OBJECTIVE:Vaginitis may be diagnosed as bacterial vaginosis, vulvovaginal candidiasis, trichomoniasis, or coinfection. A new molecular test assays the vaginal microbiome and organisms that cause ...three common infections. The objective of the trial was to evaluate the clinical accuracy of the investigational test for vaginal swabs collected by patients (self) or clinicians. The primary and secondary outcomes were to compare the investigational test with reference methods for the three most common causes of vaginitis and compare clinician-collected with self-collected swabs.
METHODS:We conducted a cross-sectional study in which women with symptoms of vaginitis were recruited at ten clinical centers and consented to the investigation between May and September 2015. The woman collected a vaginal swab, sheathed, and then handed it to the clinician. These swabs were to evaluate how self-collected swabs compared with clinician-collected swabs. The clinician collected an investigational test swab and reference test swabs. From 1,740 symptomatic patients, clinician-collected and self-collected vaginal swabs were evaluated by the molecular test and six tests. The reference methods for bacterial vaginosis were Nugentʼs score and Amselʼs criteria for intermediate Nugent results. The reference methods for Candida infection were isolation of any potential Candida microorganisms from inoculation of two culture mediachromogenic and Sabouraud agar and sequencing. The reference methods for trichomoniasis were wet mount and culture.
RESULTS:For clinician-collected swabs, by reference methods, bacterial vaginosis was diagnosed in 56.5%, vaginal candidiasis in 32.8%, trichomoniasis in 8%, and none of the three infections in 24% with a coinfection rate of 20%. The investigational test sensitivity was 90.5% (95% confidence interval CI 88.3–92.2%) and specificity was 85.8% (95% CI 83.0–88.3%) for bacterial vaginosis. The investigational test sensitivity was 90.9% (95% CI 88.1–93.1%) and specificity was 94.1% (95% CI 92.6–95.4%) for the Candida group. Sensitivity for Candida glabrata was 75.9% (95% CI 57.9–87.8%) and specificity was 99.7% (95% CI 99.3–99.9%). Investigational test sensitivity was 93.1% (95% CI 87.4–96.3%) and specificity was 99.3% (95% CI 98.7–99.6%) for trichomoniasis. Results from self-collected swabs were similar to clinician-collected swabs.
CONCLUSION:A molecular-based test using vaginal swabs collected by clinicians or patients can accurately diagnose most common bacterial, fungal, and protozoan causes of vaginitis. Women and their clinicians seeking accurate diagnosis and appropriate selection of efficacious treatment for symptoms of vaginitis might benefit from this molecular test.
Rapid HIV assays are the mainstay of HIV testing globally. Delivery of effective biomedical HIV prevention strategies such as antiretroviral pre-exposure prophylaxis (PrEP) requires periodic HIV ...testing. Because rapid tests have high (>95%) but imperfect specificity, they are expected to generate some false positive results.
We assessed the frequency of true and false positive rapid results in the Partners PrEP Study, a randomized, placebo-controlled trial of PrEP. HIV testing was performed monthly using 2 rapid tests done in parallel with HIV enzyme immunoassay (EIA) confirmation following all positive rapid tests.
A total of 99,009 monthly HIV tests were performed; 98,743 (99.7%) were dual-rapid HIV negative. Of the 266 visits with ≥1 positive rapid result, 99 (37.2%) had confirmatory positive EIA results (true positives), 155 (58.3%) had negative EIA results (false positives), and 12 (4.5%) had discordant EIA results. In the active PrEP arms, over two-thirds of visits with positive rapid test results were false positive results (69.2%, 110 of 159), although false positive results occurred at <1% (110/65,945) of total visits.
When HIV prevalence or incidence is low due to effective HIV prevention interventions, rapid HIV tests result in a high number of false relative to true positive results, although the absolute number of false results will be low. Program roll-out for effective interventions should plan for quality assurance of HIV testing, mechanisms for confirmatory HIV testing, and counseling strategies for persons with positive rapid test results.
Daily oral preexposure prophylaxis (PrEP) using the antiretroviral tenofovir disoproxil fumarate (TDF) alone or in combination with emtricitabine (FTC-TDF) reduces the risk for HIV-1 acquisition. ...Tenofovir has in vitro activity against herpes simplex virus type 2 (HSV-2).
To assess the efficacy of daily oral PrEP with tenofovir and FTC-TDF in the prevention of HSV-2 acquisition.
Subgroup analysis of data from a randomized, placebo-controlled trial with concealed allocation. (ClinicalTrials.gov: NCT00557245).
Multiple sites in Kenya and Uganda.
Heterosexual men and women who were seronegative for HIV-1 and HSV-2 and at high risk for HIV-1 acquisition due to having an HIV-1-infected partner.
Once-daily oral tenofovir disoproxil fumarate (TDF), alone or combined with emtricitabine (FTC-TDF), compared with placebo.
HSV-2 seroconversion.
A total of 131 participants seroconverted to HSV-2 (79 of 1041 assigned to tenofovir or FTC-TDF PrEP HSV-2 incidence, 5.6 per 100 person-years and 52 of 481 assigned to placebo HSV-2 incidence, 7.7 per 100 person-years). The hazard ratio (HR) for HSV-2 acquisition with daily oral PrEP was 0.70 (95% CI, 0.49 to 0.99; P = 0.047) compared with placebo, and the absolute risk reduction was 2.1 per 100 person-years. Among the 1044 participants with HSV-2-infected partners, the HR for PrEP was 0.67 (CI, 0.46 to 0.98; P = 0.038) compared with placebo, and the absolute risk reduction was 3.1 per 100 person-years.
Randomization was not stratified by HSV-2 status, and diagnostic tests to exclude participants with acute HSV-2 at baseline are not available.
Daily oral tenofovir-based PrEP significantly reduced the risk for HSV-2 acquisition among heterosexual men and women. Modest protection against HSV-2 is an added benefit of HIV-1 prevention with oral tenofovir-based PrEP.
Bill & Melinda Gates Foundation.
Abstract
New tools are needed to support pre-exposure prophylaxis (PrEP) adherence for human immunodeficiency virus (HIV) prevention, including those that enable real-time feedback. In a large, ...completed PrEP trial, adequate urine tenofovir levels measured using a novel immunoassay predicted HIV protection and showed good sensitivity and specificity for detectable plasma tenofovir.
Diagnostic options to combat the increasing rates of sexually transmitted infections recorded throughout the world increasingly include multiplex assays. Here we describe the estimated sensitivity ...and specificity of a triplex molecular assay that simultaneously detects Chlamydia trachomatis (CT), Neisseria gonorrhoeae (or gonococci GC), and Trichomonas vaginalis (TV).
Participants (2547 women and 1159 men) were recruited from 12 clinics in the United States. BD CTGCTV2 for BD MAX System assay (CTGCTV2) results were obtained from vaginal and endocervical swabs, endocervical samples in cytology medium, and female and male urine. Results were compared with infection standards that were sample type and pathogen dependent.
Female specimen sensitivity estimates ranged from 92.7% to 98.4%, 92.9% to 100%, and 86.6% to 100% for CT, GC and TV, respectively. Male urine sensitivity estimates were 96.7%, 99.2%, and 97.9% for CT, GC, and TV, respectively. Specificity estimates were >98.7% for all sample types.
BD CTGCTV2 performed well using a variety of sample types. As a true triplex assay, performed using a benchtop instrument, BD CTGCTV2 may be useful in settings where no testing is currently performed and in settings, such as reference laboratories, where testing turnaround time may be several days. Use of this assay at local laboratories may result in greater access to testing and a shorter time to result, which are important steps for improving our ability to combat sexually transmitted infections.
Much of the research examining predictors of HIV testing has used retrospective self-report to assess HIV testing. Findings. therefore, may be subject to recall bias and to difficulties determining ...the direction of associations. In this prospective study, we administered surveys to women in community clinics to identify predictors of subsequent observed HIV testing, overcoming these limitations. Eighty-three percent were tested. In the adjusted multivariable model, being born in the U.S., perceived benefits of testing, worries about being infected with HIV, having had more than 15 lifetime sexual partners, and having had one or more casual sexual partners in the previous three months predicted acceptance of testing. Perceived obstacles to testing predicted non-acceptance. Those who had never been tested for HIV and those tested two to five years previously had greater odds of test acceptance than those who had been tested within the last year. The findings from this study with observed testing as the outcome, confirm some of the results from retrospective, self-report studies. Participants made largely rational decisions about testing, reflecting assessments of their risk and their history of HIV testing. Health beliefs are potentially modifiable through behavioral intervention, and such interventions might result in greater acceptance of testing.
Abbreviations: HIV: human immunodeficiency virus; AIDS: acquired immune deficiency syndrome; CDC: Centers for Disease Control and Prevention; ACASI: audio computer-assisted self-interview; TRA: theory of reasoned action; HBM: Health Belief Model; STI: sexually transmitted infection; STD: Sexually Transmitted Disease; AOR: adjusted odds ratio; CI: confidence interval
To determine the clinical and immunological outcomes of a cohort of HIV-infected patients receiving antiretroviral therapy.
Retrospective study of prospectively collected data from consecutively ...enrolled adult HIV-infected patients in eight HIV clinics in western Kenya.
CD4 cell counts, weight, mortality, loss to follow-up and adherence to antiretroviral therapy were collected for the 2059 HIV-positive non-pregnant adult patients treated with antiretroviral drugs between November 2001 and February 2005.
Median duration of follow-up after initiation of antiretroviral therapy was 40 weeks (95% confidence interval, 38-43); 111 patients (5.4%) were documented as deceased and 505 (24.5%) were lost to follow-up. Among 1766 (86%) evaluated for adherence to their antiretroviral regimen, 78% reported perfect adherence at every visit. Although patients with and without perfect adherence gained weight, patients with less than perfect adherence gained 1.04 kg less weight than those reporting perfect adherence (P = 0.059). CD4 cell counts increased by a mean of 109 cells/microl during the first 6 weeks of therapy and increased more slowly thereafter, resulting in overall CD4 cell count increases of 160, 225 and 297 cells/microl at 12, 24, and 36 months respectively. At 1 year, a mean increase of 170 cells/microl was seen among patients reporting perfect adherence compared with 123 cells/microl among those reporting some missed doses (P < 0.001).
Antiretroviral treatment of adult Kenyans in this cohort resulted in significant and persistent clinical and immunological benefit. These findings document the viability and effectiveness of large-scale HIV treatment initiatives in resource-limited settings.
Background. Daily suppressive therapy with valacyclovir reduces risk of sexual transmission of herpes simplex virus type 2 (HSV-2) in HSV-2–serodiscordant heterosexual couples by 48%. Whether ...suppressive therapy reduces HSV-2 transmission from persons coinfected with HSV-2 and human immunodeficiency virus type 1 (HIV-1) is unknown. Methods. Within a randomized trial of daily acyclovir 400 mg twice daily in African HIV-1 serodiscordant couples, in which the HIV-1–infected partner was HSV-2 seropositive, we identified partnerships in which HIV-1–susceptible partners were HSV-2 seronegative to estimate the effect of acyclovir on risk of HSV-2 transmission. Results. We randomly assigned 911 HSV-2/HIV-1–serodiscordant couples to daily receipt of acyclovir or placebo. We observed 68 HSV-2 seroconversions, 40 and 28 in acyclovir and placebo groups, respectively (HSV-2 incidence, 5.1 cases per 100 person-years; hazard ratio HR, 1.35 95% confidence interval, .83-2.20; P=.22). Among HSV-2–susceptible women, vaginal drying practices (adjusted HR, 44.35; P = .004) and unprotected sex (adjusted HR, 9.91; P = .002) were significant risk factors for HSV-2 acquisition; having more children was protective (adjusted HR, 0.47 per additional child; P = .012). Among HSV-2–susceptible men, only age ≤30 years was associated with increased risk of HSV-2 acquisition (P = .016). Conclusions. Treatment of African HSV-2/HIV-1–infected persons with daily suppressive acyclovir did not decrease risk of HSV-2 transmission to susceptible partners. More-effective prevention strategies to reduce HSV-2 transmission from HIV-1–infected persons are needed.
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