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Before the widespread adoption of vaccination, adenovirus type 4 and type 7 were long associated with respiratory illnesses among military recruits. When supplies were depleted and vaccination was suspended in 1999 for approximately a decade, respiratory illnesses due to adenovirus infections resurged. In March 2011, a new live, oral adenovirus vaccine was licensed by the US Food and Drug Administration and was first universally administered to military recruits in October 2011, leading to rapid, dramatic elimination of the disease within a few months. As part of licensure, a postmarketing study (Sentinel Surveillance Plan) was performed to detect potential safety signals within 42days after immunization of military recruits. This study retrospectively evaluated possible adverse events related to vaccination using data from the Armed Forces Health Surveillance Branch Defense Medical Surveillance System (DMSS) database. Among 100,000 recruits who received the adenovirus vaccine, no statistically significant greater risk of prespecified medical events was observed within 42days after vaccination when compared with a historical cohort of 100,000 unvaccinated recruits. In an initial statistical analysis of International Classification of Disease, 9th Revision, Clinical Modification codes, a statistically significant higher risk for 19 other (not prespecified) medical events occurring in 5 or more recruits was observed among vaccinated compared with unvaccinated groups. After case record data abstraction for attribution and validation, two events (psoriasis [21 vs 7 cases] and serum reactions [12 vs 4 cases]) occurred more frequently in the vaccinated cohort. A causal relation of these rare events with adenovirus vaccination could not be established given confounding factors in the DMSS, such as coadministration of other vaccines and incomplete or inaccurate medical information, for some recruits. Prospective surveillance assessing these uncommon, but potentially relevant, immune-related symptoms may be beneficial in defining potential causal association with adenovirus vaccination.

Objective To assess the risk for ventricular septal defects and congenital heart defects following zidovudine exposure during pregnancy using data from the Antiretroviral Pregnancy Registry. Study design Data on 16,304 prospectively reported pregnancies were analyzed to estimate the frequency and risk of ventricular septal defects and congenital heart defects, comparing exposure between zidovudine-containing regimens and non-zidovudine antiretroviral regimens. The numerator includes defect cases in outcomes at ≥20 weeks of gestational age. The denominator includes live birth outcomes. Infants with chromosomal anomalies were excluded. Results There were 15,451 live birth outcomes; 13,073 were prenatally exposed to zidovudine-containing regimens and 2378 to non-zidovudine containing regimens. There were 36 ventricular septal defect cases: 31 exposed to prenatal zidovudine and 5 unexposed. Nine of the zidovudine-exposed cases had earliest exposure in the first trimester; 22 had second/third trimester exposure. Of the 5 ventricular septal defect cases not exposed to zidovudine, 2 had earliest exposure to non-zidovudine antiretroviral regimens in the first trimester, and 3 had exposure in the second/third trimester. The prevalence of ventricular septal defect was 0.24% (95% confidence interval: 0.16, 0.34) for infants exposed to zidovudine-containing regimens and 0.21% (95% confidence interval: 0.07, 0.49) for non-zidovudine regimens. The relative risk comparing the 2 was 1.13 (95% confidence interval: 0.44, 2.90). There were a total of 90 congenital heart defect cases; 78 were exposed prenatally to zidovudine-containing regimens, and 12 were unexposed. Twenty-six of the zidovudine-exposed cases had earliest exposure in the first trimester and 52 had second/third trimester exposure. Six congenital heart defect cases with non-zidovudine antiretroviral regimens had earliest exposure in the first trimester and 6 had exposure in the second/third trimester. The prevalence of congenital heart defects was 0.60% (95% confidence interval: 0.47, 0.74) for infants exposed to zidovudine-containing regimens and 0.50% (95% confidence interval: 0.26, 0.88) for non-zidovudine regimens. The relative risk comparing the 2 was 1.18 (95% confidence interval: 0.64, 2.17). Conclusions The prevalence and risk of ventricular septal defects and congenital heart defects among infants exposed to zidovudine-containing regimens is not significantly different from the prevalence and risk in infants exposed to non-zidovudine containing regimens. Clinical Trial Registration ClinicalTrials.gov identifier: NCT01137981 .

Background The antiretroviral (ARV) pregnancy registry, an international voluntary registry, provides information on teratogenicity and non-defect adverse pregnancy outcomes. Methods We analyzed ARV pregnancy registry prospective singleton pregnancies, estimating frequencies of and risk for nondefect adverse outcomes among HIV-infected women. Prenatal exposures to abacavir (ABC)-containing regimens vs. non-ABC ARV regimens, and lamivudine (3TC)-containing regimens vs. non-3TC regimens were compared. Results Of 2006 outcomes with prenatal ABC exposure, 95.6% were live births; 4.4% were spontaneous/induced abortions and stillbirths. Of live births, 16.2% had low birth weight (LBW); 11.9% were preterm births. Relative risks comparing exposure to ABC vs. non-ABC ARV regimens were spontaneous abortions 0.92 [95% confidence interval (CI): 0.66 to 1.27], induced abortions 0.84 (95% CI: 0.59 to 1.21), stillbirths 0.59 (95% CI: 0.35 to 1.00), preterm births 0.96 (95% CI: 0.84 to 1.09), and LBW 1.00 (95% CI: 0.90 to 1.13). Of 11,211 outcomes with prenatal 3TC exposure, 95.3% were live births; 4.7% were spontaneous/induced abortions and stillbirths. Of live births, 16.2% had LBW; 11.9% were preterm births. The relative risks comparing exposure to 3TC vs. non-3TC ARV regimens were spontaneous abortions 0.63 (95% CI: 0.50 to 0.80), induced abortions 0.54 (95% CI: 0.43 to 0.69), stillbirths 1.25 (95% CI: 0.86 to 1.80), preterm births 0.86 (95% CI: 0.77 to 0.95), and LBW 1.02 (95% CI: 0.93 to 1.12). Conclusions ABC-containing and non-ABC ARV regimens have similar risks for non-birth defect adverse pregnancy outcomes. 3TC-containing regimens have lower risk for spontaneous abortions, induced abortions, and preterm births compared with non-3TC ARV regimens, whereas both regimens had similar prevalence and risks for stillbirths and LBW.

Background Concern that the use of exogenous testosterone may increase breast cancer risk coexists with rising use of this medication in the United States. We sought to examine the relationship between the use of estrogen plus testosterone (E + T) therapy (esterified estradiol plus methyltestosterone) and the occurrence of breast cancer. Methods A total of 31 842 postmenopausal participants in the Women's Health Initiative Observational Study were followed for a mean of 4.6 years. At the 3-year visit, E + T users were compared with non–hormone therapy users for time to incident invasive breast cancer. Cox proportional hazards estimates were adjusted for known predictors of breast cancer including prior hormone use and screening mammography. Results Thirty five women using E + T at visit 3 developed invasive breast cancer. Use of E + T had a nonsignificant impact on invasive breast cancer risk (adjusted hazard ratio, 1.42; 95% confidence interval, 0.95-2.11). The most commonly used E + T preparation, Estratest, was associated with a significant elevation in invasive breast cancer (adjusted hazard ratio, 1.78; 95% confidence interval, 1.05-3.01). However, rates of breast cancer were lower in longer-term E + T users than in shorter-term E + T users. Conclusion Although our results have less strength than an initial report linking E + T to breast cancer, we found a modest, albeit nonsignificant, elevation in breast cancer risk associated with E + T use.