Shorter Time to Discontinuation Due to Treatment Failure in People Living with HIV Switched to Dolutegravir Plus Either Rilpivirine or Lamivudine Compared with Integrase Inhibitor-Based Triple Therapy in a Large Spanish Cohort.

INTRODUCTION: Standard therapy for HIV treatment has consisted of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug regimens (2DR) has been considered for selected patients in part to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase inhibitor (INSTI)-based three-drug regimens (3DR) versus 2DR of dolutegravir (DTG) + rilpivirine (RPV) or DTG + lamivudine (3TC). METHODS: All patients in the Spanish VACH cohort switching to INSTI-based 3DR or a 2DR consisting of DTG + RPV or DTG + 3TC between May 2, 2016 and May 15, 2019 were included. Kaplan-Meier curves and Cox proportional hazard models were used to assess time to/risk of discontinuation due to treatment failure (TF) (defined as virologic failure [VF], immunologic failure, or disease progression) and adverse events (AEs). Three secondary analyses were performed: (1) in restricting the analysis to patients who were virologically suppressed (HIV RNA < 50 copies/mL) at switch; (2) matched analysis (2:1, matched by age, sex, number of previous VFs, and line of regimen), and (3) using VF as the primary endpoint in all patients. RESULTS: Overall, 5047 3DR and 617 2DR patients were analyzed. Baseline characteristics differed between groups; 2DR patients were older, more treatment experienced, and more likely to be virologically suppressed at switch. Time to discontinuation due to TF was significantly shorter for 2DR (P = 0.002). The hazard ratio (HR) for discontinuation due to TF on 2DR vs 3DR was 2.33 (P = 0.003). No difference was observed for time to discontinuation (P = 0.908) or risk of discontinuation due to AEs (HR = 0.80; P = 0.488). Results were qualitatively similar in virologically suppressed patients, matched analysis, and for VF. CONCLUSION: In the real world, the risks of discontinuation due to TF and VF were more than two times higher in patients switching to DTG-based 2DR than INSTI-based 3DR, with no difference in discontinuation due to AEs.

People living with HIV (PLHIV) need lifelong treatment to prevent progression to AIDS. Standard HIV treatments use three different drugs in combination, but these can potentially cause unwanted side effects. Treatments using just two drugs have been developed. These aim to reduce side effects and treat HIV effectively. This study included 5664 participants in Spain who were split into two groups: 5047 participants switched from their old treatment to a three-drug regimen (3DR), and 617 participants switched to a two-drug regimen (2DR). The researchers measured how long it took for the participants to stop taking their treatment because it was not working, or it caused too many side effects. At the end of the study, more than 70% of participants in either group were still taking the same treatment. Of the 30% of participants who stopped treatment because it stopped working, those taking a 2DR stopped sooner than those taking a 3DR. This difference started to appear at about 18 months and got bigger until the study ended, which was 3 years after starting treatment. Participants taking a 2DR were twice as likely to stop treatment because it was not working than those taking a 3DR. There was no difference between the groups for how long it took for participants to stop their treatment because of side effects. These results show that for some PLHIV, the 2DR stopped working sooner than 3DR, without the benefit of fewer side effects.

Epidemiological and clinical characteristics of HIV infection in the Spanish VACH Cohort: a descriptive study.

BACKGROUND: knowledge of the present features of the HIV epidemic is relevant, especially to develop management programmes directed to poorly controlled patients. OBJECTIVES: to describe the epidemiological and clinical features of HIV infection in a large multicentre cohort. DESIGN: cross-sectional study. SETTING AND PARTICIPANTS: data of the Spanish VACH Cohort of HIV infected patients. MAIN OUTCOME MEASURES: a total of 53 variables were included. Descriptive statistics were used to report the results. Bivariable statistics were used to assess variation along time on prescribed antiretroviral treatment and on causes of death. RESULTS: a total of 30,843 patients belonging to most regions of Spain were included: 23,682 (76.78%) were male, mean and standard deviation of age of all patients was 34.03 ± 9.55 years in their first visit and 43.68 ± 10.52 years in their last visit; 12,677 (41.10%) were smokers, 3,521 (11.42%) had diabetes mellitus, 15,351 (49.77%) had acquired HIV via sexual route and 12,714 (41,22%) via parenteral route, 16,057 (52.06%) had positive hepatitis C virus serology. Their median and interquartile range of CD4 lymphocyte count, per cubic millimetre, were: lowest available 198 (79-337) and last available 510 (299-745). Last available HIV viral load was suppressed (<200 RNA copies per mL) in 23,485 (76.14%). Modalities of prescribed antiretroviral treatment varied substantially over time, with integrase inhibitor combinations predominating the last years. Causes of death changed from AIDS defining conditions early in the epidemic to non-AIDS defining conditions more recently. CONCLUSIONS: patients in the Spanish HIV VACH Cohort are predominantly middle-aged men. They acquired HIV via sexual or parenteral routes in similar proportions. Most of them are taking antiretroviral treatment and have their HIV infection properly controlled.

Assessment of Drug Interactions with Online Electronic Checkers in Multi-Pathological Patients.

INTRODUCTION: Multi-pathological patients are at high risk of drug interactions and side effects. We aimed to assess the usefulness of 3 online drug interaction checkers. METHODS: In a cross-sectional study, carried out in the Medicine Department of Hospital General of Castellon, Spain, in February 2020, we assessed drug interaction detection with 3 online electronic checkers, Drugs.com, Lexicomp®, and Medscape, and compared results obtained with the 3 tools. From every hospitalized patient, we obtained the list of drugs he or she had been taking until admission. Bivariable tests were used for analysis. p values <0.05 were considered significant. RESULTS: We included data from 134 patients; 68 (51%) were male; median (and interquartile range) of their age was 82 (76-88) years. A total of 1,082 substance drugs were entered in the checkers. The number of highest grade interactions found with every program was Drugs.com 85, Lexicomp® 33, and Medscape 67. Positive correlations were found between age and number of drug substances prescribed (p = 0.009) and between number of drug substances prescribed and interactions found with any of the 3 checkers (p < 0.001 in all 3 cases). Regarding highest grade interactions, agreement among all 3 checkers was poor. CONCLUSIONS: The 3 online checkers we assessed found a large number of interactions. The 3 programs gave very discrepant results. Impact on Practice Statements: The analyzed programs, Drugs.com, Lexicomp®, and Medscape Interactions, found a large number of drug interactions in the studied patients. The 3 programs gave very discrepant results among them.

eGFR-EPI changes among HIV patients who switch from F/TDF to F/TAF while maintaining the same third agent in the Spanish VACH cohort.

Background: Evidence from clinical practice on the effects of switching from emtricitabine/tenofovir disoproxil fumarate (F/TDF) to emtricitabine/tenofovir alafenamide (F/TAF)-based triple-therapy (TT) regimens on renal parameters is limited.Objective: This retrospective analysis evaluated the effects on renal function of switching from F/TDF to F/TAF-based TT regimens with no change in third agent among people living with HIV (PLWH).Methods: Data were from a multicenter Spanish PLWH cohort. Patients with a baseline estimated glomerular filtration rate (eGFR-EPI) measurement, ≥1 follow-up measurement, ≥30 days treatment with F/TAF, and who switched from F/TDF to F/TAF with no change in third agent were included. Multivariate mixed linear models were used to evaluate change from baseline over time in eGFR-EPI. eGFR-EPI changes before and after switch were analyzed in a matched patient subgroup.Results: Overall, 340 patients were included. Mean (95% CI) eGFR-EPI in patients with baseline eGFR-EPI <90 ml/min/1.73m2 (n = 125) was 79.6 (78.0; 81.2) ml/min/1.73m2 at baseline and 81.3 (79.9; 82.7) ml/min/1.73m2 at 12 months after switch. In the patient-matched subgroup (n = 175), median annual eGFR-EPI declined -4.24 ml/min/1.73m2 while on F/TDF and increased +0.93 ml/min/1.73m2 after switch to F/TAF (P < 0.0001). In patients with baseline eGFR-EPI <90 ml/min/1.73m2, median annual eGFR-EPI increased +4.19 mL/min/1.73m2 after switch (P < 0.0001).Conclusion: Switching from F/TDF to F/TAF-based TT regimens while maintaining the same third agent numerically improved eGFR-EPI in PLWH with baseline eGFR-EPI <90 mL/min/1.73m2. eGFR-EPI improved significantly when comparing progression while on F/TDF vs progression after switch, confirming beneficial renal effects of switching to F/TAF in a clinical practice setting.

Real world effectiveness of standard of care triple therapy versus two-drug combinations for treatment of people living with HIV.

BACKGROUND: Since 1996, the standard of care (SOC) therapy for HIV treatment has consisted of a backbone of two nucleoside analogue reverse transcriptase inhibitors (NRTI) paired with a third agent. Use of two-drug combinations (2DC) has been considered for selected patients to avoid toxicities associated with the use of NRTIs. This study aimed to compare the real-world outcomes of integrase strand transfer inhibitor (INSTI)-containing triple therapy (TT) to dolutegravir- (DTG) and/or boosted protease inhibitor (bPI)-based 2DC in a large Spanish cohort of HIV patients. METHODS: A retrospective analysis was performed using data from the VACH cohort, a prospective multicentre Spanish cohort of adult HIV patients. All treatment experienced patients initiating a TT of an INSTI combined with two NRTIs or a 2DC-containing DTG and/or a bPI between 01/01/2012 and 01/06/2017 were included. The unit of analysis was patient-regimens. The overall sample analysis was complemented with two sub-analyses. The first sub-analysis focused on patients treated with a backbone plus DTG compared to those treated with DTG+ one other antiretroviral. The second sub-analysis focused on patients with HIV RNA<50 copies/mL at baseline, irrespective of the regimen used. The following endpoints were assessed: time to discontinuation for any reason, time to switch due to virologic failure, and time to switch due to toxicity (reasons for discontinuation according to clinician report in the database). Time-to-event analyses were conducted using Kaplan-Meier survival curves and Cox regression models. RESULTS: Overall 7,481 patients were included in the analysis, contributing to 9,243 patient-regimens. Patient characteristics at baseline differed among groups, with the 2DC group being significantly older and having a higher proportion of women, a longer time on ART and a higher number of previous virologic failures. Median (95% Confidence Interval [C.I.]) time to switch was 2.5 years (2.3, 2.7) in 2DC group versus 2.9 years (2.7, 3.0) in TT. Adjusted hazard ratios (95% C.I.) for discontinuation due to any reason, virologic failure and toxicity in the 2DC vs TT group were 1.29 (1.15; 1.44), 2.06 (1.54; 2.77) and 1.18 (0.94; 1.48), respectively. Results were consistent in the two sub-analyses. CONCLUSION: In this analysis, time to discontinuation and probability of remaining free of virologic failure were significantly higher in patients on INSTI-based TT compared to DTG- and/or bPI-containing 2DC, with no differences in toxicity.

Factors Associated with Nonsuppression of HIV Infection in the Spanish VACH Cohort.

We aim to determine the prevalence of HIV nonsuppression and factors associated with it. This is a cross-sectional multicenter study carried out in January 2016 with data of the VACH Cohort, a registry participated by 23 hospitals from most regions of Spain. The prevalence of HIV nonsuppression, defined as HIV RNA ≥200 copies/mL, is documented. The possible association of HIV nonsuppression with sociodemographic and clinical variables is assessed with a logistic regression analysis. A total of 30,843 adult patients are included; 7,358 of them (23.86%) have nonsuppressed HIV. An association is found between nonsuppression of HIV and the following variables: lower body mass index, lower age of patients in their last registered visit, lower number of visits carried out during follow-up, lower last available CD4 cell count, higher age of patients at the time of their HIV infection diagnosis, higher lowest available CD4 cell count, higher highest available HIV RNA, enrolment in the Cohort in first years of the HIV epidemic, region of Spain where the patient is attended other than Andalusia, HIV risk factor other than sexual, occurrence of death during follow-up, hepatitis C coinfection, being a smoker, pertaining to groups A1 or A2 of the CDC groups classification, and not taking antiretroviral treatment, p < .001 in all cases. HIV nonsuppression is still common with the effective antiretroviral treatment nowadays available. HIV nonsuppression is associated with HIV risk factor other than sexual, hepatitis C coinfection, and being a smoker, among other factors.

Cervical cancer risk in women living with HIV across four continents: A multicohort study.

We compared invasive cervical cancer (ICC) incidence rates in Europe, South Africa, Latin and North America among women living with HIV who initiated antiretroviral therapy (ART) between 1996 and 2014. We analyzed cohort data from the International Epidemiology Databases to Evaluate AIDS (IeDEA) and the Collaboration of Observational HIV Epidemiological Research in Europe (COHERE) in EuroCoord. We used flexible parametric survival models to determine regional ICC rates and risk factors for incident ICC. We included 64,231 women from 45 countries. During 320,141 person-years (pys), 356 incident ICC cases were diagnosed (Europe 164, South Africa 156, North America 19 and Latin America 17). Raw ICC incidence rates per 100,000 pys were 447 in South Africa (95% confidence interval [CI]: 382-523), 136 in Latin America (95% CI: 85-219), 76 in North America (95% CI: 48-119) and 66 in Europe (95% CI: 57-77). Compared to European women ICC rates at 5 years after ART initiation were more than double in Latin America (adjusted hazard ratio [aHR]: 2.43, 95% CI: 1.27-4.68) and 11 times higher in South Africa (aHR: 10.66, 95% CI: 6.73-16.88), but similar in North America (aHR: 0.79, 95% CI: 0.37-1.71). Overall, ICC rates increased with age (>50 years vs. 16-30 years, aHR: 1.57, 95% CI: 1.03-2.40) and lower CD4 cell counts at ART initiation (per 100 cell/µl decrease, aHR: 1.25, 95% CI: 1.15-1.36). Improving access to early ART initiation and effective cervical cancer screening in women living with HIV should be key parts of global efforts to reduce cancer-related health inequities.

Palliative Sedation in Patients Hospitalized in Internal Medicine Departments.

CONTEXT: Palliative sedation is used to relieve end-of-life refractory symptoms. OBJECTIVE: The objective of this study was to describe the use of palliative sedation in patients who die in internal medicine departments. METHODS: An observational, cross-sectional, retrospective, and multicenter clinical audit study was conducted in 145 hospitals in Spain and Argentina. Each hospital included the first 10 patients who died in the internal medicine department, starting on December 1, 2015. RESULTS: We included 1447 patients, and palliative sedation was administered to 701 patients (48.4%). Having a terminal illness (odds ratio [OR] 2.469, 95% CI 1.971-3.093, P < 0.001) and the length of hospital stay (OR 1.011, 95% CI 1.002-1.021, P = 0.017) were independently associated with the use of palliative sedation. Consent was granted by the families of 582 (83%) patients. The most common refractory symptom was dyspnea, and the most commonly used drugs for sedation were midazolam (77%) and morphine (89.7%). An induction dose was administered in 25.7% of the patients. Rescue doses were scheduled for 70% of the patients, and hydration was maintained in 49.5%. Pain was more common in patients with cancer, whereas dyspnea was more common in those without cancer. Rescue doses were used more often for the patients with cancer (77.8% vs. 67.7%, P = 0.015). Monitoring the palliative sedation with a scale was more frequent in the patients with cancer (23.7% vs. 14.3%, P = 0.008). CONCLUSIONS: Palliative sedation is used more often for terminal patients. There are differences in the administration of palliative sedation between patients with and without cancer.

Within subject variability of HDL-cholesterol in HIV-infected patients.

Background and objective: Within-subject variability of cardiovascular risk factors may influence the development of cardiovascular disease. We aimed to improve knowledge on HDL-cholesterol variability and its clinical significance in HIV-infected patients, a population at high risk of cardiovascular disease.Methods: This was a cohort study to quantify the variability of HDL-cholesterol between two consecutive visits and to determine factors associated with such variability, in a group of HIV-infected patients.Results: A total of 307 patients were included, mean ± standard deviation of their age was 45.1 ± 8.5 years, and 225 of them (73.3%) were male. The absolute difference (after squaring and root squaring) of serum HDL-cholesterol level between the first and the second visit was 12.1 ± 9.2 mg/dL. In 65 patients (21.2%) the absolute value of the difference between both serum HDL-cholesterol level results were 20 mg/dL or higher. In a multivariable analysis the number of cigarettes smoked per day showed a significant, negative, correlation with the absolute difference in serum HDL-cholesterol level between the two visits (P = 0,009).Conclusions: Within-subject variability of HDL-cholesterol was substantial among our HIV-infected patients. Smoking was inversely correlated with such variability.

Typhlitis as a complication of influenza in a patient with advanced HIV infection.

The authors report the case of an HIV-infected patient who presented with typhlitis as a complication of typical influenza. To the best of their knowledge, this is the first case reported in the literature with such an association of clinical conditions.

Sarcoidosis presenting with acute dacryoadenitis.

Sarcoidosis is a systemic inflammatory disorder, pathologically characterized by noncaseating epithelioid granulomas. We report a case of the disease that presented with acute dacryoadenitis followed by acute parotitis.

Increased homocysteine plasma level is associated with shortened prothrombin time in HIV-infected patients.

OBJECTIVE: To find factors associated with increased homocysteine plasma level in HIV-infected patients. METHODS: Cross-sectional study, carried out as a supplementary task to the standard care of HIV-infected patients. The possible association of increased homocysteine plasma level with blood analyses results was assessed with a multiple linear regression analysis, using the automatic linear modeling available in SPSS version 22. RESULTS: A total of 145 patients were included. Creatinine was higher than normal in 7 patients (5%), prothrombin time was shortened in 36 patients (25%), and a monoclonal gammopathy was detected in 2 patients (1%). In the regression analysis, an association was found between high homocysteine plasma level and the following variables: low prothrombin time (ß coefficient -0.286, confidence interval -1.1854 to -0.754, p < 0.001), high creatinine (coefficient 9.926, confidence interval 6.351-15.246, p < 0.001), low folic acid (coefficient -0.331, confidence interval -0-483 to -0.187, p < 0.001), and low vitamin B12 (coefficient -0.007, confidence interval -0.01 to -0.001, p = 0.005). CONCLUSION: An association was found between increased homocysteine plasma level and shortened prothrombin time.

Alkaptonuria Presenting with Impressive Osteoarticular Changes and Severe Aortic Stenosis.

Alkaptonuria, or ochronosis, a rare autosomal recessive metabolic disorder, causes an excess of homogentisic acid that results in dark pigmentation, calcification, and inflammation of cartilaginous and other tissues. Cardiovascular complications are also typical of the disease. We report the case of a 78-year-old male who presented with impressive osteoarticular changes and aortic stenosis associated with alkaptonuria.

Comparison of extracorporeal shock wave therapy with botulinum toxin type A in the treatment of plantar fasciitis.

OBJECTIVE: To compare the efficacy of extracorporeal shock wave therapy (ESWT) with botulinum toxin type A (BoNT-A) in the treatment of plantar fasciitis (PF). DESIGN: Open label, prospective, randomized study. RESULTS: A total of 72 patients were included. In all participants the median (and interquartile range) of the visual analog scale (VAS) of pain result, when taking the first steps, was 8 (6-9) points before treatment and 6 (4-8) points after treatment (p < 0.001). In the group of patients that received ESWT, the median (and interquartile range) of improvement in the VAS of pain result, when taking the first steps, was 2 (1-4) points, and in the group of patients that received BoNT-A the same result was 1 (0-2) points (p = 0.009). In the group of patients that received ESWT, the median (and interquartile range) of improvement in the Roles and Maudsley scale of pain result was 1 (0-1) points, and in the group of patients that received BoNT-A the same result was 0 (0-1) points (p = 0.006). In a multivariate analysis use of ESWT and lower weight were associated with improvement of pain with treatment in at least one of the three VAS of pain scales used in the study. CONCLUSION: ESWT was superior to BoNT-A in the control of pain in patients with PF. Implications for Rehabilitation Plantar fasciitis is characterized by pain at the calcaneal origin of the plantar fascia, exacerbated by weight bearing after prolonged periods of rest. Although studies comparing extracorporeal shock wave therapy or botulinum toxin type A to placebo suggest a superiority of the first one, no reliable data exist about it. Extracorporeal shock wave therapy was superior to botulinum toxin type A in the control of pain in patients with PF.

Improved darunavir genotypic mutation score predicting treatment response for patients infected with HIV-1 subtype B and non-subtype B receiving a salvage regimen.

OBJECTIVES: The objective of this study was to improve the prediction of the impact of HIV-1 protease mutations in different viral subtypes on virological response to darunavir. METHODS: Darunavir-containing treatment change episodes (TCEs) in patients previously failing PIs were selected from large European databases. HIV-1 subtype B-infected patients were used as the derivation dataset and HIV-1 non-B-infected patients were used as the validation dataset. The adjusted association of each mutation with week 8 HIV RNA change from baseline was analysed by linear regression. A prediction model was derived based on best subset least squares estimation with mutational weights corresponding to regression coefficients. Virological outcome prediction accuracy was compared with that from existing genotypic resistance interpretation systems (GISs) (ANRS 2013, Rega 9.1.0 and HIVdb 7.0). RESULTS: TCEs were selected from 681 subtype B-infected and 199 non-B-infected adults. Accompanying drugs were NRTIs in 87%, NNRTIs in 27% and raltegravir or maraviroc or enfuvirtide in 53%. The prediction model included weighted protease mutations, HIV RNA, CD4 and activity of accompanying drugs. The model's association with week 8 HIV RNA change in the subtype B (derivation) set was R(2) = 0.47 [average squared error (ASE) = 0.67, P < 10(-6)]; in the non-B (validation) set, ASE was 0.91. Accuracy investigated by means of area under the receiver operating characteristic curves with a binary response (above the threshold value of HIV RNA reduction) showed that our final model outperformed models with existing interpretation systems in both training and validation sets. CONCLUSIONS: A model with a new darunavir-weighted mutation score outperformed existing GISs in both B and non-B subtypes in predicting virological response to darunavir.

The new oral anticoagulants: Reasonable alternatives to warfarin.

Dabigatran (a direct thrombin inhibitor) and rivaroxaban, apixaban, and edoxaban (direct activated factor X inhibitors) are increasingly being used in clinical practice. Compared with vitamin K antagonists, they are more convenient, do not require laboratory monitoring, have limited drug and food interactions, and have fixed dosages suitable for most patients. But the shortcomings of these agents can jeopardize their efficacy and increase the risk of bleeding. Their future role in preventing and treating thromboembolic disease will depend on building clinical experience, but current evidence indicates that they are reasonable alternatives to vitamin K antagonists.

Admissions for imported and non-imported parasitic diseases at a General Hospital in Spain: A retrospective analysis.

OBJECTIVE: To analyze imported and non-imported parasitic diseases as a cause of admission to a general hospital. METHODS: A retrospective analysis of hospital admissions for parasitic diseases between 2004 and 2013 performed by means of hospital information systems at a public hospital in the city of Castellón (Spain). RESULTS: During the period covered in this study, there were 204,349 admissions, 213 of which were for parasitic diseases (prevalence: 1.04/1000 admission). 129 were neglected parasitic tropical diseases and 61 were imported parasitic diseases. The main parasitic diseases were hydatidosis (24.9%), visceral leishmaniasis (22.5%) and malaria (12.2%). There was a decrease in admissions for visceral leishmaniasis in the 2004-2008 period from 27.7% to 15.9% in the 2009-2013 period (p < 0.001), and an increase in admissions for malaria from 5.0% to 21.3% (p < 0.001). 38 (20.3%) of the 187 patients with parasitic diseases were HIV infected. HIV infection was more common in patients with toxoplasmosis (94.1%; p < 0.001), cryptosporidiosis (66.7%; p < 0.02) and visceral leishmaniasis (46.4%; p = 0.003). There were 34 (18.2%) children with parasitic diseases. Twelve of the 28 patients with visceral leishmaniasis (42.9%; p < 0.001), and 11 of the 17 patients with soil-transmitted diseases were children (64.7%; p < 0.001). The cause of death in eight patients was parasitic disease related (mortality rate: 4.3%). The mortality rate for visceral leishmaniasis was significantly higher (14.3%; p = 0.01). CONCLUSION: The main cause is endemic parasitic diseases such as hydatidosis. Visceral leishmaniasis decreased during the period covered by the study, but malaria increased.

Impact of body weight on virological and immunological responses to efavirenz-containing regimens in HIV-infected, treatment-naive adults.

OBJECTIVE: The prevalence of overweight and obesity is increasing among HIV-infected patients. Whether standard antiretroviral drug dosage is adequate in heavy individuals remains unresolved. We assessed the virological and immunological responses to initial efavirenz (EFV)-containing regimens in heavy compared to normal-weight HIV-infected patients. DESIGN: Observational European cohort collaboration study. METHODS: Eligible patients were antiretroviral-naïve with documented weight prior to EFV start and follow-up viral loads after treatment initiation. Cox regression analyses evaluated the association between weight and time to first undetectable viral load (<50 copies/ml) after treatment initiation, and time to viral load rebound (two consecutive viral load >50 copies/ml) after initial suppression over 5 years of follow-up. Recovery of CD4 cell count was evaluated 6 and 12 months after EFV initiation. Analyses were stratified by weight (kg) group (I - <55; II - >55, <80 (reference); III - >80, <85; IV - >85, <90; V - >90, <95; VI - >95). RESULTS: The study included 19,968 patients, of whom 9.1, 68.3, 9.1, 5.8, 3.5, and 4.3% were in weight groups I-VI, respectively. Overall, 81.1% patients attained virological suppression, of whom 34.1% subsequently experienced viral load rebound. After multiple adjustments, no statistical difference was observed in time to undetectable viral load and virological rebound for heavier individuals compared to their normal-weight counterparts. Although heaviest individuals had significantly higher CD4 cell count at baseline, CD4 cell recovery at 6 and 12 months after EFV initiation was comparable to normal-weight individuals. CONCLUSION: Virological and immunological responses to initial EFV-containing regimens were not impaired in heavy individuals, suggesting that the standard 600 mg EFV dosage is appropriate across a wide weight range.

Hepatitis C virus co-infection and sexual risk behaviour are associated with a high homocysteine serum level in HIV-infected patients.

BACKGROUND AND AIMS: A better understanding of the relationship of homocysteine with cardiovascular risk factors is needed. The objectives of this study were to assess the serum level of homocysteine in HIV-infected patients and to analyse the possible association of increased levels of the amino acid with cardiovascular risk factors, demographic and clinical characteristics of participants. METHODS: Cross-sectional study carried out as a supplementary task to the usual controls necessary in HIV-infected patients in the outpatient clinic of the Hospital General of Castellon, Spain. For two consecutive visits the demographic, clinical and HIV-related characteristics and blood analyses results were obtained for each participant. Homocysteine serum level was documented and the possible association of the amino acid with all the other study variables was assessed with a multiple linear regression analysis. RESULTS: A total of 145 patients were included. The mean homocysteine serum level of all participants was 11.9 ± 5.9 µmol/L. A total of 54 patients (37%) presented homocysteine serum levels higher than the upper limit of normal. An association was found between higher homocysteine serum level and the following variables: family history of early coronary disease (P = 0.027), sexual HIV risk behaviour (P = 0.016), hepatitis C virus co-infection (P = 0.002), higher height (P = 0.002), higher diastolic blood pressure (P = 0.049), lower serum level of folic acid (P <0.001), and lower serum level of vitamin B12 (P = <0.001). CONCLUSION: In the HIV population, increased homocysteine serum level is associated with sexual risk behaviour and hepatitis C virus coinfection.