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Management of cardiovascular disease risk requires many lifestyle changes involving diet, smoking, and exercise. Individuals with arterial plaque are encouraged to adopt these changes to promote longevity through a variety of interventions. This study examined behavioral changes in response to the standard of care after detection of arterial plaque, specifically among HIV-infected cocaine users. 127 individuals (HIV - COC - n = 43, HIV + COC - n = 19, HIV + COC + n = 35, HIV - COC + n = 30) were followed after a standard of care intervention and assessed 1 and 2 years later on a variety of lifestyle (diet, exercise, smoking) and physiological (blood pressure, body mass index, number of arterial plaques) outcomes. Arterial plaque was found to increase over time (b = 0.003, SE = 0.002, p = .031), and a composite measure of cardiovascular disease risk did not change (b = - 0.004, SE = 0.01, p = .548). Following provision of a standard of care cardiovascular risk reduction intervention, important health behaviors related to CVD risk were resistant to change among both those HIV-infected and uninfected and among cocaine users and non-users.El manejo del riesgo para enfermedades cardiovasculares requiere muchos cambios en el estilo de vida, como dieta, dejar de fumar, y ejercicio. Se les recomienda a las personas, con placa arterial, adoptar estos cambios a través de una variedad de intervenciones. Este estudio examinó los cambios de comportamiento, en respuesta al estándar de atención, después de la detección de la placa arterial, específicamente entre los usuarios de cocaína infectados con VIH. 127 individuos (HIV − COC − n = 43, HIV + COC − n = 19, HIV + COC + n = 35, HIV − COC + n = 30) fueron seguidos después de una intervención de atención estándar y sus resultados fisiológicos (presión arterial, índice de masa corporal, número de placas arteriales) fueron evaluados 1 y 2 años después. Encontramos que la placa arterial aumento con el tiempo (b = 0.003, SE = 0.002, p = .031), y una formula que calcula el de riesgo de enfermedad cardiovascular no cambió (b = − 0.004, SE = 0.01, p = .548). Tras la provisión de una intervención estándar de atención para la reducción del riesgo cardiovascular, los comportamientos de salud importantes relacionados con el riesgo de enfermedades cardiovasculares fueron resistentes al cambio tanto entre los infectados y no infectados por el VIH como entre los usuarios y no usuarios de cocaína.

Background Traditional risk factors associated with cardiovascular disease (CVD) include older age, smoking, poor diet, lack of exercise, obesity, high blood pressure, high cholesterol, and family history. Young-to-middle age adults (YMAA) are less often identified as being at risk of CVD, but traditional risk scores primarily target older adults and do not accurately estimate risk among YMAA. Methods This study examined biomarkers associated with CVD risk in YMAA in the context of HIV and cocaine use; risk was assessed by two methods: (1) a relative cardiovascular (CV) risk score that includes several factors and (2) carotid atherosclerotic plaque. Associations between CVD risk (CV risk score and carotid atherosclerotic plaque) and proinflammatory cytokines, markers of immune activation, HIV status, and cocaine use were examined. Participants ( N = 506) included people with and without HIV and people who use or do not use cocaine. Results Participants’ mean age was 36 (SD = 9.53); half (51%) were men. Cocaine use and C-reactive protein were associated with greater relative CV risk scores, but no associations between biomarkers and CV risk emerged. Age and CV risk scores were associated with carotid atherosclerotic plaque, but biomarkers were not. HIV was not associated with CV risk scores or carotid atherosclerotic plaque. Conclusions Among YMAA, CV risk scores may help providers identify lifestyle changes needed among those at risk for CVD before more advanced risk (e.g., atherosclerotic plaque) is identified. Implications are discussed.

Background Electronic health record (EHR)-based computable phenotype algorithms allow researchers to efficiently identify a large virtual cohort of Human Immunodeficiency Virus (HIV) patients. Built upon existing algorithms, we refined, improved, and validated an HIV phenotype algorithm using data from the OneFlorida Data Trust, a repository of linked claims data and EHRs from its clinical partners, which provide care to over 15 million patients across all 67 counties in Florida. Methods Our computable phenotype examined information from multiple EHR domains, including clinical encounters with diagnoses, prescription medications, and laboratory tests. To identify an HIV case, the algorithm requires the patient to have at least one diagnostic code for HIV and meet one of the following criteria: have 1+ positive HIV laboratory, have been prescribed with HIV medications, or have 3+ visits with HIV diagnostic codes. The computable phenotype was validated against a subset of clinical notes. Results Among the 15+ million patients from OneFlorida, we identified 61,313 patients with confirmed HIV diagnosis. Among them, 8.05% met all four inclusion criteria, 69.7% met the 3+ HIV encounters criteria in addition to having HIV diagnostic code, and 8.1% met all criteria except for having positive laboratories. Our algorithm achieved higher sensitivity (98.9%) and comparable specificity (97.6%) relative to existing algorithms (77–83% sensitivity, 86–100% specificity). The mean age of the sample was 42.7 years, 58% male, and about half were Black African American. Patients' average follow-up period (the time between the first and last encounter in the EHRs) was approximately 4.6 years. The median number of all encounters and HIV-related encounters were 79 and 21, respectively. Conclusion By leveraging EHR data from multiple clinical partners and domains, with a considerably diverse population, our algorithm allows more flexible criteria for identifying patients with incomplete laboratory test results and medication prescribing history compared with prior studies.

Objective We aimed to identify disparities in self-reported HCV testing among persons living with HIV (PLWH) in Florida. Methods We utilized a cross-sectional study of 646 PLWH from the Florida Cohort study's baseline survey. Our analysis included chi-squared tests and logistic regression. Results Participants that were 55 years old or above had more than twice the odds of reporting a past HCV test than those 18–34 years old (OR 2.47, 95% CI 1.22–5.0), which contrasted with Non-Hispanic Blacks who had lower odds of reporting a past HCV test than non-Hispanic Whites (OR 0.63, 95% CI 0.35–1.1). Drug use was also associated with higher odds of reporting a past HCV test for injection drugs (OR 2.9, 95% CI 1.0–8.43) and non-injection drugs (OR 1.52 CI 0.99–2.21). Individuals with education beyond high school had higher odds of reporting a past HCV test than those that did not attend/complete high school (OR 1.9 CI 1.11–3.16). Conclusion Our findings highlight the success of the Center for Disease Control and the U.S. Preventive Services Task Force's campaign in groups at high risk of HCV, such as baby boomers and Injection Drug Users (IDUs). However, they also reflect the current low HCV testing in PLWH that are 18–34 years old, have a low level of education, and are non-Hispanic Black. Our findings are of crucial public health significance because untreated HCV in PLWH is a major cause of severe liver disease and death. They reveal the current deficiencies in HCV testing, which is the initial step to identify underlying reasons for inadequate testing in specific groups and develop practical solutions., Infectious disease, Hepatitis, HCV, HIV/AIDS, Disparities, Testing.

Objectives: After 14 years of no change, new blood pressure (BP) guidelines were released; yet, the impact of marijuana on BP remains unclear. Our objective was to examine the association between marijuana use and BP. Methods: We analyzed data for adults (N = 10,709; mean age 44.8 years; 50.3% men) who completed 2005-2014 National Health and Nutrition Examination Surveys. Marijuana use was defined as never (no lifetime use), past (lifetime, not in past 30 days), and current (≥ 1 in past 30 days). Frequency of use was categorized based past 30-day use. BP was categorized as elevated BP, Stage 1 hypertension (HTN-I), or Stage 2 hypertension (HTN-II) based on updated guidelines. Results: Current users had a higher prevalence of elevated BP (19.4%), HTN-I (22.7%), HTN-II (12.9%) than never users (16.1%, 21.4%, and 11.99%) respectively; p = .03). After covariate adjustment, heavy users had 1.80 higher odds of elevated BP than never users (95% CI: 1.13-2.88). There were no statistically significant differences in BP in any other marijuana use category. Conclusions: Driven by heavy use, current users had a higher prevalence of elevated BP than never users. Patients at risk for abnormal BP should use caution when engaging in heavy marijuana use.

Inclusion of women and minorities in clinical research is critical to fully assess the safety and efficacy of innovative therapies. With inadequate representation of demography, generalizability is impaired since pharmacokinetics and pharmacodynamics differ in these patient populations. This study was designed to analyze the voluntary participation rates of different demographic groups in cell-based therapy clinical trials conducted by the Interdisciplinary Stem Cell Institute (ISCI) at the University of Miami, Miller School of Medicine. ISCI conducted eight clinical trials between 2007 and 2017. The trials enrolled patients with ischemic and non-ischemic cardiomyopathy, idiopathic pulmonary fibrosis (IPF), aging-frailty, and Type-2 Diabetes. Participants received cell-based therapy (n = 218) or placebo (n = 33). Among the 251 participants, 29.5% were Hispanic and 20% were women. The proportion of individuals participating in each trial was compared to that of the respective disease populations attending University of Miami Health System clinics to calculate the participation to prevalence ratio (PPR). Distribution of women accurately reflected the population attending the University of Miami Health System in trials for dilated cardiomyopathy (DCM) and aging-frailty but was under-represented in others. Similarly, Hispanics and whites were accurately represented in three of the five disease fields, with Hispanics under-represented in frailty and diabetes, and whites over-represented in DCM and IPF. Black patients were accurately represented in the diabetes trial but were under-represented in all others. This study provides insight into challenges of achieving representative inclusion in research. Novel community engagement strategies are necessary to improve inclusion of women and under-represented minorities in clinical research of cell-based therapy.

BackgroundThere is an ongoing critical need to improve therapeutic strategies for COVID-19 pneumonia, particularly in the most severely affected patients. Adult mesenchymal stem cell (MSC) infusions have the potential to benefit critically ill patients with acute respiratory syndrome SARS-COV-2 infection, but clinical data supporting efficacy are lacking.MethodsWe conducted a case-control study of critically ill patients with laboratory-confirmed COVID-19, severe acute respiratory distress syndrome (ARDS). To evaluate clinical responsiveness in the most critically ill patient we examined outcomes in a sub-group of those requiring extracorporeal membrane oxygenation (ECMO) support. Patients (n=9) were administered with up to 3 infusions of intravenous (IV) MSCs and compared to a local ECMO control group (n=31). The primary outcome was safety, and the secondary outcomes were all-cause mortality (or rate of hospital discharge), cytokine levels, and viral clearance.FindingsMSC infusions (12 patients) were well tolerated and no side effects occurred. Of ECMO patients receiving MSC infusions, 2 out of 9 died (22.2%; 95%CI: 2.8%, 60.0%) compared with a mortality of 15 of 31 (48.4%; 95%CI: 30.2%, 66.9%; p = 0.25) in the ECMO control group. Isolated plasma exosomes containing the SARS-COV-2 Spike protein decreased after MSC infusions between day 14 or 21 after administration (p=0.003 and p=0.005, respectively) and was associated with a decrease in COVID-19 IgG Spike protein titer at same time points (p = 0.006 and p=0.007, respectively). Control ECMO patients receiving convalescent plasma did not clear COVID-19 IgG over the same time frame.InterpretationTogether these findings suggest that MSC IV infusion is well tolerated in patients with a broad range of severity including the most severe COVID-19 ARDS requiring ECMO. These data also raise the possibility that MSCs, in addition to exerting an immunomodulatory effect, contribute to viral clearance and strongly support the conduct of randomized placebo-controlled trial.

Summary Background Effective two-drug regimens could decrease long-term drug exposure and toxicity with HIV-1 antiretroviral therapy (ART). We therefore aimed to evaluate the efficacy and safety of a two-drug regimen compared with a three-drug regimen for the treatment of HIV-1 infection in ART-naive adults. Methods We conducted two identically designed, multicentre, double-blind, randomised, non-inferiority, phase 3 trials: GEMINI-1 and GEMINI-2. Both studies were done at 192 centres in 21 countries. We included participants (≥18 years) with HIV-1 infection and a screening HIV-1 RNA of 500 000 copies per mL or less, and who were naive to ART. We randomly assigned participants (1:1) to receive a once-daily two-drug regimen of dolutegravir (50 mg) plus lamivudine (300 mg) or a once-daily three-drug regimen of dolutegravir (50 mg) plus tenofovir disoproxil fumarate (300 mg) and emtricitabine (200 mg). Both drug regimens were administered orally. We masked participants and investigators to treatment assignment: dolutegravir was administered as single-entity tablets (similar to its commercial formulation, except with a different film colour), and lamivudine tablets and tenofovir disoproxil fumarate and emtricitabine tablets were over-encapsulated to visually match each other. Primary endpoint was the proportion of participants with HIV-1 RNA of less than 50 copies per mL at week 48 in the intention-to-treat-exposed population, using the Snapshot algorithm and a non-inferiority margin of −10%. Safety analyses were done on the safety population. GEMINI-1 and GEMINI-2 are registered with ClinicalTrials.gov, numbers NCT02831673 and NCT02831764, respectively. Findings Between July 18, 2016, and March 31, 2017, 1441 participants across both studies were randomly assigned to receive either the two-drug regimen (n=719) or three-drug regimen (n=722). At week 48 in the GEMINI-1 intention-to-treat-exposed population, 320 (90%) of 356 participants receiving the two-drug regimen and 332 (93%) of 358 receiving the three-drug regimen achieved plasma HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −2·6%, 95% CI −6·7 to 1·5); in GEMINI-2, 335 (93%) of 360 in the two-drug regimen and 337 (94%) of 359 in the three-drug regimen achieved HIV-1 RNA of less than 50 copies per mL (adjusted treatment difference −0·7%, 95% CI −4·3 to 2·9), showing non-inferiority at a −10% margin in both studies (pooled analysis: 655 [91%] of 716 in the two-drug regimen vs 669 [93%] of 717 in the three-drug regimen; adjusted treatment difference −1·7%, 95% CI −4·4 to 1·1). Numerically, more drug-related adverse events occurred with the three-drug regimen than with the two-drug regimen (169 [24%] of 717 vs 126 [18%] of 716); few participants discontinued because of adverse events (16 [2%] in the three-drug regimen and 15 [2%] in the two-drug regimen). Two deaths were reported in the two-drug regimen group of GEMINI-2, but neither was considered to be related to the study medication. Interpretation The non-inferior efficacy and similar tolerability profile of dolutegravir plus lamivudine to a guideline-recommended three-drug regimen at 48 weeks in ART-naive adults supports its use as initial therapy for patients with HIV-1 infection. Funding ViiV Healthcare.

Background The risk of ischemic stroke (IS) is known to be higher in people living with HIV (PLWH) than uninfected controls. However, information about the demographics and risk factors for hemorrhagic stroke (HS) in PLWH is scant. Specifically, very little is known about the differences in the stroke risk factors between HS and IS in PLWH. The goal of this study was to determine the demographics and risk factor differences between HS and IS in PLWH. Methods We retrospectively analyzed the demographic and clinical data of PLWH in OneFlorida (1FL) Clinical Research Consortium from October 2015 to December 2018. 1FL is a large statewide clinical research network and database which contains health information of over 15 million patients, 1240 clinical practices, and 22 hospitals. We compared HS and IS based on documented ICD 9 and 10 diagnostic codes and extracted information about sociodemographic data, traditional stroke risk factors, Charlson comorbidity scores, habits, HIV factors, diagnostic modalities and medications. Statistical significance was determined using 2-sample T-test for continuous variables and adjusted Pearson chi square for categorical variables. Odds ratio (OR) and 95% confidence intervals (CI) between groups were compared. Results Overall, from 1FL sample of 13986 people living with HIV, 574 subjects had strokes during the study period. The rate of any stroke was 18.2/1000 person-years (PYRS). The rate of IS was 10.8/1000 PYRS while the rate of HS was 3.7/1000 PYRS, corresponding to 25.4% HS of all strokes in the study. Table 1 summarizes the pertinent demographic and risk factors for HS and IS in PLWH in the study. Table 1: Summary of pertinent demographic and risk factors for hemorrhagic and ischemic strokes in people living with HIV from One Florida database Conclusion In this large Floridian health database, demographics and risk factor profile differs between HS and IS in PLWH. Younger age group is associated with HS than IS. However, hypertension, hyperlipidemia and coronary artery disease are more likely to contribute to IS than HS in PLWH. Further research is needed to better understand the interplay between known and yet unidentified risk factors that may be contributing to HS and IS in PLWH. Disclosures All Authors: No reported disclosures

The increased prevalence of major adverse cardiovascular events in Persons Living with HIV (PLWH) has been well documented. However, there remains a paucity of data relating to the epidemiology of valvular heart disease (VHD) in PLWH. We performed a retrospective analysis on the prevalence and

Since the advent of HIV therapy, there has been a decrease in HIV-related mortality, but an increased risk of coronary artery disease (CAD). Previous studies suggested that patients living with HIV (PLWH) underwent less cardiac procedures including cardiac catheterization (CC), compared to the

The re-emergence of Zika virus (ZIKV) and Ebola virus (EBOV) poses serious and continued threats to the global public health. Effective therapeutics for these maladies is an unmet need. Here, we show that emetine, an anti-protozoal agent, potently inhibits ZIKV and EBOV infection with a low nanomolar half maximal inhibitory concentration (IC50) in vitro and potent activity in vivo. Two mechanisms of action for emetine are identified: the inhibition of ZIKV NS5 polymerase activity and disruption of lysosomal function. Emetine also inhibits EBOV entry. Cephaeline, a desmethyl analog of emetine, which may be better tolerated in patients than emetine, exhibits a similar efficacy against both ZIKV and EBOV infections. Hence, emetine and cephaeline offer pharmaceutical therapies against both ZIKV and EBOV infection.

Effective treatment for hepatitis C virus (HCV) in patients coinfected with human immunodeficiency virus type 1 (HIV-1) remains an unmet medical need.We conducted a multicenter, single-group, open-label study involving patients coinfected with HIV-1 and genotype 1 or 4 HCV receiving an antiretroviral regimen of tenofovir and emtricitabine with efavirenz, rilpivirine, or raltegravir. All patients received ledipasvir, an NS5A inhibitor, and sofosbuvir, a nucleotide polymerase inhibitor, as a single fixed-dose combination for 12 weeks. The primary end point was a sustained virologic response at 12 weeks after the end of therapy.Of the 335 patients enrolled, 34% were black, 55% had been previously treated for HCV, and 20% had cirrhosis. Overall, 322 patients (96%) had a sustained virologic response at 12 weeks after the end of therapy (95% confidence interval [CI], 93 to 98), including rates of 96% (95% CI, 93 to 98) in patients with HCV genotype 1a, 96% (95% CI, 89 to 99) in those with HCV genotype 1b, and 100% (95% CI, 63 to 100) in those with HCV genotype 4. Rates of sustained virologic response were similar regardless of previous treatment or the presence of cirrhosis. Of the 13 patients who did not have a sustained virologic response, 10 had a relapse after the end of treatment. No patient had confirmed HIV-1 virologic rebound. The most common adverse events were headache (25%), fatigue (21%), and diarrhea (11%). No patient discontinued treatment because of adverse events.Ledipasvir and sofosbuvir for 12 weeks provided high rates of sustained virologic response in patients coinfected with HIV-1 and HCV genotype 1 or 4. (Funded by Gilead Sciences; ION-4 ClinicalTrials.gov number, NCT02073656.).

This study describes the prevalence of abuse and mental health issues among a cohort of HIV-infected Haitian women living in the United States. We present data on 96 women, ages 19–73 years ( M = 47.6, SD = 11.1), who were screened for mental health concerns between 2009 and 2012. Results demonstrated that 12.5% of the women reported a history of abuse. However, posttraumatic stress disorder (PTSD) secondary to HIV was reported by approximately 34% of women. Depression and anxiety were also highly reported, with rates of 49% and 43%, respectively. Women who reported a history of abuse were more likely to report anxiety, PTSD, and PTSD related to HIV symptoms than those without. Our findings suggest that Haitian HIV-infected women may underreport abuse and experience significant depression and anxiety. These preliminary results could be used to develop future studies and to design and implement culturally sensitive interventions for this underserved population.

Background Prior studies have reported improved adherence, persistency, virologic outcomes and lower risk of hospitalizations with single tablet (STR) vs. multi-tablet regimens (MTR) in HIV treatment. However, most studies were conducted using prescription and medical claims data limited to EFV-based therapies. In this study, we utilized EMR, prescription, and pharmacy dispensing data to assess STR and MTR adherence and persistency as observed in a network of clinical practices. Methods Data were collected for HIV-infected patients in care at six US-based HIV treatment centers. Patients eligible for the study initiated their first ARV between January 2015 and December 2016. First ARV regimen was assigned based on absence of prior ARV prescriptions and a 30-day pre-treatment period with no ARV dispensed or for rapid starts, a high baseline viral load (≥10,000 copies/mL). Adherence was assessed using proportion of days covered (PDC). Follow-up was ≥365 days with duration capped at 365 days for persistency comparisons. Results A total of 1,499 patients met the criteria for the study; 66% (982/1,499) received STR and 34% (517/1,499) MTR. Top STRs were EVG/c/TDF/FTC (265/982, 27%), EVG/c/TAF/FTC (250/982, 26%), and DTG/ABC/3TC (171/982, 17%). Top MTRs were DTG + TDF/FTC (69/517, 13%), DRV + RTV + TDF/FTC (60/517, 12%), and DRV/c + TDF/FTC (40/517, 8%). Average persistency for STRs was significantly longer at 252 days vs. 233 days for MTRs (P = 0.002). Average PDC adherence rates were significantly higher for STRs at 91% vs. 83% for MTRs (P < 0.001). Within the STR group, older age was significantly associated with greater adherence (average age: 45 in 80%+ adherent group vs. 42 in

Highly active antiretroviral therapy (ART) has improved survival of HIV patients, accompanied by an increase in prevalence of cardiovascular disease and its complications, including pulmonary hypertension (PH). While this could be attributed to a heightened inflammatory state current data on PH and

Background HIV and HCV infections are both characterized by increased oxidative stress. Information on the magnitude of this increase and its consequences in HIV/HCV co-infection and viral replication is limited. We investigated the relationship between oxidative stress and HIV-progression in HIV/HCV co-infected and HIV mono-infected adults. Methods 106 HIV/HCV co-infected and 115 HIV mono-infected participants provided demographic information and blood to determine 8-oxo-dG and percent oxidized glutathione. Results HIV/HCV co-infected subjects had higher percent oxidized glutathione, higher HIV viral load, lower mtDNA copies and higher liver fibrosis than mono-infected subjects. In a small sample of HIV/HCV co-infected participants with liver biopsy, 8-oxo-dG was significantly lower in participants with low fibrosis scores than those with high fibrosis scores, and the grade of inflammation was strongly associated with oxidized glutathione. Conclusions HIV/HCV co-infection seems to diminish the capacity of the antioxidant system to control oxidative stress, and increases HIV replication.

OBJECTIVES The aim of the study was to compare the effects on lipids, body composition and renal function of once-daily ritonavir-boosted saquinavir (SQV/r) or atazanavir (ATV/r) in combination with tenofovir/emtricitabine (TDF/FTC) over 48 weeks. METHODS An investigator-initiated, randomized, open-label, multinational trial comparing SQV/r 2000/100 mg and ATV/r 300/100 mg once daily, both in combination with TDF/FTC, in 123 treatment-naive HIV-1-infected adults was carried out. The primary endpoint was to demonstrate noninferiority of SQV/r compared with ATV/r with respect to the change in fasting cholesterol after 24 weeks. Secondary outcome measures were changes in metabolic abnormalities, body composition, renal function, and virological and immunological efficacy over 48 weeks. Patients who had used at least one dose of trial drug were included in the analysis. RESULTS Data for 118 patients were analysed (57 patients on SQV/r and 61 on ATV/r). At week 24, changes in lipids were modest, without increases in triglycerides, including a significant rise in high-density lipoprotein (HDL) cholesterol and a nonsignificant decrease in the total:HDL cholesterol ratio in both arms with no significant difference between arms. Lipid changes at week 48 were similar to the changes observed up to week 24, with no significant change in the homeostasis model assessment (HOMA) index. Adipose tissue increased regardless of the regimen, particularly in the peripheral compartment and to a lesser extent in the central abdominal compartment, with an increase in adipose tissue reaching statistical significance in the ATV/r arm. A slight decline in the estimated glomerular filtration rate (eGFR) was observed in both arms during the first 24 weeks, with no progression thereafter. The immunological and virological responses were similar over the 48 weeks. CONCLUSIONS Combined with TDF/FTC, both SQV/r 2000/100 mg and ATV/r 300/100 mg had comparable modest effects on lipids, had little effect on glucose metabolism, conserved adipose tissue, and similarly reduced eGFR. The virological efficacy was similar.

Automated Collaborative Filtering (ACF) refers to a group of algorithms used in recommender systems, a research topic that has received considerable attention due to its e-commerce applications. However, existing techniques are rarely capable of dealing with imperfections in user-supplied ratings. When such imperfections (e.g., ambiguities) cannot be avoided, designers resort to simplifying assumptions that impair the system's performance and utility. We have developed a novel technique referred to as CoFiDS-Collaborative Filtering based on Dempster-Shafer belief-theoretic framework-that can represent a wide variety of data imperfections, propagate them throughout the decision-making process without the need to make simplifying assumptions, and exploit contextual information. With its DS-theoretic predictions, the domain expert can either obtain a "hard” decision or can narrow the set of possible predictions to a smaller set. With its capability to handle data imperfections, CoFiDS widens the applicability of ACF to such critical and sensitive domains as medical decision support systems and defense-related applications. We describe the theoretical foundation of the system and report experiments with a benchmark movie data set. We explore some essential aspects of CoFiDS' behavior and show that its performance compares favorably with other ACF systems.

Background The pathogenesis of HIV/hepatitis C virus (HCV) coinfection is poorly understood. We examined markers of oxidative stress, plasma antioxidants and liver disease in HIV/HCV-coinfected and HIV-monoinfected adults. Methods Demographics, medical history, and proof of infection with HIV, hepatitis A virus (HAV), hepatitis B virus (HBV) and HCV were obtained. HIV viral load, CD4 cell count, complete blood count (CBC), complete metabolic panel, lipid profile, and plasma concentrations of zinc, selenium, and vitamins A and E were determined. Malondialdehyde (MDA) and glutathione peroxidase concentrations were obtained as measures of oxidative stress. Aminotransferase to platelet ratio index (APRI) and fibrosis index (FIB-4) markers were calculated. Results Significant differences were found between HIV/HCV-coinfected and HIV-monoinfected participants in levels of alanine aminotransferase (ALT) (mean±standard deviation: 51.4±50.6 vs. 31.9±43.1 U/L, respectively; P=0.014), aspartate aminotransferase (AST) (56.2±40.9 vs. 34.4±30.2 U/L; P

This study evaluated the long-term efficacy, safety, adherence, and quality of life (QoL) of a once-daily efavirenz-based antiretroviral regimen in two 96-week prospective open-label single-arm studies of treatment-naïve HIV-1-infected patients.Patients received once-daily efavirenz 600 mg and lamivudine 300 mg with either enteric-coated didanosine 400 mg (Daily Antiretroviral Therapy trial [DART] I) or extended-release stavudine 100 mg (DART II). The primary efficacy outcome measure was HIV RNA400 copies/mL at Week 48.In an intent-to-treat (ITT) analysis, HIV RNA level400 (50) copies/mL was reached by 82%(80%) and 74% (72%) of patients at Week 48 in DART I and II. At Week 96, the corresponding values were 74% (68%) and 55% (54%), respectively. Both regimens were well tolerated. There were no discontinuations for virologic failure. Medication adherence assessed by pill counts was above 80% in 90% of the patients in DART I and more than 80% of patients in DART II. Treatment produced a significant improvement in overall QoL.Once-daily efavirenz-based antiretroviral therapy was effective, durable, and well tolerated. In this study, a high level of adherence was achieved with improvement in overall QoL.

OBJECTIVE Present 96-week data from ongoing ARTEMIS (AntiRetroviral Therapy with TMC114 ExaMined In Naive Subjects) trial. METHODS Randomized, open-label, phase III trial of antiretroviral-naive patients with HIV-1 RNA at least 5000 copies/ml (stratified by HIV-1 RNA and CD4 cell count) receiving darunavir/ritonavir (DRV/r) 800/100 mg once daily or lopinavir/ritonavir (LPV/r) 800/200 mg total daily dose (twice daily or once daily) and fixed-dose tenofovir/emtricitabine. Primary outcome measure was noninferiority of DRV/r vs. LPV/r in virologic response (

Background Long-term (96-week) efficacy and safety of the protease inhibitor (PI) darunavir coadministered with low-dose ritonavir (DRV/r) was evaluated in HIV type-1 (HIV-1)-infected patients with extensive prior treatment experience in the POWER 1, 2 and 3 trials. Methods Patients with HIV-1 RNA≥1,000 copies/ml and ≥1 primary PI mutation were randomized to receive either DRV/r 600/100 mg twice daily plus an optimized background regimen (OBR), or an investigator- selected control PI (CPI) plus OBR (POWER 3 was a DRV/r 600/100 mg twice daily single-arm study). The proportion of patients with HIV-1 RNAResults In total, 467 patients received DRV/r 600/100 mg twice daily; 124 patients received CPI(s). At week 96, 39% of DRV/r patients in POWER 1 and 2 (pooled analysis) versus 9% of CPI patients achieved HIV-1 RNA+ T-cell count increase for DRV/r at 96 weeks was 133 cells/mm3 in POWER 1 and 2 and 103 cells/mm3 in POWER 3. Grade 2–4 treatment-emergent adverse events at least possibly related to DRV/r (≥2% incidence, excluding laboratory abnormalities) were diarrhoea (3%), vomiting (3%), nausea (2%) and headache (2%). Conclusions Treatment with DRV/r 600/100 mg twice daily was well tolerated and led to sustained virological and immunological responses in treatment-experienced HIV-1-infected patients over 96 weeks.

Direct comparison of the efficacy and safety of different agents is needed to guide selection of optimal treatment regimens for therapy-naive HIV-1-infected patients.: Gemini was a 48-week, multicenter, open-label, noninferiority trial in treatment-naive HIV-1-infected adults randomized to either saquinavir/ritonavir (SQV/r) 1000 mg/100 mg twice a day or lopinavir/ritonavir (LPV/r) 400 mg/100 mg twice a day, each with emtricitabine/tenofovir 200 mg/300 mg every day.: A similar proportion of participants in the SQV/r (n = 167) and LPV/r (n = 170) arms had HIV-1 RNA levels50 copies per milliliter at week 48: 64.7% vs 63.5% and estimated difference in proportion for noninferiority: 1.14%, 96% confidence interval: -9.6 to11.9 (P0.012), confirming that SQV/r was noninferior to LPV/r treatment. There were no significant differences in week 48 CD4 counts between arms. The rate and severity of adverse events were similar in both groups. There were no significant differences in the median change from baseline between arms in plasma lipids except for triglyceride levels, which were significantly higher in the LPV/r at week 48.: In treatment-naive, HIV-1-infected patients, SQV/r treatment was noninferior in virologic suppression at 48 weeks to LPV/r treatment and offered a better triglyceride profile.

Health literacy is emerging as a key element for successful medication management and empirical support for the efficacy of numeracy in the health context is rising as well. Little is known, however, about their unique effects among women and men. Given the importance of accurate medication management for effective treatment of HIV, the relation of these variables to medication management needs to be assessed. We therefore tested the relation of health literacy (reading comprehension) and numeracy to one's ability to manage a “mock” HIV regimen and whether men and women differed in these abilities. Results showed that women were less able than men to follow medication instructions and answer questions about the mock regimen. Numeracy mediated the relationship between gender and medication management. These findings highlight skills used in managing medication regimens and suggest avenues to target for identification and intervention in medication management among women and men with HIV.

Objectives To determine the safety and effectiveness of a once-daily highly active antiretroviral therapy (HAART) regimen in patients at risk for poor adherence using directly observed therapy (DOT) for 24 weeks followed by weekly phone contact for another 24 weeks. Methods A prospective, open-label pilot study was carried out. Antiretroviral-naive patients with advanced HIV disease were treated with once-daily amprenavir 1200 mg, ritonavir 200 mg, didanosine 400 mg and lamivudine 300 mg. After 24 weeks, DOT was substituted by weekly phone contact. Measurements of viral load and CD4 cell count, and safety laboratory measurements, were taken regularly for 48 weeks. Results Twenty-two patients were enrolled in the study, of whom 19 completed at least 4 weeks of treatment. Seventeen patients completed 24 weeks and 13 completed 48 weeks. None discontinued treatment as a result of adverse events. The median baseline HIV viral load was 5.29 log10 HIV-1 RNA copies/mL and the median CD4 cell count was 20 cells/μL. At weeks 24 and 48, 74% of the patients had viral loads

We evaluated the safety and efficacy of indinavir 400 mg and ritonavir 400 mg twice daily (RIT/IND 400/400) in HIV-1-infected individuals, using an open label, proof of concept study. All patients received indinavir 400 mg and ritonavir 400 mg twice daily. Patients were followed up to 48 weeks. Nineteen subjects were enrolled, 11 (58%) men and eight (42%) women. The majority were American Black (nine; 47%) or Haitian (eight; 42%). The median baseline plasma HIV-1 viral load (VL) was 5.13 log10 copies/mL and the median CD4 cell count was 112 cells/mm3. The proportion of compliant patients with VL 3 compared with 42.0 cells/mm3 for non-compliant patients (P=0.010). The median average changes in triglycerides and cholesterol were significantly higher in compliant patients. This is a potent, safe combination for the treatment of HIV-1. VL at week 4 is predictive of viral outcome at week 24. Fasting serum cholesterol and triglycerides were significantly elevated during the study.

In this international, noncomparative, randomized phase II trial, we evaluated the effectiveness and tolerance of atovaquone suspension (1500 mg orally twice daily) plus either pyrimethamine (75 mg per day after a 200-mg loading dose) or sulfadiazine (1500 mg 4 times daily) as treatment for acute disease (for 6 weeks) and as maintenance therapy (for 42 weeks) for toxoplasmic encephalitis (TE) in patients infected with human immunodeficiency virus. Twenty-one (75%) of 28 patients receiving pyrimethamine (95% lower confidence interval [CI], 58%) and 9 (82%) of 11 patients receiving sulfadiazine (95% lower CI, 53%) responded to treatment for acute disease. Of 20 patients in the maintenance phase, only 1 experienced relapse. Eleven (28%) of 40 eligible patients discontinued treatment as a result of adverse events, 9 because of nausea and vomiting or intolerance of the taste of the atovaquone suspension. Although gastrointestinal side effects were frequent, atovaquone-containing regimens are otherwise well tolerated and safe and may be useful for patients intolerant of standard regimens for toxoplasmic encephalitis.

OBJECTIVE: To determine the prevalence of hepatitis B virus (HBV) infection in heterosexual patients attending two genitourinary medicine (GUM) clinics in the West Midlands and to examine whether heterosexual activity is a risk factor for acquiring HBV infection with the view to extend HBV vaccination policies to cover this group. DESIGN: HBV markers were determined in the GUM study group and compared with that of the control groups. Responses to a questionnaire were used to examine sexual behaviour patterns that may be related to heterosexual acquisition of HBV infection. SETTING: The West Midlands, UK April 1992-January 1993. SUBJECTS: 788 male patients and 688 female patients attending GUM clinics were compared with 498 male blood donors and 563 females attending antenatal clinics for the seroprevalence of HBV markers. Potential risk factors related to heterosexual activity were assessed in 1436 patients in the study group. MAIN OUTCOME MEASURES: Prevalence of HBV markers in the GUM study group and the controls. The possible use of the risk factors examined as predictors for acquiring HBV infection. RESULTS: The seroprevalence of hepatitis B core antibody (anti-HBc) in GUM patients was 1.9% and 0.5% in the control group. In the study groups the prevalence of anti-HBc from Birmingham was 3.2% while that from Coventry was 0.8%. The low seroprevalence of HBV prevented a multiple logistic analysis. A limited regression analysis showed that being non-white (p < 0.001) and duration of sexual activity (p = 0.013) were risk factors for HBV infection. However, these two factors were poor predictors of the risk to exposure to HBV infection. CONCLUSION: The prevalence of HBV infection in heterosexual patients in the West Midlands is very low and does not provide any indications to broaden HBV vaccination into heterosexual patients attending GUM clinics. Risk factors were poor predictors of the exposure to HBV infection. This is partially due to the low prevalence of HBV infection in this study. Further studies are required before definitive conclusions are made regarding the potential predictive value of risk factors.

Hepatitis C virus (HCV) is a controversial indication for liver transplantation (LT) in human immunodeficiency virus (HIV)-infected patients because of reportedly poor outcomes. This prospective, multicenter US cohort study compared patient and graft survival for 89 HCV/HIV-coinfected patients and 2 control groups: 235 HCV-monoinfected LT controls and all US transplant recipients who were 65 years old or older. The 3-year patient and graft survival rates were 60% [95% confidence interval (CI) = 47%-71%] and 53% (95% CI = 40%-64%) for the HCV/HIV patients and 79% (95% CI = 72%-84%) and 74% (95% CI = 66%-79%) for the HCV-infected recipients (P < 0.001 for both), and HIV infection was the only factor significantly associated with reduced patient and graft survival. Among the HCV/HIV patients, older donor age [hazard ratio (HR) = 1.3 per decade], combined kidney-liver transplantation (HR = 3.8), an anti-HCV-positive donor (HR = 2.5), and a body mass index < 21 kg/m(2) (HR = 3.2) were independent predictors of graft loss. For the patients without the last 3 factors, the patient and graft survival rates were similar to those for US LT recipients. The 3-year incidence of treated acute rejection was 1.6-fold higher for the HCV/HIV patients versus the HCV patients (39% versus 24%, log rank P = 0.02), but the cumulative rates of severe HCV disease at 3 years were not significantly different (29% versus 23%, P = 0.21). In conclusion, patient and graft survival rates are lower for HCV/HIV-coinfected LT patients versus HCV-monoinfected LT patients. Importantly, the rates of treated acute rejection (but not the rates of HCV disease severity) are significantly higher for HCV/HIV-coinfected recipients versus HCV-infected recipients. Our results indicate that HCV per se is not a contraindication to LT in HIV patients, but recipient and donor selection and the management of acute rejection strongly influence outcomes.

Background . Studies evaluating response to treatment with Highly Active Anti- retroviral Therapy (HAART) fail to examine Haitian patients living in the U.S. as a distinct group. Methods. This study was designed to determine the effectiveness of HAART in Haitians compared with other minority groups. We conducted a retrospective cohort study of HIV patients from two clinics. The cohort included 96 Hispanics, 60 African Americans, and 49 Haitians, after reviewing a total of 891 charts. results . At 96 weeks, fewer Haitians (58.5%) achieved a suppressed viral load than African American (74.1%) or Hispanic (82.8%) patients (p.021). Median CD4 counts at baseline were lowest among Haitians, with 158 cells/mm 3 , compared with African Americans, 176 cells/mm 3 and Hispanics, 199 cells/mm 3 . Conclusions. Haitians are not doing as well on HAART as other groups. This may be explained by linguistic, cultural, or other barriers that are not currently addressed by the health care system in the United States.

The GRACE (Gender, Race and Clinical Experience) trial enrolled treatment-experienced, HIV-1-infected patients, mainly women, in North America, to assess outcomes with a darunavir/ritonavir-based regimen, which could include etravirine (ETR). We present outcomes at week 48 for men and women receiving ETR. Virologic response (HIV-1 RNA50 copies/ml) and safety were assessed; descriptive statistics are reported. To evaluate the independent contribution of ETR treatment, a post hoc analysis including a multivariate model assessed factors predictive of virologic response for the entire GRACE population (429 patients). Of 207 patients who received ETR (women, 57.5%; black or Hispanic, 81.7%), 71.4% of women and 79.5% of men completed the study. Week 48 virologic response rates in women and men (intent-to-treat population) were 58.0% and 61.4%, respectively. After censoring patients who discontinued treatment for reasons other than virologic failure, response rates were 79.3% and 73.0%, respectively. Overall, ETR was well tolerated. Women experienced more nausea (24.4% vs. 11.4%) and rash-related events (21.0% vs. 15.9%), but less diarrhea (15.1% vs. 21.6%), compared with men. Grade 3-4 hypertriglyceridemia was more common in men (9.3%) than women (1.1%). In total, 11 (9.2%) women and 7 (8.0%) men discontinued ETR due to adverse events. In the multivariate model of the entire GRACE population, ETR use was independently associated with improved virologic response. ETR is effective and well tolerated in treatment-experienced patients with HIV-1, with similar outcomes among women and men.

Background & Aims Human immunodeficiency virus (HIV) infection accelerates liver disease progression in patients with hepatitis C virus (HCV) and could shorten survival of those awaiting liver transplants. The Model for End-Stage Liver Disease (MELD) score predicts mortality in HIV-negative transplant candidates, but its reliability has not been established in HIV-positive candidates. Methods We evaluated predictors of pretransplantation mortality in HIV-positive liver transplant candidates enrolled in the Solid Organ Transplantation in HIV: Multi-Site Study (HIVTR) matched 1:5 by age, sex, race, and HCV infection with HIV-negative controls from the United Network for Organ Sharing. Results Of 167 HIVTR candidates, 24 died (14.4%); this mortality rate was similar to that of controls (88/792, 11.1%, P = .30) with no significant difference in causes of mortality. A significantly lower proportion of HIVTR candidates (34.7%) underwent liver transplantation, compared with controls (47.6%, P = .003). In the combined cohort, baseline MELD score predicted pretransplantation mortality (hazard ratio [HR], 1.27; P P = .20). After controlling for pretransplantation CD4 + cell count and HIV RNA levels, the only significant predictor of mortality in the HIV-infected subjects was pretransplantation MELD score (HR, 1.2; P Conclusions Pretransplantation mortality characteristics are similar between HIV-positive and HIV-negative candidates. Although lower CD4 + cell counts and detectable levels of HIV RNA might be associated with a higher rate of pretransplantation mortality, baseline MELD score was the only significant independent predictor of pretransplantation mortality in HIV-infected liver transplant candidates.

Yolk-sac inoculation of embryonated eggs was superseded 25 years ago by the use of cell cultures (often McCoy) for the isolation of Chlamydia trachomatis. Centrifugation of specimens onto the cell monolayers was shown to increase sensitivity, but little of late has further improved sensitivity which is at least ten-fold greater than that of eggs. However, culture is slow and labour intensive so that non-cultural techniques without these drawbacks have come to dominate. Direct fluorescent antibody (DFA) tests are rapid and have sensitivities that range from 70% to 100% for men and 68% to 100% for women, and specificities that range from 87% to 99% for men and 82% to 100% for women; if the tests are read by competent observers the values are at the top end of the ranges. The detection rate may be enhanced even further by relatively low-speed centrifugation of specimens before staining. Skilled reading is not a feature of enzyme immunoassays (EIAs) which according to the literature have sensitivities that range from 62% to 97% for men and 64% to 100% for women, and specificities that range from 92% to 100% for men and 89% to 100% for women. However, comparison against poor reference tests is responsible for most of the higher values and the clinician should not be misled into believing that EIAs have excellent sensitivity; the lower values in the ranges are closer to reality. Furthermore, EIAs that are being designed for use by general practitioners should be regarded with the greatest caution since lack of sensitivity means that chlamydia-positive patients will go undetected. The polymerase chain reaction (PCR) is not bedevilled by insensitivity but it is no more sensitive than the most sensitive cell culture or DFA tests. PCR is unsuitable for routine diagnosis but has a place as a research tool. For men, examination of "first-catch" urine samples by the best of the non-cultural procedures provides an acceptable non-invasive approach to diagnosis; for women, the value of examining urine may be less, but needs to be thoroughly tested. However, there is little doubt that a Cytobrush used to obtain cervical specimens holds no practical advantage over a swab. Serological tests are reliant on the provision of paired sera for making a diagnosis; high antibody titres in single sera may be suggestive of an aetiological association in deep-seated chlamydial infections (epididymitis, arthritis, salpingitis, etc), but unequivocal interpretation is unusual, particularly in an individual case, since the distinction between a current and past infection is problematical.

HIV/HCV co-infection is becoming one of the main causes of death in HIV+ persons. We determined quality of life, clinical symptoms and health care utilization in HIV mono-infected and HIV/HCV co-infected chronic drug users. After consenting 218 HIV+ drug users, a physical examination and questionnaires on demographics, quality of life, drugs of abuse, and healthcare utilization were completed. Blood was drawn for HCV status, CD4 cell count, HIV viral load, CBC and chemistry. HIV/HCV co-infected participants had significantly higher risk of having poorer perceived outlook and health, presented significantly more frequent depression and physical symptoms, and used significantly more healthcare services than those infected with HIV only, after adjusting for age, gender, ethnicity, CD4 cell count, and viral load. Diminished quality of life in the HIV/HCV co-infected group was explained by increased frequency of depression, physical symptoms, healthcare utilization, and poor access to HCV treatment in this population.

Summary: Blood lipids and high-sensitivity C-reactive protein (hsCRP) are used to assess cardiovascular disease (CVD) risk. We evaluated in a cross-sectional design the relationship of hsCRP to markers of liver function (aspartate and alanine transaminases [AST and ALT, respectively]), CVD risk factors and HIV-disease progression markers in 226 HIV-1 seropositive drug users. hsCRP showed a significant inverse relationship with ALT and high-density lipoprotein, independent of age, gender, viral load, CD4 cell-count and antiretroviral (ARV) use, and was not significantly associated with HIV-disease progression markers. Serum markers of liver damage, AST and ALT, were associated with lower hsCRP, total cholesterol, low-density lipoproteins and triglycerides. Elevated liver enzymes (≥40 IU/L) were predictive of hsCRP levels that are considered a low risk for CVD. In conclusion, hsCRP may not be a reliable marker of CVD risk in populations with HIV at-risk for elevated liver enzymes due to high hepatitis B virus/hepatitis C virus prevalence and ARV use.

In antiretroviral (ARV) therapy, pill burden, dosing frequency, and regimen complexity adversely affect adherence. We sought to evaluate the effect of regimen simplification on maintenance of virologic suppression and treatment adherence.In this 48-week, open-label, randomized study, 320 HIV-1-infected adult patients with a viral load of50 copies/mL on a twice-daily or more frequent ARV regimen were either switched to a once-daily regimen of efavirenz, extended-release stavudine, and lamivudine (QD arm) or continued on existing therapy (BID+ arm). Medication Event Monitoring System (MEMS) caps, AIDS Clinical Trials Group (ACTG)-validated questionnaire, and pill counts were used to evaluate adherence. Treatment satisfaction and preference were also evaluated.The QD arm was noninferior to the BID+ arm in the primary efficacy measure (proportion of patients who maintained virologic suppression at Week 48; QD arm, 80.0% vs. BID+ arm, 75.8%). Adherence and treatment satisfaction significantly favored the QD arm, in which 91.0% of patients preferred the simpler regimen. Overall, the majority of adverse events were mild to moderate in severity and resulted in a low rate of treatment discontinuations.Simplifying twice-daily or more frequent ARV therapy to a once-daily efavirenz-containing regimen in virologically suppressed HIV-1-infected patients maintains virologic suppression while improving adherence and patient satisfaction.

Background. Human immunodeficiency virus (HIV) infection has been associated with poor outcomes after orthotopic liver transplantation (OLT). Highly active antiretroviral therapy (HAART) has led to an increasing number of successful OLTs. The aim of this study was to examine survival and cause-specific mortality in HIV-infected patients after OLT at our institution. Methods. A retrospective analysis of all HIV patients that underwent OLT was compared to all non-HIV patients undergoing OLT during the same period. Cumulative patient and cause-specific survival were calculated using Kaplan-Meier methods; the log-rank test was used to compare the two cohorts. Fifteen HIV-infected patients and 857 non-HIV patients underwent OLT between June 1, 1999 and May 1, 2006. Results. The actuarial 1-, 2-, and 3-year survival rates posttransplant (±standard error) were 73.3% (±11.4%) for the HIV group (unchanged from 1 to 3 years) versus 86.9% (±1.2%), 82.0% (±1.4%), and 79.4% (±1.5%) for the non-HIV group. Cumulative survival among HIV-infected recipients was not different from the non-HIV population (P=0.20). A difference was observed between the two groups in mortality rates due to infectious causes: the percentage of HIV patients dying from infection was 26.7% (4 of 15) vs. 8.2% (70 of 857) in the non-HIV group (P=0.006). Conclusions. PostOLT survival was comparable in HIV and non-HIV recipients; however, HIV patients had significantly higher mortality from infectious complications. This difference occurred despite adequate control of HIV postOLT. These findings suggest that OLT can be safely performed for HIV-infected patients; however, these patients are at higher risk of mortality from infectious complications.

The continuing, randomised, multinational, phase IIB POWER 1 and 2 studies aim to evaluate efficacy and safety of darunavir in combination with low-dose ritonavir in treatment-experienced HIV-1-infected patients. We did a pooled subgroup analysis to update results at week 48 for patients receiving the recommended dose of darunavir-ritonavir compared with those receiving other protease inhibitors (PIs).After 24-week dose-finding phases and primary efficacy analyses, patients randomised to receive darunavir-ritonavir were given 600/100 mg twice daily, and patients receiving control PIs continued on assigned treatment into the longer-term, open-label phase; all patients continued on optimised background regimen. We assessed patients who had reached week 48 or discontinued earlier at the time of analysis; for the darunavir-ritonavir group, only patients who received 600/100 mg twice daily from baseline were included. Analyses were intention-to-treat. The POWER 2 study (TMC114-C202) is registered with ClinicalTrials.gov (NCT00071097).At week 48, 67 of 110 (61%) darunavir-ritonavir patients compared with 18 of 120 (15%) of control PI patients had viral load reductions of 1 log10 copies per mL or greater from baseline (primary endpoint; difference in response rates 46%, 95% CI 35%-57%, p0.0001). Based on a logistic regression model including stratification factors (baseline number of primary PI mutations, use of enfuvirtide, baseline viral load) and study as covariates, the difference in response was 50% (odds ratio 11.72, 95% CI 5.75-23.89). In the darunavir-ritonavir group, rates of adverse events were mostly lower than or similar to those in the control group when corrected for treatment exposure. No unexpected safety concerns were identified.Efficacy responses with darunavir-ritonavir 600/100 mg twice daily plus optimised background regimen were greater than those with control PI and were sustained to at least week 48, with favourable safety and tolerability in treatment-experienced patients. This regimen could expand the treatment options available for such patients.