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Rajib K Bhattacharya,1 Mohit Khera,2 Gary Blick,3 Harvey Kushner,4 Martin M Miner51Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA; 2Scott Department of Urology, Baylor College of Medicine, Houston, TX, USA; 3Circle Medical LLC, Norwalk, CT, USA; 4Biometrics, Auxilium Pharmaceuticals, Malvern, PA, USA; 5Men's Health Center, Miriam Hospital, Providence, RI, USABackground: Testosterone levels naturally decline with age in men, often resulting in testosterone deficiency (hypogonadism). However, few studies have examined hypogonadal characteristics and treatment in older (≥65 years) men.Objective: To compare data at baseline and after 12 months of testosterone replacement therapy (TRT) in hypogonadal men ≥65 vs 75-year-old subcohort were not significantly different from subcohorts aged 65–74 years and

Background. Rapid progression to AIDS after acute infection with a multidrug-resistant (MDR), dual-tropic strain of human immunodeficiency virus type 1 (HIV-1) was reported in a New York City man (hereafter referred to as 'NYC') who has sex with men. The probable source of this HIV-1 (hereafter referred to as 'CT01') and the development of a recombinant MDR HIV-1 in the source's partner (hereafter referred to as 'CT02') are described.Methods. After identification of the epidemiological link of CT01 and CT02 to NYC, viral sequences and phenotypic analyses were compared. Confirmatory genotypic and phenotypic analyses, replicative capacity, and viral coreceptor use were assessed. Viral recombination was assessed using a sliding window technique and phylogenetic tree analysis.Results. NYC and CT01 were linked historically and epidemiologically and were genetically confirmed from CT01's samples acquired 2 days before and subsequent to the transmission event. Genotypic, recombination, and phylogenetic analyses suggest CT02 became superinfected by CT01 with subsequent production of a recombinant panresistant HIV-1.Conclusion. The probable source of a dual-tropic, MDR HIV-1 that was associated with rapid progression to AIDS is illustrated, suggesting progression was not explained by the HIV-1 variant alone. A probable second finding of a chronically infected host becoming superinfected with MDR HIV-1 with subsequent formation of a panresistant recombinant HIV-1 is described. This case illustrates the public health implications of unsafe sex between serodiscordant and seroconcordant partners. Copyright © 2007 Infectious Diseases Society of America [ABSTRACT FROM AUTHOR]

Introduction: Dolutegravir/lamivudine (DTG/3TC) and dolutegravir/rilpivirine (DTG/RPV) are fixed-dose, complete, single-tablet, two-drug regimens (2DRs) indicated for HIV-1. DTG/3TC is approved for antiretroviral therapy (ART)-naive people with HIV-1 and virologically suppressed individuals to replace current ART; DTG/RPV is indicated for virologically suppressed individuals as a switch option. Virologic efficacy and effectiveness of these DTG-based 2DRs have been demonstrated in phase 3 clinical trials and real-world cohorts, primarily from Europe. This study characterized real-world use of DTG-based 2DRs for HIV-1 treatment in the USA., Methods: TANDEM was a retrospective medical chart review across 24 US sites. Individuals aged ≥ 18 years who initiated DTG/3TC or DTG/RPV before September 30, 2020, with ≥ 6 months of follow-up were included. One cohort included ART-naive people who initiated DTG/3TC (n = 126), and two other cohorts included virologically suppressed (HIV-1 RNA < 50 copies/mL) people on stable ART regimens for ≥ 3 months before switch to either DTG/3TC (n = 192) or DTG/RPV (n = 151). Clinical characteristics, treatment history, and outcomes are described., Results: Virologically suppressed individuals were older than those who were ART-naive, and the ART-naive cohort had higher proportions of individuals assigned male at birth and of Hispanic ethnicity. The most common healthcare provider-reported reason for choosing a DTG-based 2DR was avoidance of long-term toxicities (25-33% across cohorts), followed by simplification/streamlining of treatment. Among ART-naive people on DTG/3TC, 94% achieved virologic suppression after initiation, and 83% maintained suppression at last follow-up; discontinuation rate was < 1%. Among cohorts who switched to DTG-based 2DRs, 96% maintained virologic suppression on DTG/3TC and 93% on DTG/RPV; 2% on DTG/3TC and 3% on DTG/RPV discontinued., Conclusion: Motivation for selecting DTG-based 2DRs was primarily driven by a desire to avoid or manage toxicities and simplify treatment. Results demonstrate that DTG/3TC and DTG/RPV are effective in real-world settings, with few discontinuations, reflecting data from clinical trials., (© 2024. The Author(s).)

Background: To investigate the impact of the M184V/I mutation on virologic response to dolutegravir plus lamivudine (DTG + 3TC) in suppressed-switch populations, a meta-analysis was performed using virologic outcomes from people with human immunodeficiency virus type 1 (PWH) with and without M184V/I before DTG + 3TC switch in real-world studies identified via systematic literature review. Sensitivity analyses were performed using data from PWH with M184V/I in interventional studies identified via targeted literature review., Methods: Single-arm meta-analyses using common- and random-effects models were used to estimate proportions of PWH with virologic failure (VF) among real-world populations with and without M184V/I and interventional study participants with M184V/I at 24, 48, and 96 weeks., Results: Literature reviews identified 5 real-world studies from 3907 publications and 51 abstracts meeting inclusion criteria and 5 interventional studies from 1789 publications and 3 abstracts. All time points had low VF incidence in PWH with M184V/I (real-world: 1.43%-3.81%; interventional: 0.00%) and without (real-world: 0.73%-2.37%). Meta-analysis-estimated proportions (95% confidence interval) with VF were low at weeks 24, 48, and 96, respectively, for PWH with M184V/I (real-world: 0.01 [.00-.04], 0.03 [.01-.06], and 0.04 [.01-.07]; interventional: 0.00 [.00-.02], 0.00 [.00-.01], and 0.00 [.00-.03]) and without (real-world: 0.00 [.00-.02], 0.02 [.01-.04], and 0.02 [.00-.05]). One real-world study (n = 712) reported treatment-emergent M184V at VF in 1 of 652 (0.15%) PWH without prior M184V/I., Conclusions: Results suggest that prior M184V/I has minimal impact on virologic suppression after switching to DTG + 3TC and provide reassurance when considering switching regimens in virologically suppressed PWH with incomplete treatment history or limited treatment options., Competing Interests: Potential conflicts of interest. M. K. was a complimentary worker for ViiV Healthcare at the time of the analysis. G. V. is an employee of ViiV Healthcare. C. M. P., B. J., C. O., J. Pr., and E. L. are employees of ViiV Healthcare and own stock in GSK. T. J. B. has received grants from Gilead, MSD, Roche, and ViiV Healthcare; consulting fees and honoraria from Gilead, GSK, Janssen, MSD, Roche, Theratechnologies, and ViiV Healthcare; and travel support from Gilead and ViiV Healthcare. C. A. has received honoraria from Gilead, MSD, and ViiV Healthcare; has received travel support from Gilead and MSD; and is a member of the CPP Ouest IV Ethics Committee. A.-G. M. has received grants and honoraria from Gilead, MSD, and ViiV Healthcare; consulting fees from GSK; and travel support from Gilead. J. Pa. has received honoraria from Gilead, Janssen-Cilag, MSD, and ViiV Healthcare and travel support from Gilead and Janssen-Cilag. N. G. has received grants, honoraria, and travel support from Gilead, Janssen-Cilag, MSD, and ViiV Healthcare. J. M. L. has received grants from Gilead and ViiV Healthcare; has received speaker honoraria from Gilead, Janssen-Cilag, and ViiV Healthcare; and is a member of the Spanish Antiretroviral Treatment Guidelines panel. D. R.-C. has received honoraria from Gilead and ViiV Healthcare and travel support from Gilead. R. D. M.-B. has received speaker fees from Gilead and ViiV Healthcare and travel support from ViiV Healthcare. G. B. has received honoraria and travel support from ViiV Healthcare. M. T., C. H., and T. W. are employees of HEOR Ltd, which received funding from ViiV Healthcare to support this analysis. S. D. G. reports no potential conflicts., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Changes in global mean sea level are a clear indicator of a warming climate, but local factors including land subsidence or uplift, cause changes in relative sea level that drive shoreline shifts. These local changes and their impact on coastal hazards matter to coastal communities. NZ SeaRise produced relative sea level projections for Aotearoa to include the latest global climate and Antarctic Ice Sheet research and estimates of vertical land movement at high spatial resolution. Research-informed communication to the public and planners included a web-based projections tool supplemented by written and visual narratives, and a media engagement plan. This communication, and analysis of media impact, provided a case study for audience-relevant information on sea-level rise. Information regarding shoreline change and evolving hazards, required for risk assessment, was not included in the NZ SeaRise projections. New research is needed to reduce uncertainty in future Antarctic Ice Sheet contribution to sea level, link changes in sea surface height to our dynamic land surface and enhance communication approaches. Several examples of the required research are presented here but ongoing efforts must refine the timing and magnitude of coastline change, better define coastal hazards and risks, and develop appropriate adaptation strategies for unavoidable climate change impacts., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2023 GNS Science. Published by Informa UK Limited, trading as Taylor & Francis Group.)

Publicly funded cancer medicines listed on the New Zealand Pharmaceutical Schedule were compared with those listed on the Australian Pharmaceutical Benefits Scheme. To quantify the health gains offered by the cancer medicines funded in Australia but not in New Zealand, clinical trial data reporting median progression-free survival (PFS) and overall survival (OS) were sought. The differences in the median PFS and OS for the unfunded medicines, relative to the comparator medicine funded in NZ, were then assessed against the American Society of Clinical Oncology Cancer Research Committee (ASCO-CRC) recommended targets for clinically meaningful health gains. Our analysis confirms that, whilst New Zealand funds fewer cancer medicines than Australia, most of the additional medicines funded in Australia do not deliver clinically meaningful health gains as defined by the ASCO-CRC guidance. This suggests that New Zealand is not missing substantive opportunities for improvements to New Zealand's cancer survival rates through additional medicines funding. A policy of funding more new cancer medicines in order to achieve numerical parity with Australia or other countries would not result in substantive health improvement and would cost significantly more, and investing the millions of dollars needed to achieve funding parity with other countries would not represent good value for money in terms of delivering the best health outcomes for all New Zealanders, rather selective funding of new medicines that demonstrate clear clinical benefit and that are cost-effective and affordable is the sensible approach., (Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.)

Social networking technologies are influential among men who have sex with men (MSM) and may be an important strategy for HIV prevention. We conducted focus groups with HIV positive and negative participants. Almost all participants used social networking sites to meet new friends and sexual partners. The main obstacle to effective HIV prevention campaigns in social networking platforms was stigmatization based on homosexuality as well as HIV status. Persistent stigma associated with HIV status and disclosure was cited as a top reason for avoiding HIV-related conversations while meeting new partners using social technologies. Further, social networking sites have different social etiquettes and rules that may increase HIV risk by discouraging HIV status disclosure. Overall, successful interventions for MSM using social networking technologies must consider aspects of privacy, stigma, and social norms in order to enact HIV reduction among MSM.

Importance: Patients co-infected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) are at high risk for liver disease progression. However, interferon-based treatments for HCV infection have significant toxicities, limiting treatment uptake., Objective: To assess the all-oral 3 direct-acting antiviral (3D) regimen of ombitasvir, paritaprevir (co-dosed with ritonavir [paritaprevir/r]), dasabuvir, and ribavirin in HCV genotype 1-infected adults with HIV-1 co-infection, including patients with cirrhosis., Design, Setting, and Participants: TURQUOISE-I is a randomized, open-label study. Part 1a of this pilot study was conducted at 17 sites in the United States and Puerto Rico between September 2013 and August 2014 and included 63 patients with HCV genotype 1 and HIV-1 co-infection who were HCV treatment-naive or had history of prior treatment failure with peginterferon plus ribavirin therapy. The study allowed enrollment of patients, including those with cirrhosis, with a CD4+ count of 200/mm3 or greater or CD4+ percentage of 14% or more and plasma HIV-1 RNA suppressed while taking a stable atazanavir- or raltegravir-inclusive antiretroviral regimen., Interventions: Ombitasvir/paritaprevir/r, dasabuvir, and ribavirin for 12 or 24 weeks of treatment as randomized., Main Outcomes and Measures: The primary assessment was the proportion of patients with sustained virologic response (HCV RNA <25 IU/mL) at posttreatment week 12 (SVR12)., Results: Among patients receiving 12 or 24 weeks of 3D and ribavirin, SVR12 was achieved by 29 of 31 (94%; 95% CI, 79%-98%) and 29 of 32 patients (91%; 95% CI, 76%-97%), respectively. Of the 5 patients who did not achieve SVR, 1 withdrew consent, 2 had confirmed virologic relapse or breakthrough, and 2 patients had clinical history and phylogenetic evidence consistent with HCV reinfection. The most common treatment-emergent adverse events were fatigue (48%), insomnia (19%), nausea (18%), and headache (16%). Adverse events were generally mild, with none reported as serious or leading to discontinuation. No patient had a confirmed HIV-1 breakthrough of 200 copies/mL or greater during treatment., Conclusions and Relevance: In this open-label, randomized uncontrolled study, treatment with the all-oral, interferon-free 3D-plus-ribavirin regimen resulted in high SVR rates among patients co-infected with HCV genotype 1 and HIV-1 whether treated for 12 or 24 weeks. Further phase 3 studies of this regimen are warranted in patients with co-infection., Trial Registration: clinicaltrials.gov Identifier: NCT01939197.

Background: The Phase III VIKING-3 study demonstrated that dolutegravir (DTG) 50 mg twice daily was efficacious in antiretroviral therapy (ART)-experienced subjects harbouring raltegravir- and/or elvitegravir-resistant HIV-1. VIKING-4 (ING116529) included a placebo-controlled 7-day monotherapy phase to demonstrate that short-term antiviral activity was attributable to DTG., Methods: VIKING-4 is a Phase III randomized, double-blind study in therapy-experienced adults with integrase inhibitor (INI)-resistant virus randomized to DTG 50 mg twice daily or placebo while continuing their failing regimen (without raltegravir or elvitegravir) for 7 days (clinicaltrials.gov identifier NCT01568892). At day 8, all subjects switched to open-label DTG 50 mg twice daily and optimized background therapy including ≥1 fully active drug. The primary end point was change from baseline in plasma HIV-1 RNA at day 8., Results: The study population (n=30) was highly ART-experienced with advanced HIV disease. Patients had extensive baseline resistance to all approved antiretroviral classes. Adjusted mean change in HIV-1 RNA at day 8 was 
-1.06 log10 copies/ml for the DTG arm and 0.10 log10 copies/ml for the placebo arm (treatment difference -1.16 log10 copies/ml [-1.52, -0.80]; P<0.001). Overall, 47% and 57% of subjects had plasma HIV-1 RNA <50 and <400 copies/ml at week 24, and 40% and 53% at week 48, respectively. No discontinuations due to drug-related adverse events occurred in the study., Conclusions: The observed day 8 antiviral activity in this highly treatment-experienced population with INI-resistant HIV-1 was attributable to DTG. Longer-term efficacy (after considering baseline ART resistance) and safety during the open-label phase were in-line with the results of the larger VIKING-3 study.

Objective: Whether concomitant HIV antiretroviral therapy (ART) affects the safety and efficacy of interferon-free HCV therapies or whether HCV treatment may negatively affect HIV control is unclear. We assessed the 3 direct-acting antiviral (3D) regimen of ombitasvir, ABT-450 (identified by AbbVie and Enanta; co-dosed with ritonavir) and dasabuvir with ribavirin (RBV) in HCV/HIV-1 co-infected patients with and without cirrhosis, including HCV treatment-experienced, receiving atazanavir (ATV)- or raltegravir (RAL)-based ART therapy., Methods: HCV genotype 1-positive treatment-naïve or pegIFN/RBV-experienced patients, with or without Child-Pugh A cirrhosis, CD4+ count ≥200 cells/mm(3) or CD4 + % ≥14%, and plasma HIV-1 RNA suppressed on stable ART received open-label 3D + RBV for 12 or 24 weeks. Rates of HCV-sustained virologic response at post-treatment weeks 4 and 12 (SVR4 and SVR12, respectively) and bilirubin-related adverse events (AEs) are reported from post-hoc analyses for subgroups defined by treatment duration and ART regimen., Results: The SVR12 rate for patients receiving 12 weeks of 3D + RBV was 93.5% with comparable rates in patients receiving either ATV (93.8%) or RAL therapy (93.3%) (Table 1). The SVR4 rate for the 24-week arm was 96.9% with a single virologic breakthrough at treatment week 16 in a patient receiving RAL therapy. Patients receiving concomitant ATV had more AEs related to indirect hyperbilirubinemia including ocular icterus, jaundice and grade 3 or 4 elevations in total bilirubin (predominantly indirect). No patient discontinued the study due to AEs, and no serious AEs were reported during or after treatment. No patient had a confirmed plasma HIV-1 RNA value ≥200 copies/mL during the treatment period., Conclusions: In this first study to evaluate an IFN-free regimen in HCV genotype 1-positive treatment-naïve and experienced patients with HIV-1 co-infection, including those with cirrhosis, high rates of SVR were comparable to those with HCV monoinfection. Indirect hyperbilirubinemia was consistent with the known ABT-450 inhibition of the OATP1B1 bilirubin transporter, RBV-related haemolytic anaemia and inhibitory effect of ATV on bilirubin conjugation. The laboratory abnormalities and AEs observed did not negatively affect treatment response or lead to treatment discontinuation.

Background: Testosterone decline becomes more prevalent as men age and symptomatic testosterone deficiency is associated with potentially serious comorbidities. Despite limitations, registries can provide an opportunity to accumulate data regarding disease management in a typical patient population, including diagnosis, treatment, and outcomes., Materials and Methods: The Testim Registry in the United States (TRiUS) was a prospective, 12-month, observational cohort registry of men prescribed Testim® (1% testosterone gel; Auxilium Pharmaceuticals, Inc.) for the first time; patients previously on other forms of testosterone replacement therapy (TRT) were eligible to participate in the study as well. The registry recorded total testosterone (TT) and free testosterone (FT) levels, prostate-specific antigen (PSA), sexual function, mood/depression, and cardiometabolic and anthropometric criteria before and after TRT. Changes over time were analyzed by analysis of variance, and linear regression and Pearson product-moment correlation coefficients were used to examine relationships between variables., Results: At baseline, 849 patients from 72 sites were enrolled, with 743 of 849 started on 5 g gel/day (50 mg testosterone/day) and 106 of 849 started on 10 g gel/day (100 mg testosterone/day). Mean TT and FT levels increased significantly after 3 months of TRT (TT level, 16.8 ± 9.87 nmol/L [485 ± 284 ng/dL], P < 0.001; FT level, 286.3 ± 224.9 pmol/L [82.5 ± 64.8 pg/mL], P < 0.001) and were maintained at eugonadal levels. Mean PSA levels increased significantly (P = 0.004) from 1.12 ± 1.11 μg/L (1.12 ± 1.11 ng/mL) at baseline to 1.26 ± 1.22 μg/L (1.26 ± 1.22 ng/mL) after 12 months of TRT, although changes were well within guidelines (< 1.4 μg/L/year increase). Significant improvements were seen in sexual function and mood/depression at 3 months and in metabolic parameters at 12 months., Conclusion: Testosterone deficiency symptoms improved with TRT use in men; sexual function and mood/depression improvements were seen before metabolic improvements. Prostate-specific antigen levels increased, although increases were within guideline-determined safety limits.

Background: Although hypogonadism is common in men with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS), testosterone levels after testosterone replacement therapy (TRT) in this population have not been reported., Methods: The Testim Registry in the United States (TRiUS) was the first prospective, observational registry of men with hypogonadism who were prescribed TRT. The TRiUS cohorts with (n = 82) and without (n = 767) HIV/AIDS were followed during 12 months of treatment with Testim® (1% testosterone gel; Auxilium Pharmaceuticals, Inc.). Total testosterone (TT) and free testosterone levels, symptoms of depression, sexual function, body composition profiles, and prostate-specific antigen levels were evaluated., Results: The HIV/AIDS and non-HIV/AIDS cohorts differed at baseline in age (48.3 vs 52.5 years), TT level (13.0 vs 9.6 nmol/L), duration of hypogonadism (27.1 vs 14.6 months), prior TRT (36.6% vs 22.6%), body mass index (26.5 vs 32.0 kg/m2), and antidepressant (29% vs 15%) and opioid (20% vs 10%) use (P ≤ 0.01 for all comparisons). During the 12 months, both cohorts experienced significant elevations in TT and free testosterone levels to within normal ranges. Sexual function and depression scores improved and antidepressant medication use decreased in both cohorts. Body composition profiles improved significantly (P ≤ 0.05) in men without HIV/AIDS and remained stable in men with HIV/AIDS during the 12 months of follow-up., Conclusion: This 12-month, non-placebo-controlled, observational study of Testim® use in men with and without HIV/AIDS suggests that TRT may provide clinical benefits irrespective of the patient's HIV/AIDS status. This conclusion is supported by the higher testosterone levels, better sexual function, lower depression scores, and better body composition profiles found in both groups. However, given the loss of patients to follow-up, these results may reflect a bias toward drug responders.

Objectives: To determine the incidence of hypogonadism in men with human immunodeficiency virus (HIV)/acquired immunodeficiency virus (AIDS), the most useful serum testosterone measurement and threshold for diagnosing hypogonadism, and the comparative efficacy of 2 testosterone replacement therapy (TRT) 1% gels (AndroGel® [Abbott Laboratories] and Testim® [Auxilium Pharmaceuticals, Inc.])., Design and Subjects: This was a 2-stage observational study. In stage 1, patient records from 2 medical practices specializing in HIV/AIDS were reviewed. Eligible patients were aged ≥ 18 years; had HIV-seropositive status confirmed by enzyme-linked immunosorbent assay and western blot test or HIV-1 viremia confirmed by HIV-1 RNA polymerase chain reaction; and had prior baseline testosterone assessments for hypogonadism (ie, presence of signs/symptoms of hypogonadism as well as total testosterone [TT] and free testosterone [FT] level measurements). Stage 2 included the evaluation of patients from stage 1 who were treated with 5 to 10 g/day of TRT. The stage 2 inclusion criteria were a diagnosis of low testosterone (defined as TT level < 300 ng/dL and/or FT level < 50 pg/mL, as per The Endocrine Society guidelines and presence/absence of hypogonadal signs and symptoms); ≥ 12 months of evaluable sign and symptom assessments and TT/FT level measurements while on TRT with either Testim® or AndroGel®; and ≥ 4 weeks on initial TRT if the initial TRT was switched or discontinued., Results: Four hundred one of 422 patients met the stage 1 inclusion criteria and 167 of 401 patients (AndroGel®, n = 92; Testim®, n = 75) met the stage 2 inclusion criteria. Total testosterone level < 300 ng/dL alone identified 24% (94 of 390) of patients as hypogonadal, but failed to diagnose an additional 111 patients (67.7%) with FT levels < 100 pg/mL and hypogonadal symptoms. Through month 12, AndroGel® increased mean TT levels by +42.8% and FT levels by +66.9%, compared with +178.7% (P = 0.017) and +191% (P = 0.039), respectively, for Testim®. Patients treated with Testim® showed significantly greater improvements in libido, sexual performance, nighttime energy, focus/concentration, and abdominal girth, and trends for greater improvement in fatigue and erectile dysfunction than patients treated with AndroGel®. No patients discontinued therapy due to adverse events., Conclusion: The most useful serum testosterone measurement and threshold for diagnosing hypogonadism in men with HIV/AIDS was FT level < 100 pg/mL, which identified 64% of men as hypogonadal with the presence of ≥ 1 hypogonadal symptom. This is above currently accepted thresholds. Criteria using TT level < 300 ng/dL and FT level < 50 pg/mL only diagnosed 24% and 19% of patients, respectively, as having hypogonadism. Testim® was more effective than AndroGel® in increasing TT and FT levels and improving hypogonadal symptoms.

Background: Lentiviral vectors are being used with increasing frequency in human clinical trials. We were the first to use lentiviral vectors in clinical trials in 2003. Our lentiviral vector encoded a long RNA antisense sequence to the HIV-1 envelope and was used in an ex vivo autologous setting to provide viral load control in HIV-1 positive subjects failing anti-HIV therapy. A total of 65 subjects have been treated in Phase 1 and Phase 2 trials in six institutions., Methods: Good manufacturing practices (GMP) lots of the lentiviral vector used in our clinical trials were assayed for the presence of replication competent lentivirus (RCL). RCL assays were conducted at two stages. The first testing was performed on samples collected immediately following bulk harvest of the GMP product lot and consisted of 1 × 10(8) cells used in production. RCL assays were also performed on aliquots of the final fill of the vector by the inoculation of at least 5% of the GMP final fill volume into C8166 cells, passaged for at least ten passages and tested for RCL by p24 enzyme-linked immunosorbent assay and vesicular stomatitis virus-G envelope DNA., Results: Following 263 infusions of autologous, transduced cells, no adverse events have been detected in these subjects, with some followed for more than 8 years following infusions. More than 4.3 × 10(12) VRX496 proviral copies were administered to these 65 subjects., Conclusions: Data from this small population suggest that there is no apparent risk for serious adverse events with the use of lentiviral vectors., (Copyright © 2013 John Wiley & Sons, Ltd.)