Use of Human Immunodeficiency Virus Postexposure Prophylaxis in Adolescent Sexual Assault Victims FREE

Adolescents suffer the highest rates of sexual assault of any age group.¹ Up to 10% of adolescent females report a lifetime history of sexual assault.^2- 3 Although the risk of contracting human immunodeficiency virus (HIV) is low after a single sexual exposure (0.1%-0.2% for receptive vaginal intercourse and 0.1%-3% for receptive anal intercourse),⁴ HIV transmission has been reported after sexual assault.^5- 6 Postexposure prophylaxis (PEP), the prescription of a 28-day course of antiretroviral medications, is an established intervention among health care workers to reduce the likelihood of HIV transmission after occupational exposures.⁷ The use of PEP for nonoccupational exposures to HIV, including sexual assault, is an extension of this practice. Evidence on the efficacy of PEP for sexual exposures is limited. However, data from animal studies⁸ and observational human studies^9- 10 suggest that antiretroviral medications can reduce the risk of HIV transmission when administered within 72 hours after a sexual exposure to HIV.

During the past decade, physician attitudes and practices on providing PEP after sexual assault have varied,^11- 14 likely because of the absence of uniform guidelines recommending that HIV prophylaxis be administered to sexual assault victims. In 1998, an expert panel from the Centers for Disease Control and Prevention concluded that data at that time were lacking to recommend for or against the use of PEP for nonoccupational HIV exposures.¹⁵ In the subsequent years, several states developed guidelines advising physicians to provide PEP after sexual assault.^16- 19 National guidelines recommending that PEP be considered after sexual assault were only recently published, in January 2005.²⁰ At our 2 institutions, protocols for the use of PEP in the pediatric emergency department (ED) were independently developed in 1997.²¹ During the time covered by this retrospective study, both hospital protocols recommended that PEP be considered and offered on a case-by-case basis to adolescent survivors of sexual assault.

The use of PEP for survivors of sexual assault has been well described.^22- 26 Postexposure prophylaxis is well tolerated among sexual assault survivors, with few reported serious adverse reactions.^23- 24 Adherence to PEP among sexual assault survivors has varied from 16% to 85%.^22- 24 Few studies to date have reported specifically on the use of PEP in adolescents.^27- 29 It is likely that adolescent sexual assault survivors have unique issues complicating their adherence to PEP. The goals of the current retrospective study were to describe PEP use among adolescent sexual assault survivors, to determine rates of medication adherence and follow-up, and to explore potential obstacles to successful PEP completion in this population.

We reviewed charts for all adolescent visits after sexual assault to 2 pediatric EDs in Boston, Mass, during a 2-year period (July 1, 2001, through June 30, 2003). The 2 EDs are affiliated with urban academic medical centers and have a combined annual census of 75 000 visits per year. Both EDs have protocols for the management of sexual assault survivors that recommend HIV PEP be considered. Both EDs refer adolescents prescribed HIV PEP for follow-up with their primary care provider and/or with the sexual assault follow-up clinics affiliated with the medical centers. Location for follow-up care is based on patient and/or parental preference. The 2 adolescent sexual assault follow-up clinics are each staffed by a physician and a nurse or nurse practitioner with HIV medication expertise. The clinics have varying levels of social work involvement. Patients are advised to return for follow-up at 2 weeks, 6 weeks, 3 months, and 6 months after the assault. Testing for HIV antibody is recommended at baseline, 6 weeks, 3 months, and 6 months after the assault.

Adolescents 12 to 22 years of age visiting 1 of the 2 participating EDs during the study period were included in the chart review if they were examined within 72 hours of a penetrating sexual assault. Patients were excluded from the chart review if they were examined for a nonpenetrating sexual assault, if they were examined more than 72 hours after a sexual assault, or if there was insufficient information in the medical record to determine the nature of the exposure and/or the ED management.

We identified patients for inclusion in the chart review by searching the electronic ED medical records using the keywords trauma x, x, sexual assault, postexposure prophylaxis, and Combivir. The most common International Classification of Diseases, Ninth Revision, codes found in charts identified by the text word search were then queried for all ED visits during the study period. Specific codes searched were: “V01.89—Exposure to infectious body fluid,” “V07.9—Unspecified prophylactic measure,” “V71.5—Observation following alleged rape or seduction,” “V15.41—Psychological trauma,” “995.53—Child maltreatment syndrome,” “V15.85—Exposure to potentially hazardous body fluid,” and “E960.1—Rape.” We also reviewed social work log books, pharmacy databases, and records from the sexual assault follow-up clinics to further identify patients for inclusion.

We abstracted data from medical records from the index ED visit and from previous and subsequent outpatient and ED visits within the 2 medical centers. Data were not available for visits outside of the 2 participating medical centers.

Data collected included demographic variables (age, race, and insurance), previous history of sexual assault, psychiatric comorbidity (defined as depression, bipolar disorder, substance abuse, suicidality, attention-deficit/hyperactivity disorder, conduct disorder, psychosis or schizophrenia, anxiety disorder, or posttraumatic stress disorder documented at the index ED visit or at previous outpatient visits), assault characteristics (penile-vaginal, penile-oral, and/or penile-rectal exposure; time from assault to ED visit; use of condom; ejaculation; number of assailants; whether victim knew assailant[s]; blacking out during assault; assailant HIV risk; and genital trauma), PEP information (whether PEP was recommended, medications offered, completion of 28-day course of PEP, and medication adverse reaction). Exposures were classified as being at risk for HIV transmission, in agreement with previous research,²⁴ if there was penile-rectal exposure, genital trauma, multiple assailants, or penile-vaginal or penile-oral exposure with ejaculation and no condom. We also collected data on whether patients returned for follow-up visits and repeat HIV testing within the 2 academic medical centers.

Assault characteristics were routinely recorded at both institutions on the Sexual Assault Evidence Collection Kit issued by the Massachusetts Executive Office of Public Safety. Demographic data, psychiatric illness, PEP provision, and medication adverse events were routinely recorded in the medical record as part of standard medical care. Charts were reviewed by 3 investigators (E.O., K.H., B.H.) and 1 research assistant, using a standardized data collection form. A subset of charts was reviewed by multiple investigators, resulting in no significant disagreements. All data entry was performed by a single investigator (E.O.).

We determined rates for demographic variables, assault characteristics, provision of PEP, and psychiatric comorbidity among the adolescent sexual assault survivors included in this chart review. We compared patients referred for care in the academic center vs those referred for follow-up care with their primary care provider. We also examined whether physician provision of PEP and patient agreement to initiate PEP were associated with specific demographic variables or assault characteristics.

We limited our evaluation of documented PEP completion and return for follow-up visits and HIV testing to patients referred to 2 academic medical centers. Patients who did not return for any follow-up visits were recorded as not completing a course of PEP. We further limited our evaluation of PEP toxic effects to patients agreeing to take PEP who returned for at least 1 follow-up visit. We explored the relationship between PEP completion and return for HIV testing independently with each of the demographic variables and assault characteristics. All bivariate analyses were conducted with Pearson χ² test or Fisher exact test.

This chart review was approved by the institutional review boards of the 2 participating institutions.

Charts for 177 adolescents evaluated within 72 hours of a penetrating sexual assault were reviewed. Twenty-eight patients were excluded because of incomplete documentation of the sexual assault, 3 patients were excluded because they left the ED before medical evaluation, and 1 patient was excluded because the ED management was not documented. An additional 24 patients prescribed PEP were identified but not included in the chart review because their ED visit was outside the 72-hour window.

One hundred forty-five adolescent sexual assault survivors met study criteria and were included in the final study population. Patients were predominantly female, racially/ethnically diverse, and their insurance status varied (Table 1). Twenty-six percent had a history of depression and 47% had carried at least 1 psychiatric diagnosis before the assault. Ten patients (6%) were cognitively delayed. Ninety-seven patients were referred for follow-up at the 2 academic centers. Patients referred for follow-up at the academic centers differed significantly from those referred for follow-up with their primary care providers: they were older, were more likely to be nonwhite, were less likely to have private insurance, and had higher rates of previous sexual assault and depression (Table 1).

Assault characteristics for this cohort are detailed in Table 2. Most patients (74%) reported penile-vaginal exposure. More than one half of adolescent sexual assault survivors were unsure whether ejaculation had occurred and more than one quarter were unsure whether a condom had been used. For 38% of patients, risk of HIV transmission could not be determined from the available documentation. Twenty-one percent reported having blacked out during the assault; 14% reported assault by multiple perpetrators (Table 2). Nearly half reported knowing the perpetrator(s). None of the perpetrators were known to be HIV positive, and only 2% were thought to be at high risk for being HIV positive. There were no significant differences in the assault characteristics of patients referred for follow-up at the academic centers vs those referred for follow-up with their primary care providers.

Of the 145 adolescent sexual assault survivors included in this chart review, 129 (89%) were offered PEP and 110 (76%) agreed to take the PEP medications. Compared with patients not offered PEP, patients offered PEP were more likely to have an exposure classified as being at risk for HIV transmission. Other demographic and assault characteristics were not significantly associated with being offered PEP. Compared with patients who refused PEP, those agreeing to take PEP were more likely to have an exposure classified as being at risk for HIV transmission and less likely to report that a condom was used. Patients who were white were more likely to refuse the PEP medications (9 [17%] of 54 white patients, 4 [7%] of 55 black patients, and 1 [5%] of 21 Hispanic patients refused PEP; P = .03). Other demographic and assault characteristics were not associated with agreeing to take PEP. The 110 patients who agreed to take PEP were prescribed the following medications: lamivudine and zidovudine (94%); lamivudine, zidovudine, and nelfinavir (3%); and lamivudine, zidovudine, and indinavir (2%) (medications not documented for 1%).

Follow-up data are reported for the 97 patients who were referred for care at the 2 academic medical centers, of whom 86 (89%) agreed to take PEP. Only 37 (38%) returned for at least 1 follow-up visit, 35 of whom agreed to take PEP (34 were prescribed lamivudine and zidovudine). Medication toxicity data were available for the 35 patients taking PEP with at least 1 follow-up visit. Sixteen (46%) developed at least 1 adverse event related to PEP, including nausea in 13 (37%), diarrhea in 5 (14%), vomiting in 6 (17%), abdominal pain in 4 (11%), anemia in 3 (9%), and headaches in 2 (6%).

Of the 97 patients referred for follow-up at the academic medical centers, 23 (24%) had at least 1 follow-up HIV test and only 1 patient had all 3 recommended HIV tests. There were no seroconversions in this population. Of the 86 patients referred for follow-up at the academic medical centers who initiated PEP, 13 (15%) completed a full 28-day course of PEP.

On bivariate analysis, history of at least 1 previous psychiatric illness was associated with being less likely to complete a 28-day course of PEP (Table 3). No other demographic variables or assault characteristics were associated with PEP completion. No demographic or assault characteristics were associated with returning for follow-up HIV testing (Table 4).

In this chart review, we report on a large cohort of adolescent sexual assault survivors examined at 2 urban academic medical centers during a 2-year period. In accordance with hospital-based protocols, 89% of adolescent sexual assault survivors were offered HIV PEP, and 76% agreed to take the PEP medications. We observed a low rate of PEP completion among adolescent sexual assault survivors. Only 15% of patients who initiated PEP and were referred for follow-up at the academic medical centers were documented to complete a 28-day course of antiretroviral medications. This rate is comparable with that reported in 2 previous small series of adolescent patients who received PEP^27- 28 and in 1 report of adult sexual assault survivors.²² However, our rate of PEP completion is substantially lower than that reported among Brazilian (61%)²⁴ and South African (87%)²³ sexual assault survivors. The Brazilian and South African studies likely had improved adherence because patients were tracked prospectively and because the studies occurred in areas of high HIV prevalence, where the perceived risk of acquiring HIV after sexual assault was substantial. In contrast, in our population, none of the assailants were known to be HIV positive and only 2% were thought to be at high risk for being HIV positive. Furthermore, we assessed outcomes through retrospective chart review and thus may have underestimated our true adherence rate. Nevertheless, such low rates of medication adherence highlight the need for improved patient education and outreach.

Results of this study highlight some of the difficulties of administering PEP to adolescents after sexual assault. First, to assess the need for PEP, it is important to know specific details related to the assault. Recently released national guidelines on nonoccupational HIV PEP²⁰ recommend that when a source is of unknown HIV status, PEP should be provided on a case-by-case basis, after weighing the risks and benefits of treatment. However, in many cases of adolescent sexual assault, the risks of HIV transmission cannot be determined. Among patients in our study, 21% reported having blacked out during the assault, 54% were unsure whether ejaculation had occurred, and 27% were unsure whether a condom had been used.

A second factor complicating the provision of PEP to adolescent sexual assault survivors is their high rate of psychiatric comorbidity. In our study, 47% of patients had a previous psychiatric diagnosis, including 26% with a history of depression and 10% with a history of suicidality. These rates are higher than previously reported rates of mental illness among sexual assault survivors.^30- 31 Previous population-based studies^2,31 have shown an association in adolescents between sexual assault and depressive symptoms. Because of their cross-sectional design, these studies were unable to evaluate the temporal relationship between sexual assault and depression. Many have postulated that depression among sexual assault survivors is a response to the trauma of the assault. Indeed, 33% of sexual assault survivors develop posttraumatic stress disorder.³² However, our high rates of psychiatric comorbidity before the assault suggest that mental illness may also be a risk factor for future victimization. Furthermore, in our study population, previous psychiatric illness was associated with decreased PEP adherence.

A third factor complicating the provision of PEP to adolescent sexual assault survivors is the low rate of return for follow-up care. Fewer than half of the patients who received PEP and were referred for follow-up at our institutions returned for at least 1 follow-up visit. Medical monitoring of patients taking PEP is important to promote medication adherence, to manage frequent medication side effects, and to monitor for acute seroconversion syndrome. Follow-up visits are also important for adolescents taking PEP to provide risk-reduction counseling and follow-up HIV testing. Our low follow-up rates also served as a study limitation because we were unable to fully evaluate medication adherence and medication toxic effects in this population.

Further limitations of this research should be noted. As a chart review, the study could report only on information documented in the medical records at the 2 participating academic centers. It is likely that certain variables were underreported in the medical records. Also, we were unable to assess outcomes for patients who sought care outside the 2 academic medical centers. The group of patients referred for follow-up with their primary care providers did differ demographically from those referred for follow-up at the academic medical centers, possibly affecting the generalizability of our findings.

A final limitation was that we reviewed charts only at 2 urban academic medical centers. Our cohort was diverse in racial/ethnic background and insurance coverage. Assault characteristics for our cohort (including whether the perpetrator was known, number of assailants, and presence of trauma on examination) were comparable with those in published reports of adolescent sexual assault.^33- 36 However, our patients may have differed from adolescent sexual assault survivors seen in other clinical settings. Furthermore, provision of PEP was determined by hospital-based protocols and follow-up clinics. Factors associated with PEP initiation, PEP completion, and return for follow-up may be specific to our institutions.

Despite these limitations, our study provides further data on the use of PEP in adolescent sexual assault survivors. The use of PEP in this population can be difficult because of patient uncertainty regarding exposure, high rates of psychiatric comorbidity, and low rates of follow-up. We agree with published recommendations that PEP be offered to adolescent sexual assault survivors for exposures that pose a risk of HIV transmission. Patient education and a comprehensive follow-up system with extensive outreach and case management are necessary to encourage PEP adherence and return for follow-up care among adolescent sexual assault survivors.

Correspondence: Elyse Olshen, MD, MPH, Department of Pediatrics, Columbia University, 622 W 168th St, VC-402, New York, NY 10032 (Eo85@columbia.edu).

Accepted for Publication: January 5, 2006.

Author Contributions:Study concept and design: Olshen, Hsu, Woods, Harper, and Samples. Acquisition of data: Olshen, Hsu, Harper, and Harnisch. Analysis and interpretation of data: Olshen, Hsu, Harnisch, and Samples. Drafting of the manuscript: Olshen and Samples. Critical revision of the manuscript for important intellectual content:Olshen, Hsu, Woods, Harper, Harnisch, and Samples. Statistical analysis: Woods and Harper. Obtained funding: Olshen and Woods. Administrative, technical, and material support: Hsu, Harnisch, and Samples. Study supervision: Hsu, Woods, and Samples.

Funding/Support: This study was supported by the Aerosmith Endowment Fund for the Prevention and Treatment of HIV, Leadership Education in Adolescent Health Project, Maternal and Child Health Bureau, US Department of Health and Human Services (5T71-MC00009-13-00), and the Boston University School of Medicine Summer Research Scholarship Program.

Previous Presentations: This study was presented in part at the 2005 Annual Meeting of the Pediatric Academic Society; May 15, 2005; Washington, DC.

Acknowledgment: Hope Mitchell, MD, assisted with reviewing medical records.