Time to Endorse A Sensitive Method for Scoring Endoscopic Activity of Ulcerative Colitis in Clinical Research.

The endoscopic scoring of ulcerative colitis is routinely used for both individual patient management and as an endpoint in clinical trials. The most commonly used scoring system is the Mayo endoscopic subscore, which scores endoscopic disease activity on a scale between 0 and 3. With only four possible scores and consideration of only the most involved area of the colon, the Mayo endoscopic subscore lacks sensitivity to change in measuring the totality of the endoscopic inflammatory involvement in patients with ulcerative colitis. Here, we present one case study from clinical practice and one from clinical trials in which using the Mayo endoscopic score leads to potentially incorrect conclusions. Further, in a post-hoc analysis, we re-examined endoscopic videos from a clinical trial and demonstrate that assessing involved ulcerated and affected areas on a segmental level of the colon or summing Mayo scores of colonic segments can identify improvements in endoscopic disease activity in almost twice as many subjects as identified by the Mayo endoscopic subscore alone. Although the alternative scoring systems we have used in this report will need further validation, our findings demonstrate the need for a more sensitive endoscopic scoring system in ulcerative colitis.

PTG-100, an Oral α4ß7 Antagonist Peptide: Preclinical Development and Phase 1 and 2a Studies in Ulcerative Colitis.

BACKGROUND & AIMS: Oral therapies targeting the integrin α4ß7 may offer unique advantages for the treatment of inflammatory bowel disease. We characterized the oral α4ß7 antagonist peptide PTG-100 in preclinical models and established safety, pharmacokinetic/pharmacodynamic relationships, and efficacy in a phase 2a trial in patients with ulcerative colitis (UC). METHODS: In vitro studies measured binding properties of PTG-100. Mouse studies measured biomarkers and drug concentrations in blood and tissues. The phase 1 study involved healthy volunteers. In phase 2a, patients with moderate to severe active UC were randomized to receive PTG-100 (150, 300, or 900 mg) or placebo once daily for 12-weeks. RESULTS: PTG-100 potently and selectively blocks α4ß7. Oral dosing of PTG-100 in mice showed high levels of target engagement and exposure in gut-associated lymphoid tissues. In healthy volunteers, PTG-100 showed dose-dependent increases in plasma exposure and blood target engagement. Although this phase 2a study initially did not meet the primary endpoint, a blinded reread of the endoscopy videos by a third party indicated clinical efficacy in conjunction with histologic remission at doses correlating with less than 100% receptor occupancy in peripheral blood. CONCLUSIONS: PTG-100 showed local gastrointestinal tissue target engagement and inhibition of memory T-cell trafficking in mice. It was safe and well tolerated in phase 1 and 2 studies. Phase 2a data are consistent with biological and clinical response and showed a dose response reflecting similar activities in preclinical models and healthy individuals. These data suggest that local gut activity of an oral α4ß7 integrin antagonist, distinct from full target engagement in blood, are important for efficacy and the treatment of UC. (ClinicalTrials.gov, Number NCT02895100; EudraCT, Number 2016-003452-75).

Adherence to pan-genotypic glecaprevir/pibrentasvir and efficacy in HCV-infected patients: A pooled analysis of clinical trials.

BACKGROUND & AIMS: Adequate adherence to hepatitis C virus (HCV) treatment is believed to be a key component of treatment success because non-adherence can potentially result in treatment failure and the emergence of resistant viral variants. This analysis assessed factors associated with non-adherence to glecaprevir/pibrentasvir (G/P) therapy and the impact of non-adherence on sustained virological response at post-treatment week 12 (SVR12) rates in HCV genotype (GT) 1-6-infected patients. METHODS: Adherence was calculated by pill counts at study visits during treatment, and defined as having a lowest treatment adherence of ≥80% and ≤120% at each study visit. Exploratory logistic regression modelling assessed predictors of non-adherence to G/P therapy. SVR12 rates by treatment adherence were assessed in the intent-to-treat (ITT) population and modified ITT (mITT) population, which excludes non-virological failures. RESULTS: Overall, 97% (2024/2091) of patients were adherent to G/P therapy at all consecutive study visits. Alcohol use was the only baseline characteristic independently associated with non-adherence to G/P therapy (OR: 2.38; 95% CI: 1.13-5.01; P = .022). In the mITT population, overall SVR12 rates were high both in patients who were adherent to G/P therapy and those who were not (99% [1983/2008] and 95% [58/61] respectively; P = .047). Corresponding SVR12 rates in the ITT population were 98% (1983/2024) and 87% (58/67) respectively. CONCLUSIONS: Most patients adhered to G/P therapy. SVR12 rates were high both in patients who were adherent to G/P treatment and those who were not. Patient education on treatment adherence should remain an important part of HCV treatment. CLINICAL TRIALS REGISTRATION: NCT02604017, NCT02640482, NCT02640157, NCT02636595, NCT02642432, NCT02651194, NCT02243293, NCT02446717.

Drug-Drug Interactions of Tacrolimus or Cyclosporine With Glecaprevir and Pibrentasvir in Healthy Subjects.

A fixed-dose combination of glecaprevir and pibrentasvir is approved for treatment of chronic infection with hepatitis C virus (HCV) genotypes 1-6. Three phase 1 open-label studies were conducted in healthy volunteers to evaluate the potential for clinically relevant drug-drug interactions of the glecaprevir 300-mg and pibrentasvir 120-mg combination with the immunosuppressants tacrolimus (1 mg) or cyclosporine (100 and 400 mg). Glecaprevir and pibrentasvir exposure was unaffected by tacrolimus, whereas the tacrolimus area under the curve (AUC) value was 45% higher with glecaprevir and pibrentasvir. Cyclosporine 100 mg had a limited effect on glecaprevir or pibrentasvir exposure (≤37% AUC increase), but cyclosporine 400 mg increased exposure of both glecaprevir and pibrentasvir (410% and 93% AUC increase, respectively). Cyclosporine concentration was unaffected by glecaprevir and pibrentasvir at either cyclosporine dose (≤14% AUC change). Adverse events were all grade 1 (mild), with the most common nausea and flushing attributed to cyclosporine. Findings from these studies supported evaluation of glecaprevir/pibrentasvir in HCV-infected kidney and liver transplant recipients receiving tacrolimus without additional dose adjustment or receiving cyclosporine up to 100 mg per day.

Pharmacokinetics and safety of glecaprevir and pibrentasvir in HCV-negative subjects with hepatic impairment.

PURPOSE: This study characterized the effects of hepatic impairment on the pharmacokinetics and safety of glecaprevir and pibrentasvir, two direct-acting antivirals used for treatment of chronic HCV infection. METHODS: HCV-negative subjects with normal hepatic function, or with mild (Child-Pugh [CP]-A), moderate (CP-B), or severe (CP-C) hepatic impairment received single doses of pibrentasvir 120 mg alone or with glecaprevir 200 mg or 300 mg (n = 6/functional group/dose). Plasma pharmacokinetics and protein binding were evaluated. Doses were separated by ≥ 14 days of washout. RESULTS: For the approved combination of glecaprevir 300 mg with pibrentasvir 120 mg, glecaprevir AUC was increased by 33% (CP-A), to 2.0-fold (CP-B), and to 11-fold (CP-C) relative to normal subjects; pibrentasvir AUC was ≤ 26% different (CP-A or CP-B) and increased to 2.1-fold (CP-C). For glecaprevir 200 mg with pibrentasvir 120 mg, glecaprevir AUC was increased by 80% (CP-A) or to 2.8-fold (CP-B), while pibrentasvir AUC was unaffected in the same subjects (≤ 12% difference). Pibrentasvir 120 mg alone AUC increased 51% (CP-A), 31% (CP-B), and to 5.2-fold (CP-C). The unbound fraction of glecaprevir was higher in CP-C subjects than normal subjects and pibrentasvir protein binding was similar across groups. The most common adverse event was headache; no events were serious. CONCLUSION: This study supported evaluation of the glecaprevir 300 mg with pibrentasvir 120-mg combination in HCV-infected subjects with CP-A hepatic impairment without dose adjustment. Elevated glecaprevir and/or pibrentasvir exposures are expected in HCV-infected patients with CP-B or CP-C hepatic impairment.

Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 1 hepatitis C virus infection with and without cirrhosis.

BACKGROUND: The once-daily, all oral, RBV-free, pangenotypic direct-acting anti-viral regimen consisting of co-formulated NS3/4A protease inhibitor glecaprevir and NS5A inhibitor pibrentasvir (G/P), demonstrated high rates of sustained virologic response (SVR) in phase 2 and 3 studies outside Japan. METHODS: CERTAIN-1 is a phase 3, open-label, multicenter study assessing the safety and efficacy of G/P (300/120 mg) once daily in Japanese patients with chronic HCV GT1 infection. Patients without cirrhosis received 8 weeks of G/P or 12 weeks of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r, 25/150/100 mg); patients with cirrhosis received G/P for 12 weeks. The primary efficacy endpoint was non-inferiority of G/P compared to OBV/PTV/r by assessing SVR at post-treatment week 12 (SVR12) among non-cirrhotic patients without the NS5A Y93H polymorphism. RESULTS: SVR12 was achieved by 128/129 (99.2%; one patient lost to follow-up) non-cirrhotic patients in the 8-week G/P Arm (including 23/23 patients with the NS5A Y93H polymorphism) and 52/52 (100%) patients in the 12-week OBV/PTV/r Arm. No patients from the G/P Arm prematurely discontinued the study drug or experienced a treatment-emergent serious adverse event (TESAE). Three patients from the OBV/PTV/r Arm experienced five TESAEs and one of these patients discontinued the study drug due to TESAEs. All 38 (100%) patients with compensated cirrhosis achieved SVR12; in this group, no TESAEs were reported and one patient discontinued treatment due to an AE. CONCLUSIONS: CERTAIN-1 study results demonstrate high efficacy and favorable tolerability of G/P in GT1-infected Japanese patients including those with the NS5A Y93H polymorphism, with no virologic failures observed.

Efficacy and safety of glecaprevir/pibrentasvir in Japanese patients with chronic genotype 2 hepatitis C virus infection.

Glecaprevir (nonstructural protein 3/4A protease inhibitor) and pibrentasvir (nonstructural protein 5A inhibitor) (G/P), a coformulated once-daily, all oral, ribavirin (RBV)-free, direct-acting antiviral regimen, was evaluated for safety and efficacy in hepatitis C virus genotype 2 (GT2)-infected Japanese patients, including those with compensated cirrhosis. CERTAIN-2 is a phase 3, open-label, multicenter study assessing the safety and efficacy of G/P (300/120 mg) once daily in treatment-naive and interferon ± RBV treatment-experienced Japanese patients without cirrhosis but with GT2 infection. Patients were randomized 2:1 to receive 8 weeks of G/P (arm A) or 12 weeks of sofosbuvir (400 mg once daily) + RBV (600-1000 mg weight-based, twice daily) (arm B). The primary endpoint was noninferiority of G/P compared to sofosbuvir + RBV by assessing sustained virologic response at posttreatment week 12 (SVR12) among patients in the intent-to-treat population. SVR12 was also assessed in treatment-naive and interferon ± RBV treatment-experienced patients with GT2 infection and compensated cirrhosis who received G/P for 12 weeks in the CERTAIN-1 study. A total of 136 patients were enrolled in CERTAIN-2. SVR12 was achieved by 88/90 (97.8%) patients in arm A and 43/46 (93.5%) patients in arm B. No patient in arm A experienced virologic failure, while 2 did in arm B. The primary endpoint was achieved. In CERTAIN-1, 100% (18/18) of GT2-infected patients with compensated cirrhosis achieved SVR12. Treatment-emergent serious adverse events were experienced by 2 patients without cirrhosis in each arm and no patient with cirrhosis. Conclusion: The results demonstrate high efficacy and favorable tolerability of G/P in GT2-infected Japanese patients. (Hepatology 2018;67:505-513).

Effects of Renal Impairment and Hemodialysis on the Pharmacokinetics and Safety of the Glecaprevir and Pibrentasvir Combination in Hepatitis C Virus-Negative Subjects.

Hepatitis C virus (HCV) infection is an independent risk factor for developing chronic renal impairment and end-stage renal disease. Limited treatment options are available for HCV genotype 2, 3, 5, and 6 infections in patients with an estimated glomerular filtration rate (eGFR) of <30 ml/min. Glecaprevir and pibrentasvir are active against all six major HCV genotypes, are primarily excreted in the bile, and have minimal renal elimination. Therefore, combined treatment with these direct-acting antivirals may be useful for patients with HCV infection and chronic kidney disease. A phase 1, multicenter, open-label study evaluated the effects of renal impairment on the pharmacokinetics and safety of glecaprevir-pibrentasvir. In substudy 1, 38 subjects with stage 2 to 5 chronic kidney disease who were not on dialysis or who had normal renal function received single doses of the combination of 300 mg glecaprevir and 120 mg pibrentasvir. In substudy 2, 8 subjects requiring hemodialysis received single doses of the combination of 300 mg glecaprevir and 120 mg pibrentasvir under dialysis and nondialysis conditions. Regression analyses demonstrated increased glecaprevir and pibrentasvir plasma exposures, as determined by the area under the curve, with decreasing renal function, up to 56% and 46%, respectively, in subjects with an eGFR of <15 ml/min/1.73 m2 In dialysis-dependent subjects, glecaprevir and pibrentasvir exposures were similar (≤18% difference) when study drugs were administered before hemodialysis or on a nondialysis day. Adverse events were mostly mild, with the most common being self-limited fatigue (3 subjects). The study findings support the clinical evaluation of glecaprevir-pibrentasvir without dose adjustment in HCV-infected subjects with renal impairment. (This study has been registered at ClinicalTrials.gov under registration number NCT02442258.).

Correction to: Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection.

Unfortunately, in the original publication of this article, the copyright line was incorrectly published in PDF as "© The Author(s) 2017" instead of "©The Author(s) 2017 This article is an open access publication" and also the CC-BY description was not included. The description should be as follows.

Efficacy and safety of glecaprevir/pibrentasvir in HCV-infected Japanese patients with prior DAA experience, severe renal impairment, or genotype 3 infection.

BACKGROUND: Once-daily, orally administered, co-formulated glecaprevir (NS3/4A protease inhibitor) and pibrentasvir (NS5A inhibitor) (G/P) demonstrated pangenotypic activity and high sustained virologic response (SVR) rates in studies outside Japan. Here we report safety and efficacy in a subset of Japanese patients with chronic HCV infection who received G/P 300/120 mg in a phase 3, open-label, multicenter study (CERTAIN-1). METHODS: This analysis focuses on three difficult-to-treat subgroups: HCV GT1/2-infected patients who failed to achieve SVR after treatment with a direct acting antiviral (DAA)-containing regimen; GT1/2-infected patients with severe renal impairment (estimated glomerular filtration rate < 30 mL/min/1.73 m2); and GT3-infected patients. Patients in the renal impairment and GT3 cohorts were treatment-naive or interferon treatment-experienced. Noncirrhotic GT1/2-infected, DAA-naïve patients in the renal impairment cohort received G/P for 8 weeks; all other patients were treated for 12 weeks. Primary outcome was SVR (HCV RNA < 15 IU/mL) 12 weeks post-treatment (SVR12). RESULTS: The study enrolled 33 GT1/2-infected patients who failed previous DAA treatment (four with cirrhosis); 12 GT1/2-infected patients with severe renal impairment (two with cirrhosis); and 12 GT3-infected patients (two with cirrhosis). SVR12 was achieved by 31/33 (93.9%), 12/12 (100%), and 10/12 (83.3%) patients, respectively. One serious adverse event (fluid overload, not related to G/P) occurred in a patient on chronic intermittent hemodialysis. CONCLUSIONS: G/P achieved high SVR12 rates and was well tolerated in three difficult-to-treat patient subgroups with limited treatment options in Japan (DAA-experienced patients, patients with severe renal impairment, and GT3-infected patients). These results support the potential suitability of this regimen for these special populations in Japan.

Glecaprevir and Pibrentasvir in Patients with HCV and Severe Renal Impairment.

BACKGROUND: Chronic hepatitis C virus (HCV) infection is more prevalent among patients who have chronic kidney disease than among those who do not have the disease. Patients with chronic kidney disease who also have HCV infection are at higher risk for progression to end-stage renal disease than those who have chronic kidney disease without HCV infection. Patients with both HCV infection and advanced chronic kidney disease have limited treatment options. METHODS: We conducted a multicenter, open-label, phase 3 trial to evaluate the efficacy and safety of treatment with the combination of the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir for 12 weeks in adults who had HCV genotype 1, 2, 3, 4, 5, or 6 infection and also had compensated liver disease (with or without cirrhosis) with severe renal impairment, dependence on dialysis, or both. Patients had stage 4 or 5 chronic kidney disease and either had received no previous treatment for HCV infection or had received previous treatment with interferon or pegylated interferon, ribavirin, sofosbuvir, or a combination of these medications. The primary end point was a sustained virologic response 12 weeks after the end of treatment. RESULTS: Among the 104 patients enrolled in the trial, 52% had genotype 1 infection, 16% had genotype 2 infection, 11% had genotype 3 infection, 19% had genotype 4 infection, and 2% had genotype 5 or 6 infection. The sustained virologic response rate was 98% (102 of 104 patients; 95% confidence interval, 95 to 100). No patients had virologic failure during treatment, and no patients had a virologic relapse after the end of treatment. Adverse events that were reported in at least 10% of the patients were pruritus, fatigue, and nausea. Serious adverse events were reported in 24% of the patients. Four patients discontinued the trial treatment prematurely because of adverse events; three of these patients had a sustained virologic response. CONCLUSIONS: Treatment with glecaprevir and pibrentasvir for 12 weeks resulted in a high rate of sustained virologic response in patients with stage 4 or 5 chronic kidney disease and HCV infection. (Funded by AbbVie; ClinicalTrials.gov number, NCT02651194 .).

Virologic and immunologic outcomes in HIV-infected Cambodian children after 18 months of highly active antiretroviral therapy (HAART).

This observational cohort study was conducted among HIV-infected, antiretroviral therapy (ART) naive children in Phnom Penh, Cambodia, to evaluate the feasibility and efficacy of highly active antiretroviral therapy (HAART) delivered using a modified directly observed therapy (MDOT) protocol. From August 2004 to March 2006, 26 children were enrolled and started on a first-line HAART regimen, which was continued for 18 months. The study included a directly observed therapy phase (months 1-3) and a medication self-administration phase (months 4-18). CD4 percentage (CD4%) and HIV-1 RNA plasma viral load (PVL) were measured at baseline and at months 6, 12, and 18. At baseline, the median age was 5.5 years (range: 13 months-12 years), the median CD4% was 4, and the median PVL was 7.5x10(5) copies/ml. At 18 months, 23 (88%) children were alive and participating in the study. Of these children, 20 (87%) had a PVL <400 copies/ml and 12 (52%) had PVL < 50 copies/ml. The median CD4% increased to 23, while the median change in height-for-weight z-score was 0.64. Genotypic resistance typing in 2 children with PVL > 400 copies/ml at 18 months demonstrated mutations associated with resistance to lamivudine (M184V) and non-nucleoside reverse transcriptase inhibitors (Y181C and G190A). The virologic and immunologic outcomes achieved in this study compare favorably with those reported by other pediatric HIV treatment programs worldwide. The study results suggest that MDOT may be effective for HAART administration in limited-resource settings like Cambodia.

Case report: an example of international telemedicine success.

An 8-month old girl presented to the Angkor Hospital for Children in Siem Riep, Cambodia with fevers, bilateral eye discharge and an extensive body rash. The rash consisted of large, fluid-filled bullae and significant desquamation. The patient was admitted to the hospital and given intravenous cloxacillin for presumed bullous impetigo. Despite treatment with antibiotics, the skin lesions did not improve and the fevers continued. Telemedicine consultations were initiated by email between Angkor Hospital for Children and paediatric specialists in the USA. Several diagnoses were entertained throughout the subsequent collaborative dialogue. Ultimately, teleconsultation led to a diagnosis of chronic bullous dermatosis of childhood (CBDC), a rare sub-epidermal blistering disease. The child was started on appropriate medications. Within 24 hours, the lesions showed significant improvement and fevers resolved. By enabling advice from distant providers on diagnosis and treatment of paediatric patients, telemedicine may improve health care in developing countries.

Correlates of heterosexual anal intercourse among at-risk adolescents and young adults.

OBJECTIVES: We sought to learn what factors are associated with anal intercourse among adolescents and young adults. We examined demographic, behavioral, relationship context, attitudinal, substance use, and mental health correlates of recent heterosexual anal intercourse among adolescents and young adults who reported engaging in recent unprotected sex. METHODS: Among 1348 at-risk adolescents and young adults aged 15 to 21 years in 3 US cities, we assessed sexual risk behavior with each sexual partner in the past 90 days. Data were collected from 2000 to 2001. RESULTS: Recent heterosexual anal intercourse was reported by 16% of respondents. Females who engaged in anal intercourse were more likely to be living with a sexual partner, to have had 2 or more partners, and to have experienced coerced intercourse. For males, only a sexual orientation other than heterosexual was a significant predictor of engaging in heterosexual anal intercourse. CONCLUSIONS: Our findings document the prevalence of heterosexual anal intercourse among adolescents and young adults who had recent unprotected sex. Among females, the variables associated with anal intercourse relate to the context and power balance of sexual relationships. Different influences for males and females suggest different foci for interventions.

Condom use among high-risk adolescents: anticipation of partner disapproval and less pleasure associated with not using condoms.

OBJECTIVE: We determined the association of demographic, psychosocial, and contextual factors with condom use among a large community sample of at-risk adolescents recruited from four locations in the U.S. METHODS: We enrolled 1,410 adolescents/young adults between the ages of 15 and 21 with a history of unprotected sex in the past 90 days at four study sites. Subjects completed an audio-assisted, computerized assessment that gathered information about sexual behavior and its contexts, substance use, and relevant risk and protective attitudes. RESULTS: Nearly two-thirds of adolescents did not use condoms at the time of last intercourse and adolescents reported a mean of 15.5 (median = 5) unprotected intercourse occasions in the past 90 days. Controlling for relevant demographic variables, not using condoms was associated with the perception that condoms reduce sexual pleasure, the perception that partners will not approve of condom use, and less discussion with partners about condoms. CONCLUSIONS: Even across racial/ethnic groups, gender, and geographic locations, several important correlates of adolescents' sexual risk reduction were identified. Many adolescents may feel that condoms reduce their sexual pleasure and fear partner reactions if they initiate condom use. These attitudes may be malleable through clinical and community-based interventions.

Compliance in Rhode Island emergency departments with American Academy of Pediatrics recommendations for adolescent sexual assaults.

OBJECTIVES: We assessed the offering of American Academy of Pediatrics-recommended tests and prophylaxes after sexual assault to adolescents who presented to Rhode Island emergency departments for 3 categories of sexual exposures: sexual assault, consensual sex, and suspected sexual abuse. PATIENTS AND METHODS: This study entailed a retrospective review of visits for adolescent sexual exposures across 11 Rhode Island emergency departments between January 1995 and June 2001. Cases were identified through billing codes. Offering of each test and prophylaxis was compared by gender, category of sexual exposure, and type of sexual assault. Multivariable linear regression models were used to identify factors associated with the offering of a greater number of tests and prophylaxes after sexual assault. RESULTS: The vast majority of emergency department visits for adolescent sexual exposures were by sexually assaulted girls (82.5%). Across the 3 sexual exposure categories, girls were offered tests and prophylaxes more often than boys (eg, chlamydia or gonorrhea testing and prophylaxis). Among sexually assaulted adolescents, 32.8% of girls and no boys were offered all recommended tests and prophylaxes. The multivariable linear regression found that vaginally and/or anally assaulted girls were offered, on average, 2.5 more tests and prophylaxes than patients with other types of sexual assaults. Girls presenting for care at the state's women's health care specialty hospital emergency departments were offered 1.7 more tests and prophylaxes than those evaluated in general hospital emergency departments. CONCLUSIONS: Many adolescents did not receive American Academy of Pediatrics-recommended tests and prophylaxes after sexual assault. Boys received fewer tests than girls. Testing and prophylaxis varied by type of emergency department. Efforts are needed to improve and standardize emergency department medical management of adolescent sexual exposures.

Suicide attempt and sexual risk behavior: relationship among adolescents.

The objective of this study was to examine the relationship between a history of suicide attempt and a range of current sexual risk behaviors in a large sample of sexually high-risk adolescents. Baseline data from 1,245 sexually active 15 to 21 year olds were collected as part of a multi-site, randomized trial of a brief HIV prevention program. Measures were collected using audio computer assisted self-interviews. Accounting for demographic, contextual, and substance use variables, a lifetime history of suicide attempt significantly added to multivariate regression models predicting sexual risk. Inconsistent condom users were almost twice as likely to have attempted suicide, and adolescents with an STI diagnosis were approximately twice as likely to have a history of suicide attempt. A history of suicidal behavior can be identified by clinicians and appears to be an important marker for sexual risk, which may represent an expression of emotional distress or a passive form of self-injury for suicidal adolescents.

HIV testing among at-risk adolescents and young adults: a prospective analysis of a community sample.

PURPOSE: Little is known about predictors of human immunodeficiency virus (HIV) testing among sexually active adolescents, who account for a large proportion of new HIV infections. This study sought to determine predictors of HIV testing among a large community-based sample of adolescents in three cities who had recent unprotected sexual intercourse. METHODS: Sexually active adolescents (N = 1222) completed baseline and 3-month assessments of sexual behavior, substance use and HIV testing behaviors as part of a larger, multi-site, brief HIV prevention program. RESULTS: Approximately half of the adolescents reported having previously been tested for HIV, and of those one third were tested in the next 3 months without a specific intervention. Adolescents who received HIV testing were more likely at baseline to have ever been tested, to have a STI diagnosis, to have not used substances during sex and to have been assertive about condom use with a partner. CONCLUSIONS: Health care models encouraging more widespread, universal testing may be an important public health initiative to curb the spread of HIV. Regular HIV screenings provide an opportunity to enhance awareness of behavioral risk and HIV status, as well as provide opportunities for early detection and care.

Psychosis in a 12-year-old HIV-positive girl with an increased serum concentration of efavirenz.

Clearance and adverse effects of efavirenz are associated with CYP2B6-G516T polymorphism. Little is known about the prevalence of genotypes and implications for screening in children. We report (to our knowledge, for the first time in a child) the emergence of psychosis in a 12-year old white girl with an increased efavirenz concentration and heterozygous gene polymorphism of the CYP2B6-G516T.