Antiretroviral preexposure prophylaxis for heterosexual HIV transmission in Botswana.

BACKGROUND: Preexposure prophylaxis with antiretroviral agents has been shown to reduce the transmission of human immunodeficiency virus (HIV) among men who have sex with men; however, the efficacy among heterosexuals is uncertain. METHODS: We randomly assigned HIV-seronegative men and women to receive either tenofovir disoproxil fumarate and emtricitabine (TDF-FTC) or matching placebo once daily. Monthly study visits were scheduled, and participants received a comprehensive package of prevention services, including HIV testing, counseling on adherence to medication, management of sexually transmitted infections, monitoring for adverse events, and individualized counseling on risk reduction; bone mineral density testing was performed semiannually in a subgroup of participants. RESULTS: A total of 1219 men and women underwent randomization (45.7% women) and were followed for 1563 person-years (median, 1.1 years; maximum, 3.7 years). Because of low retention and logistic limitations, we concluded the study early and followed enrolled participants through an orderly study closure rather than expanding enrollment. The TDF-FTC group had higher rates of nausea (18.5% vs. 7.1%, P<0.001), vomiting (11.3% vs. 7.1%, P=0.008), and dizziness (15.1% vs. 11.0%, P=0.03) than the placebo group, but the rates of serious adverse events were similar (P=0.90). Participants who received TDF-FTC, as compared with those who received placebo, had a significant decline in bone mineral density. K65R, M184V, and A62V resistance mutations developed in 1 participant in the TDF-FTC group who had had an unrecognized acute HIV infection at enrollment. In a modified intention-to-treat analysis that included the 33 participants who became infected during the study (9 in the TDF-FTC group and 24 in the placebo group; 1.2 and 3.1 infections per 100 person-years, respectively), the efficacy of TDF-FTC was 62.2% (95% confidence interval, 21.5 to 83.4; P=0.03). CONCLUSIONS: Daily TDF-FTC prophylaxis prevented HIV infection in sexually active heterosexual adults. The long-term safety of daily TDF-FTC prophylaxis, including the effect on bone mineral density, remains unknown. (Funded by the Centers for Disease Control and Prevention and the National Institutes of Health; TDF2 ClinicalTrials.gov number, NCT00448669.).

Malignancy in U.S. Air Force fighter pilots and other officers, 1986-2017: A retrospective cohort study.

OBJECTIVE: This study sought to determine the incidence rates of cancer, overall and by site, among active component U.S. Air Force fighter pilots, and to compare the rates with those in other active component Air Force officers. METHODS: Using a matched retrospective cohort design, U.S. Air Force fighter pilots were compared with other commissioned officers who entered active component service between 1 January 1986 and 31 December 2006. The cohort was followed for cancer diagnoses in TRICARE and the Veterans Health Administration from 1 October 1995 through 31 December 2017. Fighter pilots and non-fighter pilot officers were compared after matching on sex, age at first observation (15 age groups), and age at last observation (15 age groups). Sex-stratified overall and site-specific cancer rates were compared with matched Poisson regression to determine incidence rate ratios with 95% confidence intervals. RESULTS: During 1,412,590 person-years of follow-up, among the study population of 88,432 service members (4,949 fighter pilots and 83,483 matched officers), 977 incident cancer cases were diagnosed (86 in fighter pilots and 891 in matched officers). Male fighter pilots and matched officers had similar rates of all malignant cancers (RR = 1.04; 95% CI: 0.83-1.31) and of each cancer site. Female fighter pilots and matched officers also had similar rates of all malignant cancers (RR = 0.99; 95% CI: 0.25-4.04). DISCUSSION: In the active component U.S. Air Force, fighter pilots and their officer peers had similar overall and site-specific cancer rates.

Positive predictive value of an algorithm used for cancer surveillance in the U.S. Armed Forces.

Recent large-scale epidemiologic studies of cancer incidence in the U.S. Armed Forces have used International Classification of Disease, 9th and 10th Revision (ICD-9 and ICD-10, respectively) diagnostic codes from administrative medical encounter data archived in the Defense Medical Surveillance System. Cancer cases are identified and captured according to an algorithm published by the Armed Forces Health Surveillance Branch. Standardized chart reviews were performed to provide a gold standard by which to validate the case definition algorithm. In a cohort of active component U.S. Air Force, Navy, and Marine Corps officers followed from 1 October 1995 through 31 December 2017, a total of 2,422 individuals contributed 3,104 algorithm-derived cancer cases. Of these cases, 2,108 (67.9%) were classified as confirmed cancers, 568 (18.3%) as confirmed not cancers, and 428 (13.8%) as unclear. The overall positive predictive value (PPV) of the algorithm was 78.8% (95% confidence interval [CI]: 77.2-80.3). For the 12 cancer sites with at least 50 cases identified by the algorithm, the PPV ranged from a high of 99.6% for breast and testicular cancers (95% CI: 97.8-100.0 and 97.7-100.0, respectively) to a low of 78.1% (95% CI: 71.3-83.9) for non-Hodgkin lymphoma. Of the 568 cases confirmed as not cancer, 527 (92.7%) occurred in individuals with at least 1 other confirmed cancer, suggesting algorithmic capture of metastases as additional primary cancers.

Evaluation of serological testing for Lyme disease in Military Health System beneficiaries in Germany, 2013-2017.

Lyme disease diagnostic workups conducted on active and retired U.S. service members and their dependents at U.S. Air Force military treatment facilities (MTFs) in Germany between 2013 and 2017 were assessed to determine the appropriateness of laboratory testing and antibiotic prescriptions. Of the 1,176 first-tier immunoassays, 1,114 (94.7%) were negative, and of the 285 immunoglobulin M (IgM) immunoblots, 242 (84.9%) followed a negative first-tier assay or were performed without an antecedent first-tier assay. Eighty-three positive IgM immunoblot tests were adjudicated using modified published criteria, of which 40 (48.2%) were deemed false positives. Thirtytwo patients with false-positive tests were treated with an antibiotic. Additionally, 30 patients with uncomplicated erythema migrans could have been treated without laboratory confirmation. Understanding the use and limitations of 2-tier diagnostic criteria, as well as the common pitfalls in diagnosing Lyme disease, may help prevent overdiagnosis, reduce unnecessary testing, and promote antibiotic stewardship.

Physical and Mental Health of US Air Force Military Training Instructors.

INTRODUCTION: Many epidemiologic studies have been performed in military recruit populations, but little is known about the health of those who conduct the training. This study aims to characterize the physical and mental health of a military trainer cohort. MATERIALS AND METHODS: All US Air Force military training instructors (MTIs) who served between 1 October 2011 and 30 September 2016 were included in this retrospective descriptive study. All International Classification of Diseases, Ninth or Tenth Revision codes received by MTIs as inpatients or outpatients in the TRICARE system were obtained and mapped to Clinical Classifications Software levels. After excluding routine and administrative codes, the relative burden of disease by diagnostic category and subcategory was calculated, with further classification of musculoskeletal conditions by anatomic site. For all conditions accounting for at least 1.0% of the burden of care, incidence density rates and incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated to compare males and females. RESULTS: A total of 1,269 MTIs received 32,601 non-administrative, non-routine diagnoses while accumulating 50,376 person-months of exposure during the surveillance period. Musculoskeletal conditions were the greatest contributor to overall disease burden, accounting for 39.1% of all diagnoses, followed by mental health (10.4%), respiratory (10.1%), and neurologic and sensory (9.8%). The burden attributed to mental health conditions decreased by 54% over the 5-year period. Twenty-three conditions accounted for at least 1.0% of the healthcare burden. The highest incidence conditions were connective tissue disease (27.18 per 1,000 person-months), non-traumatic joint disorders (25.74), upper respiratory infections (25.14), and back pain (23.70). As compared to males, females had a higher incidence of several conditions, including adjustment disorders (IRR: 2.57; 95% CI: 1.61, 4.11) and anxiety disorders (IRR: 2.24; 95% CI: 1.33, 3.77). CONCLUSIONS: Musculoskeletal conditions are the leading contributor to burden of care among US Air Force MTIs, followed by mental health, respiratory, and neurologic and sensory conditions. The burden of healthcare among US Air Force MTIs more closely resembles active component service members than recruit trainees.

Randomized trial of clinical safety of daily oral tenofovir disoproxil fumarate among HIV-uninfected men who have sex with men in the United States.

OBJECTIVES: To evaluate the clinical safety of daily tenofovir disoproxil fumarate (TDF) among HIV-negative men who have sex with men. DESIGN: Randomized, double-blind, placebo-controlled trial. Participants were randomized 1:1:1:1 to immediate or delayed study drug (TDF, 300 mg orally per day, or placebo). METHODS: Four hundred healthy HIV-uninfected men who have sex with men reporting anal sex with another man within the previous 12 months enrolled in Atlanta, Boston, and San Francisco. HIV serostatus, clinical and laboratory adverse events (AEs), adherence (pill count, Medication Event Monitoring System, and self-report), and sexual and other sociobehavioral data were assessed at 3-month intervals for 24 months. Primary outcomes were clinical safety, assessed by incidence of AEs and laboratory abnormalities. RESULTS: Study drug was initiated by 373 (93%) participants (186 TDF and 187 placebo), of whom 325 (87%) completed the final study visit. Of 2428 AEs reported among 334 (90%) participants, 2366 (97%) were mild or moderate in severity. Frequencies of commonly reported AEs did not differ significantly between TDF and placebo arms. In multivariable analyses, back pain was more likely among TDF recipients (P = 0.04); these reports were not associated with documented fractures or other objective findings. There were no grade ≥3 creatinine elevations; grades 1 and 2 creatinine increases were not associated with TDF receipt. Estimated percentage of study drug doses taken was 92% by pill count and 77% by Medication Event Monitoring System. Seven seroconversions occurred: 4 on placebo and 3 among delayed arm participants not yet on study drug. CONCLUSIONS: Daily oral TDF was well tolerated, with reasonable adherence. No significant renal concerns were identified.