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.

Peer Mentoring at the Uganda Cancer Institute: A Novel Model for Career Development of Clinician-Scientists in Resource-Limited Settings.

Cancer centers are beginning to emerge in low- and middle-income countries despite having relatively few oncologists and specialists in related fields. Uganda, like many countries in sub-Saharan Africa, has a cadre of highly motivated clinician-scientists-in-training who are committed to developing the capacity for cancer care and research. However, potential local mentors for these trainees are burdened with uniquely high demands on their time for clinical care, teaching, institutional development, advocacy, and research. Facilitated peer mentoring helps to fill skills and confidence gaps and teaches mentoring skills so that trainees can learn to support one another and regularly access a more senior facilitator/role model. With an added consultant component, programs can engage limited senior faculty time to address specific training needs and to introduce junior investigators to advisors and even potential dyadic mentors. Two years after its inception, our facilitated peer mentoring career development program at the Uganda Cancer Institute in Kampala is successfully developing a new generation of researchers who, in turn, are now providing role models and mentors from within their group. This program provides a practical model for building the next generation of clinical scientists in developing countries.

Seroprevalence of herpes simplex virus type 1 in children in the United States.

OBJECTIVES: To describe HSV-1 seroprevalence in children in the United States and to examine factors associated with herpes simplex virus type 1 (HSV-1) infection in children. STUDY DESIGN: Sera samples available from 2989 children age 6 to 13 years who participated in the National Health and Nutrition Examination Surveys (NHANES) 1999-2002 were tested for HSV-1 antibodies using a type-specific immunodot assay. HSV-1 seroprevalence in children age 12 to 13 years was compared with that reported in an earlier survey (NHANES 1988-1994). RESULTS: Overall, HSV-1 seroprevalence in children age 6 to 13 years was 31.1% (95% confidence interval [CI], 28.6% to 33.9%). Seroprevalence increased with age, from 26.3% in 6- to 7-year-olds to 36.1% in 12-to 13-year-olds, and varied by race/ethnicity, birthplace, and poverty level. Among US-born children age 12 to 13 years, the point estimate of HSV-1 seroprevalence was lower in NHANES 1999-2002 than in NHANES 1988-1994 (34.3% vs 38.1%), but the differences were not statistically significant. CONCLUSIONS: HSV-1 is a common infection in US children, with more than 25% infected by age 7. Race/ethnicity, birthplace, and poverty level are predictors for HSV-1 infection in children.

Brief communication: fatal human metapneumovirus infection in stem-cell transplant recipients.

BACKGROUND: Human metapneumovirus (hMPV), a recently discovered respiratory virus, is associated with clinical disease in young and elderly persons. OBJECTIVE: To determine the importance of hMPV in hematopoietic stem-cell transplant recipients. DESIGN: Retrospective survey of patients with consecutive residual bronchoalveolar lavage (BAL) samples. SETTING: Referral cancer center. PATIENTS: Hematopoietic stem-cell transplant recipients who underwent BAL because of lower respiratory tract disease. MEASUREMENTS: Bronchoalveolar lavage specimens were assayed by quantitative real-time polymerase chain reaction methods. RESULTS: Human metapneumovirus was detected in BAL specimens from 5 of 163 patients (3.0%). Persistent viral infection was noted in 3 patients with several samples, and hMPV was detected in 1 of 2 lung specimens tested. Infected patients became symptomatic within the first 40 days after transplantation. Initial symptoms included fever, cough, nasal congestion, and sore throat. Clinical findings included respiratory failure, pulmonary hemorrhage, and culture-negative septic shock. Four of 5 patients died with acute respiratory failure. LIMITATIONS: This retrospective study did not evaluate asymptomatic patients or those with mild disease. CONCLUSION: Human metapneumovirus infection in the lower respiratory tract is associated with respiratory failure in immunocompromised adults who were previously considered to have "idiopathic pneumonia." The infection may result in fulminant respiratory decompensation and shock after transplantation.