Khalil G. Ghanem

Primary Care Guidelines for the Management of Persons Infected With HIV: 2013 Update by the HIV Medicine Association of the Infectious Diseases Society of America

Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America. These updated guidelines replace those published in 2009. The guidelines are intended for use by healthcare providers who care for HIV-infected patients. Since 2009, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself or its treatment. HIV-infected persons should be managed and monitored for all relevant age- and sex-specific health problems. New information based on publications from the period 2009-2013 has been incorporated into this document.

Audio computer assisted self interview and face to face interview modes in assessing response bias among STD clinic patients

Background: Audio computer assisted self interview (ACASI) may minimise social desirability bias in the ascertainment of sensitive behaviours. The aim of this study was to describe the difference in reporting risk behaviour in ACASI compared to a face to face interview (FFI) among public sexually transmitted diseases (STD) clinic attendees. Study design: Randomly selected patients attending a public STD clinic in Baltimore, Maryland, sequentially took an ACASI formatted risk behaviour assessment followed by an FFI conducted by a single clinician, with both interview modalities surveying sexual and drug use behaviours. Binary responses were compared using the sign test, and categorical responses were compared using the Wilcoxon signed rank test to account for repeated measures. Results: 671 (52% men, mean age 30 years, 95% African American) of 795 clinic attendees screened consented to participate. Subjects affirmed sensitive sexual behaviours such as same sex contact (p = 0.012), receptive rectal sexual exposure (p<0.001), orogenital contact (p<0.001), and a greater number of sex partners in the past month (p<0.001) more frequently with ACASI than with an FFI. However, there were no differences in participant responses to questions on use of illicit drugs or needle sharing. Conclusions: Among STD clinic patients, reporting of sensitive sexual risk behaviours to clinicians was much more susceptible to social desirability bias than was reporting of illegal drug use behaviours. In STD clinics where screening of sexual risk is an essential component of STD prevention, the use of ACASI may be a more reliable assessment method than traditional FFI.

Neurosyphilis in a clinical cohort of HIV-1-infected patients

Objectives:To describe the risk factors, clinical presentation, and long-term follow up of patients enrolled in a clinical cohort of HIV-infected patients who were diagnosed and treated for neurosyphilis. Methods:Comprehensive demographic, clinical, and therapeutic data were collected prospectively on all patients between 1990 and 2006. Patients were diagnosed with neurosyphilis if they had positive syphilis serologies and any of the following: (a) one or more cerebrospinal fluid abnormalities on lumbar puncture [white blood cells >10/μl; protein >50 mg/dl; reactive venereal diseases research laboratory], (b) an otherwise unexplained neurological finding. Results:Of 231 newly diagnosed syphilis cases, 41 neurosyphilis cases met entry criteria (median age 38.6 years, 79.1% male). Risk factors for neurosyphilis included a CD4 cell count of less than 350 cells/ml at the time of syphilis diagnosis (odds ratio: 2.87; 95% confidence interval: 1.18–7.02), a rapid plasma regain titer >1: 128 (2.83; 1.11–7.26), and male sex (2.46; 1.06–5.70). Use of any highly active antiretroviral therapy before syphilis infection reduced the odds of neurosyphilis by 65% (0.35; 0.14–0.91). Sixty-three percent of cases presented with early neurosyphilis and the median time to neurosyphilis diagnosis was 9 months. Symptomatic patients had more cerebrospinal fluid abnormalities on initial lumbar puncture than asymptomatic patients (P = 0.01). Follow-up lumbar puncture within 12 months revealed that only 38% had resolution of all cerebrospinal fluid abnormalities. At 1 year, 38% had persistence of their major symptom despite adequate treatment for neurosyphilis. Twelve of 41 (29%) patients were retreated for syphilis. Conclusion:Early neurosyphilis was common in this cohort. Highly active antiretroviral therapy to reverse immunosuppression may help mitigate neurological complications of syphilis.

Executive Summary: Primary Care Guidelines for the Management of Persons Infected With HIV: 2013 Update by the HIV Medicine Association of the Infectious Diseases Society of America

Evidence-based guidelines for the management of persons infected with human immunodeficiency virus (HIV) were prepared by an expert panel of the HIV Medicine Association of the Infectious Diseases Society of America. These updated guidelines replace those published in 2009. The guidelines are intended for use by healthcare providers who care for HIV-infected patients. Since 2009, new antiretroviral drugs and classes have become available, and the prognosis of persons with HIV infection continues to improve. However, with fewer complications and increased survival, HIV-infected persons are increasingly developing common health problems that also affect the general population. Some of these conditions may be related to HIV infection itself or its treatment. HIV-infected persons should be managed and monitored for all relevant age- and sex-specific health problems. New information based on publications from the period 2009-2013 has been incorporated into this document.

Serological response to syphilis treatment in HIV-positive and HIV-negative patients attending sexually transmitted diseases clinics

Background: HIV-positive patients treated for syphilis may be at increased risk for serological failure. Objective: To compare follow-up serologies and serological responses to treatment between HIV-positive and HIV-negative patients attending two sexually transmitted disease (STD) clinics. Study design: Existing records were reviewed from HIV-positive patients who were diagnosed and treated for syphilis at the public STD clinics in Baltimore, Maryland, USA, between 1992 and 2000. Results of their serological follow-up were compared with those of HIV-negative clinic patients at the time of syphilis treatment. Failure was defined as lack of a fourfold drop in rapid plasma reagin (RPR) titre by 400 days after treatment or a fourfold increased titre between 30 and 400 days. Results: Of the 450 HIV-positive patients with syphilis, 288 (64%) did not have documented follow-up serologies and 129 (28.5%) met the inclusion criteria; 168 (17%) of 1000 known HIV-negative patients were similarly eligible. There were 22 failures in the HIV-positive group and 5 in the HIV-negative group (p<0.001). The median times to successful serological responses in both groups were 278 (95% confidence interval (CI) 209 to 350) and 126 (95% CI 108 to 157) days, respectively (p<0.001). A multivariate Cox’s proportional hazards model showed an increased risk of serological failure among the HIV-positive patients (hazards ratio 6.0, 95% CI 1.5 to 23.9; p = 0.01). Conclusion: HIV-positive patients treated for syphilis may be at higher risk of serological failure. Despite recommendations for more frequent serological follow-up, most patients did not have documentation of serological response after standard treatment for syphilis.

Lumbar Puncture in HIV-Infected Patients with Syphilis and No Neurologic Symptoms

BACKGROUND The decision to perform lumbar puncture in patients with asymptomatic human immunodeficiency virus (HIV) infection and syphilis is controversial. The Centers for Disease Control and Prevention recommend certain criteria that warrant lumbar puncture. Here, we assess the performance of these criteria for detecting asymptomatic neurosyphilis (ANS). METHODS Eligible subjects consisted of all patients with concurrent HIV infection and syphilis in a prospective clinical cohort who had no neurologic symptoms at the time of lumbar puncture. We retrospectively applied different stratification criteria to calculate the performance of lumbar puncture in detecting ANS: (1) lumbar puncture in patients with late latent syphilis or syphilis of an unknown duration, regardless of the CD4 cell count or rapid plasma reagin titer; (2) lumbar puncture if the CD4 cell count was 350 cells/mL and/or the rapid plasma reagin titer was 1:32, regardless of the syphilis stage; and (3) lumbar puncture in the context of serologic nonresponse to syphilis therapy. RESULTS Two hundred two of 231 patients with syphilis did not have neurologic symptoms. Immediate lumbar puncture was performed for 46 patients, and 10 cases (22%) of ANS were detected. With use of the first criterion, 2 (14%) of 10 cases of ANS in patients with early-stage syphilis would have been missed (sensitivity, 80% [95% confidence interval [CI], 44%-97%]; specificity, 23% (95% confidence interval [CI], 11.4%-40.2%) [corrected] Criterion 2 would not have missed any cases of ANS (sensitivity, 100% [95% CI, 70%-100%]; specificity, 13.2% (95% CI, 4.4%-29.1%) [corrected] but would have required that a lumbar puncture be performed for 88% of patients. Performance of lumbar puncture performed in 13 cases based on serologic nonresponse to syphilis therapy yielded 4 cases (31%) of ANS. CONCLUSIONS In patients with concurrent HIV infection and syphilis, the use of criteria based on rapid plasma reagin titer and CD4 cell count, instead of stage-based criteria, improved the ability to identify ANS.

Male Circumcision and Risk of HIV Infection among Heterosexual African American Men Attending Baltimore Sexually Transmitted Disease Clinics

BACKGROUND Male circumcision has received international attention as an intervention for reducing HIV infection among high-risk heterosexual men; however, few US studies have evaluated its association with the risk of HIV infection. METHODS We analyzed visit records for heterosexual African American men who underwent HIV testing while attending sexually transmitted disease (STD) clinics in Baltimore, Maryland, from 1993 to 2000. We used multivariable binomial regression to evaluate associations between circumcision and the risk of HIV infection among visits by patients with known and unknown HIV exposure. RESULTS Overall, 1096 (2.7%) of 40,571 clinic visits yielded positive HIV test results. Among 394 visits by patients with known HIV exposure, circumcision was significantly associated with lower HIV prevalence (10.2% vs. 22.0%; adjusted prevalence rate ratio [PRR], 0.49 [95% confidence interval [CI], 0.26-0.93]). Conversely, among 40,177 visits by patients with unknown HIV exposure, circumcision was not associated with reduced HIV prevalence (2.5% vs. 3.3%; adjusted PRR, 1.00 [95% CI, 0.86-1.15]), and age >or=25 years old and diagnosis of ulcerative STD were associated with increased prevalence. CONCLUSIONS Circumcision was associated with substantially reduced HIV risk in patients with known HIV exposure, suggesting that results of other studies demonstrating reduced HIV risk for circumcision among heterosexual men likely can be generalized to the US context.

Antiretroviral Therapy Is Associated with Reduced Serologic Failure Rates for Syphilis among HIV-Infected Patients

BACKGROUND Syphilis and human immunodeficiency virus (HIV) frequently coexist in patients, but the effects of immunosuppression on the course of syphilis are unknown. Our goal was to determine whether the degree of HIV-mediated immunosuppression and the use of highly active antiretroviral therapy impact syphilis serologic responses. METHODS We assessed all cases of syphilis with positive serologic test results from 1990 through 2006 in a prospective, observational clinical cohort of HIV-infected patients. We defined seroreversion as the loss of reactivity in a patient who previously had a serologic test result positive for syphilis. We defined serologic failure as the lack of a 4-fold decrease in rapid plasma reagin titers 270-365 days after therapy or a 4-fold increase in titers > or =30 days after therapy. We used Cox proportional hazards models with statistical adjustments for multiple failure instances. RESULTS One hundred eighty subjects experienced 231 cases of syphilis. The median follow-up time was 5.3 years. A total of 71 episodes of serologic failure were documented. A CD4 cell count of <200 cells/mL at the time of syphilis diagnosis was associated with an increased risk of serologic failure (adjusted hazard ratio, 2.48; 95% confidence interval, 1.26-4.88). The receipt of highly active antiretroviral therapy was associated with a 60% reduction in the rate of serologic failure (adjusted hazard ratio, 0.40; 95% confidence interval, 0.21-0.75), independent of concomitant CD4 cell response. Rapid plasma reagin seroreversion was infrequent (16.1%) and inconsistent, and it was more likely to occur among patients who received macrolides. CONCLUSION The use of highly active antiretroviral therapy to reverse immunosuppression and the routine use of macrolides for the prevention of opportunistic infections may reduce syphilis serologic failure rates among HIV-infected patients who have syphilis.

Disseminated Acanthamebiasis in a Renal Transplant Recipient with Osteomyelitis and Cutaneous Lesions: Case Report and Literature Review

Disseminated acanthamebiasis is a rare disease that occurs predominantly in patients with human immunodeficiency virus (HIV) infection or acquired immunodeficiency syndrome but also in immunosuppressed transplant recipients. Few reports have focused on non-HIV-infected patients, in whom the disease is more likely to go unsuspected and undiagnosed before death. We describe a renal transplant recipient with Acanthamoeba infection and review the literature. The patient presented with osteomyelitis and widespread cutaneous lesions. No causative organism was identified before death, despite multiple biopsies with detailed histological analysis and culture. Disseminated Acanthamoeba infection was diagnosed after death, when cysts were observed in histological examination of sections of skin from autopsy, and trophozoites were found in retrospectively reviewed skin biopsy and surgical bone specimens. In any immunosuppressed patient, skin and/or bone lesions that fail to show improvement with broad-spectrum antibiotic therapy should raise the suspicion for disseminated acanthamebiasis. Early recognition and treatment may improve clinical outcomes.

Doxycycline Compared with Benzathine Penicillin for the Treatment of Early Syphilis

BACKGROUND Doxycycline is the preferred recommended second-line agent for the treatment of syphilis, although efficacy data from controlled trials are lacking. We compared the serological responses of patients with early syphilis treated with doxycycline with the responses of patients treated with benzathine penicillin G (BPG). METHODS All patients who received a diagnosis of early syphilis attending 2 public sexually transmitted disease clinics in Baltimore, Maryland, who were treated with doxycycline (100 mg orally, twice daily for 14 days) between October 1993 and June 2000 were eligible. Patients treated with BPG (a single dose of 2.4 million units intramuscularly) were selected as the control group. Inclusion criteria included a clinician-recorded diagnosis of primary, secondary, or early latent syphilis with reactive serological test results at the time of diagnosis and at least 1 follow-up serological test titer. Serological failure was defined as lack of a 4-fold drop in rapid plasma reagin titer 270-400 days after treatment, or a 4-fold increase in titer 30-400 days after therapy. RESULTS During the study period, 1558 patients were treated for early syphilis, and 87 received doxycycline. Of those treated with doxycycline, 34 met the inclusion criteria. Seventy-three patients from a randomly selected group of 200 age-matched individuals treated with BPG met the inclusion criteria. There were 4 patients with serological failure in the BPG group (5.5%; 95% confidence interval [CI], 1.6%-13.8%) and 0 patients with serological failure in the doxycycline group (0%; 95% CI, 0%-10.3%; P=.2). The median times to successful serological responses for patients in the doxycycline and BPG groups were 106 days (95% CI, 75-149 days) and 137 days (95% CI, 111-172 days), respectively (P=.6). CONCLUSION Doxycycline appears to be an effective agent for the treatment of early syphilis.