Claire C. Bristow

Multisite Laboratory Evaluation of a Dual Human Immunodeficiency Virus (HIV)/Syphilis Point-of-Care Rapid Test for Simultaneous Detection of HIV and Syphilis Infection

Background.  Recently, test developers have created rapid point-of-care tests that can simultaneously detect multiple infections within the same specimen using a single device. The SD BIOLINE Duo HIV/Syphilis rapid point-of-care test uses a solid-phase immunochromatographic assay to detect immunoglobulin (Ig)G, IgM, and IgA antibodies to human immunodeficiency virus (HIV)-specific antigens (HIV-1 gp41, sub O, HIV-2 gp36) and recombinant Treponema pallidum antigen (17 kDa) in human serum. This study was a multisite laboratory-based evaluation of the performance of SD BIOLINE HIV/Syphilis Duo test using previously characterized sera in 6 countries. Methods.  Laboratories in Ghana, Mexico, Laos, Togo, Kenya, and Myanmar participated in the evaluation during 2012–2013. Each site characterized sera using T pallidum particle agglutination assay or T pallidum hemagglutination assay and HIV enzyme immunoassay, Western blot, and/or HIV antibody rapid tests. Those gold standard test results were compared with SD BIOLINE Duo test results. We calculated the sensitivity and specificity of test performance and used the exact binomial method to calculate 95% confidence intervals (CIs). Results.  The sensitivity and specificity for the HIV antibody test component (n = 2336) were estimated at 99.91% (95% CI, 99.51% and 100%) and 99.67% (95% CI, 99.16% and 99.91%), respectively. For the T pallidum test component (n = 2059), the sensitivity and specificity were estimated at 99.67% (95% CI, 98.82% and 99.96%) and 99.72% (95% CI, 99.29% and 99.92%), respectively. Conclusions.  The sensitivity and specificity of the SD BIOLINE HIV/Syphilis Duo test were consistently high across sera specimens from 6 countries around the world. Dual rapid tests should be considered for improved HIV and syphilis screening coverage.

A Systematic Review of Point of Care Testing for Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis

Objectives. Systematic review of point of care (POC) diagnostic tests for sexually transmitted infections: Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Trichomonas vaginalis (TV). Methods. Literature search on PubMed for articles from January 2010 to August 2015, including original research in English on POC diagnostics for sexually transmitted CT, NG, and/or TV. Results. We identified 33 publications with original research on POC diagnostics for CT, NG, and/or TV. Thirteen articles evaluated test performance, yielding at least one test for each infection with sensitivity and specificity ≥90%. Each infection also had currently available tests with sensitivities <60%. Three articles analyzed cost effectiveness, and five publications discussed acceptability and feasibility. POC testing was acceptable to both providers and patients and was also demonstrated to be cost effective. Fourteen proof of concept articles introduced new tests. Conclusions. Highly sensitive and specific POC tests are available for CT, NG, and TV, but improvement is possible. Future research should focus on acceptability, feasibility, and cost of POC testing. While pregnant women specifically have not been studied, the results available in nonpregnant populations are encouraging for the ability to test and treat women in antenatal care to prevent adverse pregnancy and neonatal outcomes.

Meningitis in HIV-positive patients in sub-Saharan Africa: a review

Meningitis is one of the leading causes of death among patients living with HIV in sub‐Saharan Africa. There is no widespread tracking of the incidence rates of causative agents among patients living with HIV, yet the aetiologies of meningitis are different than those of the general population.

Piloting an HIV self-test kit voucher program to raise serostatus awareness of high-risk African Americans, Los Angeles

BackgroundUp to half of all new HIV cases in Los Angeles may be caused by the 20-30% of men who have sex with men (MSM) with unrecognized HIV infection. Racial/ethnic minority MSM are at particularly high risk for being sero-unaware and due to stigma and poor healthcare access might benefit from novel private, self-testing methods, such as the recently FDA-approved OraQuick® In-Home HIV Test.MethodsFrom July-November 2013, we undertook a pilot study to examine the feasibility of a voucher program for free OraQuick® tests targeting African American MSM in Los Angeles. We determined feasibility based on: (1) the establishment of a voucher redemption and third-party payment system, (2) the willingness of community-based organizations (CBOs) to disseminate vouchers, and (3) the collection of user demographics, test and linkage-to-care results with an anonymous telephone survey.ResultsWe partnered with Walgreens® to create a voucher and third-party reimbursement system for free OraQuick® tests. Voucher distribution was divided into two periods. In total, 641 vouchers were supplied to CBOs: 274 (42.7%) went to clients and of those 53 (19.3%) were redeemed. Fifty (18.2%) of the 274 clients were surveyed: 44 (88%) were African American, 39 (78%) reported being likely to repeat voucher use, 44 (88%) reported reviewing pre-test information, and 37 (74%) the post-test information. Three (6%) of 50 survey respondents reported newly testing HIV-positive of whom all (100%) reported seeking medical care. Two withheld their results, both of whom also sought medical care.ConclusionsDeveloping and partnering with a commercial pharmacy to institute a voucher system to facilitate HIV self-testing with linkage-to-care was feasible. Our findings suggest the voucher program was associated with increasing the identification of new cases of HIV infection with high rates of linkage to care. Expanded research and evaluation of voucher programs for HIV self-test kits among high-risk groups is warranted.

Chlamydia and Gonorrhea in HIV-Infected Pregnant Women and Infant HIV Transmission.

Background Sexually transmitted infections (STIs) such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) can lead to adverse pregnancy and neonatal outcomes. The prevalence of STIs and its association with HIV mother-to-child transmission (MTCT) were evaluated in a substudy analysis from a randomized, multicenter clinical trial. Methodology Urine samples from HIV-infected pregnant women collected at the time of labor and delivery were tested using polymerase chain reaction testing for the detection of CT and NG (Xpert CT/NG; Cepheid, Sunnyvale, CA). Infant HIV infection was determined by HIV DNA polymerase chain reaction at 3 months. Results Of the 1373 urine specimens, 249 (18.1%) were positive for CT and 63 (4.6%) for NG; 35 (2.5%) had both CT and NG detected. Among 117 cases of HIV MTCT (8.5% transmission), the lowest transmission rate occurred among infants born to CT- and NG-uninfected mothers (8.1%) as compared with those infected with only CT (10.7%) and both CT and NG (14.3%; P = 0.04). Infants born to CT-infected mothers had almost a 1.5-fold increased risk for HIV acquisition (odds ratio, 1.47; 95% confidence interval, 0.9–2.3; P = 0.09). Conclusions This cohort of HIV-infected pregnant women is at high risk for infection with CT and NG. Analysis suggests that STIs may predispose to an increased HIV MTCT risk in this high-risk cohort of HIV-infected women.

Predictors of serological failure after treatment in HIV-infected patients with early syphilis in the emerging Era of universal antiretroviral therapy use

BackgroundThe optimal treatment of early syphilis (primary, secondary and early latent) in HIV-infected patients remains controversial. The Center for Diseases Control STD Treatment Guidelines recommended 1 dose of benzathine penicillin G (BPG) regardless of HIV infection. However, many providers modify the treatment for early syphilis.MethodsWe performed a retrospective chart review of all cases of early syphilis with positive serologic test results in HIV-infected patients from May 2006 to May 2011 in 2 large, urban HIV clinics. Early syphilis includes primary, secondary, and early latent syphilis. Serological failure was defined as a lack of 4-fold decrease in rapid plasma reagent (RPR) titers 9 to 12 months after syphilis treatment. Patients whose RPR titers decreased after treatment and subsequently increased 4-fold at 9 to 12 months were excluded from the analysis of serological response because of possibility as “reinfection”. Baseline characteristics were tested as predictive factors of serological failure using a univariate and multivariate logistic regression model, respectively.ResultsOf 560 patients with confirmed cases of early syphilis, 51 (9.0%) experienced serological failure. Multivariate logistic regression modeling demonstrated that the predictive factors associated with serological failure after early syphilis treatment were baseline RPR titer ≤ 1:16 (OR 3.91 [95% CI, 2.04-7.47]), a previous history of syphilis (OR 3.12 [95% CI, 1.55-6.26]), and a CD4 T-cell count below 350 cells/ml (OR 2.41 [95% CI, 1.27-4.56]). Of note, type of syphilis treatment (1 dose versus 3 doses of BPG) did not appear to affect the proportion of serological failure (4% versus 10%, P = 0.29), however the power of this study to detect small differences was limited.ConclusionsHIV-infected patients with baseline RPR titer ≤1:16, syphilis history, and/or a CD4 T-cell count <350 cells/ml should be closely monitored for serologic failure after early syphilis treatment. This study did not detect a substantial difference between treatment with > 1 dose of BPG and decreased frequency of serological failure, supporting the current recommendation that one dose of BPG is adequate treatment for early syphilis in HIV-infected patients.

Laboratory Evaluation of a Dual Rapid Immunodiagnostic Test for HIV and Syphilis Infection

ABSTRACT New dual tests for HIV and syphilis have been developed. Our study aimed to evaluate the laboratory performance of a dual rapid immunodiagnostic test for HIV and syphilis. Our evaluation showed high performance of this dual rapid test, which should be considered for implementation to increase screening coverage and efficiency.

Field evaluation of a dual rapid diagnostic test for HIV infection and syphilis in Lima, Peru

Objectives Screening for HIV and syphilis in key populations is recommended by the WHO to reduce the morbidity, mortality and transmission associated with undiagnosed and untreated infections. Rapid point-of-care tests that can detect multiple infections with a single fingerprick whole blood specimen using a single device are gaining popularity. We evaluated the field performance of a rapid dual HIV and syphilis test in people at high risk of HIV and syphilis infections. Methods Participants included men who have sex with men and transgender women recruited in Lima, Peru. Reference standard testing for detection of HIV and syphilis infections, conducted using blood samples from venipuncture, included Treponema pallidum particle agglutination and fourth-generation HIV enzyme immunoassay for which positive results had a confirmation HIV Western blot test. For the evaluation test, SD BIOLINE HIV/Syphilis Duo test (Standard Diagnostics, Korea), a fingerprick blood specimen was used. Sensitivity and specificity were calculated and the exact binomial method was used to determine 95% CIs. Results A total of 415 participants were recruited for the study. The dual test sensitivity for detection of T. pallidum infection was 89.2% (95% CI 83.5% to 93.5%) and specificity 98.8% (95% CI 96.5% to 99.8%). For detection of HIV infection, the sensitivity of the dual test was 99.1% (95% CI 94.8% to 100%) and specificity 99.4% (95% CI 97.7% to 99.9%). Conclusions This high performing dual test should be considered for the use in clinical settings to increase uptake of simultaneous testing of HIV and syphilis and accelerate time to treatment for those who need it.

Laboratory Evaluation of Three Rapid Diagnostic Tests for Dual Detection of HIV and Treponema pallidum Antibodies

ABSTRACT The performance of three research-use-only, dual HIV and syphilis rapid diagnostic tests (RDTs) was evaluated for 150 patient serum samples and compared to reference HIV and Treponema pallidum antibody detection methods. The RDTs performed comparably, with sensitivities of 93 to 99% and specificities of 97 to 100%. The kappa statistic between the RDTs was 0.95.

Chlamydia trachomatis and Neisseria gonorrhoeae in HIV-infected Pregnant Women and Adverse Infant Outcomes

Background: Sexually transmitted infections (STIs) in pregnancy such as Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) may lead to adverse infant outcomes. Methods: Individual urine specimens from HIV-infected pregnant women diagnosed with HIV during labor were collected at the time of infant birth and tested by polymerase chain reaction for CT and NG. Infant HIV infection was determined at 3 months with morbidity/mortality assessed through 6 months. Results: Of 1373 maternal urine samples, 277 (20.2%) were positive for CT and/or NG; 249 (18.1%) for CT, 63 (4.6%) for NG and 35 (2.5%) for both CT and NG. HIV infection was diagnosed in 117 (8.5%) infants. Highest rates of adverse outcomes (sepsis, pneumonia, congenital syphilis, septic arthritis, conjunctivitis, low birth weight, preterm delivery and death) were noted in infants of women with CT and NG (23/35, 65.7%) compared with NG (16/28, 57.1%), CT (84/214, 39.3%) and no STI (405/1096, 37%, P = 0.001). Death (11.4% vs. 3%, P = 0.02), low birth weight (42.9% vs. 16.9%, P = 0.001) and preterm delivery (28.6% vs. 10.2%, P = 0.008) were higher among infants of CT and NG-coinfected women. Infants who had any adverse outcome and were born to women with CT and/or NG were 3.5 times more likely to be HIV infected after controlling for maternal syphilis (odds ratio: 3.5, 95% confidence interval: 1.4–8.3). By adjusted multivariate logistic regression, infants born to mothers with any CT and/or NG were 1.35 times more likely to have an adverse outcome (odds ratio, 1.35; 95% confidence interval, 1.03–1.76). Conclusions: STIs in HIV-infected pregnant women are associated with adverse outcomes in HIV-exposed infected and uninfected infants.