Showing papers by "Jeffrey L. Lennox published in 2011"

Long-term Treatment With Raltegravir or Efavirenz Combined With Tenofovir/Emtricitabine for Treatment-Naive Human Immunodeficiency Virus-1–Infected Patients: 156-Week Results From STARTMRK

Abstract: Background. We compared 3 years of antiretroviral therapy with raltegravir or efavirenz as part of a combination regimen in the ongoing STARTMRK study of treatment-naive patients infected with human immunodeficiency virus (HIV). Methods. Eligible patients with HIV-1 RNA (vRNA) levels .5000 copies/mL and without baseline resistance to efavirenz, tenofovir, or emtricitabine were randomized in a double-blind, noninferiority study to receive raltegravir or efavirenz, each combined with tenofovir/emtricitabine. Outcomes included viral suppression, adverse events, and changes from baseline metabolic parameters. Dual energy X-ray absorptiometry scans were obtained on a convenience sample of patients at prespecified time points to assess changes in body fat composition. Results. At week 156 counting noncompleters as failures, 212 (75.4%) of 281 versus 192 (68.1%) of 282 had vRNA levels ,50 copies/mL in the raltegravir and efavirenz groups, respectively [D (95% CI) 5 7.3% (20.2, 14.7), noninferiority P , .001]. Mean changes from baseline CD4 count were 332 and 295 cells/mm 3 in the raltegravir and efavirenz arms, respectively [D (95% CI) 5 37 (4, 69)]. Consistent virologic and immunologic efficacy was maintained across prespecified demographic and baseline prognostic subgroups for both treatment groups. Fewer drug-related clinical adverse events (49% vs 80%; P , .001) occurred in raltegravir than efavirenz recipients, with discontinuations due to adverse events in 5% and 7%, respectively. Elevations in fasting lipid levels (including LDL- and HDL-cholesterol) were consistently lower in the raltegravir than efavirenz group (P , .005). Fat gain was 19% in 25 raltegravir recipients and 31% in 32 efavirenz recipients at week 156. Conclusions. When combined with tenofovir/emtricitabine in treatment-naive patients, raltegravir produced durable viral suppression and immune restoration that was at least equivalent to efavirenz through 156 weeks of therapy. Both regimens were well tolerated, but raltegravir was associated with fewer drug-related clinical adverse events and smaller elevations in lipid levels. Clinical Trials Registration. NCT00369941

Tuberculosis Biomarker and Surrogate Endpoint Research Roadmap

Abstract: The Centers for Disease Control and Prevention and National Institutes of Health convened a multidisciplinary meeting to discuss surrogate markers of treatment response in tuberculosis. The goals were to assess recent surrogate marker research and to provide specific recommendations for (1) the qualification and validation of biomarkers of treatment outcome; (2) the standardization of specimen and data collection for future clinical trials, including a minimum set of samples and collection time points; and (3) the creation of a specimen repository to support biomarker testing. This article summarizes these recommendations and provides a roadmap for their implementation.

HIV-1 RNA Rectal Shedding Is Reduced in Men With Low Plasma HIV-1 RNA Viral Loads and Is Not Enhanced by Sexually Transmitted Bacterial Infections of the Rectum

Abstract: Over half (53%) of new human immunodeficiency virus (HIV) infection diagnoses in the United States from 2001–2006 were among men who have sex with men (MSM), accounting for almost 100 000 new infections [1]. During this time period, both the incidence and prevalence of HIV among MSM increased significantly after both trends had steadily declined during the 1990s [2–4]. Anal intercourse, principally among MSM, remains the primary mode of HIV transmission in the United States, and insertive anal intercourse among MSM accounts for 28% of new infections [5], making rectal secretions an important potential source of HIV transmission. MSM, including HIV-infected MSM, also experience high incidences of other sexually transmitted infections (STIs), notably rectal and oral Neisseria gonorrhoeae (GC) and Chlamydia trachomatis (CT). Although urethral STIs increase HIV shedding in semen, the effect of rectal STIs on HIV shedding into rectal secretions, especially among MSM with suppressed plasma HIV viral loads, is largely undescribed [6–8]. No studies have explored the influence of rectal GC or CT infection on HIV shed in rectal secretions. The vast majority of transmitted HIV is CCR5-tropic for reasons that are incompletely understood [9–11]. There are few data on the molecular characteristics of HIV shed in the rectum, as most previous studies have focused on rectal biopsies or feces [12–15]. Further exploration into the molecular characteristics of HIV in rectal secretions is therefore warranted in light of the potential significant role they play in HIV transmission and as a target for biomedical prevention interventions. One barrier to this research is the difficulty in obtaining clinical samples, as previous methods employed anoscopy [16–19]. Therefore, we sought to determine the applicability of rectal swabs collected without anoscopy for GC and CT screening for measuring HIV shedding in rectal secretions. In addition, we sought to determine the effect of rectal GC or CT infection on HIV rectal viral load in a contemporary US sample of HIV-infected MSM with access to combination antiretroviral therapy (cART). Finally, to enhance our understanding of the molecular factors that contribute to HIV transmission from rectal secretions, we compared HIV coreceptor (CCR5 vs CXCR4) usage between viruses found in plasma and rectal secretions among a subset of men in the cohort.

High prevalence of persistent parasitic infections in foreign-born, HIV-infected persons in the United States.

Abstract: Background Foreign-born, HIV-infected persons are at risk for sub-clinical parasitic infections acquired in their countries of origin. The long-term consequences of co-infections can be severe, yet few data exist on parasitic infection prevalence in this population. Methodology/Principal Findings This cross-sectional study evaluated 128 foreign-born persons at one HIV clinic. We performed stool studies and serologic testing for strongyloidiasis, schistosomiasis, filarial infection, and Chagas disease based on the patient's country of birth. Eosinophilia and symptoms were examined as predictors of helminthic infection. Of the 128 participants, 86 (67%) were male, and the median age was 40 years; 70 were Mexican/Latin American, 40 African, and 18 from other countries or regions. Strongyloides stercoralis antibodies were detected in 33/128 (26%) individuals. Of the 52 persons from schistosomiasis-endemic countries, 15 (29%) had antibodies to schistosome antigens; 7 (47%) had antibodies to S. haematobium, 5 (33%) to S. mansoni, and 3 (20%) to both species. Stool ova and parasite studies detected helminths in 5/85 (6%) persons. None of the patients tested had evidence of Chagas disease (n = 77) or filarial infection (n = 52). Eosinophilia >400 cells/mm3 was associated with a positive schistosome antibody test (OR 4.5, 95% CI 1.1–19.0). The only symptom significantly associated with strongyloidiasis was weight loss (OR 3.1, 95% CI 1.4–7.2). Conclusions/Significance Given the high prevalence of certain helminths and the potential lack of suggestive symptoms and signs, selected screening for strongyloidiasis and schistosomiasis or use of empiric antiparasitic therapy may be appropriate among foreign-born, HIV-infected patients. Identifying and treating helminth infections could prevent long-term complications.

Immune activation mediated change in alpha-1-acid glycoprotein: impact on total and free lopinavir plasma exposure.

Abstract: Background Immune mediated changes in circulating α-1-acid glycoprotein (AAG), a type 1 acute phase protein, which binds protease inhibitors (PI), may alter protein binding and contribute to PI's pharmacokinetic (PK) variability.