Objective: The purpose of this study was to evaluate differences in vaginal immune cell populations, vaginal tissue gene expression, anti-microbial activity of the cervicovaginal (CV) fluid lavage (CVL), vaginal flora and p24 antigen production from CV tissues after ex vivo HIV infection between the follicular (FOL) and luteal (LUT) phases of the menstrual cycle. Methods: CV tissue biopsies, CV secretions and blood samples were obtained as part of two longitudinal clinical trials of healthy women (CONRAD D11-119 and A12-124 studies). Participants (n = 39) were HIV seronegative women not using exogenous hormone supplementation, with normal menstrual cycles, who were screened to exclude sexually transmitted and reproductive tract infections. Results: Serum levels of estradiol and progesterone were significantly higher in the LUT versus the FOL phase of the menstrual cycle. Controlling for race, reported contraceptive use/sexual practices, and clinical trial, we found no differences in vaginal tissue immune cell populations and activation status, transcriptomes, inhibition of HIV, herpes simplex virus type 2 (HSV2) and Escherichia coli (E. coli) by the CVL, vaginal pH or Nugent score or production of p24 antigen after ex vivo infection by HIV-1BaL between CV samples obtained in the FOL versus the LUT phase of the menstrual cycle. There were no significant correlations between serum estradiol and progesterone levels and CV endpoints. Conclusion: The hypothesis that the LUT phase of the menstrual cycle represents a more vulnerable stage for mucosal infection with HIV was not supported by data from samples obtained from the lower genital tract (ectocervix and vagina) from these two clinical trials. Key Words: Follicular, Luteal, Menstrual Cycle, HIV acquisition, mucosa

We examined the mechanism of human immunodeficiency virus (HIV) type 1 infection of human uterine epithelial cells to gain a clearer understanding of the events by which HIV-1 infects cells within the female reproductive tract. We demonstrated that these cells can be productively infected by HIV-1 and that infection is associated with viral RNA reverse transcription, DNA transcription, and secretion of infectious virus. Levels of viral DNA and secreted virus decreased gradually after infection. Moreover, virus released by the uterine epithelial cells shortly after infection was able to infect human T cell lines, but virus released later did not. In contrast, human CD4⁺ T cell lines were infected after cocultivation with epithelial cells at both early and late stages of infection. These data demonstrated that HIV-1 infects human epithelial cells of upper reproductive tract origin and that productive viral infection of epithelial cells may be an important mechanism of transmission of HIV-1 infection in women

Objectives: The interferon-gamma–induced chemokine CXCL9 is expressed in a wide range of inflammatory conditions including those affecting the female genital tract. CXCL9 promotes immune cell recruitment, activation, and proliferation. The role of CXCL9 in modulating HIV-1 infection of cervicovaginal tissues, a main portal of viral entry, however, has not been established. We report a link between CXCL9 and HIV-1 replication in human cervical tissues and propose CXCL9 as a potential target to enhance the anti–HIV-1 activity of prophylactic antiretrovirals. Design: Using ex vivo infection of human cervical tissues as a model of mucosal HIV-1 acquisition, we described the effect of CXCL9 neutralization on HIV-1 gene expression and mucosal CD4⁺ T-cell activation. The anti-HIV-1 activity of tenofovir, the leading mucosal pre-exposure prophylactic microbicide, alone or in combination with CXCL9 neutralization was also studied. Methods: HIV-1 replication was evaluated by p24 ELISA. HIV-1 DNA and RNA, and CD4, CCR5, and CD38 transcription were evaluated by quantitative real-time polymerase chain reaction. Frequency of activated cervical CD4⁺ T cells was quantified using fluorescence-activated cell sorting. Results: Antibody blocking of CXCL9 reduced HIV-1 replication by decreasing mucosal CD4⁺ T-cell activation. CXCL9 neutralization in combination with suboptimal concentrations of tenofovir, possibly present in the cervicovaginal tissues of women using the drug inconsistently, demonstrated an earlier and greater decrease in HIV-1 replication compared with tissues treated with tenofovir alone. Conclusions: CXCL9 neutralization reduces HIV-1 replication and may be an effective target to enhance the efficacy of prophylactic antiretrovirals.

While vitamin D insufficiency is known to impact a multitude of health outcomes, including HIV-1, little is known about the role of vitamin D-mediated immune regulation in the female reproductive tract (FRT). We performed a pilot clinical study of 20 women with circulating 25(OH)D levels <62.5 nmol/L. Participants were randomized into either weekly or daily high-dose oral vitamin D supplementation groups. In addition to serum vitamin D levels, genital mucosal endpoints, including soluble mediators, immune cell populations, gene expression, and ex vivo HIV-1 infection, were assessed. While systemic vitamin D levels showed a significant increase following supplementation, these changes translated into modest effects on the cervicovaginal factors studied. Paradoxically, post-supplementation vitamin D levels were decreased in cervicovaginal fluids. Given the strong correlation between vitamin D status and HIV-1 infection and the widespread nature of vitamin D deficiency, further understanding of the role of vitamin D immunoregulation in the female reproductive tract is important.

Background: Respiratory viral infections are a major public health challenge and the most diagnosed medical condition, particularly for individuals living in close proximity, like military personnel. We compared the sensitivity and specificity of the Biomeme FranklinTM and Truelab® RT-PCR thermocyclers to determine which platform is more sensitive and specific at detecting SARS-CoV-2 and influenza A and B viruses. Methodology: RNA extracted from nasopharyngeal swabs of infected and uninfected individuals was tested on the Biomeme FranklinTM at Lackland and the Truelab® at Wright Patterson Air Force bases. Results: We found an 88% and 71% positivity rate in SARS-CoV-2-infected samples tested on Biomeme and Truelab®, respectively. Likewise, we found a 49% and 80% positivity rate in influenza-positive samples tested on Biomeme and Truelab®, respectively. One hundred percent of uninfected swab samples tested negative for SARS-CoV-2 on both platforms. Conversely, 91% and 100% of uninfected swabs tested negative for flu on Biomeme and Truelab®, respectively. Significance: Differences in specificity and sensitivity in detection of SARS-CoV-2 and influenza between Biomeme and Truelab® suggest that Truelab® is a more promising and potentially deployable diagnostic platform for SARS-CoV-2 and influenza viruses’ detection in an austere environment.

The coronavirus disease 2019 (COVID-19) pandemic magnified long-standing disparities in health care. Among the general population, racial/ethnic minorities often face disproportional barriers, such as poverty, reduced health literacy, a generational mistrust of health-care institutions, and limited access to health care, contributing to the disparities reported in severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection and outcomes. Racial/ethnic minorities in the military comprise nearly 43% of active-duty service members and face disproportionate health burdens influenced by systemic and individual factors. As a result, minority service members within the military health system had similar rates of SARS-CoV-2 testing compared to those of white service members. Reports have found that while the rates of testing are similar, SARS-CoV-2 infection remained disproportionately higher among Black and Hispanic service members. This perspective examines disparities in the United States military, focusing on the role of social determinants of health, comorbidities, risk factors, and access to care in shaping COVID-19 health outcomes.