Systemic sclerosis (SSc) is an autoimmune fibrotic disease whose pathogenesis is poorly understood and lacks effective therapies. We undertook quantitative analyses of T cell infiltrates in the skin of 35 untreated patients with early diffuse SSc and here show that CD4⁺ cytotoxic T cells and CD8⁺ T cells contribute prominently to these infiltrates. We also observed an accumulation of apoptotic cells in SSc tissues, suggesting that recurring cell death may contribute to tissue damage and remodeling in this fibrotic disease. HLA-DR–expressing endothelial cells were frequent targets of apoptosis in SSc, consistent with the prominent vasculopathy seen in patients with this disease. A circulating effector population of cytotoxic CD4⁺ T cells, which exhibited signatures of enhanced metabolic activity, was clonally expanded in patients with systemic sclerosis. These data suggest that cytotoxic T cells may induce the apoptotic death of endothelial and other cells in systemic sclerosis. Cell loss driven by immune cells may be followed by overly exuberant tissue repair processes that lead to fibrosis and tissue dysfunction.

Background: Cervicovaginal bacterial communities composed of diverse anaerobes with low Lactobacillus abundance are associated with poor reproductive outcomes such as preterm birth, infertility, cervicitis, and risk of sexually transmitted infections (STIs), including human immunodeficiency virus (HIV). Women in sub-Saharan Africa have a higher prevalence of these high-risk bacterial communities when compared to Western populations. However, the transition of cervicovaginal communities between high- and low-risk community states over time is not well described in African populations. Results: We profiled the bacterial composition of 316 cervicovaginal swabs collected at 3-month intervals from 88 healthy young Black South African women with a median follow-up of 9 months per participant and developed a Markov-based model of transition dynamics that accurately predicted bacterial composition within a broader cross-sectional cohort. We found that Lactobacillus iners-dominant, but not Lactobacillus crispatus-dominant, communities have a high probability of transitioning to high-risk states. Simulating clinical interventions by manipulating the underlying transition probabilities, our model predicts that the population prevalence of low-risk microbial communities could most effectively be increased by manipulating the movement between L. iners- and L. crispatus-dominant communities. Conclusions: The Markov model we present here indicates that L. iners-dominant communities have a high probability of transitioning to higher-risk states. We additionally identify transitions to target to increase the prevalence of L. crispatus-dominant communities. These findings may help guide future intervention strategies targeted at reducing bacteria-associated adverse reproductive outcomes among women living in sub-Saharan Africa.

Smoking and human immunodeficiency virus 1 (HIV-1) infection are risk factors for chronic obstructive pulmonary disease (COPD), which is among the most common comorbid conditions in people living with HIV-1. HIV-1 infection leads to persistent expansion of CD8+ T cells, and CD8+ T cell–mediated inflammation has been implicated in COPD pathogenesis. In this study, we investigated the effects of HIV-1 infection and smoking on T-cell dynamics in patients at risk of COPD. BAL fluid, endobronchial brushings, and blood from HIV-1 infected and uninfected nonsmokers and smokers were analyzed by flow cytometry, and lungs were imaged by computed tomography. Chemokines were measured in BAL fluid, and CD8+ T-cell chemotaxis in the presence of cigarette smoke extract was assessed in vitro. HIV-1 infection increased CD8+ T cells in the BAL fluid, but this increase was abrogated by smoking. Smokers had reduced BAL fluid concentrations of the T cell–recruiting chemokines CXCL10 and CCL5, and cigarette smoke extract inhibited CXCL10 and CCL5 production by macrophages and CD8+ T-cell transmigration in vitro. In contrast to the T cells in BAL fluid, CD8+ T cells in endobronchial brushings were increased in HIV-1–infected smokers, which was driven by an accumulation of effector memory T cells in the airway mucosa and an increase in tissue-resident memory T cells. Mucosal CD8+ T-cell numbers inversely correlated with lung aeration, suggesting an association with inflammation and remodeling. HIV-1 infection and smoking lead to retention of CD8+ T cells within the airway mucosa.

Preexposure prophylaxis (PrEP) for HIV prevention uptake remains low among Black cisgender women in the United States, despite their disproportionate HIV burden. This study aimed to examine factors associated with Black women’s comfort discussing PrEP with healthcare providers and its link to their interest in PrEP use. A cross-sectional survey was conducted with a national sample of 315 Black cisgender women. Descriptive statistics and logistic regression models were utilized for data analysis. The results showed that 79% of Black women felt comfortable discussing PrEP with their healthcare provider. Age, recent healthcare provider visit, interest in PrEP, and positive social norms were associated with increased odds of comfort in discussing PrEP, while anticipated PrEP disapproval and stigma were associated with decreased odds. Older age was related to greater comfort, potentially due to increased familiarity and self-efficacy in discussing sexual health. Recent healthcare utilization indicated positive provider relationships, facilitating discussions about sexual health. Anticipating support from social networks positively influenced comfort levels. Conversely, PrEP-related stigma and anticipated disapproval were barriers to comfort. These findings highlight the importance of provider–patient communication and social support in facilitating PrEP engagement among Black cisgender women. Interventions should consider age-appropriate strategies and address structural and provider biases to improve PrEP discussions and promote HIV prevention.

Sexually transmitted infections (STIs) are highly prevalent in sub-Saharan Africa, where there is a severe HIV epidemic. Thus, accurate recognition and diagnosis of STIs are essential for successful HIV prevention programs in the region. Due to lack of trained personnel and adequate laboratory infrastructure in the region, information regarding the profile of STIs relies essentially on self-reported or physician-diagnosed symptoms. The main objective of the study was to assess the effectiveness of the syndromic diagnosis of STIs, which is often used as a proxy for laboratory diagnosis of STIs in sub-Saharan Africa and other resource-limited settings. The study builds on previously collected data from a community-based survey in Northern Tanzania. We found no significant agreements between patient-reported STIs symptoms and laboratory-confirmed STIs tests. The reported STIs symptoms had high specificity (range = 85–99%) and poor sensitivity (range = 2–17%). Knowledge gained from our study will have significant public health implications, and can help improve the syndromic diagnosis of STIs.

Treatments for HIV and other STIs are not readily available in sub-Saharan Africa and other resource-limited areas, where the prevalence of HIV and other STIs is high. In the absence of treatment and laboratory infrastructure to monitor treatment efficacy, increasing awareness of STIs and STI screening are crucial components of STI prevention programs. In the current study, we sought to estimate the awareness of STIs in resource-limited countries and evaluate the strength of the association between the awareness of STIs and STIs infection. We did a secondary analysis of data obtained from 2019 women and 794 men enrolled in a community-based study that was conducted from November 2002 to March 2003 in the Moshi Urban District of Northern Tanzania. We found gonorrhea, syphilis, and HIV/AIDS were well-known among the study participants. However, their awareness of other STIs, including herpes, was very low. We also found that the awareness of STIs was not associated with STIs in men, but women who had prior knowledge of gonorrhea, syphilis, and HIV had a twofold higher risk of testing positive for an STI. Education programs aimed at increasing awareness of STIs are needed in the region. The majority of the existing STI education programs in the region focus exclusively on HIV/AIDS. The expansion of the existing AIDS/HIV education programs needs to be strengthened to include information about other STIs.