Clinical Performance of the BD CTGCTV2 Assay for the BD MAX System for Detection of Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis Infections.

BACKGROUND: 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). METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Behavior and health beliefs as predictors of HIV testing among women: a prospective study of observed HIV testing.

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.

Transient Increase in Herpes Simplex Virus Type 2 (HSV-2)-Associated Genital Ulcers Following Initiation of Antiretroviral Therapy in HIV/HSV-2-Coinfected Individuals.

BACKGROUND: Immune reconstitution inflammatory syndrome (IRIS) in human immunodeficiency virus (HIV)-infected persons beginning antiretroviral therapy (ART) has been incompletely characterized for herpes simplex virus type 2 (HSV-2). METHODS: We evaluated genital ulcer disease (GUD) and HSV-2-associated GUD at quarterly visits or when spontaneously reported at monthly visits in 3381 HIV/HSV-2-coinfected individuals in a placebo-controlled trial of suppressive acyclovir therapy to prevent HIV transmission, 349 of whom initiated ART during the study. Incidence was calculated for months before and after ART initiation, and incidence rate ratios (IRRs) were calculated. RESULTS: GUD incidence increased from 15.0 episodes per 100 person-years before ART to 26.9 episodes per 100 person-years in the first full quarter after ART initiation (IRR, 1.83;P= .03), and the incidence of HSV-2-associated GUD increased from 8.1 to 19.0 episodes per 100 person-years (IRR, 2.20;P= .02). Subsequently, the incidence of GUD was similar to that before ART, although the numbers were small. Persons receiving suppressive acyclovir had fewer GUD episodes, but the IRR after beginning ART was similar in the acyclovir and placebo groups. CONCLUSIONS: Initiation of ART in HIV/HSV-2-coinfected persons is associated with a transient increase in GUD and HSV-2 GUD. Acyclovir reduces the incidence of GUD but does not prevent an increase in GUD incidence during the first quarter following initiation of ART.

Effect of Condom Use on Per-act HSV-2 Transmission Risk in HIV-1, HSV-2-discordant Couples.

BACKGROUND: The efficacy of condoms for protection against transmission of herpes simplex virus type 2 (HSV-2) has been examined in a variety of populations with different effect measures. Often the efficacy has been assessed as change in hazard of transmission with consistent vs inconsistent use, independent of the number of acts. Condom efficacy has not previously measured on a per-act basis. METHODS: We examined the per-act HSV-2 transmission rates with and without condom use among 911 African HSV-2 and human immunodeficiency virus type 1 (HIV-1) serodiscordant couples followed for an average of 18 months in an HIV prevention study. Infectivity models were used to associate the log10 probability of HSV-2 transmission over monthly risk periods with reported numbers of protected and unprotected sex acts. Condom efficacy was computed as the proportionate reduction in transmission risk for protected relative to unprotected sex acts. RESULTS: Transmission of HSV-2 occurred in 68 couples, including 17 with susceptible women and 51 with susceptible men. The highest rate of transmission was from men to women: 28.5 transmissions per 1000 unprotected sex acts. We found that condoms were differentially protective against HSV-2 transmission by sex; condom use reduced per-act risk of transmission from men to women by 96% (P < .001) and marginally from women to men by 65% (P = .060). CONCLUSIONS: Condoms are recommended as an effective preventive method for heterosexual transmission of HSV-2.

Antiretroviral prophylaxis for HIV prevention in heterosexual men and women.

BACKGROUND: Antiretroviral preexposure prophylaxis is a promising approach for preventing human immunodeficiency virus type 1 (HIV-1) infection in heterosexual populations. METHODS: We conducted a randomized trial of oral antiretroviral therapy for use as preexposure prophylaxis among HIV-1-serodiscordant heterosexual couples from Kenya and Uganda. The HIV-1-seronegative partner in each couple was randomly assigned to one of three study regimens--once-daily tenofovir (TDF), combination tenofovir-emtricitabine (TDF-FTC), or matching placebo--and followed monthly for up to 36 months. At enrollment, the HIV-1-seropositive partners were not eligible for antiretroviral therapy, according to national guidelines. All couples received standard HIV-1 treatment and prevention services. RESULTS: We enrolled 4758 couples, of whom 4747 were followed: 1584 randomly assigned to TDF, 1579 to TDF-FTC, and 1584 to placebo. For 62% of the couples followed, the HIV-1-seronegative partner was male. Among HIV-1-seropositive participants, the median CD4 count was 495 cells per cubic millimeter (interquartile range, 375 to 662). A total of 82 HIV-1 infections occurred in seronegative participants during the study, 17 in the TDF group (incidence, 0.65 per 100 person-years), 13 in the TDF-FTC group (incidence, 0.50 per 100 person-years), and 52 in the placebo group (incidence, 1.99 per 100 person-years), indicating a relative reduction of 67% in the incidence of HIV-1 with TDF (95% confidence interval [CI], 44 to 81; P<0.001) and of 75% with TDF-FTC (95% CI, 55 to 87; P<0.001). Protective effects of TDF-FTC and TDF alone against HIV-1 were not significantly different (P=0.23), and both study medications significantly reduced the HIV-1 incidence among both men and women. The rate of serious adverse events was similar across the study groups. Eight participants receiving active treatment were found to have been infected with HIV-1 at baseline, and among these eight, antiretroviral resistance developed in two during the study. CONCLUSIONS: Oral TDF and TDF-FTC both protect against HIV-1 infection in heterosexual men and women. (Funded by the Bill and Melinda Gates Foundation; Partners PrEP ClinicalTrials.gov number, NCT00557245.).

Daily oral tenofovir and emtricitabine-tenofovir preexposure prophylaxis reduces herpes simplex virus type 2 acquisition among heterosexual HIV-1-uninfected men and women: a subgroup analysis of a randomized trial.

BACKGROUND: 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). OBJECTIVE: To assess the efficacy of daily oral PrEP with tenofovir and FTC-TDF in the prevention of HSV-2 acquisition. DESIGN: Subgroup analysis of data from a randomized, placebo-controlled trial with concealed allocation. (ClinicalTrials.gov: NCT00557245). SETTING: Multiple sites in Kenya and Uganda. PARTICIPANTS: 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. INTERVENTION: Once-daily oral tenofovir disoproxil fumarate (TDF), alone or combined with emtricitabine (FTC-TDF), compared with placebo. MEASUREMENTS: HSV-2 seroconversion. RESULTS: 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. LIMITATION: Randomization was not stratified by HSV-2 status, and diagnostic tests to exclude participants with acute HSV-2 at baseline are not available. CONCLUSION: 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. PRIMARY FUNDING SOURCE: Bill & Melinda Gates Foundation.

The effects of HIV testing advocacy messages on test acceptance: a randomized clinical trial.

BACKGROUND: Nearly 1 in 5 people living with HIV in the United States are unaware they are infected. Therefore, it is important to develop and evaluate health communication messages that clinicians can use to encourage HIV testing. METHODS: The objective was to evaluate health communication messages designed to increase HIV testing rates among women and evaluate possible moderators of message effect. We used a randomized four-arm clinical trial conducted at urban community outpatient health clinics involving 1,919 female patients, 18 to 64 years old. The four health message intervention groups were: i) information-only control; ii) one-sided message describing the advantages of HIV testing; iii) two-sided message acknowledging a superficial objection to testing (i.e., a 20 minute wait for results) followed by a description of the advantages of testing; and iv) two-sided message acknowledging a serious objection (i.e., fear of testing positive for HIV) followed by a description of the advantages of testing. The main outcome was acceptance of an oral rapid HIV test. RESULTS: Participants were randomized to receive the control message (n = 483), one-sided message (n = 480), two-sided message with a superficial objection (n = 481), or two-sided message with a serious objection (n = 475). The overall rate of HIV test acceptance was 83%. The two-sided message groups were not significantly different from the controls. The one-sided message group, however, had a lower rate of testing (80%) than the controls (86%) (OR, 0.66; 95% CI, 0.47-0.93; P = 0.018). "Perceived obstacles to HIV testing" moderated this effect, indicating that the decrease in HIV test acceptance for the one-sided message group was only statistically significant for those who had reported high levels of obstacles to HIV testing (OR, 0.36; 95% CI, 0.19-0.67; P = 0.001). CONCLUSIONS: None of the messages increased test acceptance. The one-sided message decreased acceptance and this effect was particularly true for women with greater perceived obstacles to testing, the very group one would most want to persuade. This finding suggests that efforts to persuade those who are reluctant to get tested, in some circumstances, may have unanticipated negative effects. Other approaches to messaging around HIV testing should be investigated, particularly with diverse, behaviorally high-risk populations. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00771537. Registration date: October 10. 2008.

Daily acyclovir to decrease herpes simplex virus type 2 (HSV-2) transmission from HSV-2/HIV-1 coinfected persons: a randomized controlled trial.

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.

Plasma viral loads during early HIV-1 infection are similar in subtype C- and non-subtype C-infected African seroconverters.

Recent data suggest that infection with human immunodeficiency virus type 1 (HIV-1) subtype C results in prolonged high-level viremia (>5 log10 copies/mL) during early infection. We examined the relationship between HIV-1 subtype and plasma viremia among 153 African seroconverters. Mean setpoint viral loads were similar for C and non-C subtypes: 4.36 vs 4.42 log10 copies/mL (P = .61). The proportion of subtype C-infected participants with viral loads >5 log10 copies/mL was not greater than the proportion for those with non-C infection. Our data do not support the hypothesis that higher early viral load accounts for the rapid spread of HIV-1 subtype C in southern Africa.

Herpes simplex virus type 2 suppressive therapy with acyclovir or valacyclovir does not select for specific HIV-1 resistance in HIV-1/HSV-2 dually infected persons.

Recent in vitro studies suggest that acyclovir may directly inhibit HIV-1 replication and can select for a specific HIV-1 reverse transcriptase mutation (V75I) with concomitant loss of an anti-HIV-1 effect. We tested for HIV-1 genotypic resistance at reverse transcriptase codon 75 in plasma from 168 HIV-1-infected persons from Botswana, Kenya, Peru, and the United States taking daily acyclovir or valacyclovir for between 8 weeks and 24 months. No V75I cases were detected (95% confidence interval, 0%-2.2%). These prospective in vivo studies suggest that standard-dose acyclovir or valacyclovir does not select for HIV-1 resistance.

Daily acyclovir for HIV-1 disease progression in people dually infected with HIV-1 and herpes simplex virus type 2: a randomised placebo-controlled trial.

BACKGROUND: Most people infected with HIV-1 are dually infected with herpes simplex virus type 2. Daily suppression of this herpes virus reduces plasma HIV-1 concentrations, but whether it delays HIV-1 disease progression is unknown. We investigated the effect of acyclovir on HIV-1 progression. METHODS: In a trial with 14 sites in southern Africa and east Africa, 3381 heterosexual people who were dually infected with herpes simplex virus type 2 and HIV-1 were randomly assigned in a 1:1 ratio to acyclovir 400 mg orally twice daily or placebo, and were followed up for up to 24 months. Eligible participants had CD4 cell counts of 250 cells per mL or higher and were not taking antiretroviral therapy. We used block randomisation, and patients and investigators were masked to treatment allocation. Effect of acyclovir on HIV-1 disease progression was defined by a primary composite endpoint of first occurrence of CD4 cell counts of fewer than 200 cells per microL, antiretroviral therapy initiation, or non-trauma related death. As an exploratory analysis, we assessed the endpoint of CD4 falling to <350 cells per microL. Analysis was by intention to treat. The trial is registered with ClinicalTrials.gov, number NCT00194519. FINDINGS: At enrollment, the median CD4 cell count was 462 cells per microL and median HIV-1 plasma RNA was 4.1 log(10) copies per microL. Acyclovir reduced risk of HIV-1 disease progression by 16%; 284 participants assigned acyclovir versus 324 assigned placebo reached the primary endpoint (hazard ratio [HR] 0.84, 95% CI 0.71-0.98, p=0.03). In those with CD4 counts >or=350 cells per microL, aciclovir delayed risk of CD4 cell counts falling to <350 cells per microL by 19% (0.81, 0.71-0.93, p=0.002) INTERPRETATION: The role of suppression of herpes simplex virus type 2 in reduction of HIV-1 disease progression before initiation of antiretroviral therapy warrants consideration. FUNDING: Bill & Melinda Gates Foundation.

Performance of the Focus HerpeSelect-2 enzyme immunoassay for the detection of herpes simplex virus type 2 antibodies in seven African countries.

OBJECTIVE: To compare the performance of the Focus HerpeSelect-2 enzyme immunoassay (EIA) with the gold standard herpes simplex virus (HSV) type 2 western blot, among HIV-1-uninfected men and women in east and southern Africa. METHODS: 3399 HIV-1-uninfected women and men from seven countries in east and southern Africa were tested for HSV-2 antibody using the Focus HerpeSelect-2 EIA. The performance of the HerpesSelect-2 EIA was compared with the gold standard HSV-2-specific western blot. RESULTS: Two-thirds (2294/3399) of participants were male and two-thirds (2242/3399) were from east Africa. By western blot testing, HSV-2 prevalence was 68%; 59% in men and 85% in women. At the manufacturer's recommended cut-off value of greater than 1.1, the HerpeSelect-2 EIA had a sensitivity of 98.3% and specificity of 80.3%. Receiver operating characteristic plot analysis indicated that the optimum cut-off was 2.1 or greater, with sensitivity 93.9% and specificity 90.5%. Diagnostic accuracy was modestly higher for southern Africa (area under the curve (AUC) 0.979, 95% CI 0.970 to 0.988) compared with east Africa (AUC 0.954, 95% CI 0.942 to 0.965; p<0.001 for southern vs east Africa). CONCLUSIONS: The Focus HerpeSelect-2 EIA has acceptable diagnostic accuracy for the determination of HSV-2 serostatus in African HIV-1-uninfected adults. An assay cut-off value of 2.1 or greater results in approximately 90% sensitivity and specificity, against a gold standard HSV-2 western blot. Diagnostic accuracy differed slightly by geographical region.

Imiquimod 3.75% cream applied daily to treat anogenital warts: combined results from women in two randomized, placebo-controlled studies.

OBJECTIVE: To evaluate if new imiquimod formulations using a shorter treatment duration are safe and efficacious to treat anogenital warts. METHODS: In two studies 534 women ≥12 years of age (mean 33.4) with 2-30 warts (mean 7.9) and total wart area ≥10 mm(2) (mean 166.3) were randomized (1:2:2) to placebo (106), imiquimod 2.5% (212) or 3.75% (216) creams applied once daily until complete clearance or a maximum of 8 weeks. RESULTS: For placebo, imiquimod 2.5% and 3.75%, respectively, complete clearance of all warts was achieved in 14.2%, 28.3%, and 36.6% of women (intent-to-treat, P = 0.008 imiquimod 2.5%, and P < 0.001 3.75% versus placebo). Mean changes in wart counts were -10.7%, -50.9%, and -63.5% (per-protocol, P < 0.001 each active versus placebo) and safety-related discontinuation rates 0.9%, 1.4%, and 2.3%. CONCLUSIONS: Imiquimod 3.75% applied daily for up to 8 weeks was well tolerated and superior to placebo in treating women with external anogenital warts.

Herpes simplex virus type 2 infection in young adult women: risk factors for infection and frequency of viral shedding.

BACKGROUND: Population-based studies suggest that acquisition of herpes simplex virus 2 (HSV 2) is most common between ages 20 and 29, especially in minority women. We examined HSV 2 infection and viral shedding in a cohort of young women. METHODS: Women, age 18 to 24 (median 21), who were part of an observational cohort enrolled between ages 14 to 17, had blood obtained for HSV 2 antibody. Intensive diary collections on sexual behavior and genital symptoms and weekly vaginal swabs were obtained at regular intervals. RESULTS: HSV 2 antibodies were detected in 43 of 127 participants (33.9%), only 4 of whom were previously known to be positive. Factors associated with a positive test included older age, years of sexual activity, and number of lifetime partners. Testing for HSV 2 DNA by polymerase chain reaction on weekly vaginal swabs from a 13-week sampling period for each HSV 2 antibody positive participant showed 32 of 43 (74.4%) were positive at least once. The positive predictive value of pain for viral shedding was poor. CONCLUSIONS: HSV 2 infection is very common among young adult women, but symptomatic genital herpes is not. Shedding of HSV 2 DNA can be detected in most antibody positive persons. Early intervention strategies will be needed to control HSV 2 infection.

Implementation of routine access to herpes simplex virus type 2 antibody testing in a public health sexually transmitted disease clinic.

BACKGROUND: Testing for herpes simplex virus type 2 (HSV-2) antibody is not common in clinical practice. Client characteristics associated with HSV-2 rapid antibody test uptake and test positivity were analyzed in clients attending an urban sexually transmitted disease clinic. METHODS: This optional test was available for $30. The HerpeSelect Express assay was performed on serum. Demographic and behavioral characteristics were compared between clients who requested testing and those who did not and between those who were HSV-2 antibody positive and negative. RESULTS: In 4 months, 3498 individuals attended the clinic and 443 (12.7%) opted for HSV-2 testing. Clients who were black, younger, or female were less likely to request testing. Recent sexual behavior and self-reported sexual orientation were not associated with uptake of testing. Of the 442 clients with results available, 109 were positive for HSV-2 antibody (24.7%). Women were significantly (P <0.001) more likely to test positive; 42 of 111 (38.4%) versus only 67 of 331 (20.2%) men. A positive HSV-2 antibody test was also associated with increasing age and black race. There was an association with the number of partners in the last 30 days, but no association with the number of partners in the last year. Of the 109 clients who had a positive HSV-2 antibody test, 71 (64.5%) accepted a prescription for suppressive acyclovir therapy. CONCLUSIONS: Uptake of testing was modest in this population, especially among the highest risk individuals, possibly due to the cost of the test. Improved education regarding HSV-2 and subsidized testing may be needed in the populations that have the highest prevalence in order to encourage testing.

Once daily valacyclovir for reducing viral shedding in subjects newly diagnosed with genital herpes.

OBJECTIVE: Genital herpes (GH) recurrences and viral shedding are more frequent in the first year after initial HSV-2 infection. The objective of this study was to provide the first evaluation of valacyclovir 1 g once daily compared to placebo in reducing viral shedding in subjects newly diagnosed with GH. METHODS: 70 subjects were randomized to receive valacyclovir 1 g daily or placebo in a crossover design for 60 days with a 7-day washout period. A daily swab of the genital/anal-rectal area was self-collected for HSV-2 detection by PCR. Subjects attended the clinic for routine study visits and GH recurrence visits. Treatment differences were assessed using a nonparametric crossover analysis. RESULTS: 52 subjects had at least one PCR measurement in both treatment periods and comprised the primary efficacy population. Valacyclovir significantly reduced HSV-2 shedding during all days compared to placebo (mean 2.9% versus 13.5% of all days (P < .01), a 78% reduction). Valacyclovir significantly reduced subclinical HSV-2 shedding during all days compared to placebo (mean 2.4% versus 11.0% of all days (P < .01), a 78% reduction). However, 79% of subjects had no GH recurrences while receiving valacyclovir compared to 52% of subjects receiving placebo (P < .01). CONCLUSION: In this study, the frequency of total and subclinical HSV-2 shedding was greater than reported in earlier studies involving subjects with a history of symptomatic genital recurrences. Our study is the first to demonstrate a significant reduction in viral shedding with valacyclovir 1 g daily compared to placebo in a population of subjects newly diagnosed with HSV-2 infection.

The Centers for Disease Control and Prevention revised recommendations for HIV testing: reactions of women attending community health clinics.

The purpose of this study was to examine reactions to the Centers for Disease Control and Prevention revised recommendations for HIV testing by women attending community health clinics. A total of 30 women attending three community clinics completed semistructured individual interviews containing three questions about the recommendations. Thematic content analysis of responses was conducted. Results were that all agreed with the recommendation for universal testing. Most viewed opt-out screening as an acceptable approach to HIV testing. Many emphasized the importance of provision of explicit verbal informed consent. The majority strongly opposed the elimination of the requirement for pretest prevention counseling and spontaneously talked about the ongoing importance of posttest counseling. The conclusion was that there was strong support for universal testing of all persons 13 to 64 years old but scant support for the elimination of pretest prevention counseling. In general, respondents believed that verbal informed consent for testing as well as provision of HIV-related information before and after testing were crucial.

Clinical Validation of a Test for the Diagnosis of Vaginitis.

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 Nugent's score and Amsel's criteria for intermediate Nugent results. The reference methods for Candida infection were isolation of any potential Candida microorganisms from inoculation of two culture media: chromogenic 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.