Safety and tolerability of antiretrovirals during pregnancy.

Combination antiretroviral therapy (CART) dramatically decreases mother-to-child HIV-1 transmission (MTCT), but maternal adverse events are not infrequent. A review of 117 locally followed pregnancies revealed 7 grade ≥ 3 AEs possibly related to antiretrovirals, including 2 hematologic, 3 hepatic, and 2 obstetric cholestasis cases. A fetal demise was attributed to obstetric cholestasis, but no maternal deaths occurred. The drugs possibly associated with these AE were zidovudine, nelfinavir, lopinavir/ritonavir, and indinavir. AE or intolerability required discontinuation/substitution of nevirapine in 16% of the users, zidovudine in 10%, nelfinavir in 9%, lopinavir/ritonavir in 1%, but epivir and stavudine in none. In conclusion, nevirapine, zidovudine, and nelfinavir had the highest frequency of AE and/or the lowest tolerability during pregnancy. Although nevirapine and nelfinavir are infrequently used in pregnancy at present, zidovudine is included in most MTCT preventative regimens. Our data emphasize the need to revise the treatment recommendations for pregnant women to include safer and better-tolerated drugs.

Novel approach to parental permission and child assent for research: improving comprehension.

OBJECTIVE: The aim of this research was to test a multimedia permission/assent (P/A) process. The overall hypothesis was that children and their parents exposed to a multimedia P/A process would have better comprehension compared with those exposed to a text-based process. METHODS: Traditional and multimedia P/A processes were created by using an innovative learning-objective approach. A total of 194 parent-child dyads (children aged 11-14 years) were enrolled: 24 dyads in a prestudy testing P/A components for preference and effect on comprehension and 170 dyads in a randomized trial of a multimedia or paper P/A process for a hypothetical study. Participants were predominantly white and were from a metropolitan area served by a tertiary care pediatric hospital and outpatient facility. Comprehension of 8 essential elements of the P/A process was assessed. RESULTS: The majority of prestudy subjects preferred the video version of the dual-energy radiograph absorptiometry description over the animated and paper versions combined (41 of 48 [85%]; P < .0001), and there were similar results for the abdominal ultrasound description (38 of 47 [81%]; P < .0001). Children exposed to the novel process showed significantly better overall comprehension compared with the paper P/A process (P = .0009), and there were highly significant differences in understanding of study procedures (P = .0002) and risks (P < .0001). The parental multimedia group had significantly better overall comprehension (P = .03). CONCLUSIONS: Multimedia approaches to the research P/A process may improve overall understanding of research participation for children and parents. Improved understanding of study-specific research components (rather than research rights) may improve overall comprehension.

The diagnostic validity of hip provocation maneuvers to detect intra-articular hip pathology.

OBJECTIVE: To determine which hip provocation maneuvers best predict the presence of an intra-articular hip pathology. DESIGN: Prospective diagnostic study. SETTING: Musculoskeletal clinic at a university-based multispecialty group practice. PARTICIPANTS: Fifty subjects referred for intra-articular hip injection under fluoroscopic guidance. INTERVENTIONS: Subjects were examined with 4 pain provocation maneuvers before and after anesthetic intra-articular hip injection administered under fluoroscopic guidance. MAIN OUTCOME MEASUREMENTS: Presence of intra-articular hip pain generator was confirmed by > or =80% improvement on visual analog scale after intra-articular hip injection. RESULTS: The most sensitive tests were flexion abduction external rotation (FABER) test and internal rotation over pressure (IROP) maneuver. For the FABER test, sensitivity was 0.82 (95% CI 0.57-0.96); sensitivity for the IROP maneuver was 0.91 (95% CI 0.68-0.99). The most specific test was the Stinchfield maneuver, with specificity at 0.32 (95% CI 0.14-0.55). FABER and IROP had the highest positive predictive value, with 0.46 (95% CI 0.28-0.65) and 0.47 (95% CI 0.29-0.64), respectively. IROP had the highest negative predictive value at 0.71 (95% CI 0.25-0.98). CONCLUSIONS: IROP and FABER may be worthwhile components of the clinical evaluation of hip pain to determine intra-articular hip pathology. These tests are nonspecific and therefore not necessarily negative in the absence of intra-articular hip pathology. These hip provocation maneuvers are a useful part of an evaluation that includes history, further examination findings, and other diagnostic studies.

Resistance to antiretrovirals in HIV-infected pregnant women.

BACKGROUND: Antiretrovirals suppress HIV replication and prevent mother-to-child-transmission of HIV (PMTCT). Resistance to antiretrovirals may reduce the efficacy of PMTCT and/or complicate treatment of maternal or infant infection. OBJECTIVES: To assess resistance to antiretrovirals during pregnancy. DESIGN: Retrospective chart review of 44 pregnancies. RESULTS: Twenty-two patients were antiretroviral treatment-naïve, 8 were on therapy, and 14 had prior therapy, but were off medication when the genotyping was performed. Major mutations were found in 10 antiretroviral-experienced women, including 5 women with major mutations to 2 classes of drugs (none to 3 classes). Major mutations were most common for lamivudine, nevirapine, zidovudine, stavudine, and abacavir. Three women had significant resistance to zidovudine/lamivudine, a combination recommended in PMTCT guidelines. Despite significant antiretroviral resistance, 6 of 8 women with plasma HIV RNA measured within 4 weeks of delivery achieved <50 copies/mL. All neonates were uninfected. Among 6 women who received antiretrovirals exclusively for PMTCT, there were no remarkable changes of the HIV genotype before and after pregnancy. CONCLUSIONS: Resistance to antiretrovirals was common in antiretroviral-experienced pregnant women, but not in naïve women. The 14% prevalence of resistance to zidovudine and lamivudine in antiretroviral-experienced women suggests that alternative NRTI are desirable for this group of patients.