A5053042121- HIV/AIDS Research and Interventions
- HIV Research and Treatment
- HIV/AIDS drug development and treatment
- HIV-related health complications and treatments
- Pneumocystis jirovecii pneumonia detection and treatment
- Tuberculosis Research and Epidemiology
- Infectious Diseases and Tuberculosis
- Cytomegalovirus and herpesvirus research
- Immune Cell Function and Interaction
- Animal Genetics and Reproduction
- Virus-based gene therapy research
- Spinal Hematomas and Complications
- Herpesvirus Infections and Treatments
- Lipid metabolism and disorders
- Syphilis Diagnosis and Treatment
- RNA Research and Splicing
- Mobile Health and mHealth Applications
- Amoebic Infections and Treatments
- Cancer Immunotherapy and Biomarkers
- RNA and protein synthesis mechanisms
- Bone health and osteoporosis research
- Whipple's Disease and Interleukins
- Peripheral Neuropathies and Disorders
- Mycobacterium research and diagnosis
- Autoimmune and Inflammatory Disorders Research
Social and Scientific Systems (United States)
2013-2023
Scientific Systems (United States)
2015-2021
AIDS Clinical Trials Group
2006-2017
University of Pennsylvania
1986
Optimal timing of ART initiation for individuals presenting with AIDS-related OIs has not been defined.A5164 was a randomized strategy trial "early ART"--given within 14 days starting acute OI treatment versus "deferred after is completed. Randomization stratified by and entry CD4 count. The primary week 48 endpoint 3-level ordered categorical variable: 1. Death/AIDS progression; 2. No progression incomplete viral suppression (ie HIV load (VL) >or=50 copies/ml); 3. optimal VL <50 copies/ml)....
Antiretroviral therapy (ART) is indicated during tuberculosis treatment in patients infected with human immunodeficiency virus type 1 (HIV-1), but the timing for initiation of ART when diagnosed various levels immune compromise not known.We conducted an open-label, randomized study comparing earlier (within 2 weeks after tuberculosis) later (between 8 and 12 HIV-1 CD4+ T-cell counts less than 250 per cubic millimeter suspected tuberculosis. The primary end point was proportion who survived...
Antiretroviral therapy (ART) reduces levels of HIV-1 and immune activation but both can persist despite clinically effective ART. The relationships among pre-ART on-ART are incompletely understood, in part because prior studies have been small or cross-sectional. To address these limitations, we evaluated measures persistence, inflammation, T cell cycling a longitudinal cohort 101 participants who initiated ART had well-documented sustained suppression plasma viremia for median 7 years....
Background: Decreased bone mineral density (BMD) is prevalent in HIV-infected patients. Bisphosphonates are currently the mainstay of treatment for postmenopausal and male osteoporosis HIV-uninfected individuals; however, their efficacy safety patients remains unclear. Methods: In this prospective, randomized, placebo-controlled multicenter trial, we studied effectiveness calcium vitamin D supplementation with or without alendronate improving BMD subjects receiving stable antiretroviral...
Immune reconstitution inflammatory syndrome (IRIS) is reported widely in patients initiating antiretroviral therapy (ART). However, few studies are prospective, and no study has evaluated the impact of timing ART when allocated randomly during an acute opportunistic infection (OI).A5164 randomized 282 subjects with AIDS-related OIs (tuberculosis excluded), to early or deferred ART. IRIS was identified prospectively using pre-defined criteria. We associations between baseline variables...
Peripartum administration of single-dose nevirapine reduces mother-to-child transmission human immunodeficiency virus type 1 (HIV-1) but selects for nevirapine-resistant virus.In seven African countries, women infected with HIV-1 whose CD4+ T-cell counts were below 200 per cubic millimeter and who either had or not taken at least 6 months before enrollment randomly assigned to receive antiretroviral therapy tenofovir–emtricitabine plus tenofovir-emtricitabine lopinavir boosted by a low dose...
Abstract Background HIV-1 proviruses persist in people on antiretroviral therapy (ART) but most are defective and do not constitute a replication-competent reservoir. The decay of infected cells carrying intact compared with has been well defined ART. Methods We separately quantified proviruses, residual plasma viremia, markers inflammation activation long-term Results Among 40 participants tested longitudinally from median 7.1 years to 12 after ART initiation, provirus levels declined...
BACKGROUND. Persistence of HIV in sanctuary sites despite antiretroviral therapy (ART) presents a barrier to remission and may affect neurocognitive function. We assessed persistence cerebrospinal fluid (CSF) associations with inflammation performance during long-term ART.
Introduction: Fish oil has been shown to reduce serum triglyceride (TG) concentrations. In HIV-infected patients on antiretroviral therapy, high TG concentrations likely contribute increased risk of cardiovascular disease. AIDS Clinical Trials Group A5186 examined the safety and efficacy fish plus fenofibrate in subjects not achieving levels ≤200 mg/dL with either agent alone. Methods: One hundred highly active therapy ≥400 low-density lipoprotein cholesterol ≤160 were randomized 3 g twice...
Rifampin (RIF) upregulates CYP 450 isoenzymes, potentially lowering efavirenz (EFV) exposure. The US EFV package insert recommends an dose increase for patients on RIF weighing ≥50 kg. We conducted a pharmacokinetic study to evaluate trough concentrations (Cmin) and human immunodeficiency virus (HIV) virologic suppression in (600 mg) RIF-based tuberculosis treatment the multicenter randomized trial (ACTG A5221).EFV Cmin was measured 20-28 hours post-EFV at weeks 4, 8, 16, 24 on-RIF 8...
<h2>Summary</h2><h3>Background</h3> Antiretroviral therapy (ART) non-adherence causes HIV treatment failure. Past behaviour might predict future behaviour; failing second-line ART could indicate ongoing risk for subsequent non-adherence. We aimed to find out whether a two-way mobile phone-based communication intervention would increase success by improving medication adherence. <h3>Methods</h3> did multinational, randomised controlled trial of patients at 17 sites in nine lower-income and...
Abstract Fourteen people with human immunodeficiency virus type 1 had longitudinal measurements of intact, defective, and total proviral DNA over the course two decades antiretroviral therapy. Three patterns intact decay were revealed: (1) biphasic decline markedly slower second-phase decline, (2) initial that transitions to a zero-slope plateau, (3) followed by later increases in DNA. Defective levels essentially stable. Mechanisms slowing or reversal may include inability clear cells but...
Nevirapine (NVP) is widely used in antiretroviral treatment (ART) of HIV-1 globally. The primary objective the AA5208/OCTANE trial was to compare efficacy NVP-based versus lopinavir/ritonavir (LPV/r)-based initial ART.In seven African countries (Botswana, Kenya, Malawi, South Africa, Uganda, Zambia, and Zimbabwe), 500 antiretroviral-naïve HIV-infected women with CD4<200 cells/mm(3) were enrolled into a two-arm randomized initiate open-label ART tenofovir (TDF)/emtricitabine (FTC) once/day...
Objective: We evaluated frequencies of T cells with high PD-1 expression (PD-1HI) before and after long-term effective antiretroviral therapy (ART), determined if on-ART correlated positively measures HIV persistence negatively HIV-specific responses. Methods: enrolled individuals who started ART during chronic infection had durable suppression viremia for at least 4 years (N = 99). assessed PD-1HI T-cell timepoints pre-ART using flow cytometry, how are associated persistence, immune...
Short-term (48-week) results of the OPTIONS trial showed that nucleoside reverse transcriptase inhibitors (NRTIs) can be safely omitted from salvage therapy as long regimen has a cumulative activity >2 active antiretroviral medications. The long-term durability this approach and outcomes in persons who have more-extensive HIV-1 drug resistance are uncertain.Participants with virologic failure anticipated susceptibility received an optimized were randomized to omit or add NRTIs. A separate...
We have examined EcoRI-restricted cellular DNA from mouse-hamster somatic cell hybrids. Results of this analysis show that the unit II mouse mammary tumor virus proviral genome is located on chromosome 6. Restriction (C3H/OuJ X Czech II) backcross mice showed a strong linkage between and Igk. The gene order these markers 6 relative to Raf Kirsten murine sarcoma ras-2 proto-oncogenes was established.
Background: Limited comparative, prospective data exist regarding cardiovascular risk factors in HIV-infected women starting antiretroviral therapy Africa. Methods: In 7 African countries, 741 with CD4 <200 cells/mm3 were randomized to tenofovir/emtricitabine (TDF/FTC) plus either nevirapine (NVP, n = 370) or lopinavir/ritonavir (LPV/r, 371). Lipids and blood pressure (BP) evaluated at entry, 48, 96, 144 weeks. Multivariable linear logistic regression models used evaluate mean factor changes...
Tenofovir disoproxil fumarate (TDF) has been associated with renal insufficiency. Co-administration boosted protease inhibitors, which increases its exposure, may further increase the risk of insufficiency.We compared incidence events among women taking TDF co-administered lopinavir/ritonavir (LPV/r) versus those co-administering nevirapine (NVP). Renal were defined as a confirmed drop in creatinine clearance serum grade 2 or higher, that leading to treatment modification.Overall, 741...
Data on the relationship of antiretroviral exposure to measures human immunodeficiency virus (HIV) persistence are limited. To address this gap, multiple viral, immunologic, and pharmacologic were analyzed from individuals with sustained virologic suppression therapy (median 7 years) in AIDS Clinical Trials Group A5321 cohort. Among 110 participants tenofovir-(TFV)-disoproxil-fumarate (TDF)/emtricitabine (FTC)-containing regimens, we found no significant correlation between hair...
ABSTRACT Rifapentine is a potent antituberculosis drug currently in phase III trials. Bioavailability decreases with increasing dose, yet high daily exposures are likely needed to improve efficacy and shorten the tuberculosis treatment duration. Further, limits of tolerability poorly defined. The I multicenter trial healthy adults described here investigated two strategies increase rifapentine exposures: dividing dose or giving high-fat meal. In arm 1, was administered at 10 mg/kg body...
Statins exert pleiotropic anti-inflammatory and immune-modulatory effects, which might translate into antiviral activity. We evaluated whether reported current statin exposure is associated with lower levels of markers HIV persistence immune activation/inflammation.We compared viral [cell-associated RNA (CA-RNA), CA-DNA, single copy assay plasma RNA] activation/inflammation (IL-6, IP-10, neopterin, sCD14, sCD163, TNF-alpha) between users nonusers among participants ACTG A5321 who initiated...
Abstract Introduction ACTG A5288 was a strategy trial conducted in diverse populations from multiple continents of people living with HIV (PLWH) failing second‐line protease inhibitor (PI)‐based antiretroviral therapy (ART) 10 low‐ and middle‐income countries (LMICs). Participants resistant to lopinavir (LPV) and/or nucleotide reverse transcriptase inhibitors started on third‐line regimens that included raltegravir (RAL), darunavir/ritonavir (DRV/r) etravirine (ETR) according their...
Objective: We evaluated the safety, tolerability and antiretroviral activity of β-D-2,6-diaminopurine dioxolane (DAPD; amdoxovir) with or without mycophenolate mofetil (MMF) in HIV-1 infection following extensive therapy (ART). Methods: Oral DAPD 500 mg twice daily placebo MMF was added to failing ART. RNA viral load (VL) decline week 2 analyzed by intent-to-treat, using rank-based tests. Patients VL > 0.5 log10 copies/ml at (virologic response, VR) optimized ART continued for up 96 weeks....