HIV Clinical Trials[JOURNAL]
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200 papers
Getting pregnant in HIV clinical trials: women's choice and safety needs. The experience from the ANRS12169-2LADY and ANRS12286-MOBIDIP trials.
Serris A, Zoungrana J, Diallo M … +9 more , Toby R, Mpoudi Ngolle M, Le Gac S, Coutherut J, Cournil A, De Beaudrap P, Koulla-Shiro S, Delaporte E, Ciaffi L
HIV Clin Trials · 2016 Nov · PMID 27801628 · Publisher ↗
INTRODUCTION: Pregnancy is an exclusion criteria in most clinical trials involving antiretroviral therapy (ART) and modern contraception methods are systematically proposed to women of childbearing age. Nevertheless preg...
INTRODUCTION: Pregnancy is an exclusion criteria in most clinical trials involving antiretroviral therapy (ART) and modern contraception methods are systematically proposed to women of childbearing age. Nevertheless pregnancies are often observed. Reproductive choices during clinical trials should be understood to adapt interventions to the level of risk for mother and baby safety. Our goal was to describe the reproductive behavior and pregnancy outcomes among HIV-infected women on second-line antiretroviral treatment enrolled in two clinical trials and to compare them with those of HIV-positive women in non-research settings. METHODS: The number and outcomes of pregnancies were recorded among 281 non menopausal women enrolled in the ANRS 12169-2LADY and ANRS 12286-MOBIDIP clinical trials in Cameroon, Senegal and Burkina Faso. All participants had agreed to use a least one contraceptive method (barrier or non-barrier) which was provided for free during the study. Data were collected through revision of pregnancy notification forms and by data extraction from the study database, regularly updated and checked during the study. RESULTS: Sixty-six women had 84 pregnancies between January 2010 and July 2015 resulting in a pregnancy rate of 8.0 per 100 women-years (WY) (95% CI 6.5-9.9) which is similar to the ones observed in cohort studies in Sub-Saharan Africa (varying from 2.5 to 9.4 pregnancies per 100 WY). Among 60 live births, 10 (16.6%) were born prematurely and 9 (15%) had a low birth weight. Sixteen miscarriages/stillbirths occurred (19.5%). This percentage is comparable to the one expected in the seronegative population which is reassuring for HIV-positive women considering pregnancy on ART. Only one minor birth defect was diagnosed. In univariate and multivariate analysis, miscarriages/stillbirths were not associated either with age, nadir of CD4 count, duration of ART, CD4 count, or viral load at the beginning of pregnancy. CONCLUSION: HIV-positive women participating in clinical trials conducted in Sub-Saharan Africa tend to get pregnant as often as seropositive women who received medical care in non-research settings. It is therefore essential to adopt a pragmatic approach by re-evaluating the relevance of the criteria for exclusion of pregnant women according to the risk associated with exposure and to seek more effective and innovating contraceptive strategies when using potentially teratogenic molecules.
Telmisartan increases vascular reparative capacity in older HIV-infected adults: a pilot study.
Lake JE, Seang S, Kelesidis T … +2 more , Currier JS, Yang OO
HIV Clin Trials · 2016 Nov · PMID 27658740 · Full text
BACKGROUND: Endothelial progenitor cells (EPCs) are bone marrow-derived cells that contribute to vascular repair. EPCs may be reduced in HIV-infected (HIV+) persons, contributing to cardiovascular disease (CVD). Telmisar...
BACKGROUND: Endothelial progenitor cells (EPCs) are bone marrow-derived cells that contribute to vascular repair. EPCs may be reduced in HIV-infected (HIV+) persons, contributing to cardiovascular disease (CVD). Telmisartan is an angiotensin receptor blocker that increases EPCs in HIV-uninfected adults. OBJECTIVE: To assess telmisartan's effects on EPC number and immunophenotype in older HIV + adults at risk for CVD. METHODS: HIV + persons ≥50 years old with HIV-1 RNA < 50 copies/mL on suppressive antiretroviral therapy and ≥1 CVD risk factor participated in a prospective, open-label, pilot study of oral telmisartan 80 mg daily for 12 weeks. Using CD34 and CD133 as markers of early maturity and KDR as a marker of endothelial lineage commitment, EPCs were quantified via flow cytometry and defined as viable CD3/CD33/CD19/glycophorin cells of four immunophenotypes: CD133/KDR, CD34/KDR, CD34/CD133, or CD34/KDR/CD133. The primary endpoint was a 12-week change in EPC subsets (NCT01578772). RESULTS: Seventeen participants (88% men, median age 60 years and peripheral CD4 T lymphocyte count 625 cells/mm) enrolled and completed the study. After 6 and 12 weeks of telmisartan, frequencies of all EPC immunophenotypes were higher than baseline (all p < 0.10 except week 12 CD133/KDR EPC, p = 0.13). Participants with lower baseline EPC levels had the largest gains. Additionally, the percentage of CD34 cells with endothelial commitment (KDR) increased. CONCLUSIONS: Our data suggest that telmisartan use is associated with an increase in circulating EPCs in older HIV + individuals with CVD risk factors. Further controlled studies are needed to assess whether EPC increases translate to a reduction in CVD risk in this population.
Increased homocysteine plasma level is associated with shortened prothrombin time in HIV-infected patients.
Roca B, Roca M, Girones G
HIV Clin Trials · 2016 Sep · PMID 27561455 · Publisher ↗
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....
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 (β 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.
Development and psychometric evaluation of a condom use self-efficacy measure in Spanish and English.
McCabe BE, Schaefer Solle N, Gattamorta K … +4 more , Villegas N, Cianelli R, Mitrani VB, Peragallo N
HIV Clin Trials · 2016 Sep · PMID 27491797 · Full text
BACKGROUND: Condom self-efficacy is an important construct for HIV/STI prevention and intervention. A psychometrically sound measure of the self-efficacy for using condoms that has been designed for Hispanic women to res...
BACKGROUND: Condom self-efficacy is an important construct for HIV/STI prevention and intervention. A psychometrically sound measure of the self-efficacy for using condoms that has been designed for Hispanic women to respond in Spanish or English is needed. OBJECTIVES: The goal of this study was to develop and evaluate a brief self-report measure of condom use self-efficacy. METHODS: We developed a 15-item measure of condom use self-efficacy based on expert knowledge of measurement and HIV/STI prevention with Hispanic women using a translation-back translation approach. Participants were 320 Hispanic women from the Southeastern US. RESULTS: Internal consistency of the full measure was 92. A short form of the instrument with a subset of five items also had acceptable internal consistency, alpha = .80, and was significantly correlated with the full scale, rs = .93, p < .001. A single latent factor explained 9-48% of the variation in these items. Evidence of construct validity of the short form was provided by correlations of the scale with two self-report measures of condom use: rs = .34** with condom use, rs = .37** with condom use during vaginal sex. CONCLUSIONS: Either the full measure or the five-item measure could be used in studies where condom use is an important behavioral outcome, such as evaluating prevention interventions, with Hispanic women. Future studies should examine the performance of this measure with other groups, including Hispanic men and members of other ethnic and language groups.
Predictors of late virologic failure after initial successful suppression of HIV replication on efavirenz-based antiretroviral therapy.
Singini I, Campbell TB, Smeaton LM … +8 more , Kumarasamy N, La Rosa A, Taejareonkul S, Safren SA, Flanigan TP, Hakim JG, Hughes MD, ACTG A5175/PEARLS Study Team.
HIV Clin Trials · 2016 · PMID 27472067 · Full text
BACKGROUND: Practical issues, including cost, hinder implementing virologic monitoring of patients on antiretroviral therapy (ART) in resource-limited settings. We evaluated factors that might guide monitoring frequency...
BACKGROUND: Practical issues, including cost, hinder implementing virologic monitoring of patients on antiretroviral therapy (ART) in resource-limited settings. We evaluated factors that might guide monitoring frequency and efforts to prevent treatment failure after initial virologic suppression. METHODS: Participants were the 911 HIV-infected antiretroviral-naïve adults with CD4 count <300 cells/μL who started efavirenz-based ART in the international A5175/PEARLS trial and achieved HIV-1 RNA <1000 copies/mL at 24 weeks. Participant report of ART adherence was evaluated using a structured questionnaire in monthly interviews. Adherence and readily available clinical and laboratory measures were evaluated as predictors of late virologic failure (late VF: confirmed HIV-1 RNA ≥1000 copies/mL after 24 weeks). RESULTS: During median follow-up of 3.5 years, 82/911 participants (9%) experienced late VF. Of 516 participants reporting missed doses during the first 24 weeks of ART, 55 (11%) experienced late VF, compared with 27 (7%) of 395 participants reporting no missed doses (hazard ratio: 1.73; 95% CI: 1.08, 2.73). This difference persisted in multivariable analysis, in which lower pre-ART hemoglobin and absence of Grade ≥3 laboratory results prior to week 24 were also associated with higher risk of late VF. DISCUSSION: In this clinical trial, the late VF rate after successful suppression was very low. If achievable in routine clinical practice, virologic monitoring involving infrequent (e.g. annual) measurements might be considered; the implications of this for development of resistance need evaluating. Patients reporting missed doses early after ART initiation, despite achieving initial suppression, might require more frequent measurement and/or strategies for promoting adherence.
Long-term follow-up of HIV seroconverters in microbicide trials - rationale, study design, and challenges in MTN-015.
Riddler SA, Husnik M, Gorbach PM … +11 more , Levy L, Parikh U, Livant E, Pather A, Makanani B, Muhlanga F, Kasaro M, Martinson F, Elharrar V, Balkus JE, MTN-015 Protocol Team for the Microbicide Trials Network
HIV Clin Trials · 2016 Sep · PMID 27465646 · Full text
BACKGROUND: As the effect of biomedical prevention interventions on the natural history of HIV-1 infection in participants who seroconvert is unknown, the Microbicide Trials Network (MTN) established a longitudinal study...
BACKGROUND: As the effect of biomedical prevention interventions on the natural history of HIV-1 infection in participants who seroconvert is unknown, the Microbicide Trials Network (MTN) established a longitudinal study (MTN-015) to monitor virologic, immunological, and clinical outcomes, as well as behavioral changes among women who become HIV-infected during MTN trials. We describe the rationale, study design, implementation, and enrollment of the initial group of participants in the MTN seroconverter cohort. METHODS: Initiated in 2008, MTN-015 is an ongoing observational cohort study enrolling participants who acquire HIV-1 infection during effectiveness studies of candidate microbicides. Eligible participants from recently completed and ongoing MTN trials are enrolled after seroconversion and return for regular follow-up visits with clinical and behavioral data collection. Biologic samples including blood and genital fluids are stored for future testing. RESULTS: MTN-015 was implemented initially at six African sites and enrolled 100/139 (72%) of eligible women who seroconverted in HIV Prevention Trials Network protocol 035 (HPTN 035, conducted by the MTN). The median time from seroconversion in HPTN 035 to enrollment in MTN-015 was 18 months. Retention was good with >70% of visits completed. Implementation challenges included regulatory reviews, translation, and testing of questionnaires, and site readiness. CONCLUSIONS: Enrollment of HIV-seroconverters into a longitudinal observational follow-up study is feasible and acceptable to participants. Data and samples collected in this protocol will be used to assess safety of investigational HIV microbicides and answer other important public health questions for HIV infected women.
Cytotoxic chemotherapy and the evolution of cellular and viral resistance to antiretroviral therapy in HIV- infected individuals with lymphoma.
McFaul K, Liptrott N, Cox A … +8 more , Martin P, Egan D, Owen A, Kelly S, Karolia Z, Shaw K, Bower M, Boffito M
HIV Clin Trials · 2016 Sep · PMID 27454119 · Publisher ↗
BACKGROUND: The use of combination antiretroviral therapy (cART) and cytotoxic chemotherapy for HIV-associated lymphoma runs the risks of inducing HIV drug resistance. This study examined two possible mechanisms: altered...
BACKGROUND: The use of combination antiretroviral therapy (cART) and cytotoxic chemotherapy for HIV-associated lymphoma runs the risks of inducing HIV drug resistance. This study examined two possible mechanisms: altered expression of membrane drug transporter protein (MTP) and acquisition of mutations in pro-viral DNA. METHODS: Expression levels of MTP and pro-viral DNA resistance mutation analysis were performed on peripheral blood mononuclear cells (PBMC) before, during, and after chemotherapy. RESULTS: Twenty nine patients completed the three time point estimations. There were no significant variations before, during, and after chemotherapy in the expression of four MTPs: ABCB1, ABCC1, ABCC2, and SLCO3A1 (OATP3A1). Pro-viral DNA sequencing revealed that only one patient developed a new nucleos/tide reverse transcriptase inhibitor-associated mutation (184V) during the course of the study, giving a mutation rate of 0.0027 per person per year. CONCLUSIONS: In conclusion, concomitant administration of cytotoxic chemotherapy and cART does not induce expression of MTP. Furthermore, no significant changes in viral resistance were observed pre- and post-chemotherapy, suggesting mutagenic cytotoxic chemotherapy seems not to induce mutations in HIV pro-viral DNA.
Severe dyslipidemia and immune activation in HIV patients with dysglycemia.
Jin C, Ji S, Xie T … +8 more , Höxtermann S, Fuchs W, Lu X, Wu H, Cheng L, Skaletz-Rorowski A, Brockmeyer NH, Wu N
HIV Clin Trials · 2016 Sep · PMID 27409415 · Publisher ↗
BACKGROUND AND OBJECTIVE: Diabetes mellitus (DM) is common in human immunodeficiency virus (HIV)-infected patients. However, the relationship between dysglycemia, lipid metabolism, and immune activation in HIV patients i...
BACKGROUND AND OBJECTIVE: Diabetes mellitus (DM) is common in human immunodeficiency virus (HIV)-infected patients. However, the relationship between dysglycemia, lipid metabolism, and immune activation in HIV patients is poorly understood. METHODS: We retrospectively analyzed the clinical data of 180 HIV patients, including 153 patients undergoing highly active antiretroviral therapy (HAART) and 27 HAART-naive patients. DM was defined as fasting serum glucose levels ≥126 mg/dl, and impaired fasting glucose (IFG) was defined as serum glucose levels of 101-125 mg/dl at two different time points. Lipid metabolic indexes were measured. CD4+, CD8+, and CD8+ HLA-DR+ T cells were determined by flow cytometry. RESULTS: IFM and DM percentages were higher in the HAART group than in the HAART-naive group (59.5% vs. 48.1% and 21.6% vs. 7.4%, respectively; p < 0.01). Additionally, DM percentage was high in patients receiving HAART containing protease inhibitors. Serum levels of triglycerides and very low-density lipoprotein cholesterol were higher in IFG and DM HAART patients than in euglycemic HAART patients (p < 0.05). Serum triglyceride levels were higher in HAART-naive DM patients than in other patients (p < 0.05). CD8+ and CD8+ HLA-DR+ cell counts were higher in IFG and DM HAART patients than in euglycemic HAART patients (p < 0.05). Ordinal logistic regression analysis suggested that TRIG, VLDL, CD8, and HAART were predictors of glucose metabolic disorders. CONCLUSION: HIV patients with hyperglycemia have severe dyslipidemia and immune activation, and HAART is an important impact factor of glucose and lipid metabolic disorders.
An observational study on the incidence of tuberculosis among a cohort of HIV infected adults in a setting with low prevalence of tuberculosis.
Manavi K, Hodson J
HIV Clin Trials · 2016 · PMID 27378421 · Publisher ↗
BACKGROUND: Tuberculosis (TB) remains a main cause of morbidity and mortality among individuals infected with HIV. We investigated the incidence of TB among a cohort of HIV infected patients attending a setting with low...
BACKGROUND: Tuberculosis (TB) remains a main cause of morbidity and mortality among individuals infected with HIV. We investigated the incidence of TB among a cohort of HIV infected patients attending a setting with low TB burden where screening for latent TB infection is not routinely carried out. METHODS: an observational cohort study on HIV-infected adults attending the HIV clinic at Queen Elizabeth Hospital Birmingham, UK between 1 January 2011 and 30 September 2015. Patients with culture-proven TB after HIV diagnosis, or those treated for clinical diagnosis of the infection, were classified as having "active TB". RESULTS: 1824 patients were included in the study (5347 patient years of follow up), of whom 21 patients developed TB (16 microbiology confirmed). Of the 666 new HIV diagnoses, six patients developed TB within one month, giving a TB prevalence at the time of HIV diagnosis of 0.9%. The total TB incidence for the remaining 1818 patients was 2.81 cases per 1000 patient years (95% CI: 1.63-4.53). TB incidence was significantly more common among patients with CD4 ≤ 200 cells/mm compared to those with CD4 > 500 cells/mm (28.2 vs. 1.22 per 1000 patient years, p < 0.001), and in patients with VL ≥ 40 copies/mL compared to <40 copies/mL (8.30 vs. 1.42, p < 0.001). CONCLUSION: In settings with low TB prevalence, early start of combined antiretroviral therapy and intensified TB case finding protocols may significantly reduce the incidence of TB.
Characteristics associated with virologic failure in high-risk HIV-positive participants with prior failure: a post hoc analysis of ACTG 5251.
Robbins GK, Cohn SE, Harrison LJ … +9 more , Smeaton L, Moran L, Rusin D, Dehlinger M, Flynn T, Lammert S, Wu AW, Safren SA, Reynolds NR
HIV Clin Trials · 2016 Jul · PMID 27347650 · Full text
UNLABELLED: Patients with prior virologic failure (VF) are at an increased risk of subsequent failure, emergence of resistance, and death. This analysis identifies outcomes and correlates of VF in a high-risk population....
UNLABELLED: Patients with prior virologic failure (VF) are at an increased risk of subsequent failure, emergence of resistance, and death. This analysis identifies outcomes and correlates of VF in a high-risk population. METHODS: A5251 was designed to evaluate an enhanced adherence counseling intervention delivered by nurses from a central call site on virologic suppression. Due to slow enrollment, the study was closed prematurely and revised study endpoints were evaluated (week 24 VF (HIV-1 RNA ≥200 copies/ml) and non-perfect adherence (<100% self-reported using both the ACTG adherence questionnaire and visual analog scale (VAS)). RESULTS: Fifty-nine participants were enrolled, 43 (73%) black non-Hispanic and 23 (39%) women. Median prior antiretroviral regimen changes were three and the co-morbidity in this population was higher than typical for HIV clinical trials. At week 24 (n = 41), 24 (59%) failed to reach virologic suppression (HIV-1 RNA <200 copies/ml) and 25 (63%) reported non-perfect adherence. Higher depression (CES-D10) and adverse illness perceptions (IPQ-B) were associated with week 24 non-adherence. Early clinical assessments (week 12 HIV-RNA ≥200 copies/mL and non-perfect adherence) as well as higher depression and adverse illness perceptions were associated with week 24 VF. DISCUSSION: In this high-risk population, the proportion of participants with suboptimal adherence and VF was unacceptably high. Interventions to address this treatment gap are clearly needed. Depression and a higher illness perception score, failure to achieve virologic suppression by week 12, and less than perfect adherence could be used to target individuals for early interventions in treatment-experienced, high-risk individuals at high risk for VF.
CXCR4-using HIV variants in a cohort of Black men who have sex with men: HIV Prevention Trials Network 061.
Chen I, Huang W, Connor MB … +15 more , Frantzell A, Cummings V, Beauchamp GG, Griffith S, Fields SD, Scott HM, Shoptaw S, Del Rio C, Magnus M, Mannheimer S, Tieu HV, Wheeler DP, Mayer KH, Koblin BA, Eshleman SH
HIV Clin Trials · 2016 Jul · PMID 27300696 · Full text
OBJECTIVE: To evaluate factors associated with HIV tropism among Black men who have sex with men (MSM) in the United States enrolled in a clinical study (HIV Prevention Trials Network 061). METHODS: HIV tropism was analy...
OBJECTIVE: To evaluate factors associated with HIV tropism among Black men who have sex with men (MSM) in the United States enrolled in a clinical study (HIV Prevention Trials Network 061). METHODS: HIV tropism was analyzed using a phenotypic assay (Trofile assay, Monogram Biosciences). Samples were analyzed from 43 men who were HIV infected at enrollment and reported either exclusive insertive intercourse or exclusive receptive intercourse; samples were also analyzed from 20 men who were HIV uninfected at enrollment and seroconverted during the study. Clonal analysis of individual viral variants was performed for seroconverters who had dual/mixed (DM) viruses. RESULTS: DM viruses were detected in samples from 11 (26%) of the 43 HIV-infected men analyzed at the enrollment visit; HIV tropism did not differ between those reporting exclusive insertive vs receptive intercourse. DM viruses were also detected in five (25%) of the 20 seroconverters. DM viruses were associated with lower CD4 cell counts. Seroconverters with DM viruses had dual-tropic viruses only or mixed populations of CCR5- and dual-tropic viruses. CONCLUSIONS: DM viruses were frequently detected among Black MSM in this study, including seroconverters. Further studies are needed to understand factors driving transmission and selection of CXCR4- and dual-tropic viruses among Black MSM.
Effect of rosuvastatin on plasma coenzyme Q10 in HIV-infected individuals on antiretroviral therapy.
Morrison JT, Longenecker CT, Mittelsteadt A … +3 more , Jiang Y, Debanne SM, McComsey GA
HIV Clin Trials · 2016 Jul · PMID 27294339 · Full text
BACKGROUND: Coenzyme Q10 (CoQ10) deficiency has been associated with statin-induced myopathy, and supplementation with CoQ10 may reduce inflammation markers. The effects of statins on CoQ10 and its anti-inflammatory prop...
BACKGROUND: Coenzyme Q10 (CoQ10) deficiency has been associated with statin-induced myopathy, and supplementation with CoQ10 may reduce inflammation markers. The effects of statins on CoQ10 and its anti-inflammatory properties have not been investigated in HIV-positive patients. OBJECTIVE: The objectives of this study were to examine the effect of rosuvastatin on CoQ10 and CoQ10/LDL ratio over 24-week SATURN-HIV trial, explore the associations between CoQ10 levels and markers of vascular disease, inflammation, and immune activation, and assess whether changes in CoQ10 affected the anti-inflammatory effects of statin therapy or were associated with myalgia symptoms. METHODS: This was a secondary analysis of the SATURN-HIV trial, a 96-week randomized clinical trial of 10 mg daily rosuvastatin vs. placebo in HIV-infected patients on antiretroviral therapy. We assessed the statin treatment effect on CoQ10 levels and CoQ10/LDL ratios and whether changes in these markers were related to myalgias. Relationships between CoQ10, subclinical vascular disease, and biomarkers of inflammation and immune activation were explored using Spearman correlations and multivariable regression models. RESULTS: Overall, 147 patients were included. Median age was 46 years; 78% were male and 68% African American. At baseline, CoQ10 levels and CoQ10/LDL ratio were modestly correlated with markers of HIV disease, immune activation, and carotid distensibility. After 24 weeks of statin therapy, CoQ10 levels decreased (p = 0.002 for between group difference) and CoQ10/LDL ratio increased (p = 0.036). In the statin treatment arm, we did not find evidence of a relationship between changes in CoQ10 or CoQ10/LDL ration and changes in markers of inflammation or immune activation. There was a borderline statistically significant association between changes in CoQ10 and myalgia symptoms [OR 4.0 per 0.1 mg/L decrease in CoQ10, p = 0.07]. CONCLUSION: Twenty-four weeks of 10 mg daily rosuvastatin decreases CoQ10 concentration and increases CoQ10/LDL ratio in HIV-infected patients on antiretroviral therapy.
Can Probiotics Reduce Inflammation and Enhance Gut Immune Health in People Living with HIV: Study Designs for the Probiotic Visbiome for Inflammation and Translocation (PROOV IT) Pilot Trials.
Kim CJ, Walmsley SL, Raboud JM … +6 more , Kovacs C, Coburn B, Rousseau R, Reinhard R, Rosenes R, Kaul R
HIV Clin Trials · 2016 Jul · PMID 27267710 · Publisher ↗
OBJECTIVES: Despite substantial improvements in HIV outcomes with combination antiretroviral therapy (cART), morbidity and mortality remain above population norms. The gut mucosal immune system is not completely restored...
OBJECTIVES: Despite substantial improvements in HIV outcomes with combination antiretroviral therapy (cART), morbidity and mortality remain above population norms. The gut mucosal immune system is not completely restored by cART, and the resultant microbial translocation may contribute to chronic inflammation, inadequate CD4 T-cell recovery, and increased rates of serious non-AIDS events. Since the microbial environment surrounding a CD4 T cell may influence its development and function, we hypothesize that probiotics provided during cART might reduce inflammation and improve gut immune health in HIV-positive treatment-naïve individuals (PROOV IT I) and individuals with suboptimal CD4 recovery on cART (PROOV IT II). METHODS: These prospective, double-blinded, randomized, placebo-controlled, multicenter pilot studies will assess the impact of the probiotic Visbiome at 900 billion bacteria daily. Forty HIV positive cART-naïve men will be randomized in the PROOV IT I study, coincident with antiretroviral initiation, and be followed for 24 weeks. In PROOV IT II, 36 men on cART, but with a CD4 T-cell count below 350 cells/mm(3) will be followed for 48 weeks. The primary outcome for both studies is the comparison of blood CD8 T-cell immune activation. Secondary analyses will include comparison of blood inflammatory biomarkers, microbial translocation, blood and gut immunology and HIV levels, the bacterial community composition, diet, intestinal permeability, and the safety, adherence and tolerability of the study product. DISCUSSION: These studies will evaluate the ability of probiotics as a safe and tolerable therapeutic intervention to reduce systemic immune activation and to accelerate gut immune restoration in people living with HIV.
The Framingham function overestimates the risk of ischemic heart disease in HIV-infected patients from Barcelona.
Herrera S, Guelar A, Sorlì L … +8 more , Vila J, Molas E, Grau M, Marrugat J, Esteve E, Güerri-Fernández R, Montero M, Knobel H
HIV Clin Trials · 2016 Jul · PMID 27169692 · Publisher ↗
BACKGROUND: Cardiovascular risk (CVR) assessment helps to identify patients at high CVR. The Framingham CVR score (FRS) is the most widely used methods but may overestimate risk in regions with low incidence of cardiovas...
BACKGROUND: Cardiovascular risk (CVR) assessment helps to identify patients at high CVR. The Framingham CVR score (FRS) is the most widely used methods but may overestimate risk in regions with low incidence of cardiovascular disease. The objective was to compare the 10-year performance of the original and the adapted REGICOR - Framingham CVR functions in HIV-infected individuals. METHODS: We carried out a longitudinal study of HIV-infected patients with CVR evaluation in a hospital in Barcelona between 2003 and 2013. STATISTICS: Risk probability was calculated using the FRAMINGHAM function and REGICOR adaptation to the Spanish population, and individuals were categorized in three groups (low, 0 < 5%; moderate, 5-10%; and high, >10%). For each risk group, the number of events over 10 years was calculated using the Kaplan-Meier method, and the expected number of events was calculated by multiplying the frequency of participants in the group by the mean of the probabilities from the risk function. We used the X(2) goodness-of-fit test to assess agreement between observed and expected. RESULTS: Six hundred and forty-one patients were followed up for a median of 10.2 years, and 20 ischemic heart events (IHE) were observed. The mean (95% CI) number of IHEs per 1000 person-years was 3.7 (2.06-5.27). The estimates from the Framingham and REGICOR functions were 40 and 14 IHEs, respectively. The estimate from the original Framingham function differed significantly from the observed incidence (p < 0.001), whereas that from the REGICOR-adapted function did not (p = 0.15). In terms of the number of cardiovascular events (38 events observed), the REGICOR function significantly underestimated risk (p = 0.01), whereas the estimate from the Framingham function was similar to observed (p:0.93). CONCLUSIONS: The FRS significantly overestimates risk of IHE events in our HIV-infected patients, while the REGICOR function is a better predictor of these events. In terms of cardiovascular events, the REGICOR function significantly underestimates risk, whereas the FRS is a better estimator. We recommend using CVR scales and adjusting them to the origin of the population being studied.
A cross-sectional study to evaluate the association of hyperbilirubinaemia on markers of cardiovascular disease, neurocognitive function, bone mineral density and renal markers in HIV-1 infected subjects on protease inhibitors.
Barber TJ, Moyle G, Hill A … +7 more , Jagjit Singh G, Scourfield A, Yapa HM, Waters L, Asboe D, Boffito M, Nelson M
HIV Clin Trials · 2016 May · PMID 27125367 · Publisher ↗
BACKGROUND: Ongoing inflammation in controlled HIV infection contributes to non-AIDS comorbidities. High bilirubin appears to exhibit an anti-inflammatory effect in vivo. We therefore examined whether increased bilirubin...
BACKGROUND: Ongoing inflammation in controlled HIV infection contributes to non-AIDS comorbidities. High bilirubin appears to exhibit an anti-inflammatory effect in vivo. We therefore examined whether increased bilirubin in persons with HIV was associated with differences in markers of inflammation and cardiovascular, bone, renal disease, and neurocognitive (NC) impairment. METHODS: This cross-sectional study examined inflammatory markers in individuals with stable HIV infection treated with two nucleoside reverse transcriptase inhibitors and a boosted protease inhibitor. Individuals recruited were those with a normal bilirubin (NBR; 0-17 μmol/L) or high bilirubin (>2.5 × upper limit of normal). Demographic and anthropological data were recorded. Blood and urine samples were taken for analyses. Pulse wave velocity (PWV) measurement, carotid intimal thickness (CIT), and calcaneal stiffness (CSI) were measured. Males were asked to answer a questionnaire about sexual function; NC testing was performed using CogState. RESULTS: 101 patients were screened, 78 enrolled (43 NBR and 35 HBR). Atazanavir use was significantly higher in HBR. Whilst a trend for lower CIT was seen in those with HBR, no significant differences were seen in PWV, bone markers, calculated cardiovascular risk (Framingham), or erectile dysfunction score. VCAM-1 levels were significantly lower in the HBR group. HBR was associated with lower LDL and triglyceride levels. NBR was associated with a calculated FRAX significantly lower than HBR although no associations were found after adjusting for tenofovir use. No difference in renal markers was observed. Component tests of NC testing revealed differences favouring HBR but overall composite scores were similar. DISCUSSION: High bilirubin in the context of boosted PI therapy was found not to be associated with differences in with the markers examined in this study. Some trends were noted and, on the basis of these, a larger, clinical end point study is warranted.
Non-classical monocytes predict progression of carotid artery bifurcation intima-media thickness in HIV-infected individuals on stable antiretroviral therapy.
Chow DC, Kagihara JM, Zhang G … +11 more , Souza SA, Hodis HN, Li Y, Mitchell BI, Nakamoto BK, Kallianpur KJ, Keating SM, Norris PJ, Kohorn LB, Ndhlovu LC, Shikuma CM
HIV Clin Trials · 2016 May · PMID 27125366 · Full text
BACKGROUND: Inflammation may contribute to cardiovascular disease (CVD) among antiretrovirally suppressed HIV-infected individuals. We assessed relationships of monocyte, CD8 T-cell activation and plasma biomarkers to ch...
BACKGROUND: Inflammation may contribute to cardiovascular disease (CVD) among antiretrovirally suppressed HIV-infected individuals. We assessed relationships of monocyte, CD8 T-cell activation and plasma biomarkers to changes in carotid artery intima-media thickness (CIMT). METHODS: Longitudinal study of HIV-infected subjects ≥40 years and on stable antiretroviral therapy (ART) ≥3 months. Peripheral blood mononuclear cells were immunophenotyped by multiparameteric flow cytometry to quantify classical (CD14(++)CD16(-)), intermediate (CD14(++)CD16(+)), non-classical (CD14(low/+)CD16(++)) and transitional (CD14(+)CD16(-)) monocyte subsets and activated (CD38(+)HLA-DR(+)) CD8(+) T-cells at baseline. Plasma biomarkers were assessed by multiplex Luminex assay. High-resolution B-mode ultrasounds of right carotid arteries were obtained. Changes in CIMT over two years at the right common carotid artery (CIMTCCA) and right bifurcation (CIMTBIF) were outcome variables. RESULTS: We studied 50 subjects: 84% male, median age 49 (Q1, Q3; 46, 56) years, median CD4 count 461 (317, 578) cells/mm(3), and with HIV RNA ≤ 50 copies/mL in 84%. Change in CIMTBIF correlated with log values of baseline absolute count of non-classical monocytes (r = 0.37, p = 0.020), and with MCP-1 (r = 0.42, p = 0.0024) and TNF-α (r = 0.30, p = 0.036) levels. In multivariable linear regression, only non-classical monocytes and MCP-1 predicted the change in CIMTBIF, independent of Framingham Risk Score and baseline CIMTBIF. No correlation was noted between CD8 T-cell activation and CIMTBIF change. Monocyte subsets, CD8 T-cell activation, and biomarker concentrations were not correlated with changes in CIMTCCA. CONCLUSIONS: Our findings highlight the role of non-classical monocytes and MCP-1 in the progression of CIMTBIF in HIV-infected individuals on stable ART independent of traditional cardio-metabolic risk factors.
Integrase Strand Transfer Inhibitors (INSTIs) Resistance Mutations in HIV-1 Infected Turkish Patients.
Sayan M, Gündüz A, Ersöz G … +14 more , İnan A, Deveci A, Özgür G, Sargın F, Karagöz G, İnci A, İnan D, Ülçay A, Karaoğlan I, Kaya S, Kutlu SS, Süer K, Çağatay A, Akalın H
HIV Clin Trials · 2016 May · PMID 27125365 · Publisher ↗
OBJECTIVES: Integrase strand transfer inhibitor (INSTI) is a new class of antiretroviral (ARV) drugs designed to block the action of the integrase viral enzyme, which is responsible for insertation of the HIV-1 genome in...
OBJECTIVES: Integrase strand transfer inhibitor (INSTI) is a new class of antiretroviral (ARV) drugs designed to block the action of the integrase viral enzyme, which is responsible for insertation of the HIV-1 genome into the host DNA. The aim of this study was to evaluate for the first time INSTI resistance mutations in Turkish patients. METHODS: This study was conducted in Turkey, between April 2013 and April 2015 using 169 HIV-1-infected patients (78 ARV naive patients and 91 ARV-experienced patients). Laboratory and clinical characteristics of ARV naive and ARV-experienced patients were as follows: gender (M/F): 71/7 and 80/11, median age: 38 and 38.4; median CD4(+) T-cell: 236 and 216 cells/mm(3), median HIV-1 RNA: 4.95+E5 and 1.08E+6 copies/ml. Population-based seqeunces of the reverse transcriptase, protease, and integrase domains of the HIV-1 pol gene were used to detect HIV-1 drug resistance mutations. RESULT: INSTI resistance mutations were not found in recently diagnosed HIV-1-infected patients. However, ARV-experienced patients had major resistance mutations associated with raltegravir and elvitegravir; the following results were generated:F121Y, Y143R, Q148R and E157Q (6/91 - 6.6%). CONCLUSIONS: The prevalence of INSTI resistant mutations in ART-experienced patients suggested that resistance testing must be incorporated as an integral part of HIV management with INSTI therapies.
Fosamprenavir/ritonavir in patients with viral hepatitis coinfection: an observational multicohort study.
Nasta P, Salmon D, d'Arminio Monforte A … +5 more , Pimenta JM, Cerini C, Giralda M, Winnock M, Cozzi-Lepri A
HIV Clin Trials · 2016 May · PMID 27125364 · Publisher ↗
OBJECTIVE: Safety and tolerability evaluation of adapted dose regimens containing fosamprenavir/ritonavir (FPV/r) in HIV-infected subjects with viral hepatitis co-infection. METHODS: A retrospective multicohort analysis...
OBJECTIVE: Safety and tolerability evaluation of adapted dose regimens containing fosamprenavir/ritonavir (FPV/r) in HIV-infected subjects with viral hepatitis co-infection. METHODS: A retrospective multicohort analysis was conducted. Subjects from three European cohorts who started FPV/r or lopinavir/ritonavir (LPV/r) as a comparator contributed data to a centralized database. Subjects were divided into five groups by treatment regimen and level of hepatic impairment (aspartate aminotransferase [AST] platelet ratio index [APRI] score < or ≥2). Multivariable Cox regression analyses controlling for demographic factors, baseline CD4 count, FIB-4 score, use of antiretroviral therapy, and laboratory markers (bilirubin and platelet count) were performed to identify factors independently associated with risk of developing adverse events or safety events (eg, drug discontinuation, alanine aminotransferase (ALT) elevation, hepatic decompensation/death). RESULTS: A total of 1096 patients contributed data to the study. Fosamprenavir/ritonavir (except in subjects with APRI ≥2 receiving standard dose) was associated with a higher two-year risk of drug discontinuation compared with LPV/r. Restricting the analysis to discontinuations due to adverse events (AEs), only subjects who received the reduced dose were more likely to discontinue ≥1 drug in the FPV/r regimen. There were no statistical differences in ALT elevation between groups. Incidence of hepatic decompensation events was similar among groups except for subjects who received non standard doses of FPV, though the number of events was small. CONCLUSIONS: Fosamprenavir/ritonavir discontinuation rate due to AEs or ALT elevation was similar across all European-approved FPV/r doses and to that of LPV/r subjects. Although liver tolerated antiretrovirals, such as integrase inhibitor and entry inhibitor, the use of FPV/r is acceptable in HIV infected patients with viral hepatitis.
Improvement of BMD after Switching from Lopinavir/R Plus Two Nucleos(T)ide Reverse Transcriptase Inhibitors to Lopinavir/R Plus Lamivudine: OLE-LIP Substudy.
Crespo M, Navarro J, Martinez-Rebollar M … +8 more , Podzamczer D, Domingo P, Mallolas J, Saumoy M, Mateo GM, Curran A, Gatell J, Ribera E
HIV Clin Trials · 2016 May · PMID 27125363 · Publisher ↗
OBJECTIVE: To compare 48-week changes in bone mineral density (BMD) and body fat distribution between patients continuing lopinavir/ritonavir and two NRTIs and those switching to lopinavir/ritonavir and lamivudine. METHO...
OBJECTIVE: To compare 48-week changes in bone mineral density (BMD) and body fat distribution between patients continuing lopinavir/ritonavir and two NRTIs and those switching to lopinavir/ritonavir and lamivudine. METHODS: Substudy of a randomized, open-label, multicenter OLE study was carried out. Adult HIV-infected patients with <50 copies/mL for ≥6 months were randomized (1:1) to continue lopinavir/ritonavir and two NRTIs or switching to lopinavir/ritonavir and lamivudine. Dual-energy X-ray absorptiometry (DXA) was performed at baseline and after 48 weeks to measure bone composition and body fat distribution in both the groups. RESULTS: Forty-one patients (dual-therapy, n = 23; triple-therapy, n = 18) of 239, who received at least one dose of study medication, completed the study: median age, 42 years, 71% male, 73% Caucasian. At week 48, total BMD increased by 1.04% (95% CI, 0.06 to 2.01%) among patients switching to dual-therapy, whereas no significant changes occurred in patients maintaining triple-therapy. Dual-therapy and older age were independently associated with total BMD increase. Among patients discontinuing tenofovir-DF, a significant increase was seen in total BMD (1.43; 95% CI, -0.04 to 2.91) and total hip (1.33%; 95% CI, 0.44 to 2.22%). A non-statistically significant decrease in femoral and spinal BMD was observed in patients who discontinued abacavir and in those continuing triple-therapy. Regarding fat distribution, no significant changes were seen in both the treatment groups. DISCUSSION: BMD increased following switching to lopinavir/ritonavir plus lamivudine in HIV-infected patients on suppressive triple-therapy with lopinavir/ritonavir and two NRTIs including tenofovir-DF.
Addition of boceprevir to PEG-interferon/ribavirin in HIV-HCV-Genotype-1-coinfected, treatment-experienced patients: efficacy, safety, and pharmacokinetics data from the ANRS HC27 study.
Poizot-Martin I, Bellissant E, Garraffo R … +12 more , Colson P, Piroth L, Solas C, Renault A, Bourlière M, Halfon P, Ghosn J, Alric L, Naqvi A, Carrieri P, Molina JM, ANRS HC27 BOCEPREVIH Study Group
HIV Clin Trials · 2016 Mar · PMID 27077673 · Publisher ↗
BACKGROUND: Scarce data exist on the efficacy and safety of the PEGylated-interferon/ribavirin/boceprevir regimen in HIV/HCV-coinfected patients who failed to respond to PEGylated-interferon/ribavirin treatment. OBJECTIV...
BACKGROUND: Scarce data exist on the efficacy and safety of the PEGylated-interferon/ribavirin/boceprevir regimen in HIV/HCV-coinfected patients who failed to respond to PEGylated-interferon/ribavirin treatment. OBJECTIVES: To evaluate the efficacy and safety of this drug regimen and the impact of the addition of boceprevir(BOC) on atazanavir (ATV) or raltegravir (RAL) pharmacokinetic parameters in a subgroup of patients. METHODS: In this single-arm phase 2 trial, HIV-1/HCV-genotype-1-coinfected patients received PEGylated-interferonα2b (1.5 μg/kg/week)+ ribavirin (800-1400 mg/day) alone until W4 and with BOC(800 mgTID) until W48. Based on virologic response at W8, the three drugs were stopped or PEGylated-interferon/ribavirin was continued alone until W72. The primary endpoint was SVR at W24 off-therapy (SVR24). RESULTS: 64 patients were included. SVR24 was achieved in 53% of patients (CI90%: 43-63%) and in 90% of previous relapsers. In univariate analysis, SVR24 was associated with response to previous HCV treatment, HCV-1b subtype, HCV-RNA decline, ribavirin-Ctrough at W4, and HCV-RNA at W8 but not to fibrosis score, IL28B genotype, or boceprevir-Ctrough at W8. In multivariate analysis, SVR24 remained associated with response to previous HCV treatment [non-responders versus null responders: OR=5.0(1.3-20.0); relapsers vs. null responders: OR=28.8(4.9-169.5)]. HCV treatment was discontinued for adverse events in 17% of patients. A 51% decrease in ATV/r-AUC0-8 h (p<0.01) and a 57% increase in RAL-AUC0-8 h (p<0.01) were observed, although atazanavir/r or raltegravir did not affect BOC-AUC0-8 h significantly. The ATV mean Cthrough fell from 763.8 ng/mL (CI 95%: 230.3-1297.3) without BOC to 507.7 ng/mL (CI 95%: 164-851.4) with BOC. CONCLUSIONS: Boceprevir-based regimen demonstrated a high SVR24 rate in treatment-experienced HIV-HCV genotype-1-coinfected relapsers.
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