HIV Clinical Trials[JOURNAL]
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200 papers
Long-term immunologic and virologic responses on raltegravir-containing regimens among ART-experienced participants in the HIV Outpatient Study.
Buchacz K, Wiegand R, Armon C … +4 more , Chmiel JS, Wood K, Brooks JT, Palella FJ
HIV Clin Trials · 2015 Aug · PMID 26126549 · Full text
OBJECTIVES: Raltegravir (RAL)-containing antiretroviral therapy (ART) produced better immunologic and virologic responses than optimized background ART in clinical trials of heavily ART-experienced patients, but few data...
OBJECTIVES: Raltegravir (RAL)-containing antiretroviral therapy (ART) produced better immunologic and virologic responses than optimized background ART in clinical trials of heavily ART-experienced patients, but few data exist on long-term outcomes in routine HIV care. METHODS: We studied ART-experienced HIV outpatient study (HOPS) participants seen at 10 US HIV-specialty clinics during 2007-2011.We identified patients who started (baseline date) either continuous ≥ 30 days of RAL-containing or RAL-sparing ART, and used propensity score (PS) matching methods to account for baseline clinical and demographic differences. We used Kaplan-Meier methods and log-rank tests for the matched subsets to evaluate probability of death, achieving HIV RNA < 50 copies/ml, and CD4 cell count (CD4) increase of ≥ 50 cells mm(- 3) during follow-up. RESULTS: Among 784 RAL-exposed and 1062 RAL-unexposed patients, 472 from each group were matched by PS. At baseline, the 472 RAL-exposed patients (mean nadir CD4, 205 cells mm(- 3); mean baseline CD4, 460 cells mm(- 3); HIV RNA < 50 copies ml(- 1) in 61%; mean years on prescribed ART, 7.5) were similar to RAL unexposed. During a mean follow-up of over 3 years, mortality rates and immunologic and virologic trajectories did not differ between the two groups. Among patients with detectable baseline HIV RNA levels, 76% of RAL-exposed and 63% of RAL-unexposed achieved HIV RNA < 50 copies ml(- 1) (P = 0.51); 69 and 58%, respectively, achieved a CD4 increase ≥ 50 cells mm(- 3) (P = 0.70). DISCUSSION: In our large cohort of US ART-experienced patients with a wide spectrum of clinical history, similar outcomes were observed when prescribed RAL containing versus other contemporary ART.
Long-lasting humoral immune response induced in HIV-1-infected patients by a synthetic peptide (AT20) derived from the HIV-1 matrix protein p17 functional epitope.
Focà E, Iaria ML, Caccuri F … +5 more , Fiorentini S, Motta D, Giagulli C, Castelli F, Caruso A
HIV Clin Trials · 2015 Aug · PMID 26057863 · Publisher ↗
OBJECTIVE: A therapeutic vaccination based on a synthetic peptide (AT20) representative of the HIV-1 matrix protein p17 (p17) functional region, coupled to keyhole limpet hemocyanin (KLH) AT20-KLH was capable of inducing...
OBJECTIVE: A therapeutic vaccination based on a synthetic peptide (AT20) representative of the HIV-1 matrix protein p17 (p17) functional region, coupled to keyhole limpet hemocyanin (KLH) AT20-KLH was capable of inducing the production of high-avidity antibodies (Abs) toward a previous untargeted p17 hotspot of functional activity in highly active antiretroviral therapy (HAART)-treated HIV-1-infected patients. Since avidity of Abs after immunization and the retention of antigens are important in sustaining the long-lasting production of specific humoral responses, we asked whether AT20-KLH vaccination would result in development of a long-lived immune response. METHODS: The long-term duration of Ab response to AT20-KLH has been evaluated in 10 patients previously enrolled for the AT20-KLH vaccination trial at day 898 post-immunization. Ab titer and their avidity was assessed using specifically designed ELISA assays, whereas their neutralizing capacity was estimated in vitro using a 'wound sealing assay'. RESULTS: Data obtained show that high titers of specific anti-AT20 Abs were maintained at more than 2 years after the last immunization. Furthermore, these Abs were capable to neutralize exogenous p17, as assessed by ability of sera derived from AT20-KLH-immunized patients to block the ability of p17 to promote cell migration in vitro. CONCLUSION: This finding attests for a successful AT20-KLH vaccine molecule formulation and for an effective HAART-dependent Ab persistence.
HIV and coronary artery calcium score: comparison of the Hawaii Aging with HIV Cardiovascular Study and Multi-Ethnic Study of Atherosclerosis (MESA) cohorts.
Chow D, Young R, Valcour N … +6 more , Kronmal RA, Lum CJ, Parikh NI, Tracy RP, Budoff M, Shikuma CM
HIV Clin Trials · 2015 Aug · PMID 26038953 · Full text
OBJECTIVES: To determine the association of HIV, immunologic, and inflammatory factors on coronary artery calcium (CAC), a marker of subclinical atherosclerosis. METHODS: Cross-sectional study comparing baseline data of...
OBJECTIVES: To determine the association of HIV, immunologic, and inflammatory factors on coronary artery calcium (CAC), a marker of subclinical atherosclerosis. METHODS: Cross-sectional study comparing baseline data of males from Hawaii Aging with HIV - Cardiovascular Study (HAHCS) with the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. The cohorts were pooled to determine effects of HIV on CAC and explore immunologic and inflammatory factors that may explain development of CAC in HIV. Multivariable regression models compared CAC prevalence in HAHCS with MESA adjusting for coronary heart disease (CHD) risk profiles. RESULTS: We studied 100 men from HAHCS and 2733 men from MESA. Positive CAC was seen in 58% HAHCS participants and 57% MESA participants. Mean CAC was 260.8 in HAHCS and 306.5 in MESA. Using relative risk (RR) regression, HAHCS participants had a greater risk (RR = 1.20, P < 0.05) of having positive CAC than MESA when adjusting for age, smoking status, diabetes, antihypertensive therapy, BMI, systolic blood pressure, total cholesterol, and HDL cholesterol. Among participants with positive CAC, HIV infection was not associated with larger amounts of CAC. Among HAHCS participants, current HIV viral load, CD4, length of HIV, interleukin 6 (IL-6), fibrinogen, C-reactive protein (CRP), and D-dimer were not associated with the presence or amount of CAC. DISCUSSION: HIV was independently associated with a positive CAC in men with increased likelihood occurring between 45 and 50 years of age. Current HIV viral load, CD4 count, length of HIV, and inflammatory markers were unrelated to either presence or amount of CAC.
Removing inactive NRTIs in a salvage regimen is safe, maintains virological suppression and reduces treatment costs: results from the VERITAS study (TMC114HIV4054).
Trottier B, Galanakis C, Longpré D … +8 more , Dion H, Vézina S, Lavoie S, Boissonnault M, Costiniuk C, Jenabian MA, Machouf N, Thomas R
HIV Clin Trials · 2015 · PMID 25997535 · Publisher ↗
BACKGROUND: Despite the benefit of maintaining inactive Nucleotide/side reverse transcriptase inhibitors (NRTIs) in salvage regimens, they are associated with increased toxicity and treatment costs. Current evidence sugg...
BACKGROUND: Despite the benefit of maintaining inactive Nucleotide/side reverse transcriptase inhibitors (NRTIs) in salvage regimens, they are associated with increased toxicity and treatment costs. Current evidence suggests that NRTI-sparing regimens in patients failing ART are non-inferior to NRTI-including regimens. This study aimed to evaluate the impact of removing at least one inactive NRTI on virologic, safety, and financial outcomes. METHODS: Drug-resistant, virologically suppressed patients with CD4 >250 cells/ml on a stable regimen of four or more antiretrovirals (ARVs) were enrolled in a 48-week prospective, open-label pilot trial. One inactive NRTI was removed at baseline. Patients taking over five ARVs had a second inactive NRTI removed at 24 weeks. Viral load, CD4 count, and adverse events were assessed at baseline, 24, and 48 weeks. RESULTS: Thirty-one male patients participated. Twenty-nine (94%) patients had lamivudine (3TC) or emtricitabine (FTC) removed and four patients had an additional NRTI removed. One patient was excluded at week 26 for discontinuing an active NRTI. All patients maintained undetectable viral loads at weeks 24 (100%) and 48 [PP = 100%; Intent-to-treat (ITT) = 97%]. At 48 weeks, patients had a median gain of 20 CD4 (IQR: - 50, +133; mean +39) compared to baseline. Three patients exhibited Grade III bilirubin elevation (two Grade II and one Grade III at baseline), which returned to baseline levels. No serious adverse events were observed. Removal of one or two ARVs equated to a mean annual savings of $3319 CDN (11%) and $8630 CDN (24%), respectively. CONCLUSION: Removing inactive NRTIs in patients with a controlled viral load appears to be safe, maintains virological suppression, and reduces treatment costs.
Differences in antiretroviral safety and efficacy by sex in a multinational randomized clinical trial.
Firnhaber C, Smeaton LM, Grinsztejn B … +8 more , Lalloo U, Faesen S, Samaneka W, Infante R, Rana A, Kumarasamy N, Hakim J, Campbell TB
HIV Clin Trials · 2015 · PMID 25979186 · Full text
BACKGROUND AND OBJECTIVE: Worldwide, 50% of human immunodeficiency virus (HIV)-infected people are women. This study was to evaluate whether the safety and efficacy outcomes of three initial antiretroviral regimens (ARVs...
BACKGROUND AND OBJECTIVE: Worldwide, 50% of human immunodeficiency virus (HIV)-infected people are women. This study was to evaluate whether the safety and efficacy outcomes of three initial antiretroviral regimens (ARVs) differed by sex. METHODS: Antiretroviral regimen naive participants from nine countries in four continents were assigned to ARVs with efavirenz (EFV) plus lamivudine-zidovudine, atazanavir (ATV) plus didanosine (ddI)-EC/emtricitabine (FTC) or EFV plus FTC-tenofovir-DF. The primary objective was to estimate the sex difference on efficacy outcome of treatment failure defined as one of the following: 1. Time to 1st of confirmed virologic failure, 2. WHO Stage 4 progression or 3. death with hazard ratio (HR) and 95% confidence interval (CI) from adjusted Cox regression models. RESULTS: In all, 739 (47%) women and 832 (53%) men with HIV were evaluated. Women had higher pretreatment CD4+(182 vs 165 cells/mm(3); P < 0.001) and lower HIV-1 RNA (4.9 log10 vs 5.2 log10 copies/ml; P < 0.001) compared to men. Association of sex with time to regimen failure differed by treatment arm (P = 0.018). For atazanavir plus didanosine-EC plus emtricitabine, women had a longer time to treatment failure compared to men [adjusted HR (aHR) = 0.59; 95% CI 0.40-0.87]. Women were less likely to prematurely discontinue treatment prematurely (aHR = 0.74; 95% CI 0.56-0.98). Women assigned to efavirenz plus lamivudine-zidovudine were more likely to have a primary safety event compared to men (aHR = 1.49; 95% CI 1.18-1.88). CONCLUSION: Antiretroviral efficacy and safety differed by sex in this study. Consideration of potential effects of sex on antiretroviral outcomes is important for the design of future clinical trials and for HIV treatment guidelines.
Prevalence of concomitant medications in older HIV+ patients and comparison with general population.
Gimeno-Gracia M, Crusells-Canales MJ, Javier Armesto-Gómez F … +1 more , Rabanaque-Hernández MJ
HIV Clin Trials · 2015 · PMID 25978302 · Publisher ↗
OBJECTIVE: The increasing population of human immunodeficiency virus (HIV)-infected elderly patients results in a higher number of comorbidities and greater incidence of polypharmacy in addition to antiretroviral therapy...
OBJECTIVE: The increasing population of human immunodeficiency virus (HIV)-infected elderly patients results in a higher number of comorbidities and greater incidence of polypharmacy in addition to antiretroviral therapy (ART). The aim of this study is to describe the use of concomitant medication in older HIV-infected patients and to compare it with older general population. METHODS: The study included HIV-positive outpatients (>49 years) who received ART in 2011. Co-medication dispensed by pharmacies in that year was collected. Defined daily dose (DDD) for each drug was calculated by patient. A comparison was made between the use of co-medication among men between 50 and 64 years old in general population against the HIV-infected population. RESULTS: The study was based on 118 patients (77% men), of which 82% took at least one co-medication and 58% at least five. The commonest co-medications used by HIV-positive patients were antibiotics (44%); analgesics (44%); anti-inflammatories (39%); antacids (38%); and psycholeptics (38%). The medicines used for the greatest number of days per HIV-positive patient were those related to the renin-angiotensin system; anti-diabetics; lipid modifying agents; antithrombotics; and calcium channel blockers. In comparison with the general male population, a higher proportion of HIV-infected patients used antibiotics (42 vs 30%, P = 0.018), antiepileptics (16 vs 5%, P = 0.000), psycholeptics (35 vs 17%, P = 0.000) and COPD medications (14 vs 7%, P = 0.008). The duration of antibiotics and psycholeptic use in HIV-infected patients was longer compared to the general population (P < 0.05). CONCLUSIONS: Older HIV-positive patients frequently take a higher number of co-medication, which increases the risk of adverse events, interactions with other medication, and may lead to poorer treatment adherence.
Changes in quality of life, healthcare use, and substance use in HIV/hepatitis C coinfected patients after hepatitis C therapy: a prospective cohort study.
Yeung MW, Young J, Moodie E … +9 more , Rollet-Kurhajec KC, Schwartzman K, Greenaway C, Cooper C, Cox J, Gill J, Hull M, Walmsley S, Klein MB
HIV Clin Trials · 2015 · PMID 25972048 · Publisher ↗
OBJECTIVE: Clinical benefits of achieving a sustained virologic response (SVR) with hepatitis c virus (HCV) therapy beyond reducing liver-related outcomes have not been documented in HIV-coinfected patients, who have mul...
OBJECTIVE: Clinical benefits of achieving a sustained virologic response (SVR) with hepatitis c virus (HCV) therapy beyond reducing liver-related outcomes have not been documented in HIV-coinfected patients, who have multiple competing health problems. To gauge the potential benefits of curing HCV in coinfected people, we examined changes in health-related quality of life (HRQOL), healthcare and substance use, and overall mortality after treatment for HCV Coinfection. DESIGN: Prospective multicentre cohort study. METHODS: Among patients treated for HCV in the Canadian Coinfection Cohort study, self-reported HRQOL (using the EQ-5D), inpatient and outpatient medical visits, and substance use were assessed before, 6 months and 1 year after completing HCV therapy, comparing SVR-achievers and non-responders. Analysis of covariance and zero-inflated negative binomial regression were used to model the effects of SVR on HRQOL and healthcare use, respectively. RESULTS: Of 1145 patients chronically infected with HCV, 223 (19%) received treatment while under follow-up in the cohort and had HRQOL data collected - 86 (36%) achieved SVR, 68 (29%) did not, 30 (13%) had ongoing treatment, and 39 (17%) had unknown responses. Compared to non-responders, those achieving a SVR had higher HRQOL scores over time (11-unit increase 1 year posttreatment, 95% CI: 2, 21 measured 1 year posttreatment) and a lower rate of health service utilization (adjusted incidence rate ratio: 0.5, 95% CI: 0.3, 0.9). Short-term mortality was low but appeared lower in SVR-achievers (incidence rates: 0.10 vs 0.12 deaths per 100 person-years). However, after successful treatment, a substantial number of patients increased alcohol consumption and continued to inject drugs. CONCLUSIONS: Successful HCV treatment results in a range of health benefits for HIV/HCV-coinfected patients. Ongoing substance use, however, may mitigate the short- and long-term benefits associated with curing HCV.
Hepatic safety in subjects with HIV-1 and hepatitis C and/or B virus: a randomized, double-blind study of maraviroc versus placebo in combination with antiretroviral agents.
Rockstroh JK, Soriano V, Plonski F … +9 more , Bansal M, Fätkenheuer G, Small CB, Asmuth DM, Pialoux G, Mukwaya G, Jagannatha S, Heera J, Pineda JA
HIV Clin Trials · 2015 · PMID 25923596 · Publisher ↗
BACKGROUND: One of the more clinically relevant co-morbidities in HIV-infected patients is the development of progressive liver disease due to hepatitis B virus (HBV) or hepatitis C virus (HCV). In addition, hepatotoxici...
BACKGROUND: One of the more clinically relevant co-morbidities in HIV-infected patients is the development of progressive liver disease due to hepatitis B virus (HBV) or hepatitis C virus (HCV). In addition, hepatotoxicity has been observed with prolonged use of antiretroviral agents. OBJECTIVE: To evaluate the hepatic safety of maraviroc in combination with other antiretroviral agents in HIV-1-infected subjects co-infected with HCV and/or HBV. METHODS: In this 148-week randomized, double-blind, placebo-controlled, multicentre study (NCT01327547), subjects received maraviroc twice daily (n = 70) or placebo (n = 67) in combination with other antiretroviral agents. PRIMARY ENDPOINT: the percentage at week 48 of subjects with Grade 3 and Grade 4 ALT abnormalities, defined as >5 × upper limit of normal (ULN) if baseline ALT ≤ ULN or >3.5 × baseline if baseline ALT>ULN in the maraviroc versus the placebo arm. RESULTS: At week 48, one subject in each group had met the primary endpoint definition. No subjects met protocol-defined liver stopping criteria and there were no cases of Hy's law or treatment-related hepatobiliary serious adverse events. No significant difference in change from baseline in enhanced liver fibrosis or hepatic elastography was observed between groups. Treatment-related hepatobiliary adverse events were reported in one and two subjects receiving maraviroc and placebo, respectively; discontinuations due to treatment-related AEs occurred in four and two subjects receiving maraviroc and placebo, respectively; two deaths were reported in the placebo group. CONCLUSIONS: The use of maraviroc does not increase hepatotoxicity in HIV-1-infected subjects co-infected with HCV and/or HBV through 48 weeks of treatment.
Cardiovascular risk factors and lifetime risk estimation in HIV-infected patients under antiretroviral treatment in Spain.
Estrada V, Bernardino JI, Masiá M … +9 more , Iribarren JA, Ortega A, Lozano F, Miralles C, Olalla J, Santos J, Elías MJ, Domingo P, Cruz AF
HIV Clin Trials · 2015 · PMID 25874992 · Publisher ↗
BACKGROUND AND OBJECTIVES: Cardiovascular disease is a major concern in HIV-infected patients. Lifetime risk estimations use the risk of developing it over the course of remaining lifetime, and are useful in communicatin...
BACKGROUND AND OBJECTIVES: Cardiovascular disease is a major concern in HIV-infected patients. Lifetime risk estimations use the risk of developing it over the course of remaining lifetime, and are useful in communicating this risk to young patients. We aim to describe the prevalence of cardiovascular risk factors among a representative sample of HIV-infected subjects under antiretroviral therapy in Spain, and to estimate their lifetime risk of cardiovascular disease. METHODS: Cross-sectional survey about cardiovascular risk factors in 10 HIV units across Spain. Lifetime risk assessed according to Barry was classified in two major categories: low and high lifetime risk. RESULTS: We included 895 subjects, 72% men, median age 45.7 years; median CD4 lymphocyte count 598 cells/μl, median time since HIV diagnosis 11 years, median time on antiretroviral treatment 6.3 years, 87% had undetectable HIV viral load. Tobacco smoking was the most frequent risk factor (54%), followed by dyslipidemia (48.6%) and hypertension (38.6%). Estimated 10-year coronary risk (Framingham/Regicor Risk Score) risk was low ( < 5%) in 78% of the patients, and intermediate (5-10%) in 20%. Lifetime risk estimation showed a high risk profile for 71.4% of the population studied, which was associated with increasing age, prolonged antiretroviral therapy and patient's place of origin. CONCLUSIONS: Modifiable cardiovascular risk factors in this population are very common. There are significant disparities between the low 10-year risk estimated with the Framingham/Regicor score and the higher lifetime risk in HIV patients on antiretroviral therapy. A more aggressive management of modifiable cardiovascular risk factors in these patients seems advisable.
Tripterygium wilfordii Hook F extract in cART-treated HIV patients with poor immune response: a pilot study to assess its immunomodulatory effects and safety.
Li T, Xie J, Li Y … +10 more , Routy JP, Li Y, Han Y, Qiu Z, Lv W, Song X, Sun M, Zhang X, Wang F, Jiang H
HIV Clin Trials · 2015 · PMID 25874991 · Publisher ↗
BACKGROUND: Despite combination antiretroviral therapy (cART), 20% of HIV-infected patients are unable to achieve adequate immunologic recovery, in which immune activation plays a crucial role. We hypothesize that extrac...
BACKGROUND: Despite combination antiretroviral therapy (cART), 20% of HIV-infected patients are unable to achieve adequate immunologic recovery, in which immune activation plays a crucial role. We hypothesize that extract of Tripterygium wilfordii Hook F (TwHF), a Chinese medication used to treat autoimmune diseases, has immunomodulatory effects that may help CD4 cell recovery. METHODS: Eighteen cART-treated HIV-infected patients virally suppressed for over 12 months with suboptimal CD4 cell recovery were enrolled. TwHF extract was administered at a dosage of 10 mg three times daily for 12 months. T-cell subsets and activation markers were evaluated at baseline and during follow-up. The trial was registered at Clinicaltrials.gov (NCT02002286). RESULTS: TwHF extract was associated with a mean increase in CD4 cell count of 88 cells/μl (95% confidential interval [CI], 72-105 cells/μl) after one year of treatment. A significant increase in the mean rate of CD4 cell recovery (26 before vs 75 cells/μl/year after TwHF use, P < 0.001) was observed. Analysis of 13 patients with activation profiles suggested that TwHF extract was associated with a decrease in T-cell immune activation which was temporally correlated with CD4 cell recovery. No discontinuation of TwHF extract was reported. CONCLUSION: Use of TwHF extract in HIV-infected patients was associated with a reduction in T-cell activation and improved CD4 recovery with an excellent safety profile.
Cerebral function in perinatally HIV-infected young adults and their HIV-uninfected sibling controls.
Ashby J, Foster C, Garvey L … +6 more , Wan T, Allsop J, Paramesparan Y, Taylor-Robinson SD, Fidler S, Winston A
HIV Clin Trials · 2015 · PMID 25874990 · Publisher ↗
BACKGROUND: Perinatally acquired HIV-infected (PaHIV) young adults undergo neurodevelopment in the presence of HIV infection and antiretroviral therapy, which may lead to neurocognitive (NC) impairment. Knowledge of NC f...
BACKGROUND: Perinatally acquired HIV-infected (PaHIV) young adults undergo neurodevelopment in the presence of HIV infection and antiretroviral therapy, which may lead to neurocognitive (NC) impairment. Knowledge of NC function in this group is sparse and control data lacking. We compared cerebral function in young adults with PaHIV infection to aged matched HIV negative family controls. METHODS: 16-25-year-old PaHIV young adults (Group 1, n = 33) and HIV-uninfected family controls (Group 2, n = 14) were recruited. Cerebral function was evaluated by: a computerized battery assessing NC function (CogState(TM)), International HIV Dementia Scale (IHDS) and the prospective and retrospective memory questionnaire (PRMQ). Eight cases and four controls also underwent (1)H cerebral magnetic resonance spectroscopy ((1)H-MRS) scanning measuring basal ganglia (BG) metabolites. Cases and controls were compared. RESULTS: Group 1 mean (SD) CD4 count; 444 (319) cells/μl, plasma HIV viral load < 50 in 55%. There were no statistically significant differences between study groups in NC function or IHDS results (P>0.27 all observations). PRMQ scores were significantly higher (42 versus 35, P = 0.02) and MRS BG inflammatory-metabolites (choline- and myo-inositol- to creatine ratios) were significantly greater in Group 1 versus Group 2 (0.83 versus 0.63, P = 0.02 and 3.43 versus 3.03.P = 0.09 respectively). No significant association between PRMQ score and MRS metabolites was observed (P = 0.89). CONCLUSION: Statistically significant differences in cerebral function parameters were observed in PaHIV young adults compared to a well-matched control population. The cognitive deficit observed, in memory, rather than fine motor function, differs from the cerebral impairment often reported in HIV-infected adults.
Differential skeletal impact of tenofovir disoproxil fumarate in young versus old HIV-infected adults.
Grant PM, Kitch D, McComsey GA … +3 more , Tierney C, Ha B, Brown TT
HIV Clin Trials · 2015 · PMID 25872972 · Full text
BACKGROUND: Lower peak bone mass in early adulthood predicts subsequent fragility fractures. Antiretroviral toxicity could contribute to young HIV-infected individuals not achieving adequate peak bone mass. OBJECTIVE: To...
BACKGROUND: Lower peak bone mass in early adulthood predicts subsequent fragility fractures. Antiretroviral toxicity could contribute to young HIV-infected individuals not achieving adequate peak bone mass. OBJECTIVE: To determine if tenofovir disoproxil fumarate's (TDF) effect on bone mineral density (BMD) differs by age. METHODS: We examined BMD data at the lumbar spine and hip from AIDS Clinical Trials Group (ACTG) A5224s and ASSERT and randomized treatment-naive studies comparing TDF/emtricitabine versus abacavir/lamivudine (with efavirenz or atazanavir/ritonavir). In this post hoc analysis, we defined the TDF effect as the difference between mean 48-week BMD per cent changes for lumbar spine and hip in individuals randomized to TDF versus abacavir. We used multivariable linear regression to compare the TDF effect in individuals younger and older than 30 years. If TDF effect by age did not differ significantly between studies, we pooled study populations. Otherwise, analyses were conducted separately within each study population. RESULTS: Among 652 subjects, 21% were below age 30 years. The relationship between age and TDF effect significantly differed between A5224s and ASSERT (P = 0.008 for lumbar spine; P = 0.007 for hip). In A5224s, there was more bone loss with TDF at lumbar spine and hip in subjects under 30 years old versus in older subjects ( - 4.5% vs - 1.4%; P = 0.045; - 4.3% vs - 1.6%; P = 0.026, respectively). There was no significant evidence for this age-associated TDF effect in ASSERT. CONCLUSIONS: There was heterogeneity in the observed effect of TDF on bone density in young adults compared to older adults, suggesting that further investigation is required to understand the impact of age on BMD decline with TDF.
Renal safety of coformulated tenofovir/emtricitabine vs other nucleoside analogues in combination therapy in antiretroviral-naive patients aged 50 years or older in Spain: The TRIP study.
Pedrol E, Caro-Murillo AM, Castaño MA … +11 more , Riera M, Olalla J, Domingo P, Arazo P, Gómez-Sirvent JL, Pulido F, Romero-Palacios A, Aguirrebengoa K, Vera F, Ferrer P, Blanco Ramos JR
HIV Clin Trials · 2015 · PMID 25777189 · Publisher ↗
OBJECTIVES: Our aim is to describe the impact of emtricitabine (FTC)/tenofovir (TDF) versus other nucleoside reverse transcriptase inhibitor (NRTIs)-based regimens on renal function of human immunodeficiency virus (HIV)...
OBJECTIVES: Our aim is to describe the impact of emtricitabine (FTC)/tenofovir (TDF) versus other nucleoside reverse transcriptase inhibitor (NRTIs)-based regimens on renal function of human immunodeficiency virus (HIV) naïve patients >50 years old who started combination antiretroviral therapy (cART). DESIGN: National, retrospective cohort analysis of patients >50 years old when they started cART (January 1, 2006-December 31, 2009). METHODS: We compared renal safety (changes in estimated glomerular filtration rate [eGFR] during the first year, and time to renal events during 4 years of follow-up) in FTC/TDF versus non-FTC/TDF users. Among FTC/TDF users, we compared protease inhibitors vs non-nucleoside reverse transcriptase inhibitors and Lopinavir/ritonavir vs Efavirenz. RESULTS: We included 103 patients: median age: 54.9 years, 84% males, median CD4 count 247 cells/μl, median viral load 4.7 log; median follow up 18 months (max: 48 months); 73 started with FTC/TDF and 30 with other NRTIs. Change in eGFR was significantly worse for ritonavir-boosted lopinavir (LPV/r) vs efavirenz (EFV) users in the FTC/TDF group (71.2 vs 98.9 ml/min/1.73 m(2) at month 12, P < 0.05). The risk of renal events (progression to an Chronic Kidney Disease Epidemiology Collaboration value < 60 ml/min/1.73 m(2) in subjects with baseline values >60) was comparable for FTC/TDF users and non users, but was higher and almost significant for LPV/r as compared to EFV users in the FTC/TDF group (adjusted hazard ratio 6.1, 95% CI 0.8-45.5). CONCLUSIONS: In our study with a population of HIV infected subjects ≥ 50 years old, renal safety was similar for FTC/TDF and other NRTI-based regimens, but worse for LPV/r as compared to other regimens.
The pharmacokinetic profile of raltegravir-containing antiretroviral therapy in HIV-infected individuals over 60 years of age.
Vera JH, Jackson A, Dickinson L … +6 more , Else L, Barber T, Mora-Peris B, Back D, Boffito M, Winston A
HIV Clin Trials · 2015 · PMID 25777188 · Publisher ↗
BACKGROUND: Antiretroviral safety and efficacy and may differ in older versus younger HIV-infected patients. The objective of this study was to assess the pharmacokinetic (PK) profile in older HIV-infected subjects (>60 ...
BACKGROUND: Antiretroviral safety and efficacy and may differ in older versus younger HIV-infected patients. The objective of this study was to assess the pharmacokinetic (PK) profile in older HIV-infected subjects (>60 years) switching combination antiretroviral therapy (cART) to a raltegravir (RAL) containing regimen. METHODS: Nineteen HIV-infected patients over 60 years of age on effective cART (HIV-RNA < 50 copies/ml) were enrolled in this prospective 24-week study. On day 1, patients switched to tenofovir/emtricitabine (245/200 mg once daily) and RAL (400 mg twice daily). On day 28, intensive PK sampling was undertaken in a fasted state and RAL plasma concentrations determined. Neurocognitive function was assessed at baseline and week 24 using a neuropsychological battery. RAL PK parameters were compared to those of two younger historical HIV-infected control groups that received twice-daily RAL co-administered with darunavir/ritonavir (DRV/r) 800/100 once daily by nonlinear mixed effects modelling. RESULTS: In HIV-infected subjects over the age of 60 (mean ± SD age: 66 ± 3.4 years, n = 19) switching to a RAL containing regimen, we observed no safety concerns, no plasma virological rebounds, and no differences in RAL apparent oral clearance when compared to younger HIV-infected populations (mean ± SD age: 41 ± 9.2 years, n = 38) based on population pharmacokinetic analysis. After 24 weeks of study therapy a decline in cognitive function was observed [change in (SD) global score of (0.91 (1.3), P = 0.018]. CONCLUSIONS: No significant changes in RAL exposure associated with age were observed.
96-week resistance analyses of the STaR study: rilpivirine/emtricitabine/tenofovir DF versus efavirenz/emtricitabine/tenofovir DF in antiretroviral-naive, HIV-1-infected subjects.
Porter DP, Kulkarni R, Fralich T … +2 more , Miller MD, White KL
HIV Clin Trials · 2015 · PMID 25777187 · Publisher ↗
BACKGROUND: STaR (GS-US-264-0110) was a 96-week phase 3b study evaluating the safety and efficacy of two single-tablet regimens, rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF) and efavirenz/emtricitabine/tenofovir...
BACKGROUND: STaR (GS-US-264-0110) was a 96-week phase 3b study evaluating the safety and efficacy of two single-tablet regimens, rilpivirine/emtricitabine/tenofovir DF (RPV/FTC/TDF) and efavirenz/emtricitabine/tenofovir DF (EFV/FTC/TDF) in treatment-naive, HIV-1-infected subjects. METHODS: Genotypic analyses (population sequencing) of HIV-1 protease (PR) and reverse transcriptase (RT) were performed at screening; subjects with pre-existing resistance to study drugs were excluded. The protocol-defined resistance analysis population had genotypic/phenotypic analyses at failure and baseline for PR and RT. RESULTS: Through week 96, the resistance analysis population included 24/394 subjects (6.1%) receiving RPV/FTC/TDF and 9/392 subjects (2.3%) receiving EFV/FTC/TDF. In the RPV/FTC/TDF arm, HIV-1 isolates from 21/394 subjects (5.3%) developed non-nucleoside reverse transcriptase inhibitor (NNRTI) and/or nucleoside reverse transcriptase inhibitor (NRTI) resistance mutations and 20/21 isolates had both NNRTI and NRTI genotypic and/or phenotypic resistance. In the EFV/FTC/TDF arm, isolates from 4/392 subjects (1.0%) developed NNRTI and/or NRTI resistance mutations. Resistance development after week 48 was infrequent (1.0% RPV/FTC/TDF; 0.3% EFV/FTC/TDF). When stratified by baseline HIV-1 RNA ≤ or >100 000 copies/ml, 9/260 (3.5%) versus 12/134 (9.0%) RPV/FTC/TDF-treated subjects and 3/250 (1.2%) versus 1/142 (0.7%) EFV/FTC/TDF-treated subjects developed resistant isolates, respectively. Pre-existing NRTI- and NNRTI-associated resistance mutations (not related to study drugs) did not impact treatment response to either regimen. CONCLUSIONS: Resistance development to RPV/FTC/TDF consisted of NNRTI and NRTI mutations and was more frequent than resistance development to EFV/FTC/TDF through week 96. Emergent resistance after week 48 was infrequent in both arms. Within the RPV/FTC/TDF arm, resistance development was more frequent in subjects with baseline HIV-1 RNA >100 000 copies/ml compared to baseline HIV-1 RNA ≤ 100 000 copies/ml.
Effectiveness and safety of rilpivirine, a non-nucleoside reverse transcriptase inhibitor, in treatment-naive adults infected with HIV-1: a meta-analysis.
Li SL, Xu P, Zhang L … +2 more , Sun GX, Lu ZJ
HIV Clin Trials · 2015 · PMID 25777186 · Publisher ↗
OBJECTIVES: The aim of this study was to determine the effectiveness and safety of rilpivirine in treatment-naive adults infected with HIV-1. METHODS: We ran duplicate searches of multiple databases and searchable websit...
OBJECTIVES: The aim of this study was to determine the effectiveness and safety of rilpivirine in treatment-naive adults infected with HIV-1. METHODS: We ran duplicate searches of multiple databases and searchable websites of major HIV conferences (up to October 2013) to identify randomized controlled trials reporting the effectiveness and safety of rilpivirine in treatment-naive adults infected with HIV-1. Reference lists from retrieved articles were also reviewed. Data were extracted independently in duplicate using predefined data fields. All analyses used random-effects models to calculate the summary treatment effect estimates. RESULTS: Four randomized controlled trials with a total of 2522 patients were included in the inclusion criteria. The primary efficacy endpoint was the proportion of patients with confirmed HIV-1 RNA levels of < 50 copies/ml (viral load) at 48 weeks. Rilpivirine demonstrated non-inferior antiviral efficacy in viral load comparable with efavirenz at 48 weeks [relative risk (RR) = 1.03, 95% confidence interval (CI): 0.99-1.07]. The mean changes from baseline in CD4 count were similar in both rilpivirine and efavirenz (RR = 1.05, 95% CI: 0.85-1.24). Rilpivirine showed higher and significant difference in virological failure rates comparing with the efavirenz group (RR = 1.70, 95% CI: 1.21-2.38). The incidences of the most commonly reported adverse events related to study medication, including rash, and neurological events, were lower with rilpivirine than with efavirenz (RR = 0.11, 95% CI: 0.03-0.33; RR = 0.52, 95% CI: 0.45-0.60, respectively). CONCLUSIONS: Current evidence suggests a range of favorable effects and a generally favorable safety profile of rilpivirine in treatment-naive adults infected with HIV-1 at week 48.
The maraviroc expanded access program - safety and efficacy data from an open-label study.
Lazzarin A, Reynes J, Molina JM … +6 more , Valluri S, Mukwaya G, Heera J, Craig C, van der Ryst E, Sierra-Madero JG
HIV Clin Trials · 2015 · PMID 25777185 · Publisher ↗
PURPOSE: The maraviroc (MVC) expanded access program (EAP) was initiated to increase MVC availability to patients with limited treatment options. Darunavir (DRV), raltegravir (RAL), and etravirine (ETV) were either recen...
PURPOSE: The maraviroc (MVC) expanded access program (EAP) was initiated to increase MVC availability to patients with limited treatment options. Darunavir (DRV), raltegravir (RAL), and etravirine (ETV) were either recently approved or under regulatory review at study initiation and available for coadministration with MVC. Thus, the safety of MVC in combination with new antiretroviral therapies (ARVs) could be assessed. This open-label safety study of MVC was conducted at 262 sites worldwide in 1032 R5 HIV-positive treatment-experienced patients with limited/no therapeutic options. METHODS: Study visits included screening, baseline, end of study or early discontinuation, and follow-up 30 days after last dose. Interim visits for HIV-1 RNA and CD4 cell counts occurred according to local HIV infection management guidelines. Safety data were analyzed overall and by subgroup based on ARV combination [MVC+optimized background therapy (OBT), MVC ± OBT+DRV/r, MVC ± OBT+RAL, MVC ± OBT+RAL+DRV/r, MVC ± OBT+RAL+ETV ± DRV/r]. RESULTS: Most (90.3%) adverse events (AEs) were of mild or moderate severity with few grade 3/4 events, discontinuations, or temporary discontinuations/dose reductions due to AEs or serious AEs. Similar results were observed across subgroups. Of treated patients, 79.9% and 50% had HIV-1 RNA < 400 copies/ml and < 50 copies/ml respectively, at the end of the study, early termination visits, or at last known status. Tropism changes and selection of MVC-resistant R5 virus, including high-level MVC dependence, were mechanisms of viral escape. CONCLUSION: MVC was well tolerated with virologic suppression observed in most patients.
Reliability and validity of a single-item rating scale to monitor medication adherence for people living with HIV and lower health literacy.
Pellowski JA, Kalichman SC, Finitsis DJ
HIV Clin Trials · 2015 · PMID 25777184 · Full text
BACKGROUND: Monitoring medication adherence in clinical and research settings may be especially challenging for people with lower literacy skills. OBJECTIVE: The current study examined the measurement properties of a sin...
BACKGROUND: Monitoring medication adherence in clinical and research settings may be especially challenging for people with lower literacy skills. OBJECTIVE: The current study examined the measurement properties of a single-item rating scale (SIRS) for assessing medication adherence in a sample of 468 people living with HIV and lower health literacy skills. METHODS: Participants completed two versions (computerized and telephone interview) of an SIRS as well as unannounced monthly pill counts. We also collected measures of common correlates of adherence and obtained participants' HIV RNA viral load from medical records. RESULTS: Results indicated that the SIRS is time stable over one month (r = 0.46 to 0.52). There was limited evidence for modality effects between the computerized and phone administered SIRS. Associations with unannounced pill counts demonstrated concurrent and predictive validity of the SIRS, and criterion-related validity by associations with viral load. However, the SIRS also demonstrated inflated adherence estimates relative to unannounced pill counts and these discrepancies were greatest for persons of lower income and who reported alcohol use. CONCLUSIONS: A simple SIRS to monitor medication adherence may therefore be reliable and valid for use with people challenged by lower literacy skills in both clinical and research settings.
Cobicistat-boosted protease inhibitors in HIV-infected patients with mild to moderate renal impairment.
McDonald CK, Martorell C, Ramgopal M … +10 more , Laplante F, Fisher M, Post FA, Liu Y, Curley J, Abram ME, Custodio J, Graham H, Rhee MS, Szwarcberg J
HIV Clin Trials · 2014 · PMID 25433666 · Publisher ↗
BACKGROUND: Cobicistat (COBI) is a pharmacoenhancer that optimizes systemic exposures of protease inhibitors (PIs) such as atazanavir (ATV) and darunavir (DRV). OBJECTIVE: To evaluate the efficacy and safety of switching...
BACKGROUND: Cobicistat (COBI) is a pharmacoenhancer that optimizes systemic exposures of protease inhibitors (PIs) such as atazanavir (ATV) and darunavir (DRV). OBJECTIVE: To evaluate the efficacy and safety of switching ritonavir (RTV) to COBI in patients with creatinine clearance (CrCl) 50 to 89 mL/min who are virologically suppressed on a stable regimen containing ritonavir (RTV)-boosted ATV or DRV. Other components of the regimen remained unchanged. METHODS: A phase 3, non-comparative, open-label clinical trial. RESULTS: Seventy-three patients were enrolled. At week 48, 82% maintained virologic suppression. No emergent resistance developed. Serious adverse events (AEs) occurred in 7%, and study drug discontinuation due to AEs occurred in 10% (7 patients). There were 2 renal discontinuations and no cases of proximal renal tubulopathy. Small reductions in CrCl (median [IQR]) were observed as early as week 2, after which they were nonprogressive through week 48 (-3.8 [-9 to 0.8]). Changes in CrCl by baseline CrCl (< 70 vs ≥ 70) were -1.1 [-6.5 to 6.3] versus -6.6 [-12.4 to -0.7], respectively. CONCLUSIONS: In HIV-1-infected patients with CrCl 50 to 89 mL/min switching from RTV to COBI, COBI-boosted PIs in combination with 2 nucleos(t)ide reverse transcriptase inhibitors were well-tolerated and effective in maintaining virologic suppression. The renal safety profile of COBI in this study was consistent with the long-term data in patients without renal impairment from the phase 3 studies of COBI-containing regimens.
Effectiveness and safety of rilpivirine, a non-nucleoside reverse transcriptase inhibitor, in treatment-naive adults infected with HIV-1: a meta-analysis.
Li SL, Xu P, Zhang L … +2 more , Sun GX, Lu ZJ
HIV Clin Trials · 2014 · PMID 25433665 · Publisher ↗
OBJECTIVE: The aim of this study was to determine the effectiveness and safety of rilpivirine in treatment-naive adults infected with HIV-1. METHODS: We ran duplicate searches of multiple databases and searchable Web sit...
OBJECTIVE: The aim of this study was to determine the effectiveness and safety of rilpivirine in treatment-naive adults infected with HIV-1. METHODS: We ran duplicate searches of multiple databases and searchable Web sites of major HIV conferences (May to October 2013) to identify randomized controlled trials reporting the effectiveness and safety of rilpivirine in treatment-naive adults infected with HIV-1. Reference lists from retrieved articles were also reviewed. Data were extracted independently in duplicate using predefined data fields. All analyses used random effects models to calculate the summary treatment effect estimates. RESULTS: Four randomized controlled trials with a total of 2,522 patients were included. The primary efficacy endpoint was the proportion of patients with confirmed HIV-1 RNA levels of <50 copies/mL (viral load) at 48 weeks. Rilpivirine demonstrated noninferior antiviral efficacy in viral load comparable with efavirenz at 48 weeks (relative risk [RR], 1.03; 95% CI, 0.99-1.07). The mean changes from baseline in CD4 count were similar in both rilpivirine and efavirenz (RR, 1.05; 95% CI, 0.85-1.24). Rilpivirine showed higher and significant difference in virological failure rates compared with the efavirenz group (RR, 1.70; 95% CI, 1.21-2.38). The incidences of the most commonly reported adverse events related to study medication, including rash and neurological events, were lower with rilpivirine than with efavirenz (RR, 0.11; 95% CI, 0.03-0.33; RR, 0.52; 95% CI, 0.45-0.60, respectively). CONCLUSIONS: Current evidence suggests a range of favorable effects and a generally favorable safety profile of rilpivirine in treatment-naive adults infected with HIV-1 at week 48.
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