Abstract
Sexually transmitted infections (STIs) are known to promote the transmission of HIV. Diagnosing these infections can identify patients engaging in high-risk behaviors and provides an opportunity for intervention and education. The Centers for Disease Control and Prevention (CDC) recommends STI screening as part of routine HIV care. Ninety HIV-infected inpatients admitted to the University of Maryland Hospital were screened for gonorrhea, chlamydia, and syphilis. None of the nucleic acid amplification probes were positive for gonorrhea, and 1 was positive for chlamydia. A total of 8 rapid plasma reagin (RPR) tests were positive, 2 of which are believed to be associated with new infection or treatment failure. Rapid plasma reagin positivity was found to be associated with men who have sex with men (MSM), low CD4 count, and high HIV viral load. Routine inpatient screening for asymptomatic STIs in HIV-infected patients may be beneficial, particularly patients not engaged in routine outpatient care.
Introduction
Sexually transmitted infections cause significant morbidity and even mortality. The prevalence of these infections varies in different parts of the United States, as well as within different age groups, genders, and races. In Baltimore City in 2008, the prevalence of gonorrhea, chlamydial infection, and syphilis was 501.8, 1327.7, and 31.1 per 100 000, respectively. 1 The syphilis epidemic in particular is in a state of evolution. National syphilis rates decreased during the 1990s but are now on the rise. Groups described as being disproportionately affected by the current syphilis epidemic include men who have sex with men (MSM), injection drug users, and individuals who engage in sex for money or drugs. These are the same groups most affected by the HIV epidemic in the United States. 2
The relationship between HIV and other sexually transmitted infections (STIs) is complex. Ulcerative STIs such as syphilis have clearly been shown to increase transmission of HIV, and there are limited data to suggest that nonulcerative STIs such as gonorrhea and chlamydial infection may impact HIV transmission as well. 3 -5 Screening for, diagnosing, and treating asymptomatic STIs may decrease HIV transmission. Additionally, STI screening can help identify HIV-infected persons that are practicing unsafe or high-risk sexual behaviors, thereby providing an opportunity for intervention and education.
The Centers for Disease Control and Prevention (CDC) recommends STI screening for gonorrhea, chlamydia, and syphilis among HIV-infected patients that are sexually active. 6,7 The most practical place for such screening to occur is in the outpatient setting. Unfortunately, some patients do not participate in routine ongoing outpatient HIV care. In action, screening rates for syphilis, gonorrhea, and chlamydia in outpatient HIV clinics are not particularly high. In one survey of health care providers caring for HIV-infected individuals, 36.4% of providers reported that they do not perform annual STI screening in woman and 48.6% reported that they do not perform annual STI screening in men. 8 Alternative screening sites such as schools, prisons, substance abuse clinics, and emergency departments have been proposed. 9 -12 Another site that may be feasible for STI screening is the inpatient unit of the hospital. The objective of this study is to determine the utility and feasibility of screening for gonorrhea, chlamydial infection, and syphilis in HIV-infected patients admitted to the hospital to determine whether the hospital could serve as a novel site for the detection of STIs. To the best of our knowledge, this is the first study to conduct STI screening on hospitalized patients.
Materials and Methods
This study was approved by the University of Maryland Medical Center Institutional Review Board (IRB). Gonorrhea, chlamydial infection, and syphilis screening were offered to HIV-infected inpatients admitted to an HIV service at the University of Maryland Medical Center from October 2007 to January 2009. Inclusion criteria for the study include age greater than 18, HIV infection, ability to speak English, ability to sign informed consent, ability to urinate, and not admitted specifically for an STI. Research team members attend team rounds to learn of potential participants in the study. Sicker patients often were not referred because of difficulty with informed consent. Of the patients referred, about 20 patients declined participation primarily because they had already spoken to multiple health care providers and they wanted time to rest or time to spend with visiting family and friends. A few patients refused because of general mistrust of medical research. Ninety patients were ultimately enrolled in the study. After signing an informed consent, urine and serum specimens were collected from each patient. Testing for gonorrhea and chlamydia was performed using urine nucleic acid amplification procedures (Luminex, Austin, Texas). Syphilis was diagnosed with serum rapid plasma reagins (RPRs) and confirmatory fluorescent treponemal antibodies (FTA-abs). Prior treatment history for syphilis was confirmed through the Baltimore City or Maryland State Health Departments.
At the time that consent was obtained, each patient completed a researcher-administered questionnaire regarding demographics, sexual history, drug history, HIV treatment history, and genitourinary symptoms. Additional information, such as CD4 counts, HIV viral loads, and hepatitis serologies, was collected from the electronic medical record.
Prevalence of each STI was calculated. Continuous variables such as CD4 count and HIV viral load were examined for normality. Differences in means were tested with t tests, and differences in proportions were tested by chi-square or Fisher exact test (where appropriate). Statistical analyses performed on SAS v9.1.
Results
A total of 90 patients were enrolled in the study. The mean age was 42.6 ± 9.1. Eighty-one percent of patients were African American. Patients had a mean CD4 count of 223.8 cells/mm3, a mean HIV viral load of 334 961 copies/mL, and 33% were receiving antiretroviral therapy (ART) at the time of enrollment (Table 1). Of the 90 enrolled patients, CD4 and viral load data were available for 85 patients, RPR data were available for 83 patients, and gonorrhea and chlamydial infection data were available for 73 patients. These data are incomplete for several patients because blood and/or urine specimens were not able to be collected prior to the patient being discharged.
Baseline Characteristics of Study Participants a
Abbreviations: SD, standard deviation; STIs, sexually transmitted infections.
a Data are number (%) of participants, unless otherwise indicated.
Eight (9.6%) participants had positive RPRs, 1 (1.37%) had a positive nucleic acid amplification probe for chlamydia (confidence interval (CI.95) 0.33-7.30), and none (0%) tested positive for gonorrhea (CI.95 0-4.86). All 8 of the positive RPRs were confirmed with a positive FTA-abs. One of the participants with a positive RPR had no prior positive titers and was treated as a new infection. Another one had a titer of 1:32 but had a prior titer as high as 1:16 tested in another laboratory, which did not show the 2-fold rise that one would expect with new infection. Six of the remaining 8 participants with positive RPRs had titers of ≤1:2 at the time of the study and had documented prior positive RPR results; hence, these were not thought to represent cases of active infection, but rather cases of prior infection with serofast serologies.
Positive RPR titers were found in 3 (42.9%) of 7 men whose sexual preference was men as compared to only 5 (7.1%) of 70 persons who classified themselves as heterosexuals (P = .02; Table 2). The mean CD4 count in participants with a positive RPR was 94.3 cells/mm3 compared with 239.0 cells/mm3 in participants with a negative RPR (P = .02; Table 3; Figure 1). The mean HIV viral load in patients with positive RPR and negative RPR was 4.91 log10 and 4.26 log10 copies/mL, respectively (P = .007; Table 3; Figure 2). Variables such as condom use, number of partners, commercial sex work, and illicit drug use were not found to be associated with RPR positivity.
Box plot of CD4 count by rapid plasma reagin (RPR) results.
Box plot of plasma HIV RNA by rapid plasma reagin (RPR) results.
Risk Factors for RPR Positivity among HIV-Infected Inpatients a
Abbreviations: RPR, rapid plasma reagin; MSM, men who have sex with men; WSW, women who have sex with women; HAART, highly active antiretroviral therapy; HBV, hepatitis B virus; HCV, hepatitis C virus.
a Data are number (%) of participants, unless otherwise indicated.
b Total patients enrolled = 90, but 7 patients did not have RPR results available.
c Comparing heterosexual to MSM.
Comparison of Age, CD4 Count, and HIV Viral Load between RPR-Positive Patients and RPR-Negative Patients a
Abbreviation: RPR, rapid plasma reagin.
a Values are mean ± standard deviation.
b t Test comparing means, where variances are unequal.
Discussion
This study shows that screening for STIs among HIV-infected persons admitted to a hospital is feasible but that the incidence of STIs was low and many times represented past infection. In screening for asymptomatic bacterial STIs among hospitalized HIV-infected patients, our study found 9.6% of patients had a positive RPR, 1.4% had active syphilis, 1.4% tested positive for chlaymdial infection, and no patients were found to have gonorrhea. While the incidence of asymptomatic STIs appears low, the consequences of undiagnosed and untreated STIs in this patient population are of such severity that inpatient screening may be warranted in patients not otherwise engaged in care.
Given the recent resurgence of syphilis, it is important to identify risk factors associated with syphilis infection. Our study found that hospitalized HIV-infected patients with positive RPRs were more likely to be MSM. This is not surprising, given that in 2008, per the CDC, 63% of primary and secondary syphilis cases in the United States were among MSM as compared to only 4% in 2000. 13 Not only is the syphilis epidemic disproportionately affecting MSM, the current HIV epidemic in the United States is also centered around MSM. In light of this trend, MSM should be a major focus of any STI education and screening efforts, in both inpatient and outpatient settings.
Our study also found a statistically significant association between low CD4 count and high HIV viral load and patients with a positive RPR. The nature of this association is unclear. It is possible that transmission of syphilis is higher in patients with poorly controlled HIV or that these patients’ HIV is not under control because they are not engaged in routine HIV care and are therefore not being routinely screened for STIs such as syphilis. In these patients, inpatient stays may be the only opportunity for screening and intervention. Interestingly, intuitive risk factors for STIs such as unprotected intercourse, commercial sex work, and illicit drug use were not found to be associated with RPR positivity in this study. This may be due to inaccurate questionnaire responses as is frequently observed when the study participants are asked questions about sensitive subjects.
There were several limitations to this study, the largest of which was sample size. There were patients who were unable to provide urine and/or serum specimens prior to being discharged. Another potential limitation is a lack of full disclosure when completing the questionnaire due to embarrassment or fear. Finally, the results of this study are based on positive and negative RPR values rather than on the presence or absence of active syphilis infection. Of the 8 participants identified as having positive RPRs, 6 likely had previously treated syphilis rather than a new infection. These patients’ CD4 count, viral load, and risk factors for STIs at the time of the study may not be representative of their HIV status and STI risk factors at the time of syphilis acquisition.
In conclusion, the findings of our study suggest that there may be a role for routine inpatient bacterial STI screening of HIV-infected patients. A larger study is necessary to better determine the incidence of bacterial STIs in hospitalized HIV-infected patients. However, based on this study, syphilis and chlamydia are more likely to be found in asymptomatic patients than gonorrhea. Sexual preference, CD4 count, and HIV viral load may correlate with syphilis infection and should also be further assessed with additional, larger studies. While engaging patients in routine, outpatient HIV care is the ultimate goal, this is not always able to be accomplished. It is therefore important to make the most out of each encounter patients have with the health care system.
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
The author(s) received no financial support for the research, authorship, and/or publication of this article.