characteristics of IDUs diagnosed with HIV, HCV and tuberculosis (TB).Materials and MethodsProspective study on HIV infected IDUs with HCV and TB admitted in a single centre between January 2009 and April 2014. Data were compared to a group of HIV infected IDUs without TB. Statistical analysis was performed using Graphpad Prism 4.01.ResultsOut of 450 HIV infected IDUs, 134 (29.7%) were diagnosed with HIV, HCV and TB. TB incidence among IDUs increases from 0% in 2009 to 30.2% in 2013. The TB coinfected patients had a mean age at diagnosis of 30 [15–56] years; were in majority males, 106 (84.4%); from urban areas, 120 (89.5%); and had significantly lower education level (85% vs 68.3%, p<0.0001) and higher rates of unemployment (80% vs 55%, p<0.0001) than those without TB. The median CD4 cell count was lower in the TB versus non TB IDUs (143 vs 472/mm3, p<0.0001). TB infected IDUs tend to be more frequently late presenters (59.7 vs 24.6, p<0.0001) and to have advanced HIV disease (47.7 vs 7.59%, p<0.0001) than those without TB. TB cultures were positive in 64 (47.7%) patients, 3 (2.2%) had multidrug resistant TB and 2 (1.5%) had extended drug resistance. Disseminated and/or extrapulmonary TB was diagnosed in 51 patients (38%). The overall mortality rate was higher in TB compared to non TB IDUs (19.4% vs 8.2%, p=0.0007), disseminated TB being associated with the most severe immunosuppression (median CD4 cell count 42/mm3) and the highest mortality rate (27.4%).ConclusionsThe incidence of TB in HIV/HCV coinfected IDUs was high and rose over the time. TB infection was more frequent in patients with severe immunosuppression and the mortality rate was higher in IDUs with disseminated and/or extrapulmonary disease. IDUs are important candidates for acquiring and transmitting HIV infection, viral hepatitis and TB, being difficult to control due to their high‐risk behaviours. Strengthening of HIV transmission prevention strategies, particularly in identified risk groups, is mandatory.

IntroductionDaclatasvir (DCV) is a potent hepatitis C virus (HCV) NS5A replication complex inhibitor with pangenotypic (1–6) activity in vitro. Methadone (MET) and buprenorphine (BUP) are opioid medications used to treat opioid addiction; patients on HCV therapy may require MET or BUP treatment. The effect of DCV on the pharmacokinetics (PK) of MET or BUP/naloxone (NLX) was assessed in subjects on stable MET or BUP.Materials and MethodsAn open‐label, two‐part study assessed the effect of steady‐state oral administration of DCV on the PK of MET (Part 1, P1) or BUP/NAL (Part 2, P2). Safety/tolerability and pharmacodynamics (PD, opioid withdrawal scales/overdose assessment) were also assessed. Subjects (P1, N=14; P2, N=11) received daily single‐dose oral MET (40–120mg) or BUP/NLX (8/2–24/6mg) based on their prescribed stable dose throughout, in addition to DCV (60mg QD) on Days 2–9. Serial PK sampling occurred predose and postdose till 24 hours on Day 1 (MET/BUP) and Day 10 (MET/BUP/DCV). Noncompartmental PK were derived. Geometric mean ratios (GMR) and 90% confidence intervals (90% CI) for MET/BUP/norBUP Cmax and AUCTAU were derived from linear mixed effects models.ResultsSubjects were aged 19–39 years, mostly white (P1, 93%; P2, 100%) and male (P1, 71%; P2, 91%). All subjects completed the study. No clinically meaningful effect was demonstrated as the GMR and 90% CIs fell within the prespecified interval (P1, 0.7–1.4; P2, 0.5–2.0: see Table 1). DCV coadministration was well‐tolerated: overall, six (43%) subjects had adverse events (AEs) (all mild and resolved without treatment). DCV had no clinically significant effect on the PD of MET or BUP/NLX.ConclusionsSteady‐state administration of DCV 60mg QD had no clinically meaningful effect on the PK of MET or BUP/NLX and was generally well‐tolerated, suggesting that no dose adjustments will be required.

IntroductionSeveral factors such as duration of infection, age, male gender, consumption of alcohol, HIV infection and low CD4 count have been associated with fibrosis progression rate. However, it is relatively scarce, the knowledge about the liver fibrosis progression rate in HIV‐infected patients with undetectable HIV viral load (VL). For this reason, we performed the present study.Materials and MethodsObservational and multicenter study (2008–2012) conducted in four hospitals of the northern Spain. HIV/HCV (hepatitis c) virus coinfected patients ≥18 years on stable combination antiretroviral therapy (cART) (≥6 months) and with a HIV VL <50 copies/mL were selected to analyze their liver fibrosis progression. Fibrosis progression was assessed using a Fibroscan® (502 STEP 3 model) and measuring a basal test and a second one at least 12 months apart from baseline. This evolution was compared with different variables such as duration of HIV/HCV coinfection, gender, age, previous treatment for HCV, HCV genotype, CD4 lymphocyte counts and the cART employed at the basal test.ResultsA total of 608 patients were included (median age 29.4 years, 71.7% men). Of these, 463 patients met the inclusion criteria. In these patients, the liver fibrosis progression was nearly flat and the only variables related to a higher liver fibrosis progression were the increasing age of the patients (p=0.02) and the duration of the coinfection (p=0.001). CD4 lymphocyte counts showed a tendency to improved liver fibrosis (p=0.056).ConclusionsIn HIV/HCV coinfected patients on stable cART and HIV undetectable VL, the increase in liver fibrosis rate progression was nearly flat, although it was significantly associated with the duration of the coinfection and the age of the patient. The beneficial effects of the cART were independent of the antiretroviral drug employed. A tendency to a lower fibrosis progression was observed in those patients with a higher CD4 count.

IntroductionChronic liver disease leads to neurocognitive impairment (NCI) and more advanced liver fibrosis is associated with greater deficits. Further, cognitive performances do not differ significantly among patients affected by diverse types of chronic liver diseases. Thus, it would be useful to have a clinical tool associated with early cognitive change applicable to the HIV‐infected population with high HCV prevalence. Aim of the analysis was to assess the association between NCI and aspartate aminotransferase‐platelet ratio index (APRI) or Fibrosis‐4, which are non‐invasive scores used to assess liver fibrosis.Materials and MethodsSingle‐centre, retrospective, cross‐sectional analysis of cART‐treated HIV‐infected patients undergoing neuropsychological assessment (NPA) by a set of 14 standardized and comprehensive tests on five different domains: concentration and speed of mental processing; mental flexibility; memory, fine motor functioning; visual‐spatial and constructional abilities. NPA obtained from the same patient were included, if collected while receiving different cART. Patients were classified as having NCI, if they scored >1 SD below the normative mean in at least two tests, or below >2 SD in one test. HIV‐associated neurocognitive disorders (HAND) were classified according to Frascati's criteria, controlling for confounding comorbidities. Univariable analysis and multivariable logistic regression models were carried out.ResultsA total of 556 HIV‐infected cART‐treated patients from 2006 to 2013 were included: male 78%; IVDUs 14%; CDC stage C 31%; median CD4 nadir 200/mm3; median current CD4 501/mm3; undetectable HIV‐RNA in 368 (67%); and HCV‐positivity in 150 (29%). Frequency among score levels was for FIB‐4: min‐1.44=404 (73%), 1.45–3.25=118 (21%), 3.26‐max=28 (5%); for APRI: min‐0.5=414 (75%), 0.5–1.5=112 (20%), 1.5‐max=24 (4%). Median FIB‐4 and APRI were 0.98 and 0.27 in HIV+/HCV‐ and 1.40 and 0.50 in HIV+/HCV+ individuals, respectively. HAND was found in 176 (32%): 91 ANI, 73 MND, 12 HAD. Association of variables with NCI are shown in Table 1.ConclusionsIn this large population, HAND was not associated with commonly used non‐invasive liver fibrosis scores. As aetiology of cognitive dysfunction in HIV mono‐ and HCV co‐infected patients is multifactorial and partially unknown, our results support the hypothesis of a direct or indirect effect on cognitive function of the viruses, rather than the consequence of alterations residing outside the brain.

IntroductionThe prevalence of risky alcohol consumption, associated factors and its impact on the brain is not well established in clinically stable HIV patients.Materials and MethodsWithin the PIVOT neurocognitive sub‐study, effectively suppressed HIV‐infected adults on either standard cART or ritonavir‐boosted PI monotherapy completed the Alcohol Use Disorders Identification Test (AUDIT) designed to detect risky alcohol consumption. They also completed a brief neuropsychological assessment (NPZ 5) composed by five measures. For this cross‐sectional analysis, we calculated rates of hazardous (AUDIT=8–15) or harmful (AUDIT=16–19) consumption and likely dependence (AUDIT>20). We explored the association between risky alcohol intakes (AUDIT>8) and clinical/demographical variables, conducting logistic regressions when significant association was found (p<.05). Also, the association between cognitive performance and alcohol consumption was calculated and adjusted by potential confounders.ResultsOf the 146 included participants, the majority were male (86.3%), white (81.5%) and educated (mean years on formal education=15, SD=3.9). Average age was 47.6 years (SD=8.7), and 36.3% had risky consumption (29.5% hazardous, 6.2% harmful, 0.7% likely dependence). White ethnicity and male sex were positively associated with risky consumption (Table 1). After adjustments, white ethnicity remained significantly associated with risky consumption (1.64 [95% CI 0.34–2.95]; p=0.013). Better cognitive performance was associated with risky alcohol consumption in the univariate analysis (p<.001). After adjustment by ethnicity, sex and years of education, cognitive performance and risky alcohol consumption maintained significant association (0.45 [95% CI 0.19–0.70] p=0.001).ConclusionsDespite the substantially high prevalence of risky alcohol consumption, it was not associated with worse adherence, immunological or quality of life measures in this cohort of effectively suppressed patients but prevalence of likely alcohol dependency was extremely low. White patients were more vulnerable to risky consumption. Moreover, positive association between cognitive performance and risky alcohol consumption remained after adjustment. In our study, the association we found between cognitive function and alcohol consumption does not reflect the effect of alcohol dependency on cognition.

IntroductionEmotional processing is basic for social behaviour. We examine for the first time the facial emotion processing in long‐term HIV‐suppressed patients.Materials and MethodsCross‐sectional study comparing (ANOVA) six facial emotional processing tasks (two discrimination, two memory and two recognition) between HIV‐suppressed patients (HIV+) on effective antiretroviral therapy (>2 years) and matched (age, gender) healthy controls (HCs). Accuracy in the recognition of basic emotions (neutral, happiness, sadness, anger and fear) in each recognition task was also compared (Mann–Whitney U test) between HIV+ and HCs. In the subset of HIV+, we evaluate which factors were associated with impaired recognition of basic emotions (accuracy below 50%) by multiple logistic regression analysis. Overall performance in all six emotional tasks were separately compared between neurocognitive impaired and non‐impaired HIV+.ResultsWe included 107 HIV+, mainly Caucasian (89%) male (72%) with a mean age of 47.4 years, neurocognitively non‐impaired (75.5%), and 40 HCs. Overall discrimination (p=0.38), memory (p=0.65) and recognition tasks (p=0.29) were similar in both groups. However, HIV+ had lower sadness recognition in both recognition tasks and lower sadness, anger and fear recognition in the facial affect selection task (Figure 1). Only estimated pre‐morbid functioning (WAIS‐III‐R vocabulary subtest score) was significantly associated with sadness (1.99 [95% CI 1.18–3.58]; p=0.01) and anger recognition deficits (2.06 [95% CI 1.14–3.45]; p=0.015) in the facial affect selection task. In HIV+ individuals, neurocognitive impairment was associated with worse memory task results (p<0.01, d=0.88; p<0.01, d=1.48).ConclusionsWe did not find difference in the overall emotion processing between HIV+ and HIV‐ individuals. However, we found particular recognition deficits in the entire HIV+ sample. Estimated pre‐morbid functioning was associated with sadness and anger recognition deficits in the facial affect selection task. Neurocognitive impaired HIV+ had additional memory deficits. These recognition deficits might conduct to social difficulties.

IntroductionDespite plasma levels of certain HIV drugs decreasing in the third trimester of pregnancy there is no definitive evidence that therapeutic drug monitoring (TDM) improves HIV control and prevents mother‐to‐child transmission (MTCT). Indeed "one‐off" TDM measurements are thought to poorly correlate with overall drug exposure [1]. We aim to describe baseline demographic and clinical characteristics of pregnant women with HIV, and to compare their HIV control, management during pregnancy and neonatal outcomes with respect to whether TDM was performed.Materials and MethodsRetrospective cross‐sectional case note analysis was performed on pregnant women with HIV who attended North Manchester General Hospital and Manchester Royal Infirmary from 1st January 2008 to 28th May 2013.ResultsA total of 171 pregnancies were included; 39% (n=66) had TDM. The majority of patients were of African origin (85%) and age range was 16–42 years (median 32 years). TDM was found to be associated with a history of poor adherence to therapy (TDM 23%, vs no TDM 10%, p=0.017), although baseline viral load (VL) and CD4 counts were comparable between TDM and non‐TDM groups (p=0.4756 and 0.9492, respectively). TDM was also associated with protease inhibitors (PI) (TDM 94% vs no TDM 77%, p= 0.004). Within the PI group, TDM was more strongly associated with atazanavir use than other PI's (55%, p=0.023). TDM was not associated with any other demographic variable or with either of the two hospital sites (p=0.427). TDM was associated with medication alterations during pregnancy (TDM 67% vs no TDM 13%, p=0.052), but was not associated with any difference in outcomes with similar proportions of newly detectable VL during pregnancy (TDM 12% vs no TDM 7%, p=0.220) and VL detectable at birth (TDM 14% vs no TDM 9%, p= 0.293). There were no instances of MTCT.ConclusionsTDM was associated with PI use and a history of poor adherence at baseline. TDM was not associated with improved HIV control during pregnancy and there was no MTCT. TDM was not shown to have any additional benefit in pregnancy and its routine use is not recommended to improve HIV control or reduce MTCT.

IntroductionThe aim was to determine the prevalence of lung and heart abnormalities on thoracic CT scans in HIV‐infected patients who were treated with antiretroviral therapy (ART).Material and MethodsThoracic CT scans of 903 patients infected with HIV (mean age 48±7 yrs, 29% females) were reviewed by three radiologists by consensus. Patients were phenotyped according to smoking status, pack years and years since cessation for ex‐smokers. Individuals known to have active lung or heart disease at the time of CT scanning were excluded. Multimorbidity lung and heart disease (MLHD) was defined by the presence of >2 lung or heart abnormalities on the CT scan.ResultsPrevalence of lung abnormalities were: 326 patients (36.1%) with emphysema, 271 (30.0%) with bronchiolitis, 44 (4.9%) with non‐calcified lung nodules, 568 (63%) with significant bronchial wall thickening, 150 (16.7%) with bronchiectasis, 9 (1%) with interstitial lung disease. Overall, 445 patients (49.3%) had >2 lung abnormalities. Imaging findings suggestive of prior myocardial infarction (MI) were found in 1.4% (13 patients); 26.6% (240 patients) had CAC scores of 1 to 100, and 9.8% (89 patients) had CAC>100. 13.6% (123 patients) of the patients had CAC>100 and/or previous MI. MLHD was present in 484 patients (53.6%) and among 78 patients (16%) who never smoked. Table 1 describes CT findings according to pack year and stop smoking groups vs never smokers.MLHD increased proportional to cumulative smoking history (p for trend <0.001) and decreased in proportion to the number of years since smoking cessation (p for trend=0.017). Independent predictors for MLHD were: age (OR=1.07, CI 1.05–1.10), sex (OR=1.59, CI 1.15–2.19), current smoking (OR=1.76, CI 1.08–2.89), and pack‐years history of smoking (OR=1.03, CI 1.02–1.05). In patients who never smoked, nadir CD4<200 was significantly associated with MLHD after adjustment for age and sex (OR=1.98, CI 1.98–3.63).ConclusionsMLHD is common in HIV‐infected individuals even in non‐smokers. Reduced CD4 count (hence severity of HIV infection) may be an important risk factor for chronic lung and heart disease. Thoracic CT scans may provide an excellent screening tool to detect MLHD in HIV‐infected patients.

IntroductionMetabolic syndrome (MS) is common in HIV‐infected individuals and it is associated with higher cardiovascular risk (CVR). Mediterranean diet has been associated with a better metabolic control and lower CVR.Materials and MethodsFrom December 2013 to May 2014, individuals between 18 and 65 years of age, who attended the outpatient HIV Clinic at the University Hospital Santa Maria, Lisbon, were selected. Adherence to Mediterranean diet was evaluated with MedDietScore, a scale from 0 to 55 that punctuates 11 food items according to the frequency of intake. Higher scores represent higher adherence. CVR was assessed using D.A.D tool (classified as low, moderate or high risk). We excluded individuals with opportunistic disease, hospitalized in the past three months or with renal disease diagnosis. All participants gave written informed consent.ResultsIn the 571 HIV patients included, 67.1% (n=383) were male, 91.6% (n=523) Caucasian, with a mean age of 46.5±8.9 years. Patients were divided in two groups: naïve (7.5%; n=43) or on antiretroviral treatment (ART) (92.5%; n=528). Mean length of HIV diagnosis was 6.7±6.5 years (naïve) and 13.3±6.1 years (ART); TCD4+ counts were above 500 cel/mm3 in 55.8% (n=24) and 67.6% (n=357) of the patients, respectively. MS was present in 33.9% (n=179) of patients in ART group and 16.3% (n=7) in naïve group. Presence of MS was associated with ART group (OR=2.7; p=0.018). MS was also associated with older age in this group (p=0.000). Overall, mean MedDietScore was 27.3±5.5. Higher score was associated with older age (r=0.319; p=0.000). Naïve patients presented a trend to higher adherence to Mediterranean diet (65.1% vs 51.7% in naïve group; p=0.090). No relation between MS and Mediterranean diet was found. Higher CVR was associated with the presence of MS in the ART group (p=0.001). In this group, individuals with moderate CVR presented higher rates of adherence to Mediterranean diet (p=0.036) when compared to low and high CVR score.ConclusionsIn this cross‐sectional study, naïve individuals presented a trend to higher adherence to Mediterranean diet. On the ART group, higher adherence to Mediterranean diet was found in individuals with moderate CVR score. We think that this might suggest that this group of patients adopt this diet only in the presence of metabolic alterations or perceived CVR. Prospective studies in HIV patients are required to determine the impact of adherence to Mediterranean diet on the reduction of CVR.

IntroductionThe resistance profiles of first‐line antiretroviral therapy (ART) regimens after virologic failure have yet to be studied in a clinic setting in the modern treatment era. Time to virologic failure among three standard first‐line regimens and the resistance profiles of these failures were compared.Materials and MethodsAll HIV‐positive persons aged 16 and over starting a three‐drug first‐line ART regimen were retrospectively identified at a Toronto community clinic (1 January 2006–1 January 2013). The regimens included a backbone of two NRTIs and a third agent; a PI, an NNRTI, or an II. Patients must have been on treatment for at least 14 days and have at least one VL test within 6 months after starting treatment. The primary outcome was virologic failure defined as either: no suppression by 6 months, or after suppression, two consecutive, detectable VL200 copies/mL at least 14 days apart or one VL>200 copies/mL. Time to failure was compared using a proportional hazards model adjusting for demographic and clinical factors. Resistance profiles of NRTIs and third agents are described in patients with virologic failure who had both baseline and virologic failure genotypes.ResultsSix hundred sixty patients (93% male) were included with a mean age of 38.9 and a median follow‐up period of 35.3 (32.2–39.3) months. Distribution of third agent use was: PI 37.3% (n=246), NNRTI 55.9% (n=369) and II 6.8% (n=45). Virologic failures occurred in 81/246 (33%) with PI, 87/369 (24%) with NNRTI and 11/45 (24%) with II. Compare to PIs, time to failure was longer with NNRTIs (p=0.0013) and similar for IIs (p=0.1562). No evidence that failure with NNRTIs was different from IIs (p=0.9139). Of the 660 patients, 567 (86%) had a baseline genotype. Of the 567 patients, 179 had virological failure. Of the 179, 145(81%) had a baseline genotype and only 37 (21%) had both a baseline and follow‐up genotype. Upon failure, emerging ART resistance was rare. No new PI or II mutations were identified and one new NNRTI (Y181C) mutation was identified. Three patients taking PI‐based regimens developed NRTI mutations (M184V, M184I, T215Y).ConclusionsTime to virologic failure was significantly greater in the NNRTI group compared to the PI group. If failure did occur, ART resistance rarely developed with no PI mutations but a few NRTI mutations in those taking PI‐based regimens, and NNRTI mutations in those taking NNRTI‐based regimen.

IntroductionMonotherapy with darunavir plus ritonavir (DRV/r) is a good maintenance strategy for suppressed HIV‐infected patients. The clinical trials designed to prove the efficacy of PI/r do not include patients with resistance mutation in protease gene [1,2]. Sometimes in routine practice, basically to avoid NRTIs toxicity, monotherapy with DRV/r is used despite PI resistance mutations. The aim of this study is to know the effect of previous protease resistance mutation on DRV/r monotherapy efficacy.Materials and MethodsWe designed an observational cohort study of adults in treatment with DRV/r monotherapy in a tertiary Spanish hospital since 2011 to 2014. Demographic data and clinical outcomes were described. The analysis of efficacy was done according to the snapshot algorithm (defining virological failure as viral load >50 copies/mL, ITTe, at 48 and 96 weeks). We analyzed the difference of efficacy between patients with and without baseline resistance mutations at 48 and 96 weeks by using the χ2 test; and during the follow‐up by using the Kaplan–Meier test. The statistical analysis was done with SPSS 17.0.ResultsEighty‐nine patients were included in the cohort but 14 were excluded because they had not reached more than six months with monotherapy. The cohort was composed mainly by men (78%), the medium age was 51 years (SD±10), 35% were MSM and 19% were former IDU. Twenty‐four patients (35%) had a previous diagnosis of AIDS. The mean time taking NRTIs was 10.5 years (SD±5.4). Sixty‐four patients (85%) had been treated with PI in the past. Previous failure with PI had been reported in 15 (20%). A resistance mutation test had been done at baseline in 45 patients (51%). Twenty‐two patients (29%) had some mutations in protease gene, 10 patients (13%) had major mutations and 1 patient had some mutations of resistance for darunavir (I64V). At 48 weeks, 93% (CI 95% 86–98%) had VL<50 copies/mL, and 79% (CI 95% 67–89%) at 96 weeks. There were not differences between patients with or without resistance mutations (p=0.53). After a median follow‐up of 70 weeks, 88% of patients remain free of virological failure and there were not differences between both groups.ConclusionsAccording to these data, previous resistance mutations in the protease gene, which do not affect darunavir, are not related with the efficacy in patients treated with DRV/r monotherapy.