Pharmacokinetic study of saquinavir hard gel caps/ritonavir in HIV-1-infected patients: 1600/100 mg once-daily compared with 2000/100 mg once-daily and 1000/100 mg twice-daily

Objectives: A pharmacokinetic comparison of three dosing regimens of saquinavir/ritonavir was carried out: 1600/100 mg once-daily with 1000/100 mg twice-daily, and 1600/100 mg once-daily with 2000/100 mg once-daily. Methods: Twenty patients on saquinavir hard gel caps/ritonavir 1600/100 mg once-daily in combination with two nucleoside reverse transcriptase inhibitors for at least 4 weeks were enrolled and randomized to either saquinavir hard gel caps/ritonavir 1000/100 mg twice-daily or 2000/100 mg once-daily. Two pharmacokinetic curves were plotted, at baseline (day 0) and 7 days after the switch. Plasma concentrations were measured at 0, 2, 4, 6, 8, 10, 12 (and 24 for once-daily dosing) hours after drug intake by validated high-performance liquid chromatographic assay (HPLC). The area under the plasma concentration-time curve (AUC0-24 or AUC0-12), maximum and minimum concentration (Cmax and Cmin) and elimination half-life were calculated using a non-compartmental model. Results: Compared with saquinavir/ritonavir 1600/100 mg once-daily dosing, the saquinavir AUC and Cmin improved significantly when dosed as 1000/100 mg twice-daily (53% and 299%, respectively), and as 2000/100 mg once-daily (71% and 65%, respectively). Low Cmin in three subjects at baseline was corrected after switch to the other dosages. Saquinavir/ritonavir 2000/100 mg once-daily was also associated with a significant increase in saquinavir Cmax (52%) compared with saquinavir/ritonavir 1600/100 mg once-daily. Conclusions: Saquinavir/ritonavir when dosed as 2000/100 mg once-daily or 1000/100 mg twice-daily achieves higher saquinavir plasma levels compared with saquinavir/ritonavir 1600/100 mg once-daily. Taking the convenience of once-daily dosing into consideration, dosage of 2000/100 mg once-daily may be preferre

Ambiguous Nucleotide Calls From Population-based Sequencing of HIV-1 are a Marker for Viral Diversity and the Age of Infection

The fraction of ambiguous nucleotide calls in bulk sequencing of human immunodeficiency virus type 1 (HIV-1) carries important information on viral diversity and the age of infection. In particular, a fraction of ambiguous nucleotides of >.5% provides evidence against a recent infection event <1 year ago

Published findings from the spouse assault replication program: A critical review

Published reports from seven jointly developed experiments have addressed whether or not arrest is an effective deterrent to misdemeanor spouse assault. Findings supporting a deterrent effect, no effect, and an escalation effect have been reported by the original authors and in interpretations of the published findings by other authors. This review found many methodologically defensible approaches used in these reports but not one of these approaches was used consistently in all published reports. Tables reporting the raw data on the prevalence and incidence of repeat incidents are presented to provide a more consistent comparison across all seven experiments. This review concludes that the available information is incomplete and inadequate for a definitive statement about the results of these experiments. Researchers and policy makers are urged to use caution in interpreting the findings available to date.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45108/1/10940_2005_Article_BF02221298.pd

The Influence of Victim Vulnerability and Gender on Police Officers’ Assessment of Intimate Partner Violence Risk

This study investigated the influence of victim vulnerability factors and gender on risk assessment for intimate partner violence (IPV). 867 cases of male and female perpetrated IPV investigated by Swedish police officers using the Brief Spousal Assault Form for the Evaluation of Risk (BSAFER) were examined. For male-to-female IPV, victim vulnerability factors were associated with summary risk judgments and risk management recommendations. For femaleto-male IPV, vulnerability factors were more often omitted, and consistent associations were not found between vulnerability factors, summary risk judgments, and risk management. Results indicate that B-SAFER victim vulnerability factors can assist in assessing male-to-female IPV risk. Further research is necessary to examine the use of B-SAFER victim vulnerability factors for female-to-male IPV, as results showed victim vulnerability factors to be less relevant to officers’ decision making, particularly their management recommendations. However, several variables external to the B-SAFER, such as the availability of management strategies may account for these findings

Higher Risk of Incident Hepatitis C Virus Coinfection Among Men Who Have Sex With Men, in Whom the HIV Genetic Bottleneck at Transmission Was Wide

Background. High-risk sexual behaviors have been suggested as drivers of the recent dramatic increase of sexually transmitted hepatitis C virus (HCV) among human immunodeficiency virus (HIV)-infected men who have sex with men (MSM). Methods. We assessed the association between the genetic bottleneck of HIV at transmission and the prevalence and incidence of HCV coinfection in HIV-infected MSM from the Swiss HIV Cohort Study (SHCS). As a proxy for the width of the transmission bottleneck, we used the fraction of ambiguous nucleotides detected by genotypic resistance tests sampled during early HIV infection. We defined a broad bottleneck as a fraction of ambiguous nucleotides exceeding a previously established threshold (0.5%). Results. From the SHCS, we identified 671 MSM with available results of HCV serologic tests and with an HIV genotypic resistance test performed during early HIV infection. Of those, 161 (24.0%) exhibited a broad HIV transmission bottleneck, 38 (5.7%) had at least 1 positive HCV test result, and 26 (3.9%) had an incident HCV infection. Individuals with broad HIV transmission bottlenecks exhibited a 2-fold higher odds of having ever experienced an HCV coinfection (odds ratio, 2.2 [95% confidence interval {CI}, 1.1-4.3]) and a 3-fold higher hazard of having an incident HCV infection (hazard ratio, 3.0 [95% CI, 1.4-6.6]) than individuals with narrow HIV transmission bottlenecks. Conclusions. Our results indicate that the currently occurring sexual spread of HCV is focused on MSM who are prone to exhibit broad HIV transmission bottlenecks. This is consistent with an important role of high-risk behavior and mucosal barrier impairment in the transmission of HCV among MS

Hepatitis B Virus Infection Is Associated With Impaired Immunological Recovery During Antiretroviral Therapy in the Swiss HIV Cohort Study

Hepatitis B virus (HBV) infection is a major cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected patients worldwide. It is unclear whether HIV-related outcomes are affected by HBV coinfection. We compared virological suppression and immunological recovery during antiretroviral therapy (ART) of patients of different HBV serological status in the Swiss HIV Cohort Study. CD4 cell recovery during ART was significantly impaired in hepatitis B surface antigen-positive patients and in those with anti-hepatitis B core antigen alone compared with HBV-uninfected patients, despite similar virological efficacy of ART. CD4 increase in patients with resolved HBV infection was similar to that in HBV-uninfected individual